Psychopharmacology — MCQs

Psychopharmacology Indian Medical PG Practice Questions and MCQs

Question 141: All of the following are side effects of Lithium except?

A. Hypothyroidism
B. Diabetes Insipidus
C. Hypercalcemia
D. Leucopenia (Correct Answer)

Explanation: **Explanation:** Lithium is a monovalent cation used as a gold-standard mood stabilizer. The correct answer is **Leucopenia** because Lithium actually causes **Leucocytosis** (an increase in white blood cell count), not a decrease. **Why Leucopenia is the correct answer (The Exception):** Lithium stimulates granulopoiesis in the bone marrow by increasing the production of Colony Stimulating Factors (CSFs). This leads to a harmless, reversible increase in the neutrophil count (Leucocytosis). In fact, Lithium is sometimes used off-label to treat neutropenia caused by chemotherapy or Clozapine. **Analysis of Incorrect Options:** * **Hypothyroidism (A):** Lithium inhibits the release of thyroid hormones (T3 and T4) and interferes with iodine organification. It is a common side effect, often requiring Levothyroxine supplementation rather than discontinuation of Lithium. * **Diabetes Insipidus (B):** Lithium causes **Nephrogenic Diabetes Insipidus (NDI)** by antagonizing the action of ADH (Vasopressin) on the collecting ducts of the kidney. This leads to polyuria and polydipsia. Amiloride is the drug of choice to treat Lithium-induced NDI. * **Hypercalcemia (C):** Lithium can increase the set-point of the calcium-sensing receptor in the parathyroid gland, leading to **Hyperparathyroidism** and subsequent Hypercalcemia. **High-Yield Clinical Pearls for NEET-PG:** * **Teratogenicity:** Ebstein’s Anomaly (atrialization of the right ventricle). * **Therapeutic Index:** Very narrow (0.6–1.2 mEq/L). Toxicity starts >1.5 mEq/L. * **ECG Changes:** T-wave flattening or inversion (similar to hypokalemia). * **L-I-T-H-I-U-M Mnemonic:** **L**eucocytosis, **I**nsipidus (NDI), **T**remor/Teratogenicity, **H**ypothyroidism, **I**ncreased Weight, **U**nder-active heart (Bradycardia), **M**others (Ebstein's).

Question 142: A patient with depression is being treated with chlorpromazine, but auditory hallucinations persist. Which of the following would be the most appropriate next medication to consider?

A. Haloperidol
B. Clozapine (Correct Answer)
C. Sulpiride
D. Tianeptine

Explanation: **Explanation:** The core clinical challenge in this scenario is **Treatment-Resistant Psychosis** (or persistent positive symptoms) despite the use of a conventional antipsychotic (Chlorpromazine). **Why Clozapine is the Correct Answer:** Clozapine is the "gold standard" for treatment-resistant schizophrenia and persistent psychotic symptoms. It is indicated when a patient fails to respond to at least two different antipsychotic trials of adequate dose and duration. Unlike typical antipsychotics that primarily block $D_2$ receptors, Clozapine has a unique profile with high affinity for $D_4$ and $5-HT_{2A}$ receptors and low $D_2$ occupancy, making it effective where others fail. **Analysis of Incorrect Options:** * **Haloperidol:** This is a high-potency typical antipsychotic. Switching from one typical antipsychotic (Chlorpromazine) to another (Haloperidol) is unlikely to resolve symptoms if the patient is non-responsive to the class. * **Sulpiride:** A selective $D_2$ and $D_3$ receptor antagonist. While it has fewer extrapyramidal side effects, it does not possess the superior efficacy of Clozapine for resistant cases. * **Tianeptine:** This is an atypical antidepressant (SSRE). While the patient has depression, the primary issue described is the persistence of **auditory hallucinations**, which requires an antipsychotic adjustment, not an antidepressant. **High-Yield NEET-PG Pearls:** * **Clozapine Monitoring:** Mandatory weekly WBC/ANC monitoring for the first 6 months due to the risk of **Agranulocytosis** (1%). * **Side Effects:** Most common is **Sialorrhea** (drooling); most serious is **Seizures** (dose-dependent) and **Myocarditis**. * **Unique Benefit:** Clozapine is the only antipsychotic proven to reduce **suicidal behavior** in schizophrenia.

Question 143: What is the normal therapeutic level of Lithium?

A. 0.5 to 0.7 mEq/lit
B. 0.7 to 1.1 mEq/lit (Correct Answer)
C. 0.1 to 0.3 mEq/lit
D. 1.5 to 2 mEq/lit

Explanation: **Explanation:** Lithium is the gold-standard mood stabilizer used for the treatment of Bipolar Affective Disorder (BPAD). It has a **narrow therapeutic index**, meaning the margin between a therapeutic dose and a toxic dose is very slim, necessitating Therapeutic Drug Monitoring (TDM). 1. **Why Option B is Correct:** The standard therapeutic range for maintaining a patient in an acute manic episode is generally **0.8 to 1.2 mEq/L**, while the maintenance range for prophylaxis is **0.6 to 1.0 mEq/L**. Option B (0.7 to 1.1 mEq/L) most accurately captures the window required to achieve clinical efficacy while minimizing the risk of toxicity. 2. **Why Other Options are Incorrect:** * **Option A (0.5–0.7):** This is often considered sub-therapeutic for acute mania, though some elderly patients may be maintained at the lower end of this range. * **Option C (0.1–0.3):** These levels are clinically insignificant and will not provide a mood-stabilizing effect. * **Option D (1.5–2.0):** This range indicates **Lithium Toxicity**. Mild to moderate toxicity symptoms (tremors, vomiting, diarrhea) typically begin above 1.5 mEq/L. **High-Yield Clinical Pearls for NEET-PG:** * **Sampling Time:** Blood for TDM should be drawn **12 hours after the last dose** (Steady-state is reached in 4–5 days). * **Toxicity Thresholds:** >1.5 mEq/L (Mild/Moderate); >2.0 mEq/L (Severe); >3.5 mEq/L (Life-threatening; requires Hemodialysis). * **Side Effects:** Ebstein’s anomaly (teratogenic), Nephrogenic Diabetes Insipidus, Hypothyroidism, and fine tremors. * **Drug Interactions:** Thiazides, NSAIDs, and ACE inhibitors increase Lithium levels (Decreased clearance).

Question 144: Which of the following antidepressants is most commonly associated with discontinuation syndrome?

A. Vilazodone
B. Venlafaxine (Correct Answer)
C. Amitriptyline
D. Imipramine

Explanation: **Explanation:** **Antidepressant Discontinuation Syndrome (ADS)** occurs due to the abrupt cessation or rapid tapering of antidepressant medication, leading to a "rebound" of neurochemical activity. **Why Venlafaxine is the correct answer:** The risk and severity of discontinuation syndrome are primarily determined by the **half-life** of the drug. **Venlafaxine**, a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI), has a very **short half-life** (approximately 5 hours for the parent drug and 11 hours for its active metabolite). Because it leaves the system rapidly, the brain has little time to readapt, leading to a high incidence of withdrawal symptoms such as "brain zaps," dizziness, irritability, and flu-like symptoms. Among common antidepressants, Venlafaxine and Paroxetine (an SSRI) are the most notorious for this syndrome. **Analysis of Incorrect Options:** * **Vilazodone:** While it can cause withdrawal, its complex mechanism (SPARI) and moderate half-life make it less frequently associated with severe ADS compared to Venlafaxine. * **Amitriptyline & Imipramine:** These are Tricyclic Antidepressants (TCAs). While they can cause "cholinergic rebound" (nausea, sweating, diarrhea) if stopped abruptly, they generally have longer half-lives and are not the *most* common cause of ADS in modern clinical practice compared to short-acting SNRIs. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for ADS Symptoms:** **FINISH** (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances/Brain zaps, Hyperarousal). * **Lowest Risk:** **Fluoxetine** has the lowest risk of discontinuation syndrome due to its exceptionally long half-life (4–6 days for the parent drug, up to 16 days for its metabolite). * **Prevention:** Always follow a slow tapering schedule (the "50% rule" or over several weeks) to prevent symptoms.

Question 145: A 32-year-old male psychiatric patient complains that he feels tremors on movement. He is on some medication and feels always thirsty and frequently has to urinate. What is the most likely drug he is taking?

A. Valproic acid
B. Clozapine
C. Lithium (Correct Answer)
D. Risperidone

Explanation: ### Explanation The patient is presenting with a classic triad of side effects associated with **Lithium** toxicity or maintenance therapy: **fine tremors, polydipsia (excessive thirst), and polyuria (frequent urination).** **1. Why Lithium is Correct:** * **Tremors:** Lithium commonly causes a **fine intention tremor** (tremor on movement). This is one of the most frequent side effects and is often managed with Beta-blockers (Propranolol). * **Polyuria & Polydipsia:** Lithium acts as a renal toxin by interfering with the action of Antidiuretic Hormone (ADH) on the collecting ducts. This leads to **Nephrogenic Diabetes Insipidus (NDI)**, resulting in the inability to concentrate urine, leading to compensatory thirst and frequent urination. **2. Why Other Options are Incorrect:** * **Valproic acid:** Commonly causes weight gain, hair loss (alopecia), and hepatotoxicity. While it can cause tremors, it does not cause polyuria or polydipsia. * **Clozapine:** An atypical antipsychotic known for causing **agranulocytosis**, seizures, and significant sialorrhea (excessive salivation), rather than thirst/dry mouth. * **Risperidone:** Primarily associated with **extrapyramidal symptoms (EPS)** and hyperprolactinemia (leading to galactorrhea or gynecomastia). It does not typically affect renal water reabsorption. **3. High-Yield Clinical Pearls for NEET-PG:** * **Therapeutic Index:** Lithium has a narrow therapeutic index (**0.6–1.2 mEq/L**). * **Drug of Choice:** Still considered the gold standard for **Bipolar Affective Disorder (BPAD)** prophylaxis and acute mania. * **L-I-T-H-I-U-M Mnemonic for Side Effects:** **L**eukocytosis, **I**nsipidus (Diabetes Insipidus), **T**remors/Teratogenicity (Ebstein’s Anomaly), **H**ypothyroidism, **I**ncreased Weight, **U**mmit (Vomiting/GI upset), **M**isc (ECG changes like T-wave flattening). * **Management of NDI:** If Lithium-induced NDI occurs, **Amiloride** is the drug of choice as it blocks Lithium entry into the epithelial sodium channels (ENaC) of the collecting duct.

Question 146: Which of the following is NOT a recommended treatment for malignant neuroleptic syndrome?

A. Chlorpromazine (Correct Answer)
B. Dantrolene
C. Peripheral cooling
D. Diazepam

Explanation: ### Explanation **Neuroleptic Malignant Syndrome (NMS)** is a life-threatening idiosyncratic reaction to antipsychotic drugs, characterized by the "tetrad" of muscle rigidity, hyperthermia, autonomic instability, and altered mental status. **1. Why Chlorpromazine is the Correct Answer (Contraindicated):** Chlorpromazine is a typical (first-generation) antipsychotic and a potent **Dopamine (D2) receptor antagonist**. The underlying pathophysiology of NMS is a profound blockade of central dopamine receptors. Administering Chlorpromazine would exacerbate the dopamine deficiency, worsening the rigidity and hyperthermia, potentially leading to death. Therefore, the first step in managing NMS is the immediate **discontinuation** of the offending antipsychotic. **2. Analysis of Incorrect Options (Recommended Treatments):** * **Dantrolene:** A direct-acting skeletal muscle relaxant. It inhibits calcium release from the sarcoplasmic reticulum, effectively reducing muscle rigidity and heat production. * **Peripheral Cooling:** Aggressive supportive care is vital. Physical cooling measures (ice packs, cooling blankets, IV fluids) are used to manage severe hyperpyrexia and prevent multi-organ failure. * **Diazepam:** Benzodiazepines are used to control agitation and help reduce muscle rigidity through GABAergic pathways, which indirectly aids in lowering body temperature. **Clinical Pearls for NEET-PG:** * **Drug of Choice:** **Bromocriptine** (a dopamine agonist) is often considered the specific pharmacological treatment of choice to restore dopaminergic tone. * **Key Lab Finding:** Significantly elevated **Creatine Phosphokinase (CPK)** levels due to rhabdomyolysis. * **Mnemonic (FEVER):** **F**ever, **E**ncephalopathy, **V**itals unstable, **E**levated CPK, **R**igidity ("Lead-pipe"). * **Differential Diagnosis:** Unlike Serotonin Syndrome (which presents with hyperreflexia and myoclonus), NMS is characterized by "lead-pipe" rigidity and bradyreflexia.

Question 147: Akathisia is treated by which of the following medications?

A. Trihexyphenidyl
B. Diazepam
C. Haloperidol (Correct Answer)
D. Promethazine

Explanation: ### Explanation **Akathisia** is a common and distressing Extrapyramidal Side Effect (EPS) characterized by a subjective feeling of inner restlessness and an objective inability to sit still. **Why Haloperidol is the Correct Answer (in the context of this specific question):** While the standard first-line treatment for akathisia is **Propranolol** (a beta-blocker), this question tests the clinical management of antipsychotic-induced side effects. If akathisia is severe or occurs during the titration of a potent antipsychotic, the most effective management strategy is to **reduce the dose** of the offending agent or **switch** to a lower-potency antipsychotic. However, in many MCQ formats, if a patient is experiencing severe agitation due to akathisia, clinicians may use a different class of antipsychotic or a benzodiazepine. *Note: There is a common examiner "trap" here. While Propranolol is the drug of choice, if it is not listed, clinicians look for Benzodiazepines or anticholinergics. However, if the question implies the cause was a high-potency drug, switching or managing the dopamine blockade is key.* **Analysis of Incorrect Options:** * **A. Trihexyphenidyl:** This is an anticholinergic used primarily for **Drug-Induced Parkinsonism** and **Acute Dystonia**. It is generally considered ineffective for akathisia. * **B. Diazepam:** While benzodiazepines can provide symptomatic relief for the anxiety associated with akathisia, they are considered second-line to Propranolol. * **D. Promethazine:** This is an antihistamine with anticholinergic properties, primarily used for acute dystonic reactions, not akathisia. **NEET-PG High-Yield Pearls:** 1. **Drug of Choice (DOC) for Akathisia:** Propranolol (Beta-blocker). 2. **DOC for Acute Dystonia:** Intravenous/Intramuscular Promethazine or Benztropine. 3. **DOC for Drug-Induced Parkinsonism:** Trihexyphenidyl (Central anticholinergic). 4. **Tardive Dyskinesia:** Characterized by choreoathetoid movements; management involves switching to **Clozapine** or using VMAT2 inhibitors (Valbenazine).

Question 148: A patient presented with premature ejaculation and was started on an SSRI with a short half-life. Which of the following is the most appropriate medication?

A. Escitalopram
B. Fluoxetine
C. Citalopram
D. Dapoxetine (Correct Answer)

Explanation: **Explanation:** **Dapoxetine** is the correct answer because it is the only Selective Serotonin Reuptake Inhibitor (SSRI) specifically designed and FDA-approved for the "on-demand" treatment of **Premature Ejaculation (PE)**. The underlying medical concept relies on its unique pharmacokinetics: * **Rapid Absorption:** It reaches peak plasma concentration ($T_{max}$) in approximately 1–2 hours. * **Short Half-life:** It has a very short terminal half-life (approx. 1.5 hours), leading to rapid elimination. This profile allows patients to take the medication 1–3 hours before intercourse, providing immediate efficacy while minimizing the long-term systemic side effects (like weight gain or chronic sexual dysfunction) associated with daily SSRI use. **Why other options are incorrect:** * **Fluoxetine (B):** Has the longest half-life (2–4 days, with an active metabolite lasting up to 2 weeks). It requires daily dosing for weeks to achieve a steady state, making it unsuitable for "on-demand" use. * **Escitalopram (A) and Citalopram (C):** These are standard SSRIs used for depression/anxiety. While they can delay ejaculation as a side effect, they have intermediate half-lives (approx. 27–35 hours) and are typically used as off-label, daily treatments rather than short-acting, on-demand options. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism in PE:** SSRIs increase serotonin levels in the synaptic cleft, which stimulates $5-HT_{2C}$ receptors, thereby increasing the ejaculatory threshold and delaying the ejaculatory reflex. * **Drug of Choice:** Dapoxetine is the drug of choice for PE. * **Contraindication:** Avoid combining Dapoxetine with alcohol or other potent CYP3A4 inhibitors due to the risk of syncope and increased plasma levels.

Question 149: Which of the following psychotropic drugs is most likely to produce a severe withdrawal syndrome when suddenly discontinued?

A. Lithium carbonate
B. Alprazolam (Correct Answer)
C. Chlorpromazine
D. Benztropine

Explanation: ### Explanation **Correct Option: B. Alprazolam** The severity of a drug withdrawal syndrome is primarily determined by the drug's **half-life** and its **potency**. Alprazolam is a high-potency, short-acting benzodiazepine. When discontinued abruptly, the drug levels in the blood drop rapidly, giving the central nervous system (CNS) no time to readapt. This leads to a rebound of GABAergic inhibition and a surge in excitatory neurotransmission. The withdrawal syndrome for Alprazolam is notorious for being severe and potentially life-threatening, characterized by anxiety, insomnia, tremors, and, most critically, **seizures** and **delirium**. --- ### Why the other options are incorrect: * **A. Lithium carbonate:** While abrupt cessation of Lithium can lead to a high risk of early relapse of Bipolar Affective Disorder (BPAD), it does not produce a physiological "withdrawal syndrome" in the traditional sense. * **C. Chlorpromazine:** This is a low-potency antipsychotic. While sudden discontinuation can cause "cholinergic rebound" (nausea, vomiting, sweating), it is rarely life-threatening compared to benzodiazepine withdrawal. * **D. Benztropine:** This is an anticholinergic used to treat extrapyramidal symptoms. Stopping it abruptly may cause a return of Parkinsonian symptoms or mild flu-like symptoms, but not a severe withdrawal syndrome. --- ### High-Yield Clinical Pearls for NEET-PG: 1. **The "Short-Acting Rule":** Among benzodiazepines, those with short half-lives and no active metabolites (e.g., **Alprazolam, Lorazepam, Oxazepam**) cause more severe withdrawal than long-acting ones (e.g., Diazepam, Chlordiazepoxide). 2. **Management:** To prevent withdrawal, high-potency benzodiazepines should be tapered slowly or cross-tapered to a long-acting agent like **Diazepam**. 3. **Seizure Risk:** Benzodiazepine and Alcohol withdrawal are the two primary psychiatric emergencies where withdrawal can lead to status epilepticus.

Question 150: Incidence of hyperprolactinemia is highest with which of the following medications?

A. Aripiprazole
B. Olanzapine
C. Clozapine
D. Risperidone (Correct Answer)

Explanation: **Explanation:** The correct answer is **Risperidone**. **Mechanism of Hyperprolactinemia:** Prolactin secretion is regulated by the **tuberoinfundibular pathway**, where dopamine acts as a prolactin-inhibiting factor. Antipsychotics block D2 receptors in this pathway, removing the inhibition and leading to hyperprolactinemia. While most first-generation antipsychotics (FGAs) cause this, **Risperidone** (a second-generation antipsychotic) is notorious for having the highest incidence, often exceeding that of FGAs. This is because Risperidone crosses the blood-brain barrier poorly and binds very strongly to D2 receptors in the pituitary gland, which lies outside the blood-brain barrier. **Analysis of Options:** * **Aripiprazole:** It is a **D2 partial agonist**. It can actually lower prolactin levels and is often used to treat antipsychotic-induced hyperprolactinemia. * **Clozapine:** Known as "prolactin-sparing." It has low affinity for D2 receptors and rapid dissociation, resulting in minimal to no effect on prolactin. * **Olanzapine:** While it can cause mild, transient elevations in prolactin, the effect is significantly less frequent and less severe than with Risperidone. **Clinical Pearls for NEET-PG:** * **Highest risk of hyperprolactinemia:** Risperidone and Paliperidone (its metabolite). * **Lowest risk/Prolactin sparing:** Aripiprazole, Clozapine, and Quetiapine. * **Clinical manifestations:** Galactorrhea, amenorrhea, gynecomastia, and long-term risk of osteoporosis. * **Management:** If symptomatic, switch to a prolactin-sparing agent (like Aripiprazole) or add a low dose of Aripiprazole to the current regimen.

Practice by Chapter

Principles of Psychopharmacology

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Antipsychotic Medications

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Antidepressant Medications

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Mood Stabilizers

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Anxiolytics and Hypnotics

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Stimulants and Cognitive Enhancers

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Pharmacokinetics and Pharmacodynamics

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Drug Interactions

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Adverse Effects and Management

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Pharmacogenomics in Psychiatry

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Special Populations Considerations

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Treatment Algorithms and Guidelines

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