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Psychopharmacology Mind Map
This detailed mind map, created using EdrawMind, provides a comprehensive overview of psychopharmacology, focusing on pharmacological treatments for psychotic symptoms. It branches into key categories including antipsychotics (both typical and atypical), antidepressants, anti-epileptic medications (AEDs) used in mood stabilization and anti-seizure treatments, and their applications in specific populations and conditions such as Parkinson's disease psychosis and lactating mothers with bipolar disorder, offering a structured insight into the field.
Edited at 2025-10-21 16:08:45
- Psychopharmacology Mind Map
This detailed mind map, created using EdrawMind, provides a comprehensive overview of psychopharmacology, focusing on pharmacological treatments for psychotic symptoms. It branches into key categories including antipsychotics (both typical and atypical), antidepressants, anti-epileptic medications (AEDs) used in mood stabilization and anti-seizure treatments, and their applications in specific populations and conditions such as Parkinson's disease psychosis and lactating mothers with bipolar disorder, offering a structured insight into the field.
- Classification of Psychopathology
This mind map provides a comprehensive classification of psychopathology, detailing various categories of mental disorders. It starts with the main topic "Classification of Psychopathology" and branches out into major categories such as Neurocognitive Disorders, Mood Disorders, Psychotic Disorders, Anxiety Disorders, and more. Each category is further subdivided into specific disorders, with some including additional characteristics or criteria. For example, Substance Use Disorder lists Dx Criteria including tolerance, withdrawal, and social occupational decline. This visual representation helps in understanding the complex structure and relationships within psychopathology classifications.
- Depressive Disorders Diagnosis and Assessment
This mind map provides a comprehensive overview of depressive disorders, focusing on diagnosis and assessment. It covers medications associated with depression, drugs of abuse that can induce depression, and secondary depression medical etiologies. The map details specific medical conditions that can lead to depression, such as neoplasms, immune disorders, cardiac conditions, endocrine disorders, and neurologic disorders. Additionally, it outlines the diagnosis criteria for substance/medication-induced depressive disorder and depression due to another medical condition, highlighting core symptoms and contributing factors.
Psychopharmacology Mind Map
- Psychopharmacology Mind Map
This detailed mind map, created using EdrawMind, provides a comprehensive overview of psychopharmacology, focusing on pharmacological treatments for psychotic symptoms. It branches into key categories including antipsychotics (both typical and atypical), antidepressants, anti-epileptic medications (AEDs) used in mood stabilization and anti-seizure treatments, and their applications in specific populations and conditions such as Parkinson's disease psychosis and lactating mothers with bipolar disorder, offering a structured insight into the field.
- Classification of Psychopathology
This mind map provides a comprehensive classification of psychopathology, detailing various categories of mental disorders. It starts with the main topic "Classification of Psychopathology" and branches out into major categories such as Neurocognitive Disorders, Mood Disorders, Psychotic Disorders, Anxiety Disorders, and more. Each category is further subdivided into specific disorders, with some including additional characteristics or criteria. For example, Substance Use Disorder lists Dx Criteria including tolerance, withdrawal, and social occupational decline. This visual representation helps in understanding the complex structure and relationships within psychopathology classifications.
- Depressive Disorders Diagnosis and Assessment
This mind map provides a comprehensive overview of depressive disorders, focusing on diagnosis and assessment. It covers medications associated with depression, drugs of abuse that can induce depression, and secondary depression medical etiologies. The map details specific medical conditions that can lead to depression, such as neoplasms, immune disorders, cardiac conditions, endocrine disorders, and neurologic disorders. Additionally, it outlines the diagnosis criteria for substance/medication-induced depressive disorder and depression due to another medical condition, highlighting core symptoms and contributing factors.
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- Outline
Psychopharmacology
main types of neurotransmitter receptors
DrugDrug Interactions
Smoking Effects
Induces CYP1A2 decreases plasma concentrations of certain antidepressants
Subtopic
Subtopic
Main Topic
Main Topic
Ligand:
Types of Exogenous ligands
Agonist
Full
Drug with full physiologic effect Of neurotransmitter
partial
Drug with partial physiologic effect Of neurotransmitter
Function;
– If too much 5-HT in the brain, partial agonist acts as an antagonist, reducing 5HT’s effects – If too little 5-HT in the brain, partial agonist acts as 5-HT agonist
eg
buprenorphine at mu opioid receptors
If a person is high on Opioids and he is given buprenorphine he will have a withdrawal
But if a person in withdrawal for example approximately 14days His withdrawals will decrease with Buprenorphine
aripiprazole at 5-HT1A
buspirone at 5-HT1A
Function
Molecule that mimics/facilitates the effects of the NT it is substituting for it
Antagonist
Blocker
has no intrinsic NT effects and that blocks any ligand from acting – ‘blockers’
Inverse agonist
Inverse agonist: triggers opposite action of receptor to that of agonist – Receptor activity drops below basal (or constitutive) level – Ex: Pimavanserin (Nuplazid): 5-HT2a inverse agonist
types of Endogenous Ligands
Hormones
Steroid
testosterone
cortisol
Peptide
insulin
growth hormone
Amino Acid-Derived
thyroxine
Cytokines
Tumor Necrosis Factor
Interleukins
Interferons
Neurotransmitters
Based on function
stop
Captain
GABA
Without it, your brain would be constantly over-excited, leading to seizures
Subtopic
Subtopic
Subtopic
go
Captain
Glutamate
Function
learning and memory
Subtopic
Subtopic
Based on chemical structure
Amino acid
GABA
Glutamate
Mono amine
Serotonin
Mood Stabilizer
Dopamine
Reward & Motivation Driver
Norepinephrine
Alertness & Focus Booster
Unique category
Acetylcholine
Function
Excitatory
Movement & Memory Specialist
Endorphins:
Function
Inhibitory
Natural Painkiller
Definition
means any molecule that binds to a receptor – Neurotransmitter (NT): intrinsic ligand – Medication or drug Or toxin : extrinsic ligand
Inhibitor
drug that interferes with the normal function of a NT transporter
eg SSRI block SERT
Receptor
Changes
Desensitization
Down regulation
Action of Drug on the Body; Mechanisms of action
1
Neurotransmitter release
Eg Triptans PREVENT release of presynaptic 5HT From Vesicle
5-HT 1D agonists →constrict cranial arteries
2 A
Receptor agonism, antagonism (pre-synaptic)
Provide negative feedback, high Concentration of neurotransmitter in synapse Will lead to decrease release from P synaptic vesicle
Alpha 2 agonist
Both act on presynaptic alpha 2 receptors and decrease norepinephrine release
Clonidine
Guanfacine
2 B
Receptor agonism, antagonism (post-synaptic)
Mirtazapine is a alpha two receptor antagonist which is responsible for its antidepressant effect While it serotonin antagonism is the reason for its lack of sexual dysfunction
3
Transporter reuptake inhibition
4
Inhibition of catabolic enzymes
Monoamine Oxidase Inhibitors
Mechanism
MAO an enzyme that catabolises monoamines (serotonin, norepinephrine, and dopamine) in the synapse
MAO Inhibitor
increase in the levels of these neurotransmitters in the synapse
TYPES
Classic
irreversible and non-selective, meaning they inhibit both MAO-A and MAO-B
Selective
irreversible inhibitors of MAO-B
but as the dose increases, they can also inhibit MAO-A
inhibits aldehyde dehydrogenase
Disulfiram
Phosphodiesterase (PDE) Inhibitors
sildenafil, vardenafil, tadalafil,
MOA
prevent the degradation of cyclic guanosine monophosphate (cGMP)
leads to an increase in nitric oxide, smooth muscle relaxation in the penis, and increased blood flow. used for erectile dysfunction
Catechol-O-methyl Transferase (COMT) Inhibitors
entacapone, tolcapone
Parkinson's Disease, they prolong the effectiveness of levodopa and can decrease dyskinesia
5
Second messenger system effects
Lithium:
inhibiting inositol monophosphatase
leads to the down-regulation of excitatory neurotransmitters (dopamine, glutamate)
leads to up-regulation of inhibitory neurotransmitters (GABA)
Desensitization and downregulation
Neurotransmitter
Ligand-gated ion-channel gatekeeper
Psychopharmacology
Antidepressants
SRI
SSRI
Selective Serotonin Reuptake Inhibitors SSRIs
Mechanism of Action
Inhibit serotonin 5HT reuptake
Increase 5HT in the synaptic cleft
General Clinical Points
Firstline treatment for depression and anxiety disorders
Onset of action 3 to 6 weeks for antidepressant effects, up to 2to 4 weeks for PTSD
Not necessarily more effective
Safer and better tolerated than older antidepressants
Low cardiotoxicity makes SSRIs suitable for patients with cardiac disease
Common Side Effects
Common Initial Adverse Effects
Anxiety, agitation, restlessness
Insomnia, drowsiness,
Gastrointestinal disturbances nausea, diarrhea
Dizziness, tremor, headaches
High incidence of sexual dysfunction 50 to 80%
Bupropion and Mirtazapine as alternatives
Modest weight gain with longterm use
Increased risk of GI bleeding and QTc prolongation especially citalopram and fluoxetine
Black Box Warning for increased suicidal ideation in patients under 25
Serious Adverse Effects
Bleeding/bruising risk
Hyponatremia due to SIADH
Serotonin Syndrome
Discontinuation Syndrome except fluoxetine
Acute closure glaucoma
FDA Black Box Warning
Increased suicidality risk in young adults
Withdrawal/Discontinuation Syndrome
Symptoms anxiety, irritability, dizziness, flulike symptoms
More problematic with short halflife SSRIs eg, paroxetine
insomnia
Long halflife less discontinuation syndrome
Drug Interactions
Inhibition of cytochrome P450 system
Risk of Serotonin Syndrome with other serotonergic agents
General Effectiveness & Safety
Safer and better tolerated than older antidepressants
Not necessarily more effective
Specific SSRIs
Paroxetine Paxil
Highest rates of sexual side effects
FDA approved for depression
Pregnancy Risk Category D associated with fetal heart defects
High CYP2D6 inhibitor risk with antiarrhythmics
high risk in pregnancy
Associated with cardiac defects least safe in early pregnancy
Sertraline Zoloft
FDA approved for PTSD
Best cardiovascular safety profile
FDA indicated for PTSD and PMDD
High risk of sexual adverse effects
Generally has the lowest levels in breast milk among SSRIs
Fluoxetine Prozac
Longest acting SSRI FDA approved for bulimia nervosa
Recommended for use in under 18s
Fluoxetine levels are 10 to 20% of maternal plasma
Long halflife less discontinuation syndrome
FDA approved for pediatric depression best evidence with CBT
Most studied SSRI in pregnancy no miscarriage risk
Citalopram Celexa
Associated with QTc prolongation present in high levels in breast milk
May help agitation in Alzheimer's risk of QTc prolongation
Maximum dose 40mg reduced in hepatic disease
SSRIs for PTSD
Sertraline and Paroxetine FDA approved Fluoxetine and Escitalopram also indicated
Antidepressants in Neurocognitive Disorders
Alzheimer’s Disease Citalopram may alleviate agitation
Lewy Body Disease SSRIs for depression
Huntington’s Disease SSRIs and mirtazapine for depression/anxiety
Antidepressants secreted in small quantities in breast milk benefits often outweigh risks
CYP450 System
SSRIs like fluoxetine and paroxetine are strong CYP2D6 inhibitors
Fluvoxamine inhibits multiple CYP enzymes
Treatment Duration
Continue medication for 6 to 12 months postremission
Citalopram noted for agitation in Alzheimer's disease, suggesting potential utility in dementiarelated symptoms
paraphilic disorders
SSRIs can reduce impulsiveness in paraphilic disorders
SSRIs and SNRI s as firstline MDD
increased risk of PPHN when used by the mother during late pregnancy.
Persistent pulmonary hypertension of the newborn (PPHN) is a condition where a newborn's pulmonary blood vessels constrict, leading to insufficient oxygen supply.
Escitalo
SNRI
Venlafaxine
SerotoninNorepinephrine Reuptake Inhibitors SNRIs
Mechanism of Action
Inhibit serotonin and norepinephrine transporters
Increase levels of both neurotransmitters in the synapse
FDA Approved Indications for Depression
Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran
Used when patients respond poorly to SSRIs
Effective for depressive and anxietyrelated disorders
Common Adverse Effects
Similar to SSRIs risk of sustained systolic hypertension ~12% with venlafaxine
C Common Side Effects
Nausea, insomnia, dry mouth, headache, weight gain
High risk of sexual dysfunction especially venlafaxine
Increased blood pressure, particularly with venlafaxine at higher doses
Specific SNRI Venlafaxine Effexor
FDA approved for anxiety disorders and PTSD
Considered for SSRIresistant depression with anxiety
Firstline treatments SSRIs sertraline, paroxetine, fluoxetine and SNRIs venlafaxine
High risk of sexual adverse effects minimal CYP inhibition
High prevalence of sexual dysfunction ~60%
Generally considered compatible with breastfeeding, low infant serum levels
Effective for PTSD symptom reduction not FDAapproved for PTSD
Recommended for severe and treatmentresistant depression
Discontinuation Syndrome
More problematic due to shorter halflives eg, venlafaxine
Increase levels of both neurotransmitters in the synapse
Duloxetine
SARI
Mirtazapine
Mechanism of action
Alpha2 adrenergic antagonist, increases monoamines
a2 adrenergic presynaptic antagonist causing increased release of monoamines (can contribute to serotonin syndrome and hypertensive crisis}
5-HT2 & 5-HT3 antagonist – ↓ GI and sexual side effects
Adverse effect
Risk of agranulocytosis/neutropenia: 1/1000
– Sedating at low doses: H1 blocker
Activating at high doses: noradrenergic release
Weight gain, increased appetite, dizziness, constipation
Orthostatic hypotension: 1 noradrenergic antagonist
Hypertension: increased noradrenergic drive
Mirtazapine Remeron
Mechanism
Noradrenergic and specific serotonergic antidepressant NaSSA
Common Side Effects
Sedation and weight gain
For Depression
Secondline for treatmentresistant cases helpful for insomnia
For PTSD
Some efficacy shown, but not all symptoms addressed
For Sexual Dysfunction
Low risk can counteract SSRI-induced dysfunction
Breastfeeding
Limited data, but generally reassuring useful for sleep and nausea
Agomelatine
Mechanism
Melatonergic agonist and 5HT2C antagonist
For Sexual Dysfunction
Low risk similar rates to placebo
MAO Inhibitor
Clinical Uses
1 Atypical Depression
Highyield MCQ point
2 Refractory Depression
3 Social Anxiety, Panic Attacks
5 Narcolepsy REM sleep suppressant
A Mechanism of Action MOA
1 Inhibition of monoamine oxidase
Increases neurotransmission of serotonin, norepinephrine, dopamine
nonselective
phenelzine,
4 PTSD Phenelzine effective
tranylcypromine
isocarboxazid
selective
selegiline
At lower doses, a low tyramine diet may not be necessary
D Major Adverse Effects
1 Serotonin Syndrome
when Switching Medications
1 Requires washout period
2week gap for most antidepressants 5week for Fluoxetine
Risk with other serotonergic agents
Antibiotic with MAOI activity risk of serotonin syndrome
Linezolid Interactions
Hypertensive Crisis ER mcq
Hypertensive Crisis and Its Management in Psychiatry
Overview of Hypertensive Crisis
Definition and Importance
A hypertensive crisis is a severe increase in blood pressure that can lead to stroke, myocardial infarction, or other serious health issues
Understanding its causes and treatments is crucial for psychiatrists, especially when considering psychopharmacology
Causes of Hypertensive Crisis
I Foods that Cause Hypertensive Crisis
Interaction with Monoamine Oxidase Inhibitors MAOIs
MAOIs inhibit monoamine oxidase in the gut, allowing tyramine absorption
Tyramine can lead to hypertensive crises when consumed with MAOIs
Tyraminerich foods include
• Ontap beer
• Fava beans
• Aged deli meats
• Aged cheeses
• Fermented foods eg, sauerkraut, soy sauce
II Other Substances/Medications
Drugdrug interactions with MAOIs
Certain medications can precipitate a hypertensive crisis when taken with MAOIs
Key substances include
• Noradrenergic drugs
• Pseudoephedrine
• Linezolid
• Methylene blue
• Some opiates
• Bupropion
• Ldopa
• Methylphenidate
• Amphetamine
Symptoms of Hypertensive Crisis
Recognition of Symptoms
A constellation of symptoms indicates a hypertensive crisis
Common symptoms include
• Headache
• Mydriasis dilated pupils
• Neuromuscular irritability
• Hypertension
• Cardiac arrhythmias
• Potential for stroke
• Potential for myocardial infarction
Treatment for Hypertensive Crisis
Immediate Management
Rapid intervention is crucial to prevent serious sequelae
Focus on rapidacting antihypertensive agents
Treatment approaches include
• General supportive measures Immediate medical stabilization is paramount
• Pharmacological interventions
▪ Betablockers eg, esmolol, labetalol for tachycardia and hypertension
▪ Vasodilators eg, nitroprusside, intravenous nicardipine for severe hypertension
▪ Blood pressure management in acute settings Maintain SBP below 185 mmHg or DBP below 110 mmHg during interventions, often with agents like labetalol or nicardipine
Conclusion
Importance of Awareness
Understanding the causes, symptoms, and treatments of hypertensive crises is essential for psychiatrists, particularly when prescribing MAOIs and managing patients with potential drug interactions
Key Takeaways
• MAOIs and tyraminerich foods are a critical focus for preventing hypertensive crises
• Drug interactions must be carefully monitored to avoid precipitating crises
• Prompt recognition and treatment of symptoms are vital for patient safety
TCA
Tricyclic Antidepressants TCAs
Indication
Depression Effective for melancholic and refractory cases aids chronic pain and insomnia
TCAs for melancholic features
PTSD Limited data consider for intrusive symptoms and insomnia
High overdose risk not firstline treatment
Mechanism of Action
Increase norepinephrine and serotonin levels by blocking reuptake
Nonselective with anticholinergic and antihistaminergic effects
Block muscarinic, histaminergic, and alphaadrenergic receptors
General Clinical Points
Not firstline due to side effects reserved for treatmentresistant cases
Common Side Effects
Anticholinergic effects dry mouth, blurred vision, constipation, urinary retention
Anticholinergic Dry mouth, constipation
Orthostatic hypotension, sedation, weight gain, sexual dysfunction, lower seizure threshold
Sexual Dysfunction High risk nortriptyline and desipramine may enhance function
Narrow therapeutic index high toxicity in overdose
Cardiac Arrhythmias, QTc prolongation
Specific TCA Amitriptyline Elavil
Breastfeeding Generally safe preferred TCA
MCQ Alert Avoid Doxepin during breastfeeding due to severe infant side effects
Serotonin Syndrome risk with other serotonergic agents
Trip...
NDRI
Bupropion Wellbutrin
Mechanism
Norepinephrine and dopamine reuptake inhibitor NDRI
Mild stimulant effect no serotonin impact
Common Side Effects
Headache, agitation, insomnia, weight loss seizures at high doses
For Depression
Similar remission rates to SSRIs alternative for postpartum depression
For Sexual Dysfunction
Low risk enhances sexual functioning
Breastfeeding
Limited data some drug found in milk caution with preeclampsia
Other Indications
FDA approved for smoking cessation effective for ADHD
Major Depressive Disorder, Seasonal Affective Disorder
Bupropion
Adverse effects
Seizure risk: 0.1%
Contraindicated with past/current eating disorders: due to seizure risk: increased from electrolyte disturbances
Contraindicated when withdrawing from CNS depressants: Etoh, Benzo’s
Seizure risk, agitation, insomnia
FDA Indications: MDD, seasonal affective disorder, smoking cessation
Use During Pregnancy
Bupropion considered moderately safe
General Points on Breastfeeding with Antidepressants
General Principle
Antidepressants secreted in small quantities in breast milk benefits often outweigh risks
Acceptable Risk
RID <10% considered acceptable all SSRIs below this level
Specific Risks/Considerations
Neonatal Withdrawal Mild withdrawal symptoms possible
PPHN Small increased risk with SSRI use after 20 weeks
Postpartum Haemorrhage Slight risk with SSRI/SNRI use before delivery
Drugs to AVOID or use with HIGH CAUTION
Doxepin Severe infant side effects due to metabolite accumulation
Lithium Risk of neonatal toxicity generally not advised
Benzodiazepines Can cause sedation and hypotonia in infants
Lithium L4, possibly unsafe
and Doxepin L5, contraindicated for lactation
Drugs to AVOID or use with HIGH CAUTION
Doxepin Severe infant side effects due to metabolite accumulation
Clozapine Contraindicated serious adverse effects in infants
Lithium Risk of neonatal toxicity generally not advised
Benzodiazepines Can cause sedation and hypotonia in infants
Antidepressants and Breastfeeding Considerations
Medication Transmission
All psychotropic medications, including antidepressants, are transmitted into breast milk
Risk/Benefit Assessment
Untreated maternal depression poses risks for both mother and infant
Must weigh risks of medication exposure via breast milk against untreated depression
Specific SSRI Considerations
Sertraline
Generally has the lowest levels in breast milk among SSRIs
Frequently considered option for breastfeeding mothers
Fluoxetine
Levels in breast milk are 10 to 20% of maternal plasma levels
Lactation Risk Categories
SSRIs
Generally categorized as L2 safer during lactation
Bupropion
Categorized as L3 moderately safe
Doxepin
Categorized as L5 contraindicated
Individualised Approach
Decision should involve careful consideration of risks and benefits
Ideally includes involvement of the father and family
Planning of mental health treatment options is essential
Specific Risks/Considerations
Neonatal Withdrawal Mild withdrawal symptoms possible
PPHN Small increased risk with SSRI use after 20 weeks
Postpartum Haemorrhage Slight risk with SSRI/SNRI use before delivery
Antidepressants in Neurocognitive Disorders
Alzheimer’s Disease
Citalopram may alleviate agitation
Lewy Body Disease
SSRIs for depression, cholinesterase inhibitors for psychosis
Huntington’s Disease
SSRIs and mirtazapine for depression/anxiety
Antipsychotics SE
Atypical Antipsychotics SecondGeneration Antipsychotics SGAs
Quetiapine Seroquel
Mechanism
5HT2 antagonist, α1 and histamine antagonism, weak D2 antagonism
Indications
Psychotic symptoms in Parkinson's disease
Psychotic features in young patients
Lactating mothers with bipolar disorder
Other uses schizophrenia, mania, bipolar depression
Side Effects
Sedation, weight gain, diabetes, QT prolongation, cataract formation
Dosing
150750 mg/day, titration required
Augmentation
Commonly used to augment other antipsychotics
Clozapine Clozaril, Zaponex, Denzapine
Mechanism
Blocks D4 > D1 > D2 and 5HT2A receptors
Indications
Treatmentresistant schizophrenia gold standard
Psychotic symptoms in Parkinson's disease
Suicidality reduction
Aggression management
Side Effects
Agranulocytosis/neutropenia, myocarditis, seizures, weight gain
Monitoring
Strict monitoring required for serious side effects
Augmentation
Consideration for nonresponse to clozapine
Other Atypical Antipsychotics
Olanzapine Zyprexa
Uses psychotic symptoms, acute mania, bipolar depression
Side Effects weight gain, diabetes, sedation
Approved for Bipolar 1 and Schizophrenia in youth
Risperidone Risperdal
Uses psychotic symptoms, maintenance therapy for bipolar disorder
Side Effects worsening of parkinsonism, hyperprolactinaemia
Approved for Bipolar mania ≥10 years and Schizophrenia ≥13 years
Ziprasidone Geodon
Uses psychotic symptoms, maintenance treatment for bipolar disorder
Side Effects QT prolongation, less weight gain
Brexpiprazole Rexulti
Uses schizophrenia, adjunct for major depressive disorder
Side Effects akathisia, lower weight gain risk
Cariprazine Vraylar
Uses schizophrenia, bipolar I disorder
Side Effects akathisia, moderate sedation
Aripiprazole Abilify
Uses acute psychosis, mania, treatmentresistant depression
Side Effects akathisia, minimal weight gain, decreased prolactin
Clozapine Specifics
Ability to Reduce Suicidality
Reduces suicide risk in schizophrenia by >80%
Risk of Seizure
Seizure risk increases with dosage monitor closely
Critical Side Effects
Agranulocytosis
Requires monitoring symptoms include lethargy and fever
Myocarditis and Cardiomyopathy
Significant risk of death
Pulmonary Embolism/DVT
Also a significant risk
Clozapine Augmentation
Secondline treatment for nonresponse monitor interactions with other medications
Mechanism of Action
Multiple Receptor Targets
D2, D3, D4, 5HT receptors involved in the modulation of neurotransmitters
This broad action contributes to their efficacy in treating various psychiatric disorders
Uses
Treatment of Psychiatric Disorders
Schizophrenia
Effective in managing both positive and negative symptoms
Mania
Used in acute manic episodes, particularly in bipolar disorder
Bipolar Depression
Helps stabilize mood and reduce depressive episodes
Side Effects
Extrapyramidal Symptoms EPS
Generally less frequent with SGAs compared to FGAs
Higher metabolic risks associated with SGAs
Weight gain and metabolic syndrome are significant concerns
Side Effects of Antipsychotics & Management
Neuroleptic Malignant Syndrome NMS
Characteristics
Rare but severe and lifethreatening condition
Fever, encephalopathy, vital instability, elevated CPK, rigidity
Untreated mortality rate of 520%
Symptoms
Rigidity, hyperthermia, altered mental status, autonomic instability
Risk Factors
Higher prevalence with FGAs and rapid dose changes
Treatment
Immediate discontinuation of the antipsychotic
Supportive care including IV hydration
Medications
Includes stopping neuroleptic and symptomatic care
Bromocriptine, Dantrolene, Benzodiazepines, ECT
Extrapyramidal Symptoms EPS
Overview
Movementrelated abnormalities more common with FGAs
Types & Management
Acute Dystonias
CFs
Risk Factors
high risk for psychotropic-induced acute dystonia such as young patients between ages 12 and 19 years, particularly males,
increased substance Use: Recent cocaine use
Hypocalcemia, hypoparathyroidism, dehydration
hypoparathyroidism
Etiology; parathyroid gland injury or accidental removal during thyroid surgery (iatrogenic)
Biochemical Features:
low or undetectable PTH levels
Low serum calcium levels
Rapid Onset:
Can occur within hours of starting antipsychotics
Minutes if (IM) or (IV)
Typical Window
50% of cases Occur within 48 hours of exposure
90% of cases Occur within 5 days of exposure
Trigger
occur upon initiation, dose increase, or withdrawal of antipsychotic
Resolution
Most untreated cases, resolve within 12-48 hours
Movement
sustained, often painful, muscular spasms causing repetitive, twisting movements or abnormal postures
simultaneous contractions of agonist and antagonist muscles
Painful and very frightening for the patient
Distribution: Can be focal, segmental, or generalized
can affect any muscle group but is mostly found in the head and neck area
life-threatening situations such as laryngeal and pharyngeal dystonia
Signs
Blepharospasm:
Eyelids forced shut, uncontrollable blinking and spasms around the eyes
Dysarthria: Thickened or slurred speech
Laryngeal Dystonia
Opisthotonos
Torticollis (Cervical Dystonia)
Tongue Protrusion/Dysfunction
Pisa syndrome: Lateral bending of the trunk
Rx
Treated with anticholinergics eg, Benztropine
Pathophysiology
Neurochemical Imbalance
Parkinsonism
Managed with anticholinergics
Akathisia
May respond to Benzodiazepines or betablockers
Barnes A R S
Tardive Dyskinesia TD
Higher risk with age and cumulative dose
Involuntary movements managed by switching antipsychotics
Management
Switching to atypical antipsychotics and using Valbenazine
Other Notable Side Effects
Weight Gain & Metabolic Syndrome
Highest Risk
Clozapine, Olanzapine
Significant risk of metabolic syndrome
Management Strategies
Lifestyle changes, switching medications, Metformin
QT Prolongation
Monitoring ECG recommended for all antipsychotics
Hyperprolactinaemia
Common with FGAs and Risperidone
Importance of monitoring prolactin levels
Sedation
Common with lowpotency FGAs
Beneficial for agitated patients
Ocular Side Effects
Retinal pigmentation linked to Thioridazine
Corneal deposits associated with Chlorpromazine
Seizure Threshold Lowering
All antipsychotics can lower seizure threshold
Risk is higher with lowpotency FGAs
Night Blindness
Associated with retinal effects of Thioridazine and Chlorpromazine
Caution with Antipsychotics
Risk Factors
Worsening of Parkinsonian Symptoms 🧠
Antipsychotics can exacerbate bradykinesis, rigidity, and gait disturbances
Black Box Warning
Increased Mortality Risk
In elderly patients with dementiarelated psychosis treated with antipsychotics ⚠️
Highlights significant risks in this vulnerable population
Antipsychotic Prescribing in Breastfeeding Females
General Principles of Prescribing
Transmission into Breast Milk
All psychotropic medications, including antipsychotics, are transmitted into breast milk
RiskBenefit Assessment
Evaluate risks of untreated maternal psychosis versus medication exposure to the infant
Untreated maternal psychiatric illness poses significant risks for both mother and child
Individualized Approach
Treatment decisions should be individualized
Family involvement in discussions is ideal for comprehensive care
Specific Antipsychotic Considerations
Lactation Risk Categories
Safer L2 Category
Haloperidol
Moderately Safe L3 Category
Risperidone
Other Atypical Antipsychotics
Quetiapine, Olanzapine
May increase weight of both mother and baby, leading to metabolic syndrome
Key Points for MCQs
Psychotropic Medications in Breast Milk
All psychotropic medications cross into breast milk
RiskBenefit Analysis
A thorough riskbenefit analysis is crucial before prescribing
Medication Choices
Haloperidol typical is in the "safer" category L2
Risperidone atypical is in the "moderately safe" category L3 for lactation
Clozapine Contraindicated
Serious adverse effects in infants
General Antipsychotic Information
Common Choices for Psychotic Symptoms
First Generation Antipsychotics FGAs
Effective D2 receptor antagonists but associated with higher side effects
Second Generation Antipsychotics SGAs
Broader receptor spectrum but greater metabolic risks
General Usage Principles
Reserved for Severe Symptoms
Start low and monitor closely
Key Areas of Focus
Pharmacological Effects
Quetiapine Seroquel
Notable for causing weight gain
Ophthalmologic Effects
Thioridazine Mellaril
Linked to pigmentary retinopathy, risking blindness immediate medication switch required
Chlorpromazine Thorazine
Notorious for causing dermatologic photosensitivity
Cardiac Considerations
QTc Prolongation
First Generation Antipsychotics FGAs
All FGAs can cause QT prolongation Thioridazine has a black box warning due to 5x increased risk
Second Generation Antipsychotics SGAs
Iloperidone and Ziprasidone present higher risks
Quetiapine, Asenapine, and Paliperidone may cause QTc prolongation in overdose scenarios
MCQ Point
QTc ≥ 500 ms or an increase of ≥ 60 ms necessitates risk factor correction and possible medication discontinuation
Endocrine Effects
Hyperprolactinemia
Higher Risk
Risperidone and Paliperidone are significant contributors FGAs commonly implicated
Lower Risk
Aripiprazole, Cariprazole, Clozapine, Iloperidone, Lurasidone, and Quetiapine show reduced risk
Management Strategies
Switching medications or utilizing bromocriptine for management
Sedation Levels
Sedation
Higher Risk
Clozapine, Quetiapine, Olanzapine, Lurasidone, and lowpotency FGAs are more sedative
Lower Risk
Aripiprazole, Brexpiprazole, Cariprazole, Paliperidone, and Risperidone exhibit less sedation
Blood Pressure Effects
Orthostatic Hypotension
Higher Risk
Clozapine, Iloperidone, Quetiapine, Paliperidone, and lowpotency FGAs associated with higher incidence
Lower Risk
Aripiprazole, Asenapine, Brexpiprazole, Cariprazole, and Lurasidone present lower risks of orthostatic hypotension
Preparing for a MCQ Based Exam on Antipsychotics
I Atypical Antipsychotics and Other Pharmacological Treatments
A Use in Specific Populations and Conditions
1 Psychotic Symptoms in Parkinson's Disease
Clozapine
Low dose effective for psychosis in Lewy body disease
Quetiapine
Reduces psychosis in PD without dementia conflicting data noted
Olanzapine
Similar use as quetiapine, but conflicting evidence in Lewy body disease
Pimavanserin
FDAapproved for hallucinations in PD low dopamine receptor affinity
Caution
Antipsychotics may worsen Parkinsonian symptoms
2 Psychotic Features in Young Patients
Quetiapine
Approved for Bipolar 1 ≥10 years and Schizophrenia ≥13 years
Clozapine
Approved for adults no pediatric indication
Olanzapine
Approved for Bipolar 1 and Schizophrenia in youth
Risperidone
Approved for Bipolar mania ≥10 years and Schizophrenia ≥13 years
Note
Youth sensitive to EPS and metabolic side effects
3 Lactating Mothers with Bipolar Disorder
All psychotropics cross into breast milk weigh risks vs benefits
Lactation Risk Categories
L2 safer, L3 moderately safe, L4 possibly unsafe, L5 contraindicated
Safety data overlaps with pregnancy monitor weight gain risks
B Clozapine Specifics
1 Ability to Reduce Suicidality
Reduces suicide risk in schizophrenia by >80%
2 Risk of Seizure
Seizure risk increases with dosage monitor closely
3 Critical Side Effects
Agranulocytosis
Requires monitoring symptoms include lethargy and fever
Myocarditis and Cardiomyopathy
Significant risk of death
Pulmonary Embolism/DVT
Also a significant risk
4 Clozapine Augmentation
Secondline treatment for nonresponse monitor interactions with other medications
II General Antipsychotic Information
A Common Choices for Psychotic Symptoms
FGAs
Effective D2 receptor antagonists higher side effects
SGAs
Broader receptor spectrum greater metabolic risks
B General Usage Principles
Reserved for severe symptoms start low and monitor closely
III Side Effects of Antipsychotics
A Neuroleptic Malignant Syndrome NMS
Characterized by fever, encephalopathy, vital instability, elevated CPK, rigidity
Untreated mortality rate of 520% treatment includes stopping neuroleptic and symptomatic care
B Tardive Dyskinesia TD
Involuntary movements higher risk with age and cumulative dose
Management includes switching to atypical antipsychotics and using Valbenazine
C Other Notable Side Effects
Weight Gain
Significant with Olanzapine and Clozapine metabolic syndrome risk
Metabolic side effects
Pharmacological Effects
Quetiapine Seroquel
Notable for causing weight gain
Ophthalmologic Effects
Thioridazine Mellaril
Linked to pigmentary retinopathy, risking blindness immediate medication switch required
Chlorpromazine Thorazine
Notorious for causing dermatologic photosensitivity
Cardiac Considerations
QTc Prolongation
First Generation Antipsychotics FGAs
All FGAs can cause QT prolongation Thioridazine has a black box warning due to 5x increased risk
Second Generation Antipsychotics SGAs
Iloperidone and Ziprasidone present higher risks Quetiapine, Asenapine, and Paliperidone may cause QTc prolongation in overdose scenarios
MCQ Point
QTc ≥ 500 ms or an increase of ≥ 60 ms necessitates risk factor correction and possible medication discontinuation
Endocrine Effects
Hyperprolactinemia
Higher Risk
Risperidone and Paliperidone are significant contributors FGAs commonly implicated
Lower Risk
Aripiprazole, Cariprazole, Clozapine, Iloperidone, Lurasidone, and Quetiapine show reduced risk
Management Strategies
Switching medications or utilizing bromocriptine for management
Sedation Levels
Sedation
Higher Risk
Clozapine, Quetiapine, Olanzapine, Lurasidone, and low potency FGAs are more sedative
Lower Risk
Aripiprazole, Brexpiprazole, Cariprazole, Paliperidone, and Risperidone exhibit less sedation
Blood Pressure Effects
Orthostatic Hypotension
Higher Risk
Clozapine, Iloperidone, Quetiapine, Paliperidone, and low potency FGAs are associated with higher incidence
Lower Risk
Aripiprazole, Asenapine, Brexpiprazole, Cariprazine, and Lurasidone present lower risks of orthostatic hypotension
Pharmacological Treatments for Psychotic Symptoms
Overview of Antipsychotics
Pimavanserin Nuplazid
Mechanism First antipsychotic targeting serotonin receptors 5HT2A inverse agonist
Uses FDA approved for Parkinson's diseaserelated psychosis
Side Effects Minimal extrapyramidal symptoms EPS
Atypical Antipsychotics SecondGeneration Antipsychotics SGAs
Quetiapine Seroquel
Mechanism
5HT2 antagonist, α1 and histamine antagonism, weak D2 antagonism
Indications
Psychotic symptoms in Parkinson's disease
Psychotic features in young patients
Lactating mothers with bipolar disorder
Other uses schizophrenia, mania, bipolar depression
Side Effects
Sedation, weight gain, diabetes, QT prolongation, cataract formation
Dosing
150750 mg/day, titration required
Augmentation
Commonly used to augment other antipsychotics
Clozapine Clozaril, Zaponex, Denzapine
Mechanism
Blocks D4 > D1 > D2 and 5HT2A receptors
Indications
Treatmentresistant schizophrenia gold standard
Psychotic symptoms in Parkinson's disease
Suicidality reduction
Aggression management
Side Effects
Agranulocytosis/neutropenia, myocarditis, seizures, weight gain
Monitoring
Strict monitoring required for serious side effects
Augmentation
Consideration for nonresponse to clozapine
Other Atypical Antipsychotics
Olanzapine Zyprexa
Uses psychotic symptoms, acute mania, bipolar depression
Side Effects weight gain, diabetes, sedation
Approved for Bipolar 1 and Schizophrenia in youth
Risperidone Risperdal
Uses psychotic symptoms, maintenance therapy for bipolar disorder
Side Effects worsening of parkinsonism, hyperprolactinaemia
Approved for Bipolar mania ≥10 years and Schizophrenia ≥13 years
Ziprasidone Geodon
Uses psychotic symptoms, maintenance treatment for bipolar disorder
Side Effects QT prolongation, less weight gain
Brexpiprazole Rexulti
Uses schizophrenia, adjunct for major depressive disorder
Side Effects akathisia, lower weight gain risk
Cariprazine Vraylar
Uses schizophrenia, bipolar I disorder
Side Effects akathisia, moderate sedation
Aripiprazole Abilify
Uses acute psychosis, mania, treatmentresistant depression
Side Effects akathisia, minimal weight gain, decreased prolactin
Clozapine Specifics
Ability to Reduce Suicidality
Reduces suicide risk in schizophrenia by >80%
Risk of Seizure
Seizure risk increases with dosage monitor closely
Critical Side Effects
Agranulocytosis
Requires monitoring symptoms include lethargy and fever
Myocarditis and Cardiomyopathy
Significant risk of death
Pulmonary Embolism/DVT
Also a significant risk
Clozapine Augmentation
Secondline treatment for nonresponse monitor interactions with other medications
General Antipsychotic Information
Typical FirstGeneration Antipsychotics FGAs
Mechanism Primarily block dopamine D2 receptors
Examples
Haloperidol Haldol
Uses Acute agitation/confusion IM/IV administration
Side Effects High risk of parkinsonian symptoms avoid in Parkinson's patients
Chlorpromazine Thorazine
Characteristics First antipsychotic sedative properties
Side Effects More anticholinergic effects
Pimozide Orap
Uses Tourette's Syndrome monitor for QT prolongation
Thioridazine Mellaril
Risks Retinal pigmentation highest QT prolongation risk
Atypical SecondGeneration Antipsychotics SGAs
Mechanism Act on multiple receptors D2, D3, D4, 5HT
Uses Schizophrenia, mania, bipolar depression
Side Effects Generally less EPS, but higher metabolic risk
Mood stabilizer
Lithium
Mechanism
Sub Topic
Use in Specific Populations and Conditions
FDA-approved for fibromyalgia. First-line for neuropathic pain. Used for trigeminal neuralgia. Adjunctive for anxiety
Key Takeaways
Importance of informed consent and monitoring
Awareness of drug interactions and side effects
Tailored treatment based on patient history and specific conditions
Use in Specific Conditions
PTSD
Firstline treatment with SSRIs and SNRIs
Effective medications Sertraline, Paroxetine
Depression
Major Depressive Disorder treatment options
SSRIs and SNRIs as firstline
TCAs for melancholic features
Sexual Dysfunction
Common side effect of antidepressants
Bupropion and Mirtazapine as alternatives
Psychotic Symptoms in Parkinson's Disease
Clozapine
Low dose effective for psychosis in Lewy body disease
Quetiapine
Reduces psychosis in PD without dementia conflicting data noted
Olanzapine
Similar use as quetiapine, but conflicting evidence in Lewy body disease
Pimavanserin
FDA approved for hallucinations in PD low dopamine receptor affinity
Caution
Antipsychotics may worsen Parkinsonian symptoms
Psychotic Features in Young Patients
Quetiapine
Approved for Bipolar 1 ≥10 years and Schizophrenia ≥13 years
Clozapine
Approved for adults no pediatric indication
Olanzapine
Approved for Bipolar 1 and Schizophrenia in youth
Risperidone
Approved for Bipolar mania ≥10 years and Schizophrenia ≥13 years
Note
Youth sensitive to EPS and metabolic side effects
Lactating Mothers with Bipolar Disorder
All psychotropics cross into breast milk weigh risks vs benefits
Lactation Risk Categories
L2 safer, L3 moderately safe, L4 possibly unsafe, L5 contraindicated
Safety data overlaps with pregnancy monitor weight gain risks
Anti seizure
Anti-Epileptic Medications (AEDs)
Sodium Channel Blockers
Phenytoin (PHT)
Indication
Status epilepticus (second-line agent after benzodiazepines)
Carbamazepine (CBZ)
Primarily used for Focal epilepsy
First-line for trigeminal neuralgia
Stevens-Johnson Syndrome (SJS)
especially in patients of Chinese ancestry (10-fold increased risk
Induces CYP3A4: Decreases levels of oral contraceptive pills (OCP) and valproate
Can lower lamotrigine levels and reduce lithium clearance
Side effect
During pregnancy High risk in first trimester
fetal carbamazepine syndrome (craniofacial defects, fingernail hypoplasia, developmental delay, neural tube defects)
supplement with Vitamin K
Lacosamide (LAC)
Lamotrigine (LTG)
Sodium channel blocker and glutamate receptor antagonist
prevent future depressive episodes
Side effect
Black box warning
Stevens-Johnson Syndrome (SJS),
(1/6000 with slow, 1/1000 with rapid)
first 2-8 weeks
(High-Yield): Valproic acid significantly increases lamotrigine levels (by inhibiting its metabolism
Pregnancy..... safer profile for maintenance compared to alternatives
"Stimulant" effect (insomnia, increased alertness)
Calcium Channel Blockers
Gabapentin (GBP
Pregabalin (PGB
Indication
Ethosuximide (ESM)
Absence seizures
Main choice and first-line treatment for absence seizures
Equally effective as Valproic Acid for this indication
GABAergic Agents
Valproic Acid (VPA)
CYP450 enzyme inhibitor
FDA approved for acute mania and mixed episodes in adults, and migraine prophylaxis
Target blood level for acute mania is 90 μg/m
First-line treatment for juvenile myoclonic epilepsy (JME) and Absence seizures and migraine prophylaxis
Na channel blocker and GABAergic agent (increases synaptic GABA levels)
used for generalized seizures
Side effect
elevated LFTs and liver failure, Potentially fatal hepatotoxicity (highest risk in age <2Y , first 6 months)
(1-5% risk of neural tube defects, lower IQ, possible intellectual disability, autism
hemorrhagic pancreatitis ,,,thrombocytopenia
Rash, pancreatitis, tremor, sedation – Weight gain, hair loss, PCOS
Benzodiazepines (e.g., Clonazepam, Diazepam, Lorazepam, Phenobarbital)
Clonazepam
gaba nd Na
Phenobarbital
gaba nd Na
Safety categ D in pregnancy, Causes cleft palate
Causes Dissociation
Glutamate
AMPA Receptor Blockers
NMDA Receptor Blockers
SV2A Ligands
Brivaractem (BRV)
Levetiracetam
Save anti epileptic in patients with chronic liver disease
(SV2A), a protein found on synaptic vesicles, modulating neurotransmitter release, glycine and GABA inhibitors
Carbonic Anhydrase Inhibitors
Topiramate (TPM)
glutamate receptor antagonist, and carbonic anhydrase inhibitor
Side effect
Weight loss
Word naming difficulties
Renal stones (1.5%)
Metabolic acidosis (32%)
Secondary closed-angle glaucoma
oligohidrosis
Zonisamide (ZNS)
Epilepsy
Substance use disorder
Cocaine Use Disorder
Antidepressants may help with comorbid major depressive disorder
Bupropion can reduce methamphetamine induced 'high' and cravings
Alcohol use disorder
Antidepressants generally not recommended unless cooccurring disorder is present
Sertraline may be relevant for specific alcoholic subtypes
Disulfiram
inhibits aldehyde dehydrogenase
accumulation of acetaldehyde in the body, which causes unpleasant physical symptoms upon exposure to alcohol (e.g., severe adverse reaction occurring 10-15 minutes after drinking)
Other precautions
psychosis itself is also listed as a contraindication for Disulfiram use
baseline Liver Function Tests (LFTs) before initiating
Monitor for potential serious neurological side effects, peripheral neuropathy and optic neuritis
be used only in motivated and reliable patients who fully understand the risks and are committed to
Metronidazole: Recent use of metronidazole is a direct contraindication to Disulfiram
a person can drink alcohol safely after 14 days of discontinuing Disulfiram
Alcohol Use Disorder Antidepressants not recommended unless cooccurring disorder
Opioid Withdrawal Trazodone and Doxepin for insomnia management
Opioid use disorder
Overview of Opioid Receptors
Mechanism
Bind to and activate Gproteincoupled receptors located postsynaptically
Effects include pleasure and reduced craving
Key Receptors
Mu µ
Heroin
Direct mu µ agonist
Methadone
Pure mu µ agonist
Longer acting than heroin
Orally available
Fentanyl and Sufentanil
Primarily pure mu µ receptor agonists
Oxycodone
Mu µreceptor agonist
Delta δ
Kappa κ
mu, delta, kappa
Partial agonist
Pentazocine
Partial opioid agonist
Buprenorphine
Partial agonist at mu µ receptors
Also a delta δ and kappa κ partial agonist
Key Point Has a ceiling effect and can act as an antagonist if endogenous neurotransmitter levels are high
Full agonist
Morphine
Full agonist on mu, delta, kappa, and nociception opioid receptors
Subtopic
Opioid Withdrawal
Trazodone and Doxepin for insomnia management
mood stabilizer
lithium
Li like na is excreted from PCT kidney
pts e renal impairment @ high risk of toxicity
Volume Depletion
Renal Insuff
low GFR for eg in Elderly
MOA
inhib IMPase
depletes inositol
dec Intra cellular 2nd messenger levels that involve inositol
PIP2
IP3
DAG
Li Drug Interactions
Li Level and cause Li Toxicity
NSAID
dec renal blood perfusion
ACE Inhibitors
-pril
dec GFR
Thiazide Diuretic
dec GFR
dec Li level
K sparring diuretic
amiloride
varying effect
loop diuretic
as they cause volume Depletion but also Inc Li Excretion
Adverse Effects Li lower Thyroid and P wave . and ADH effect on kidney '
Acute when drug started or dose inc
Tremor
hands
arms
better over time
also the most common symptom of Toxicity
long term
hypo thyroid
Li is a Goiterogen
inhib release of thyroid from thyroid gland
results in en larged thyroid i.e goiter
can impact to such an extent that it causes Hypothyroidism
Nephrogenic DI
ch tubulointersitial nephropathy
loss of tubules urine conc ability
dilute urine
low Urine osm
tubules dont respond to ADH
polyuria
polydipsia
na normal or inc
Rx
K sparring diuretic
Amiloride
acts by inhib Na entry into Principal cells.
Li has Similar structure as Na. So it blocks Li entry into renal cell in Principal cells and in collecting duct via ENac Channels. Amiloride block reuptake of Li. hence dec its serum level
hence dec Li level/ Toxicity
improving polyuria
Typical dosing is 5–10 mg daily, titrated to effect, but clinical monitoring for hyperkalemia is essential.
no response to ADH as this is Nephrogenic DI and only central DI responds to Vasopressin (ADH)
if pts given Vasopressin
no response or change in urine osm
so give Amiloride
K sparring Diuretic
which inhib
Cardiac
suppression Sinus Node
sinusnode depolarization= p wave on ekg
results in Bradycardia/ Pauses
and syncope
fetal
ebstein anomaly
teratogen
down to apex displacement of Tricuspid Valve
completely equilibrates across placenta
Diuretic use with lithium
Amiloride is the preferred antidiuretic medication that can be given with lithium, while thiazide diuretics and desmopressin {na} may be considered with caution and close monitoring
Amiloride blocks lithium entry into collecting duct principal cells, thereby attenuating lithium-induced polyuria and improving urine concentrating ability without increasing serum lithium levels or toxicity risk
Thiazide diuretics (e.g., hydrochlorothiazide) are also used to reduce polyuria in lithium-induced NDI, often in combination with amiloride to mitigate hypokalemia
thiazides can increase serum lithium concentrations due to enhanced proximal sodium and lithium reabsorption, necessitating close monitoring of lithium levels and renal function
Management of lithium toxicity
Gastric lavage or whole bowel irrigation may be considered in cases of recent acute significant ingestion, especially of sustained-release formulations
Supportive Care and Lithium Excretion
Vigorous Hydration: Intravenous fluids
Electrolyte Correction
maintaining sodium is key
Symptom Control
Control seizures using benzodiazepines
treat fever and underlying infection
Haemodialysis is the most effective way of rapid lithium removal and is mandatory in severe toxicity
Dialysis should continue until the patient improves clinically AND the serum lithium level is typically below 1.0 mEq/L. Post-dialysis rebound in lithium levels (due to redistribution from intracellular stores) is possible, often requiring repeat dialysis sessions
Compromised Clearance: Renal function is severely impaired or renal failure is present,
Acute-on-chronic or chronic toxicity, as these carry a higher risk for neurological sequelae due to pre-existing CNS lithium load
Lithium Levels
>1.5 mmol/L
Level ≥2.0 mEq/L (mmol/L)
Level ≥4.0 mEq/L (mmol/L)
Level ≥5.0 mEq/L (mmol/L)
Neurological (CNS/PNS):
Coarse Tremor: A highly characteristic sign of toxicity (distinguished from fine tremor seen at therapeutic levels).
Cerebellar Dysfunction: Ataxia (unsteady gait), slurred speech (dysarthria), and incoordination.
Severe Signs: Hyperreflexia, fasciculations, myoclonic jerks (muscle twitching), nystagmus, seizures, delirium, and coma
confusion, ataxia, tremor, myoclonus, seizures, and in severe cases, coma
Renal Complications:
Acute kidney failure/oliguria.
◦ Chronic renal impairment is exacerbated by repeated episodes of lithium intoxication
Cardiovascular Complications
Hypotension and circulatory collapse
Arrhythmias, T-wave changes (flattening/inversion), impaired sinus node function, and sick sinus syndrome. Lithium may unmask Brugada syndrome
SILENT:
Syndrome of Irreversible Lithium-Effectuated Neurotoxicity. This involves persistent neurological deficits, most commonly cerebellar damage and cognitive impairment
Dehydration (secondary to diarrhoea, vomiting, excessive sweating, fever, or inadequate fluid intake) is a major precipitant of lithium toxicity
Lithium is a positive ion (Li+) that is primarily excreted unmetabolised by the kidneys
Lithium elimination relies on the kidney maintaining adequate sodium levels. Approximately 70% of filtered lithium is reabsorbed in the proximal tubule, competing with sodium (Na+) for the Na+/H+ exchanger-3 (NHE3)
MCQ Alert: Replacing lost fluid with free water (rather than an electrolyte solution) exacerbates the risk by restoring volume but diluting sodium stores, promoting increased lithium reabsorption
Toxicity Pathway: When dehydration/hypovolemia occurs, the kidney attempts to compensate by retaining sodium. Because lithium is transported similarly to sodium, the kidney indiscriminately reabsorbs lithium along with sodium, leading to a rise in serum lithium concentration and subsequent toxicity
Correction of fluid and electrolyte imbalances, particularly sodium, is essential; isotonic saline is preferred to restore volume and promote renal lithium clearance.
Diuretics should be avoided, as they do not enhance lithium elimination and may worsen electrolyte disturbances; saline diuresis is safe, but forced diuresis with diuretics is not beneficial.
Hemodialysis is the preferred extracorporeal method for lithium removal
severe Li toxicity is defined by serum lithium ≥5.2 mmol/L, creatinine ≥200 μmol/L, severe neurological symptoms, or renal failure.
Substance use disorder
Cocaine Use Disorder
Antidepressants may help with comorbid major depressive disorder
Bupropion can reduce methamphetamine induced 'high' and cravings
Alcohol use disorder
Antidepressants generally not recommended unless cooccurring disorder is present
Sertraline may be relevant for specific alcoholic subtypes
Alcohol Use Disorder Antidepressants not recommended unless cooccurring disorder
Subtopic
Treatment of Alcohol Withdrawal
Supportive Care
Importance of hydration and cautious use of neuroleptics and restraints
The patient can possibly die because of
Arrhythmia
Hyperthermia
Electrolyte and fluid abnormality
Thiamine Administration
Essential to administer thiamine 100 mg IM/IV before glucose to prevent Wernicke's encephalopathy
Lookout for //// Wernicke's encephalopathy can be precipitated by glucose in thiamine deficient states
Symptom triggered therapy
CIWA Scale
Clinical Institute Withdrawal Assessment for Alcohol Every four to six hours
Give Benzodiazepine if the score is High
Benzodiazepines
Primary treatment for both alcohol withdrawal seizures and DTs
Used for
Treating and preventing seizures
Preventing and managing symptoms of DTs eg by, lorazepam IV bolus
Preference for "Out The Liver" benzodiazepines
Oxazepam, temazepam, and lorazepam are preferred in patients with hepatic impairment due to their metabolism
Usually during the First week
Treatment Reduce the risk of relapse After the initial Symptom management
FDA approved drugs
Disulfiram
inhibits aldehyde dehydrogenase
accumulation of acetaldehyde in the body, which causes unpleasant physical symptoms upon exposure to alcohol (e.g., severe adverse reaction occurring 10-15 minutes after drinking)
Subtopic
Other precautions
psychosis itself is also listed as a contraindication for Disulfiram use
baseline Liver Function Tests (LFTs) before initiating
Monitor for potential serious neurological side effects, peripheral neuropathy and optic neuritis
be used only in motivated and reliable patients who fully understand the risks and are committed to
Metronidazole: Recent use of metronidazole is a direct contraindication to Disulfiram
a person can drink alcohol safely after 14 days of discontinuing Disulfiram
Naltrexone
Acamprosate
Support group
Alcohol Anonymous
Opioid Withdrawal Trazodone and Doxepin for insomnia management
Opioid use disorder
Overview of Opioid Receptors
Mechanism
Bind to and activate Gproteincoupled receptors located postsynaptically
Effects include pleasure and reduced craving
Key Receptors
Mu µ
Heroin
Direct mu µ agonist
Methadone
Pure mu µ agonist
Longer acting than heroin
Orally available
Fentanyl and Sufentanil
Primarily pure mu µ receptor agonists
Oxycodone
Mu µreceptor agonist
Delta δ
Kappa κ
mu, delta, kappa
Partial agonist
Pentazocine
Partial opioid agonist
Buprenorphine
Partial agonist at mu µ receptors
Also a delta δ and kappa κ partial agonist
Key Point Has a ceiling effect and can act as an antagonist if endogenous neurotransmitter levels are high
Full agonist
Morphine
Full agonist on mu, delta, kappa, and nociception opioid receptors
Subtopic
Opioid Withdrawal
Trazodone and Doxepin for insomnia management
Antipsychotics SE
Atypical Antipsychotics SecondGeneration Antipsychotics SGAs
Quetiapine Seroquel
Mechanism
5HT2 antagonist, α1 and histamine antagonism, weak D2 antagonism
Indications
Psychotic symptoms in Parkinson's disease
Psychotic features in young patients
Lactating mothers with bipolar disorder
Other uses schizophrenia, mania, bipolar depression
Side Effects
Sedation, weight gain, diabetes, QT prolongation, cataract formation
Dosing
150750 mg/day, titration required
Augmentation
Commonly used to augment other antipsychotics
Clozapine Clozaril, Zaponex, Denzapine
Mechanism
Blocks D4 > D1 > D2 and 5HT2A receptors
Indications
Treatmentresistant schizophrenia gold standard
Psychotic symptoms in Parkinson's disease
Suicidality reduction
Aggression management
Side Effects
Agranulocytosis/neutropenia, myocarditis, seizures, weight gain
Monitoring
Strict monitoring required for serious side effects
Augmentation
Consideration for nonresponse to clozapine
Other Atypical Antipsychotics
Olanzapine Zyprexa
Uses psychotic symptoms, acute mania, bipolar depression
Side Effects weight gain, diabetes, sedation
Approved for Bipolar 1 and Schizophrenia in youth
Risperidone Risperdal
Uses psychotic symptoms, maintenance therapy for bipolar disorder
Side Effects worsening of parkinsonism, hyperprolactinaemia
Approved for Bipolar mania ≥10 years and Schizophrenia ≥13 years
Ziprasidone Geodon
Uses psychotic symptoms, maintenance treatment for bipolar disorder
Side Effects QT prolongation, less weight gain
Brexpiprazole Rexulti
Uses schizophrenia, adjunct for major depressive disorder
Side Effects akathisia, lower weight gain risk
Cariprazine Vraylar
Uses schizophrenia, bipolar I disorder
Side Effects akathisia, moderate sedation
Aripiprazole Abilify
Uses acute psychosis, mania, treatmentresistant depression
Side Effects akathisia, minimal weight gain, decreased prolactin
Clozapine Specifics
Ability to Reduce Suicidality
Reduces suicide risk in schizophrenia by >80%
Risk of Seizure
Seizure risk increases with dosage monitor closely
Critical Side Effects
Agranulocytosis
Requires monitoring symptoms include lethargy and fever
Myocarditis and Cardiomyopathy
Significant risk of death
Pulmonary Embolism/DVT
Also a significant risk
Clozapine Augmentation
Secondline treatment for nonresponse monitor interactions with other medications
Mechanism of Action
Multiple Receptor Targets
D2, D3, D4, 5HT receptors involved in the modulation of neurotransmitters
This broad action contributes to their efficacy in treating various psychiatric disorders
Uses
Treatment of Psychiatric Disorders
Schizophrenia
Effective in managing both positive and negative symptoms
Mania
Used in acute manic episodes, particularly in bipolar disorder
Bipolar Depression
Helps stabilize mood and reduce depressive episodes
Side Effects
Extrapyramidal Symptoms EPS
Generally less frequent with SGAs compared to FGAs
Higher metabolic risks associated with SGAs
Weight gain and metabolic syndrome are significant concerns
Side Effects of Antipsychotics & Management
Neuroleptic Malignant Syndrome NMS
Characteristics
Rare but severe and lifethreatening condition
Fever, encephalopathy, vital instability, elevated CPK, rigidity
Untreated mortality rate of 520%
Symptoms
Rigidity, hyperthermia, altered mental status, autonomic instability
Risk Factors
Higher prevalence with FGAs and rapid dose changes
Treatment
Immediate discontinuation of the antipsychotic
Supportive care including IV hydration
Medications
Includes stopping neuroleptic and symptomatic care
Bromocriptine, Dantrolene, Benzodiazepines, ECT
Extrapyramidal Symptoms EPS
Overview
Movementrelated abnormalities more common with FGAs
Types & Management
Acute Dystonias
CFs
Rapid Onset:
Can occur within hours of starting antipsychotics PO
Minutes if (IM) or (IV)
Typical Window
50% of cases Occur within 48 hours of exposure
90% of cases Occur within 5 days of exposure
Late onset
TD occurs after months to years of antipsychotic treatment
Resolution
Most untreated cases, resolve within 12-48 hours
Movement
sustained, often painful, muscular spasms causing repetitive, twisting movements or abnormal postures
jaw dislocation
simultaneous contractions of agonist and antagonist muscles
Painful and very frightening for the patient
Distribution: Can be focal, segmental, or generalized
can affect any muscle group but is mostly found in the head and neck area
life-threatening situations such as laryngeal and pharyngeal dystonia
Signs
Blepharospasm:
Eyelids forced shut, uncontrollable blinking and spasms around the eyes
Dysarthria: Thickened or slurred speech
unable to swallow or speak clearly
Laryngeal Dystonia
Opisthotonos
Severe cases
Torticollis (Cervical Dystonia)
Tongue Protrusion/Dysfunction
Pisa syndrome: Lateral bending of the trunk
Oculogyric spasm
eyes rolling upwards
Prevalence
young patients between ages 12 and 19 years, particularly males,
antipsychotic-naïve
increased substance Use: Recent cocaine use
Hypocalcemia, hypoparathyroidism, dehydration
hypoparathyroidism
Etiology; parathyroid gland injury or accidental removal during thyroid surgery (iatrogenic)
Biochemical Features:
low or undetectable PTH levels
Low serum calcium levels
high-potency medications (e.g. haloperidol)
Dystonic reactions are rare in the elderly
Approximately 10% but more common
Trigger
occur upon initiation, dose increase, or withdrawal of antipsychotic
Rx
Treated with anticholinergics eg, 1.Procyclidine 2.Benztropine
Depending on severity
PO
patient may be unable to swallow
onset half an hour or more
IM
takes around 20 minutes
IV
Response to IV administration seen within 5 minutes
1.Procyclidine
Doses of 5–10 mg
diphenhydramine (1–2 mg/kg up to 100 mg by slow IV infusion)
antihistamine
Benztropine intravenous or intramuscular treatment
M1 muscarinic cholinergic receptor antagonist
central anticholinergic medication that primarily acts as an M1 muscarinic cholinergic receptor antagonist
switching to an antipsychotic with a low propensity of EPS
TD may respond to ECT
botulinum toxin may be effective
Pathophysiology
Neurochemical Imbalance
No specific rating scale
Parkinsonism
Managed with anticholinergics
Akathisia
May respond to Benzodiazepines or betablockers
Barnes A R S
Tardive Dyskinesia TD
Prevalence
5% of patients per year of antipsychotic exposure
Higher risk with advanced age, high cumulative dose, FGA,
abnormal involuntary movements
Lip smacking or chewing
tongue protrusion (‘fly catching’)
choreiform hand movements (‘piano playing’)
dystonic and choreoathetoid movements of the limbs
Severe orofacial movement lead to difficulty speaking, eating or breathing
become worse when under stress.
Management
Stop anticholinergic
Reduce dose of antipsychotic medication
Switching to atypical antipsychotics with lower propensity for TD
Clozapine
Quetiapine
VMAT 2 Inhibitor addon
valbenazine and deutetrabenazine
Ginkgo biloba addon
Assessments Scale
Abnormal Involuntary Movement Scale
Neurobiology
Other Notable Side Effects
Weight Gain & Metabolic Syndrome
Highest Risk
Clozapine, Olanzapine
Significant risk of metabolic syndrome
Management Strategies
Lifestyle changes, switching medications, Metformin
QT Prolongation
Monitoring ECG recommended for all antipsychotics
Hyperprolactinaemia
Common with FGAs and Risperidone
Importance of monitoring prolactin levels
Sedation
Common with lowpotency FGAs
Beneficial for agitated patients
Ocular Side Effects
Retinal pigmentation linked to Thioridazine
Corneal deposits associated with Chlorpromazine
Seizure Threshold Lowering
All antipsychotics can lower seizure threshold
Risk is higher with lowpotency FGAs
Night Blindness
Associated with retinal effects of Thioridazine and Chlorpromazine
FGA
NAMES
Haloperidol
azine
Chlor
Trifluoperi
Fluphen
Thiorid
MOA
DA recep
SITES
PFC
Basal gang
Limbic
Acts via 2nd Messenger''' G protein coupled
excit= is D1R
activate adenyl cyc AC
ATP,, AC removes 2 po4 and make a cyclicadenosine monophosphate CAMP
inhib= is D2R
inhib
inhib adenyl cyc
dec CAMP
Psychosis neurobiology
Neurotransmitter pathways is linked to psychosis
Caution with Antipsychotics
Risk Factors
Worsening of Parkinsonian Symptoms 🧠
Antipsychotics can exacerbate bradykinesis, rigidity, and gait disturbances
Black Box Warning
Increased Mortality Risk
In elderly patients with dementiarelated psychosis treated with antipsychotics ⚠️
Highlights significant risks in this vulnerable population
Antipsychotic Prescribing in Breastfeeding Females
General Principles of Prescribing
Transmission into Breast Milk
All psychotropic medications, including antipsychotics, are transmitted into breast milk
RiskBenefit Assessment
Evaluate risks of untreated maternal psychosis versus medication exposure to the infant
Untreated maternal psychiatric illness poses significant risks for both mother and child
Individualized Approach
Treatment decisions should be individualized
Family involvement in discussions is ideal for comprehensive care
Specific Antipsychotic Considerations
Lactation Risk Categories
Safer L2 Category
Haloperidol
Moderately Safe L3 Category
Risperidone
Other Atypical Antipsychotics
Quetiapine, Olanzapine
May increase weight of both mother and baby, leading to metabolic syndrome
Key Points for MCQs
Psychotropic Medications in Breast Milk
All psychotropic medications cross into breast milk
RiskBenefit Analysis
A thorough riskbenefit analysis is crucial before prescribing
Medication Choices
Haloperidol typical is in the "safer" category L2
Risperidone atypical is in the "moderately safe" category L3 for lactation
Clozapine Contraindicated
Serious adverse effects in infants
General Antipsychotic Information
Common Choices for Psychotic Symptoms
First Generation Antipsychotics FGAs
Effective D2 receptor antagonists but associated with higher side effects
Second Generation Antipsychotics SGAs
Broader receptor spectrum but greater metabolic risks
General Usage Principles
Reserved for Severe Symptoms
Start low and monitor closely
Key Areas of Focus
Pharmacological Effects
Quetiapine Seroquel
Notable for causing weight gain
Ophthalmologic Effects
Thioridazine Mellaril
Linked to pigmentary retinopathy, risking blindness immediate medication switch required
Chlorpromazine Thorazine
Notorious for causing dermatologic photosensitivity
Cardiac Considerations
QTc Prolongation
First Generation Antipsychotics FGAs
All FGAs can cause QT prolongation Thioridazine has a black box warning due to 5x increased risk
Second Generation Antipsychotics SGAs
Iloperidone and Ziprasidone present higher risks
Quetiapine, Asenapine, and Paliperidone may cause QTc prolongation in overdose scenarios
MCQ Point
QTc ≥ 500 ms or an increase of ≥ 60 ms necessitates risk factor correction and possible medication discontinuation
Endocrine Effects
Hyperprolactinemia
Higher Risk
Risperidone and Paliperidone are significant contributors FGAs commonly implicated
Lower Risk
Aripiprazole, Cariprazole, Clozapine, Iloperidone, Lurasidone, and Quetiapine show reduced risk
Management Strategies
Switching medications or utilizing bromocriptine for management
Sedation Levels
Sedation
Higher Risk
Clozapine, Quetiapine, Olanzapine, Lurasidone, and lowpotency FGAs are more sedative
Lower Risk
Aripiprazole, Brexpiprazole, Cariprazole, Paliperidone, and Risperidone exhibit less sedation
Blood Pressure Effects
Orthostatic Hypotension
Higher Risk
Clozapine, Iloperidone, Quetiapine, Paliperidone, and lowpotency FGAs associated with higher incidence
Lower Risk
Aripiprazole, Asenapine, Brexpiprazole, Cariprazole, and Lurasidone present lower risks of orthostatic hypotension
Preparing for a MCQ Based Exam on Antipsychotics
I Atypical Antipsychotics and Other Pharmacological Treatments
A Use in Specific Populations and Conditions
1 Psychotic Symptoms in Parkinson's Disease
Clozapine
Low dose effective for psychosis in Lewy body disease
Quetiapine
Reduces psychosis in PD without dementia conflicting data noted
Olanzapine
Similar use as quetiapine, but conflicting evidence in Lewy body disease
Pimavanserin
FDAapproved for hallucinations in PD low dopamine receptor affinity
Caution
Antipsychotics may worsen Parkinsonian symptoms
2 Psychotic Features in Young Patients
Quetiapine
Approved for Bipolar 1 ≥10 years and Schizophrenia ≥13 years
Clozapine
Approved for adults no pediatric indication
Olanzapine
Approved for Bipolar 1 and Schizophrenia in youth
Risperidone
Approved for Bipolar mania ≥10 years and Schizophrenia ≥13 years
Note
Youth sensitive to EPS and metabolic side effects
3 Lactating Mothers with Bipolar Disorder
All psychotropics cross into breast milk weigh risks vs benefits
Lactation Risk Categories
L2 safer, L3 moderately safe, L4 possibly unsafe, L5 contraindicated
Safety data overlaps with pregnancy monitor weight gain risks
B Clozapine Specifics
1 Ability to Reduce Suicidality
Reduces suicide risk in schizophrenia by >80%
2 Risk of Seizure
Seizure risk increases with dosage monitor closely
3 Critical Side Effects
Agranulocytosis
Requires monitoring symptoms include lethargy and fever
Myocarditis and Cardiomyopathy
Significant risk of death
Pulmonary Embolism/DVT
Also a significant risk
4 Clozapine Augmentation
Secondline treatment for nonresponse monitor interactions with other medications
II General Antipsychotic Information
A Common Choices for Psychotic Symptoms
FGAs
Effective D2 receptor antagonists higher side effects
SGAs
Broader receptor spectrum greater metabolic risks
B General Usage Principles
Reserved for severe symptoms start low and monitor closely
III Side Effects of Antipsychotics
A Neuroleptic Malignant Syndrome NMS
Characterized by fever, encephalopathy, vital instability, elevated CPK, rigidity
Untreated mortality rate of 520% treatment includes stopping neuroleptic and symptomatic care
B Tardive Dyskinesia TD
Involuntary movements higher risk with age and cumulative dose
Management includes switching to atypical antipsychotics and using Valbenazine
C Other Notable Side Effects
Weight Gain
Significant with Olanzapine and Clozapine metabolic syndrome risk
Metabolic side effects
Pharmacological Effects
Quetiapine Seroquel
Notable for causing weight gain
Ophthalmologic Effects
Thioridazine Mellaril
Linked to pigmentary retinopathy, risking blindness immediate medication switch required
Chlorpromazine Thorazine
Notorious for causing dermatologic photosensitivity
Cardiac Considerations
QTc Prolongation
First Generation Antipsychotics FGAs
All FGAs can cause QT prolongation Thioridazine has a black box warning due to 5x increased risk
Second Generation Antipsychotics SGAs
Iloperidone and Ziprasidone present higher risks Quetiapine, Asenapine, and Paliperidone may cause QTc prolongation in overdose scenarios
MCQ Point
QTc ≥ 500 ms or an increase of ≥ 60 ms necessitates risk factor correction and possible medication discontinuation
Endocrine Effects
Hyperprolactinemia
Higher Risk
Risperidone and Paliperidone are significant contributors FGAs commonly implicated
Lower Risk
Aripiprazole, Cariprazole, Clozapine, Iloperidone, Lurasidone, and Quetiapine show reduced risk
Management Strategies
Switching medications or utilizing bromocriptine for management
Sedation Levels
Sedation
Higher Risk
Clozapine, Quetiapine, Olanzapine, Lurasidone, and low potency FGAs are more sedative
Lower Risk
Aripiprazole, Brexpiprazole, Cariprazole, Paliperidone, and Risperidone exhibit less sedation
Blood Pressure Effects
Orthostatic Hypotension
Higher Risk
Clozapine, Iloperidone, Quetiapine, Paliperidone, and low potency FGAs are associated with higher incidence
Lower Risk
Aripiprazole, Asenapine, Brexpiprazole, Cariprazine, and Lurasidone present lower risks of orthostatic hypotension
Antipsychotic withdrawal symptoms
Anticholinergic
Benztropine
central anticholinergic medication that primarily acts as an M1 muscarinic cholinergic receptor antagonist
blocking
mainstay treatment for parkinsonism induced by first-generation (FGAs) and second-generation (SGAs) antipsychotics
dopaminergic projections typically inhibit the release of acetylcholine (ACh)
Neurotransmitter Balance
Main Topic
Main Topic
First-Line FDA-Approved Treatments for Psychiatric Disorders
I Anxiety Disorders ☁️
Generalised Anxiety Disorder GAD
Class SSRIs and SNRIs
Specific FDAApproved Medications
SSRIs Paroxetine, Escitalopram
SNRIs Duloxetine, Venlafaxine
Note Bupropion not effective for panic Pregabalin offlabel for GAD
Panic Disorder
Class SSRIs/SNRIs
Specific FDAApproved Medications
SSRIs Paroxetine, Sertraline, Fluoxetine
SNRI Venlafaxine
Benzodiazepines Alprazolam, Clonazepam
Social Anxiety Disorder SAD
Class SSRIs
Specific FDAApproved Medications
SSRIs Paroxetine, Sertraline, Fluvoxamine CR
SNRI Venlafaxine
II Mood Disorders 🌈
Major Depressive Disorder MDD
Class SSRIs
Specific FDAApproved Medications
SSRIs Fluoxetine, Paroxetine, Sertraline, Citalopram, Escitalopram
SNRIs Venlafaxine, Desvenlafaxine, Duloxetine, Levomilnacipran
Recently Approved Agents Vortioxetine, Vilazodone
Pediatric MDD
Fluoxetine ages 8+, Escitalopram ages 12+
Adjunctive for TreatmentResistant Depression
Olanzapine/Fluoxetine Combination, Aripiprazole, Quetiapine, Brexpiprazole
Postpartum Depression
Brexanolone first FDAapproved medication
Note Fluvoxamine only for OCD, Trazodone not FDAapproved for insomnia
Bipolar Mania Acute
Mood Stabilizers
Lithium ages 7+ for Bipolar I
Divalproex ages 10+
Carbamazepine ExtendedRelease
SecondGeneration Antipsychotics SGAs
Olanzapine, Quetiapine, Aripiprazole, Risperidone, Ziprasidone, Asenapine, Cariprazine
Note Paliperidone not FDAapproved for acute mania
Bipolar Depression
Specific FDAApproved Medications
Olanzapine/Fluoxetine Combination OFC
Quetiapine monotherapy
Lurasidone monotherapy, adjunct to lithium or valproate
Cariprazine
Note Lamotrigine FDAapproved for maintenance, not acute depression
III Psychotic Disorders 🌌
Schizophrenia
FirstEpisode Psychosis FEP
Aripiprazole, Olanzapine, Risperidone
Haloperidol if others ineffective
General Treatment FDAApproved SGAs
Aripiprazole, Risperidone, Olanzapine, Quetiapine, Lurasidone, Paliperidone, Brexpiprazole
Recurrent Suicidal Behavior
Specific FDAApproved Medication
Clozapine most effective, not firstline due to side effects
Refractory Schizophrenia
Specific FDAApproved Medication
Clozapine more effective than thioridazine
IV Other Psychiatric Disorders 🌼
AttentionDeficit/Hyperactivity Disorder ADHD
Class Psychostimulants
Specific FDAApproved Stimulants
Methylphenidate ages ≥6, Amphetamine salts ages ≥3
Specific FDAApproved NonStimulants
Atomoxetine ages ≥6, Clonidine ER, Guanfacine ER, Viloxazine ages 617
Autism Spectrum Disorder ASD Irritability
Specific FDAApproved Medications
Risperidone ages 516, Aripiprazole ages 617
Binge Eating Disorder BED
Specific FDAApproved Medication
Lisdexamfetamine first drug approved for BED
Bulimia Nervosa BN
Specific FDAApproved Medication
Fluoxetine only FDAapproved drug dosage 60 mg/day
Delirium
No FDAApproved Pharmacological Intervention
Note Antipsychotics used offlabel, carry FDA warning
Dementia Secondary to Parkinson's Disease
Specific FDAApproved Medication
Rivastigmine
Fibromyalgia
Specific FDAApproved Medications
Pregabalin, Duloxetine, Milnacipran
Female Sexual Dysfunction HSDD
Specific FDAApproved Medication
Flibanserin first and only for premenopausal women
Insomnia
Specific FDAApproved Medications
Suvorexant, Flurazepam, Zolpidem, Doxepin
Note Trazodone not FDAapproved for insomnia
ObsessiveCompulsive Disorder OCD
Class SSRIs firstline
Specific FDAApproved Medications
SSRIs Fluoxetine ages 718, Fluvoxamine ages 817, Sertraline ages 617, Paroxetine
TCA Clomipramine ages 10+
Opioid Use Disorder OUD
Specific FDAApproved Medications
Methadone, Oral Naltrexone, Buprenorphine, Injectable LongActing Naltrexone
Parkinson's Disease Psychosis
FirstLine Medication
Quetiapine
Specific FDAApproved Medication
Pimavanserin firstinclass 5HT2A receptor inverse agonist
PostTraumatic Stress Disorder PTSD
Class SSRIs only FDAapproved class
Specific FDAApproved Medications
Sertraline, Paroxetine
Note Fluoxetine, Venlafaxine comparable but not FDAapproved for PTSD
Restless Legs Syndrome RLS
Specific FDAApproved Medication
Gabapentin as gabapentin enacarbil
Tourette's Syndrome
Specific FDAApproved Medications
Aripiprazole ages 618, Pimozide ages 8+, Haloperidol
Tardive Dyskinesia TD
Specific FDAApproved Medications
Valbenazine, Deutetrabenazine
Note Tetrabenazine used offlabel for TD
Side effects
Atypical Antipsychotics SecondGeneration Antipsychotics SGAs
Quetiapine Seroquel
Mechanism
5HT2 antagonist, α1 and histamine antagonism, weak D2 antagonism
Indications
Psychotic symptoms in Parkinson's disease
Psychotic features in young patients
Lactating mothers with bipolar disorder
Other uses schizophrenia, mania, bipolar depression
Side Effects
Sedation, weight gain, diabetes, QT prolongation, cataract formation
Dosing
150750 mg/day, titration required
Augmentation
Commonly used to augment other antipsychotics
Clozapine Clozaril, Zaponex, Denzapine
Mechanism
Blocks D4 > D1 > D2 and 5HT2A receptors
Indications
Treatmentresistant schizophrenia gold standard
Psychotic symptoms in Parkinson's disease
Suicidality reduction
Aggression management
Side Effects
Agranulocytosis/neutropenia, myocarditis, seizures, weight gain
Monitoring
Strict monitoring required for serious side effects
Augmentation
Consideration for nonresponse to clozapine
Other Atypical Antipsychotics
Olanzapine Zyprexa
Uses psychotic symptoms, acute mania, bipolar depression
Side Effects weight gain, diabetes, sedation
Approved for Bipolar 1 and Schizophrenia in youth
Risperidone Risperdal
Uses psychotic symptoms, maintenance therapy for bipolar disorder
Side Effects worsening of parkinsonism, hyperprolactinaemia
Approved for Bipolar mania ≥10 years and Schizophrenia ≥13 years
Ziprasidone Geodon
Uses psychotic symptoms, maintenance treatment for bipolar disorder
Side Effects QT prolongation, less weight gain
Brexpiprazole Rexulti
Uses schizophrenia, adjunct for major depressive disorder
Side Effects akathisia, lower weight gain risk
Cariprazine Vraylar
Uses schizophrenia, bipolar I disorder
Side Effects akathisia, moderate sedation
Aripiprazole Abilify
Uses acute psychosis, mania, treatmentresistant depression
Side Effects akathisia, minimal weight gain, decreased prolactin
Clozapine Specifics
Ability to Reduce Suicidality
Reduces suicide risk in schizophrenia by >80%
Risk of Seizure
Seizure risk increases with dosage monitor closely
Critical Side Effects
Agranulocytosis
Requires monitoring symptoms include lethargy and fever
Myocarditis and Cardiomyopathy
Significant risk of death
Pulmonary Embolism/DVT
Also a significant risk
Clozapine Augmentation
Secondline treatment for nonresponse monitor interactions with other medications
Management of Neuroleptic Malignant Syndrome (NMS
I Immediate and Essential Steps FirstLine
A Stop the Offending Agent Immediately
1 Discontinue antipsychotics and dopamineblocking drugs
B Supportive Measures
1 Fluid Support
a IV fluids to support circulation and kidney function
2 External Cooling Measures
a Cooling blankets and ice packs to reduce hyperthermia
3 Monitor Vitals
a Track blood pressure and urine output
4 Manage Autonomic Lability
a Correct electrolyte imbalances
b Manage cardiovascular issues eg, hypertension
i Use clonidine or nitroprusside for hypertension
5 Respiratory Support
a Ventilation may be necessary in severe cases
6 Benzodiazepines
a Treat agitation and catatonia eg, Lorazepam 1–2 mg every 4–6 hours
II Pharmacological Interventions Specific Agents
A FDA Approved Status
1 No FDAapproved medications specifically for NMS
a Recommendations based on case reports and anecdotal evidence
b Key MCQ Tip No FDAapproved drugs for NMS
B Commonly Utilised Medications
1 Dopaminergic Drugs
a Bromocriptine
i Dosing Start with 25 mg TID PO, max 45 mg/day
ii Monitor for side effects nausea, vomiting
b Amantadine
i Alternative dopamine agonist, dosing 100 mg every 12 hours
2 Muscle Relaxants
a Dantrolene
i Effective for severe NMS and rigidity
ii Dosing 1–25 mg/kg IV, max 10 mg/kg/day
3 Electroconvulsive Therapy ECT
a Effective in severe cases
4 Lithium
a No role in NMS management Important MCQ Alert
III Ongoing Monitoring and Followup
A Slow Taper of Medications
1 Taper dantrolene or bromocriptine over several days postsymptom resolution
B Continuous Monitoring
1 Ongoing observation required for patient stability
C Prevent Deep Vein Thrombosis DVT
1 Prescribe heparin for DVT prevention
IV Key Points for MCQs
A Diagnostic Features
1 Remember the "FEVER" acronym
a Fever hyperthermia
b Encephalopathy delirium
c Vitals autonomic instability
d Elevated CPK rhabdomyolysis
e Rigidity
B Biggest Risk Factor
1 Prior NMS episode increases recurrence risk
C Differentiation
1 Differentiate NMS from catatonia and serotonin syndrome
D Treatment Principles
1 Cessation of offending agent and aggressive supportive care are cornerstones of management
C. Extrapyramidal Syndromes (EPS)
Acute Dystonia
Involuntary, sustained muscle contractions causing abnormal postures.
Types: oculogyric crises (upward gaze deviation), torticollis (neck twisting), retrocollis (neck extension), dysarthria, dysphagia, repetitive jaw/face muscle contractions, tongue protrusion.
Meige Syndrome is a form of oral facial dystonia with repetitive blinking and chin thrusting (blepharospasm and oromandibular dystonia).
Onset: usually at treatment initiation or dose increase (within hours to days).
Cause: acute hypodopaminergic state in striatum.
Risk factors: young age, male sex, high-potency neuroleptics.
Treatment: parenteral antimuscarinic/anticholinergic medication (procyclidine 5mg IV/IM), or antihistamine (diphenhydramine 50mg IM).
Benzodiazepines are also an option, though they can rarely cause dystonia.
Parkinsonism
Drug-induced: bradykinesia/akinesia, rigidity, tremor, postural instability (usually develops within 4 weeks).
Can be caused by dopamine antagonists (antipsychotics).
Parkinson's Disease: Stooped posture, slow movements, rigidity, "pill-rolling" tremor, rapid shuffling gait.
Dementia occurs in 25-80%.
Intraneuronal alpha-synuclein aggregates (Lewy bodies).
Tardive Dyskinesia
Late-onset (usually > 4 months or long-term treatment) of abnormal, involuntary choreoathetoid movements (e.g., chewing, pouting of jaw, lip smacking).
May be irreversible.
Pathophysiology: dopamine D2 receptor supersensitivity in nigrostriatal pathway.
Serotonin Syndrome Management
Overview of Serotonin Syndrome
Definition and Clinical Importance
Serotonin Syndrome SS is a potentially lifethreatening condition caused by excessive serotonergic activity in the central nervous system
It is categorized as a psychiatric emergency requiring immediate intervention
FDA Approved Treatment for Serotonin Syndrome
Lack of Specific FDAApproved Medications
No medications are specifically approved for the treatment of Serotonin Syndrome
Commonly Followed Management Approaches
Immediate and Essential Steps FirstLine Management
Discontinue all serotonergic agents immediately
Supportive Care as the Mainstay of Treatment
Aggressive hydration with intravenous fluids
Correction of vital sign abnormalities eg, hypertension, tachycardia
External cooling measures for hyperthermia
Airway monitoring and protection
Monitoring for complications like rhabdomyolysis and renal failure
Pharmacological Interventions for Moderate to Severe Cases
Benzodiazepines
Firstline therapy for agitation, tremors, myoclonus, and muscle rigidity
Examples Lorazepam, Diazepam
Serotonin 5HT2A Antagonists
Cyproheptadine Initial dose of 12 mg, then 2 mg every 2 hours if symptoms persist, up to 32 mg in 24 hours
Other agents with less rigorous evidence Olanzapine, Chlorpromazine, Mirtazapine, Methysergide
Caution with Chlorpromazine in hypotension or NMS cases
Electroconvulsive Therapy ECT
Considered for severe or refractory cases
Medications/Interventions to Avoid
Propranolol
May mask the efficacy of cyproheptadine and lead to hypotension
Bromocriptine
A dopamine agonist implicated in SS
Dantrolene
Not effective and may worsen symptoms
Cyproheptadine in Neuroleptic Malignant Syndrome NMS
Should be avoided in NMS management
Tricyclic Antidepressants TCAs and Psychostimulants
Highrisk when combined with MAOIs
Important Considerations
Favorable Prognosis
SS often resolves completely with timely treatment
Medication Review PostStabilization
Caution advised when using multiple serotonergic agents
Washout Period for SSRIs
Minimum of 5 weeks for Fluoxetine before initiating an MAOI 25 weeks for other SSRIs
Risk of SS from Triptans
Considered minimal in practice at standard doses
Serotonin Syndrome
Clinical triad mental status changes, neuromuscular changes, autonomic instability
Antibiotic with MAOI activity risk of serotonin syndrome
Linezolid Interactions
St John's Wort
Induces CYP3A4 potential for contraceptive failure
Can contribute to serotonin syndrome
Key Concepts for Management
Defining Features and Urgency
Clinical Triad of Symptoms
Mental Status Changes Confusion, agitation, delirium
Neuromuscular Changes Hyperreflexia, clonus, myoclonus, muscle rigidity
Autonomic Instability Tachycardia, mydriasis, diaphoresis, increased GI motility
Rapid Progression & Potential Fatality
Can lead to severe complications like seizures, shock, and renal failure
Precipitating Medications
Antidepressants
SSRIs, SNRIs, TCAs, MAOIs, trazodone, mirtazapine, etc
Antimigraine Medications
Triptans eg, sumatriptan
Opioids
Tramadol, meperidine, fentanyl, etc
Antiemetics
Ondansetron, metoclopramide
Antibiotics
Linezolid
Dietary Supplements
St John's wort, tryptophan
Cold Medications
Dextromethorphan
Drugs of Abuse
MDMA, LSD, cocaine, amphetamines
Commonly Followed Management Principles
Immediate Discontinuation of Offending Agents
Critical first step in managing medicationinduced syndromes
Supportive Care
Intensive medical monitoring and management of complications
Conclusion
Importance for Examination Preparation
Recognizing symptoms and differentiating SS from other conditions like NMS is crucial
Awareness of the lack of explicit FDAapproved treatments for SS is a significant point for exam preparation
DrugDrug Interactions
CYP450 System
SSRIs like fluoxetine and paroxetine are strong CYP2D6 inhibitors
Fluvoxamine inhibits multiple CYP enzymes, increasing levels of other drugs
St John's Wort
Induces CYP3A4, decreasing levels of various drugs, potential for contraceptive failure
Can contribute to serotonin syndrome due to its reuptake inhibition
Smoking Effects
Induces CYP1A2, decreasing plasma concentrations of certain antidepressants
Linezolid Interactions
Antibiotic with MAOI activity, risk of serotonin syndrome when combined with antidepressants
Receptor
Drugs Acting Directly on GABA Receptors
GABA Receptors Agonists
Function
Suppresses inappropriate neurotransmitter release eg, dopamine, norepinephrine
Mechanism of Action
Increases chloride inflow
Hyperpolarizes the neuron
Reduces neuronal excitability via hyperpolarization influx of Cl
Decreases neuronal firing
Main inhibitory neurotransmitter in the brain and spinal cord
GABA A Receptor Ligands
GABA A Antagonists
Flumazenil Competitive antagonist at benzodiazepine site
Bicuculline Competitive antagonist blocking GABA binding
Picrotoxin Blocks chloride channel, proconvulsant
Pentylenetetrazol Reduces Cl channel permeability, proconvulsant
Penicillin High concentrations occlude chloride channel
GABAA Receptors Agonists
Direct Agonists
Brexanolone
Intravenous formulation of allopregnanolone, enhancing GABA functionality
Administered as continuous infusion over 60 hours
Black Box Warning for sedation requires monitoring
FDAapproved for postpartum depression PPD
Allopregnanolone Neurosteroid enhancing tonic inhibition, used for postpartum depression
Inverse Agonists
Bind to benzodiazepine site, produce opposite effects
Examples Betacarboline family eg, DMCM
Positive Allosteric Modulators PAMs
Benzodiazepines BDZs
Clinical Effects
Sedation α1 subunit
Mechanism Bind to benzodiazepine site, increase frequency of chloride channel opening
Anxiety Reduction α2, α3 subunits
Muscle Relaxation α2, α3 subunits
Anticonvulsant α1, α2 subunits
Addiction Potential α1 subunit
Benzodiazepines
OUT of the Liver. safe in CLD
Temazepam
Lorazepam
Oxazepam
Hypnotics
Flurazepam
Estazolam
Triazolam
Quazepam
Anxiolytics
Alprazolam
Diazepam
Clonazepam
Longacting benzodiazepine affecting GABAA receptors
Useful for myoclonic jerks
FDAapproved for panic disorder
clinical
Pearls
Safer options for hepatic insufficiency Lorazepam, Temazepam, Oxazepam
Caution in neurocognitive disorders shortacting agents for agitation
Firstline for alcohol withdrawal syndrome
Pregnancy Category D risk of floppy infant syndrome
Withdrawal symptoms from abrupt cessation, especially with shortacting agents
Useful in psychotic disorders for aggression and anxiety
Caution in dissociative disorders paradoxical effects in some contexts
Treatment for tardive dyskinesia and catatonia
Caution in intellectual disabilities
Zdrugs Nonbenzodiazepine hypnotics
Mechanism Bind to benzodiazepine site, increase chloride conductance
less anxiolytic effects
Selective GABAA receptor agonists with high affinity for α1 subunit
Eszopiclone
Zaleplon
Zolpidem selective for alpha1 subunit, primarily hypnotic effect
High doses of zolpidem may cause automatic sleep behaviors
Barbiturates
Mechanism Bind to distinct site, increase duration of chloride channel opening
Examples Amytal, Phenobarbital
Phenobarbital
CYP450 inducer
Alcohol Ethanol
Enhances GABAA receptor function
General Anesthetics
Enhance GABAA activity, eg, Propofol, Isoflurane
GABA B Receptor Ligands
1 Agonists
Baclofen Selective GABAB agonist, used as muscle relaxant
Antispasticity agent secondline for restless legs syndrome
GHB / Sodium Oxybate Approved for narcolepsy, induces deep sleep
FDAapproved for cataplexy and daytime drowsiness in narcolepsy
High abuse potential Schedule III drug
2 Antagonists
Saclofen & 2hydroxysaclofen Competitive antagonists
Drugs Affecting GABA Indirectly
Indirectly
GABA Reuptake Inhibitors
Tiagabine Inhibits reuptake, increases synaptic GABA concentrations, used for epilepsy
GABA Transaminase GABAT Inhibitors
Vigabatrin Irreversible GABAT inhibitor, risk of permanent vision loss
retinal atrophy
Sodium Valproate Multiple mechanisms, increases GABA levels, used as anticonvulsant
Clinical Pearls
Teratogenic avoid in pregnancy
Side effects liver failure, pancreatitis, thrombocytopenia
FDAapproved for acute mania and migraine prophylaxis
GABA Analogs
Gabapentin & Pregabalin Do not bind directly to GABA receptors, bind to α2δ subunit of calcium channels, affects GABA release
Mechanism Inhibit presynaptic release of excitatory neurotransmitters
Clinical Use Neuropathic pain, epilepsy, anxiety disorders
Renally eliminated adjust dose in renal failure
Other Drugs with Indirect GABA Influence
Acamprosate Reduces glutamate, increases GABA neurotransmission
AUD
decreased positive reinforcement of alcohol intake and decreased withdrawal cravings
balance glutamate overactivity, thereby reducing the potential for relapse
Maintenance of abstinence from alcohol in patients with alcohol dependence
Does not eliminate or diminish acute alcohol withdrawal symptoms
two 333 mg tablets three times daily (tid)
Avoid in mild to moderate renal impairment
Safe to use in liver disease due to renal elimination
Unlike Disulfiram, Acamprosate does not produce an aversive reaction if alcohol is consumed
Topiramate Blocks Na+ channels, inhibits glutamate AMPA receptors, potentiates GABAA action
Other side effects weight loss, kidney stones
Cognitive side effects
used for nightmares
Ketamine / PCP NMDA receptor antagonists, may increase glutamate release
Psychopharm
Psychopharm
Receptor
adrenergic
a
a2
a1
Block
Hypotension, particularly Orthostatic Hypotension (Postural Drop in Blood Pressure)
combined with H1, Sedation/Drowsiness
modulating various physiological functions, including blood pressure, alertness, and gastrointestinal motility
b
Dopamine Receptors Agonists/Partial Agonists
Mechanism of Action
Facilitates movement
Effects vary by receptor subtype D1 excitatory, D2 inhibitory
Key Drugs
Full Agonists primarily D2
Apomorphine
Bromocriptine
Pramipexole
Ropinirole
Rotigotine
Partial Agonists D2 and 5HT1A
Aripiprazole
Brexpiprazole
Cariprazine
Atypical antipsychotics
Alpha2 Adrenergic Receptors Agonists
Mechanism of Action
Inhibits monoamine release
Key Drugs
Clonidine α2A adrenergic receptor agonist
Guanfacine α2A adrenergic receptor agonist
Serotonin Receptors Agonists/Partial Agonists
Mechanism of Action
Mimics or modulates serotonin effects at specific receptor subtypes
Key Drugs
5HT1A Partial Agonists
Aripiprazole
Buspirone
Brexpiprazole
Cariprazine
Vilazodone
Vortioxetine
5HT1A Agonist / 5HT2A Antagonist
Flibanserin
5HT1 Agonists Triptans
Almotriptan
Eletriptan
Frovatriptan
Naratriptan
Rizatriptan
Sumatriptan
Zolmitriptan
Cause cranial artery constriction
Ergotamines
5HT1 agonist/antagonist properties
Pathyways
DA
Mesocortical
Mesolimbic/Mesostriatal Pathway
Iatrogenic after D2antagonist AP
Tuberoinfundibular
Iatrogenic after D2antagonist AP
Nigrostriatal Pathway
Iatrogenic after D2antagonist AP
Acute SE
Ch SE
Chronic blockade of D2 receptors in NSP
cause upregulation of those receptors
leads to hyperkinetic motor condition known as tardive dyskinesia
Subtopic
psychopathology neurotransmitter Abnormality
Neuropathological Insights for Exam Preparation
I Neurodegenerative Disorders and Their Pathological Hallmarks
A Alzheimer's Disease AD
1 Macroscopic Changes
Global cerebral atrophy, especially in frontal and temporal lobes
Ventricular enlargement and sulcal widening
2 Microscopic Changes
Neuronal loss in cerebral cortex and hippocampus
Shrinking of dendritic branching
Reactive astrocytosis
Neuritic Senile Plaques Extracellular deposits of insoluble betaamyloid 42 Aβ42
Neurofibrillary Tangles NFTs Composed of hyperphosphorylated tau protein
MCQ Tip Density of NFTs correlates with cognitive impairment
Hirano Bodies Rodshaped eosinophilic bodies in hippocampal pyramidal cells
3 Neurochemical Changes
Degeneration of cholinergic neurons in the nucleus basalis of Meynert
Damage to locus coeruleus affecting noradrenaline synthesis
4 Genetic Factors
ApoE E4 allele as the strongest risk factor for lateonset AD
Increased risk in Down syndrome patients due to extra APP gene copies
B Frontotemporal Lobar Degeneration FTLD / Pick's Disease
1 Macroscopic Changes
Selective atrophy of frontal and temporal lobes
2 Microscopic Changes
Characterized by Pick bodies and balloon cells
3 Proteinopathy
Associated with mutations in tau protein MAPT gene
4 Clinical Presentation
Insidious onset with behavioral changes or language impairment
Languagevariant FTD shows preserved episodic memory and perceptualmotor abilities
C Dementia with Lewy Bodies DLB
1 Microscopic Changes
Presence of Lewy bodies and neurites in cortex and brainstem
2 Proteinopathy
Lewy bodies immunoreactive for alphasynuclein
3 Associated Pathology
Moderate betaamyloid plaque burden, lower tangle burden
4 Clinical Features
Fluctuating cognition, visual hallucinations, parkinsonism
D Parkinson's Disease PD
1 Macroscopic Changes
Depigmentation of substantia nigra
2 Microscopic Changes
Characteristic Lewy bodies in surviving neurons
3 Proteinopathy
Alphasynucleinopathy
4 Neurochemical Changes
Reduced dopamine production from degeneration of dopaminergic neurons
5 Genetic Factors
LRRK2 gene mutations as common familial cause
E CreutzfeldtJakob Disease CJD
1 Pathology
Spongiosis of cerebral grey matter, neuronal loss, gliosis
2 Proteinopathy
Misfolded prion protein PrPSc
3 MRI Findings
Hyperintense signal in basal ganglia, characteristic pulvinar sign in vCJD
4 CSF Biomarkers
Elevated 1433 protein, S100B, RTQuIC test
5 Clinical Course
Rapidly progressive dementia with myoclonus and other neurological signs
F Vascular Neurocognitive Disorder / Multiinfarct Dementia
1 Pathology
Multiple lacunar infarcts and diffuse white matter lesions
2 Mechanisms
Hypoperfusion, oxidative stress, inflammation
3 Clinical Course
Stepwise progression with fluctuating cognitive function
4 Key Deficits
Decline in complex attention, frontalexecutive function
MCQ Tip Higher depression rates in vascular dementia than in AD
G Huntington's Disease HD
1 Pathology
Degeneration of striatum leading to "batwing" ventricles
2 Proteinopathy
Accumulation of huntingtin protein
3 Genetic Factors
Autosomal dominant disorder from CAG repeats
4 Clinical Features
Common symptoms include apathy, depression, personality changes
II Other Neuropathologically Relevant Conditions
A Wernicke's Encephalopathy
1 Cause
Severe thiamine vitamin B1 deficiency
2 Pathology
Petechial hemorrhages in periaqueductal grey and mammillary bodies
3 Clinical Triad
Ophthalmoplegia, ataxia, acute confusion
MCQ Tip Can progress to Korsakoff's syndrome
B Multiple Sclerosis MS
1 Pathology
Widespread demyelination of CNS white matter
MCQ Tip Bilateral internuclear ophthalmoplegia is pathognomonic
C Amyotrophic Lateral Sclerosis ALS
1 Pathology
Degeneration of upper and lower motor neurons
2 Clinical Features
Progressive muscle weakness, fasciculations, swallowing difficulties
D Lead Poisoning in children
1 Most Serious Complication
Delirium and potential neurocognitive deficits
2 Developmental Relevance
Linked to neural tube defects
E Traumatic Brain Injury TBI
1 Pathology
Neurocognitive disorders due to excitotoxic brain damage
2 Chronic Traumatic Encephalopathy CTE
Characterized by protein aggregates from repetitive trauma
F Neuroleptic Malignant Syndrome NMS
1 Mechanism
Idiosyncratic adverse effect of dopamine antagonism
2 Key Features
Fever, altered mental status, muscle rigidity, autonomic dysfunction
MCQ Tip Elevated creatine phosphokinase CPK common
G Other Neurotransmitters and Associated Conditions
1 Acetylcholine ACh
Role in memory deficient in AD involved in myasthenia gravis
2 Dopamine DA
Low in PD excess in schizophrenia linked to tardive dyskinesia
3 GABA
Main inhibitory neurotransmitter low levels linked to seizures
4 Glutamate
Excitotoxicity implicated in various neurological disorders
5 Serotonin 5HT
Low levels linked to depression and suicidality
6 Norepinephrine NE
Implicated in anxiety synthesized in locus coeruleus
General Neuropathological Concepts and Techniques
Brain Regions and Functions
Hippocampus
Critical for transferring shortterm to longterm memory declarative memories
Amygdala
Vital role in emotional responses, especially fear
Nucleus Accumbens
Implicated in reward processing and addiction
Cerebellum
Important for motor planning, balance, and coordinating rapid, alternating movements dysdiadochokinesia
Frontal Lobe
Executive functions, planning, abstract conception, personality
Bilateral lesions of anterior cingulate cortex can cause akinesia and mutism
Temporal Lobe
Recognition of faces prosopagnosia, often bilateral occipital or temporooccipital, fusiform gyrus involvement
Comprehension of language Wernicke's area
Parietal Lobe
Spatial orientation, constructional praxis nondominant parietal, awareness of illness states
Dominant temporoparietal junction lesions can cause anomic dysphasia
Thalamus
Relay station for sensory and motor information
Dorsomedial nucleus involved in motivation and emotions
Anterior nuclei in memory formation
Pulvinar in visuospatial attention
Thalamic lesions can cause sensory deficits and pain
Brainstem Midbrain, Pons, Medulla
Regulates vital functions like breathing, heartbeat, digestion
Lesions can affect cranial nerves, motor/sensory pathways
Subthalamic Nucleus
Lesions can cause hemiballismus flinging movements
Neuronal Migration & Neurodevelopment
Neuronal Migration
Disruption during gestation leads to malformations eg, lissencephaly brains without sulci/gyri due to defects in neuronal migration
Neural Tube Defects
Failure of neural tube closure eg, spina bifida, anencephaly during early gestation
Folic acid is crucial for prevention
Synapse Formation
Highest rate occurs from the second trimester through age 10, peaking around 2 years
Myelination
Occurs actively from prenatally through childhood, finishing in the third decade of life
Glial Cells
Astrocytes
Breakdown some neurotransmitters
Produce scar tissue preventing axon growth after injury
Oligodendrocytes
Form myelin sheath in the Central Nervous System CNS
Schwann Cells
Form myelin sheath in the Peripheral Nervous System PNS
Microglia
Immune cells of the brain act as macrophages
Clearing neuronal debris, plaques, and infectious agents
Diagnosis Techniques & Concepts
Neuroimaging
MRI, CT, PET, SPECT, fMRI Important for visualizing structural and functional brain changes
MRI is more sensitive than CT for tumors, stroke
Pulvinar sign on MRI is for vCJD
fMRI highlights primary motor cortex during tasks
DWI MRI shows diffusion restriction in transient global amnesia hippocampus
MRI of spinal cord is modality of choice for transverse myelitis
Neuropathological Study
Postmortem analysis is definitive for many neurodegenerative diseases
CSF Biomarkers
1433 protein, total tau, pTau, Abeta42 for CJD and AD
Neurofilament light NfL for neurodegeneration
Electrophysiology
EEG, EMG, NCS Useful for measuring electrical properties of neurons, nerve conduction velocities, and muscle activity
Patch clamp techniques examine open/closed states of ion channels
EEG can reveal periodic sharpwave complexes in CJD
EMG and NCS identify neuromuscular junctions, nerves, and muscles affected by weakness
Antidepressants
SRI
SSRI
Selective Serotonin Reuptake Inhibitors SSRIs
Mechanism of Action
Inhibit serotonin 5HT reuptake
Increase 5HT in the synaptic cleft
General Clinical Points
General Effectiveness & Safety
Safer and better tolerated than older antidepressants
Not necessarily more effective
Firstline treatment for depression and anxiety disorders
Onset of action 3 to 6 weeks for antidepressant effects, up to 2to 4 weeks for PTSD
Not necessarily more effective
Safer and better tolerated than older antidepressants
Low cardiotoxicity makes SSRIs suitable for patients with cardiac disease
Treatment Duration
Continue medication for 6 to 12 months postremission
Common Side Effects
1. Withdrawal/Discontinuation Syndrome
Symptoms anxiety, irritability, dizziness, flulike symptoms
More problematic with short halflife SSRIs eg, paroxetine
insomnia
Long halflife less discontinuation syndrome
2. Common Initial Adverse Effects
Anxiety, agitation, restlessness
Insomnia, drowsiness,
Gastrointestinal disturbances nausea, diarrhea
Dizziness, tremor, headaches
3. High incidence of sexual dysfunction 50 to 80%
Bupropion and Mirtazapine as alternatives
4. Modest weight gain with longterm use
5. Increased risk of GI bleeding and QTc prolongation especially citalopram and fluoxetine
6. Black Box Warning for increased suicidal ideation in patients under 25
7. Serious Adverse Effects
Bleeding/bruising risk
Hyponatremia due to SIADH
Serotonin Syndrome
Discontinuation Syndrome except fluoxetine
Acute closure glaucoma
8. FDA Black Box Warning
Increased suicidality risk in young adults
9. Drug Interactions
Inhibition of cytochrome P450 system
Risk of Serotonin Syndrome with other serotonergic agents
10. Antidepressants secreted in small quantities in breast milk benefits often outweigh risks
11. CYP450 System
SSRIs like fluoxetine and paroxetine are strong CYP2D6 inhibitors
Fluvoxamine inhibits multiple CYP enzymes
12. increased risk of PPHN when used by the mother during late pregnancy.
Persistent pulmonary hypertension of the newborn (PPHN) is a condition where a newborn's pulmonary blood vessels constrict, leading to insufficient oxygen supply.
Specific SSRIs
Escitalo
Paroxetine Paxil
Highest rates of sexual side effects
FDA approved for depression
Pregnancy Risk Category D associated with fetal heart defects
High CYP2D6 inhibitor risk with antiarrhythmics
high risk in pregnancy
Associated with cardiac defects least safe in early pregnancy
Sertraline Zoloft
FDA approved for PTSD
Best cardiovascular safety profile
FDA indicated for PTSD and PMDD
High risk of sexual adverse effects
Generally has the lowest levels in breast milk among SSRIs
Fluoxetine Prozac
Longest acting SSRI FDA approved for bulimia nervosa
Recommended for use in under 18s
Fluoxetine levels are 10 to 20% of maternal plasma
Long halflife less discontinuation syndrome
FDA approved for pediatric depression best evidence with CBT
Most studied SSRI in pregnancy no miscarriage risk
Citalopram Celexa
Associated with QTc prolongation present in high levels in breast milk
May help agitation in Alzheimer's risk of QTc prolongation
Maximum dose 40mg reduced in hepatic disease
SSRI for specific indications
SSRIs for PTSD
Sertraline and Paroxetine FDA approved Fluoxetine and Escitalopram also indicated
Antidepressants in Neurocognitive Disorders
Alzheimer’s Disease Citalopram may alleviate agitation
Citalopram noted for agitation in Alzheimer's disease, suggesting potential utility in dementiarelated symptoms
Lewy Body Disease SSRIs for depression
Huntington’s Disease SSRIs and mirtazapine for depression/anxiety
paraphilic disorders
SSRIs can reduce impulsiveness in paraphilic disorders
SSRIs and SNRI s as firstline MDD
SNRI
SerotoninNorepinephrine Reuptake Inhibitors SNRIs
Mechanism of Action
Inhibit serotonin and norepinephrine transporters
Increase levels of both neurotransmitters in the synapse
FDA Approved Indications for Depression
Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran
Used when patients respond poorly to SSRIs
Effective for depressive and anxietyrelated disorders
Specific SNRI Venlafaxine Effexor
FDA approved for anxiety disorders and PTSD
Considered for SSRIresistant depression with anxiety
Firstline treatments SSRIs sertraline, paroxetine, fluoxetine and SNRIs venlafaxine
High risk of sexual adverse effects minimal CYP inhibition
High prevalence of sexual dysfunction ~60%
Generally considered compatible with breastfeeding, low infant serum levels
Effective for PTSD symptom reduction not FDAapproved for PTSD
Recommended for severe and treatmentresistant depression
Discontinuation Syndrome
More problematic due to shorter halflives eg, venlafaxine
Increase levels of both neurotransmitters in the synapse
Duloxetine
Venlafaxine
Common Adverse Effects
Similar to SSRIs risk of sustained systolic hypertension ~12% with venlafaxine
C Common Side Effects
Nausea, insomnia, dry mouth, headache, weight gain
High risk of sexual dysfunction especially venlafaxine
Increased blood pressure, particularly with venlafaxine at higher doses
SARI
Mirtazapine
Mechanism of action
Noradrenergic and specific serotonergic antidepressant NaSSA
Alpha2 adrenergic antagonist, increases monoamines
a2 adrenergic presynaptic antagonist causing increased release of monoamines (can contribute to serotonin syndrome and hypertensive crisis}
5-HT2 & 5-HT3 antagonist – ↓ GI and sexual side effects
specfic Indication
For Depression
Secondline for treatmentresistant cases helpful for insomnia
For PTSD
Some efficacy shown, but not all symptoms addressed
For Sexual Dysfunction
Low risk can counteract SSRI-induced dysfunction
Breastfeeding
Limited data, but generally reassuring useful for sleep and nausea
Adverse effect
Risk of agranulocytosis/neutropenia: 1/1000
– Sedating at low doses: H1 blocker
Activating at high doses: noradrenergic release
Weight gain, increased appetite, dizziness, constipation
Orthostatic hypotension: 1 noradrenergic antagonist
Hypertension: increased noradrenergic drive
Sedation and weight gain
Agomelatine
Mechanism
Melatonergic agonist and 5HT2C antagonist
For Sexual Dysfunction
Low risk similar rates to placebo
MAO Inhibitor
A Mechanism of Action MOA
1 Inhibition of monoamine oxidase
Increases neurotransmission of serotonin, norepinephrine, dopamine
Types
nonselective
phenelzine,
4 PTSD Phenelzine effective
tranylcypromine
isocarboxazid
selective
selegiline
At lower doses, a low tyramine diet may not be necessary
Clinical Uses
1 Atypical Depression
Highyield MCQ point
2 Refractory Depression
3 Social Anxiety, Panic Attacks
5 Narcolepsy REM sleep suppressant
D Major Adverse Effects
1. 1 Serotonin Syndrome
when Switching Medications
1 Requires washout period
2week gap for most antidepressants 5week for Fluoxetine
Risk with other serotonergic agents
Antibiotic with MAOI activity risk of serotonin syndrome
Linezolid Interactions
2. Hypertensive Crisis ER mcq
Hypertensive Crisis and Its Management in Psychiatry
Overview of Hypertensive Crisis
Definition and Importance
A hypertensive crisis is a severe increase in blood pressure that can lead to stroke, myocardial infarction, or other serious health issues
Understanding its causes and treatments is crucial for psychiatrists, especially when considering psychopharmacology
Symptoms of Hypertensive Crisis
Recognition of Symptoms
A constellation of symptoms indicates a hypertensive crisis
Common symptoms include
• Headache
• Mydriasis dilated pupils
• Neuromuscular irritability
• Hypertension
• Cardiac arrhythmias
• Potential for stroke
• Potential for myocardial infarction
Causes of Hypertensive Crisis
I Foods that Cause Hypertensive Crisis
Interaction with Monoamine Oxidase Inhibitors MAOIs
MAOIs inhibit monoamine oxidase in the gut, allowing tyramine absorption
Tyramine can lead to hypertensive crises when consumed with MAOIs
Tyraminerich foods include
• Ontap beer
• Fava beans
• Aged deli meats
• Aged cheeses
• Fermented foods eg, sauerkraut, soy sauce
II Other Substances/Medications
Drugdrug interactions with MAOIs
Certain medications can precipitate a hypertensive crisis when taken with MAOIs
Key substances include
• Noradrenergic drugs
• Pseudoephedrine
• Linezolid
• Methylene blue
• Some opiates
• Bupropion
• Ldopa
• Methylphenidate
• Amphetamine
Treatment for Hypertensive Crisis
Immediate Management
Rapid intervention is crucial to prevent serious sequelae
Focus on rapidacting antihypertensive agents
Treatment approaches include
• General supportive measures Immediate medical stabilization is paramount
• Pharmacological interventions
▪ Betablockers eg, esmolol, labetalol for tachycardia and hypertension
▪ Vasodilators eg, nitroprusside, intravenous nicardipine for severe hypertension
▪ Blood pressure management in acute settings Maintain SBP below 185 mmHg or DBP below 110 mmHg during interventions, often with agents like labetalol or nicardipine
Conclusion
Importance of Awareness
Understanding the causes, symptoms, and treatments of hypertensive crises is essential for psychiatrists, particularly when prescribing MAOIs and managing patients with potential drug interactions
Key Takeaways
• MAOIs and tyraminerich foods are a critical focus for preventing hypertensive crises
• Drug interactions must be carefully monitored to avoid precipitating crises
• Prompt recognition and treatment of symptoms are vital for patient safety
TCA
Tricyclic Antidepressants TCAs
Trip...
Indication
Depression Effective for melancholic and refractory cases aids chronic pain and insomnia
TCAs for melancholic features
PTSD Limited data consider for intrusive symptoms and insomnia
High overdose risk not firstline treatment
Not firstline due to side effects reserved for treatment resistant cases
Mechanism of Action
Increase norepinephrine and serotonin levels by blocking reuptake
Nonselective with anticholinergic and antihistaminergic effects
Block muscarinic, histaminergic, and alphaadrenergic receptors
Common Side Effects
Anticholinergic effects dry mouth, blurred vision, constipation, urinary retention
Anticholinergic Dry mouth, constipation
Orthostatic hypotension, sedation, weight gain, sexual dysfunction, lower seizure threshold
Sexual Dysfunction High risk nortriptyline and desipramine may enhance function
Narrow therapeutic index high toxicity in overdose
Cardiac Arrhythmias, QTc prolongation
Specific TCA Amitriptyline Elavil
Breastfeeding Generally safe preferred TCA
MCQ Alert Avoid Doxepin during breastfeeding due to severe infant side effects
Serotonin Syndrome risk with other serotonergic agents
NDRI
Bupropion Wellbutrin
Mechanism
Norepinephrine and dopamine reuptake inhibitor NDRI
Mild stimulant effect no serotonin impact
Indication
Deoression
Major Depressive Disorder, Seasonal Affective Disorder
FDA Indications: MDD, seasonal affective disorder, smoking cessation
Similar remission rates to SSRIs alternative for postpartum depression
For Sexual Dysfunction
Low risk enhances sexual functioning
Breastfeeding
Limited data some drug found in milk caution with preeclampsia
Other Indications
FDA approved for smoking cessation effective for ADHD
Use During Pregnancy
Bupropion considered moderately safe
Common Side Effects
Headache, agitation, insomnia, weight loss seizures at high doses
Adverse effects
Seizure risk: 0.1%
Contraindicated with past/current eating disorders: due to seizure risk: increased from electrolyte disturbances
Contraindicated when withdrawing from CNS depressants: Etoh, Benzo’s
Seizure risk, agitation, insomnia
General Points on Breastfeeding with Antidepressants
General Principle
Antidepressants secreted in small quantities in breast milk benefits often outweigh risks
Acceptable Risk
RID <10% considered acceptable all SSRIs below this level
Specific Risks/Considerations
Neonatal Withdrawal Mild withdrawal symptoms possible
PPHN Small increased risk with SSRI use after 20 weeks
Postpartum Haemorrhage Slight risk with SSRI/SNRI use before delivery
Drugs to AVOID or use with HIGH CAUTION
Doxepin Severe infant side effects due to metabolite accumulation
Lithium Risk of neonatal toxicity generally not advised
Benzodiazepines Can cause sedation and hypotonia in infants
Lithium L4, possibly unsafe
and Doxepin L5, contraindicated for lactation
Drugs to AVOID or use with HIGH CAUTION
Doxepin Severe infant side effects due to metabolite accumulation
Clozapine Contraindicated serious adverse effects in infants
Lithium Risk of neonatal toxicity generally not advised
Benzodiazepines Can cause sedation and hypotonia in infants
Antidepressants and Breastfeeding Considerations
Medication Transmission
All psychotropic medications, including antidepressants, are transmitted into breast milk
Risk/Benefit Assessment
Untreated maternal depression poses risks for both mother and infant
Must weigh risks of medication exposure via breast milk against untreated depression
Specific SSRI Considerations
Sertraline
Generally has the lowest levels in breast milk among SSRIs
Frequently considered option for breastfeeding mothers
Fluoxetine
Levels in breast milk are 10 to 20% of maternal plasma levels
Lactation Risk Categories
SSRIs
Generally categorized as L2 safer during lactation
Bupropion
Categorized as L3 moderately safe
Doxepin
Categorized as L5 contraindicated
Individualised Approach
Decision should involve careful consideration of risks and benefits
Ideally includes involvement of the father and family
Planning of mental health treatment options is essential
Specific Risks/Considerations
Neonatal Withdrawal Mild withdrawal symptoms possible
PPHN Small increased risk with SSRI use after 20 weeks
Postpartum Haemorrhage Slight risk with SSRI/SNRI use before delivery
Antidepressants in Neurocognitive Disorders
Alzheimer’s Disease
Citalopram may alleviate agitation
Lewy Body Disease
SSRIs for depression, cholinesterase inhibitors for psychosis
Huntington’s Disease
SSRIs and mirtazapine for depression/anxiety