1. Answer: C. Weight gain with antipsychotic medications seems to be associated with pre-treatment BMI such that the greatest weight gain is seen in individuals with low baseline BMI. Although all antipsychotics cause a certain amount of weight gain, some of them cause more than others, and it is likely to plateau only after 6 months.

2. Answer: E. Benzodiazepine withdrawal symptoms are very uncomfortable and sometimes serious. Symptoms of benzodiazepine withdrawal include anxiety, delirium, increase in breathing rate, tachycardia, high blood pressure, hyperreflexes, depression, depersonalization and derealization, perceptual disturbances, and seizures. Both constipation and diarrhea are recognized features of benzodiazepine withdrawal. Rhinorrhea is a feature of opiate withdrawal.

3. Answer: A. Flupentixol, which is a typical antipsychotic, also has an antidepressant effect. Similarly, amoxapine has both an antipsychotic and an antidepressant effect.

4. Answer: D. MAOIs can cause pyridoxine deficiency. Pyridoxine deficiency is associated with peripheral neuropathy.

5. Answer: B. Norfluoxetine, the active metabolite of fluoxetine has a half-life of up to 5 to 7 days, and therefore, a washout period of at least 5 weeks is recommended before switching over to MAOIs. The other SSRIs’ half-life is less than 24 hours.

6. Answer: A. Serotonin syndrome is a potentially life-threatening condition associated with increased serotonergic activity in the CNS. It is seen in patients with an excess of serotonin either due to high doses of serotonergic medications, drug interactions, and sometimes drug overdoses. The diagnosis of serotonin syndrome is made on clinical grounds. Mental status changes include anxiety, delirium, and disorientation. Autonomic manifestations can include diaphoresis, tachycardia, hyperthermia, hypertension, vomiting, and diarrhea. Neuromuscular hyperactivity presents as tremors, muscle rigidity, myoclonus, hyperreflexia, and bilateral Babinski sign. NMS is associated with neuroleptics and not serotonergic medications. There is no history of alcohol abuse in this patient, and therefore, alcohol withdrawal syndrome is not the correct choice.

7. Answer: E. Serotonin syndrome can be a difficult condition to diagnose and is easily overlooked due to the high prevalence of use of SSRIs. Several criteria for the diagnosis of serotonin syndrome have been used. The Hunter criteria are 84% sensitive and 97% specific when compared with the gold standard (diagnosis by blood serotonin levels). One of the criteria is “temperature above 38°C plus ocular clonus or inducible clonus,” not 32°C.

8. Answer: D. Clomipramine, although classified as a tricyclic antidepressant, has a strong serotonin reuptake inhibition effect. It is indicated for the treatment of depression and obsessive-compulsive disorder (OCD). The serotonin reuptake inhibition is thought to be responsible for its anti-OCD properties.

9. Answer: B. Bupropion blocks reuptake of both noradrenaline and dopamine. This mechanism of action is particularly useful in patients with depression associated with psychomotor retardation. Buspirone is a 5-HT_1A agonist and is effective in treating anxiety. Fluoxetine is an SSRI, and venlafaxine is a serotonin-norepinephrine reuptake inhibitor.

10. Answer: A. Methyldopa is an antihypertensive drug that is converted to alpha-methylnoradrenaline in the central presynaptic neurons. This acts as a false neurotransmitter and reduces the overall noradrenergic neurotransmission to the postsynaptic neurons, resulting in depression.

11. Answer: B. Pindolol is a nonselective beta-blocker in terms of cardioselectivity but possesses intrinsic sympathomimetic activity. It acts on serotonin (5-HT_1A) receptors in the brain resulting in increased postsynaptic serotonin concentrations. Pindolol is sometimes added to SSRIs (particularly fluoxetine), if the patient fails to respond to standard therapy alone.

12. Answer: D. D₂ receptors are found in the mesolimbic, mesocortical, and nigrostriatal systems. There are five subtypes of dopamine receptors: D₁, D₂, D₃, D₄, and D₅. The D₁ and D₅ receptors are members of the D₁-like family of dopamine receptors, whereas the D₂, D₃ and D₄ receptors are members of the D₂-like family. There is some evidence to suggest that 5-HT_2A antagonists improve slow-wave sleep and no evidence to suggest they enhance REM sleep. 5-HT_1A agonists such as buspirone have anxiolytic properties. Most typical antipsychotics are D₂ antagonists rather than agonists. Alpha-2 adrenergic agonists decrease the release of norepinephrine and cause hypotension.

13. Answer: D. Lipophilic drugs are rapidly and completely absorbed from the gastrointestinal tract. They have a large volume of distribution and a high first-pass effect. They rapidly cross the blood-brain barrier.

14. Answer: D. All of the drugs mentioned except paroxetine induce hepatic cytochrome P450 enzymes. Knowledge of the cytochrome P450 enzyme system helps in choosing appropriate medicines and prevents untoward drug interactions in patients taking multiple medicines.

15. Answer: C. Serotonin is now considered to be an important neurotransmitter that is responsible for the regulation of various brain functions. Serotonin is implicated in alertness, activation, aggression, sleep and wakefulness regulation, weight gain, and sexual behavior. However, serotonin has no known role in the maintenance of muscle tone.

16. Answer: B. Most of the benzodiazepines are metabolized in the liver, except lorazepam, oxazepam, and temazepam.

17. Answer: E. Benzodiazepines act by increasing the frequency of Cl⁺ channel opening, and barbiturates increase the duration of Cl⁺ channel opening.

18. Answer: B. Diazepam is highly lipid soluble and diffuses rapidly into the CNS. It is 90% to 95% protein bound, stored in body fat and brain tissue, is found in breast milk, and crosses the placenta. Peak plasma levels are reached in 30 to 90 minutes. The elimination half-life is between 30 to 100 hours. Oral absorption is faster than IM absorption.

19. Answer: E. Ataxia is common in the elderly. Sedation, drowsiness, anterograde amnesia, and postural hypotension are side effects of most of the benzodiazepines. Paradoxical restlessness and behavioral disinhibition is also seen in some patients. Nightmares are a withdrawal symptom and not a side effect of benzodiazepines.

20. Answer: A. Leucopenia, eosinophilia, and changes in plasma cortisol are associated with benzodiazepine use. Respiratory depression is mainly seen with intravenous use. Benzodiazepines do not cause induction of hepatic microsomal enzymes, whereas barbiturates and alcohol do induce hepatic enzymes.

21. Answer: D. Flurazepam has a half-life that ranges between 40 to 250 hours. The half-lives of the other drugs are as follows: lorazepam, 10 to 12 hours; alprazolam, 6 to 10 hours; oxazepam, 4 to 15 hours; and temazepam, 8 to 22 hours.

22. Answer: D. The five benzodiazepines that have received FDA approval for the treatment of insomnia are temazepam, triazolam, estazolam, flurazepam, and quazepam.

23. Answer: A. Tremors, depression, tinnitus, depersonalization, derealization, insomnia, fatigue, sweating, concentration difficulties, restlessness, labile blood pressure, and heart rate are all features of benzodiazepine withdrawal. Psychotic symptoms are not common.

24. Answer: B. Cimetidine inhibits hepatic enzymes and hence raises levels of many drugs including benzodiazepines. The other drugs listed are hepatic enzyme inducers, which increase metabolism and decrease the levels of drugs metabolized by the hepatic enzymes.

25. Answer: D. Cleft lip, cleft palate, respiratory depression, and withdrawal symptoms have been reported in children born to mothers taking benzodiazepines. Absent arms and legs is a teratogenic effect of thalidomide, which was banned many years ago but is now found to have some chemotherapeutic activity.

26. Answer: D. Benzodiazepines increase stage II sleep and sleep spindles seen in this stage. A relative decrease in REM and stage III sleep is noted. Sleep latency, total sleep time, and sleep efficiency all improve depending on the half-life of the benzodiazepine used.

27. Answer: B. The risk of tolerance or dependence depends on several factors associated with the patient and the drug used. In general, tolerance to the sedative effects of benzodiazepines is seen after 2 to 3 weeks of daily use.

28. Answer: D. Cross-tolerance in patients taking benzodiazepines can occur with other benzodiazepines, barbiturates, and alcohol. This is presumed to be due to their proximity of sites of action.

29. Answer: C. Personality profiles of patients with benzodiazepine abuse and dependence have shown that it is relatively more common in individuals with passive and dependent personality traits.

30. Answer: A. Epstein’s anomaly is the downward displacement of the tricuspid valve in the right ventricle. It is relatively rare in the general population with an incidence of one in 20,000. Lithium during pregnancy is associated with a 400 times increased incidence of Epstein’s anomaly. Neural tube defects are associated with certain drugs such as sodium valproate that cause vitamin B₁₂ deficiency; and phacomelia (congenital absence of limbs) is caused by thalidomide.

31. Answer: B. Carbamazepine can produce ataxia at therapeutic doses. Imipramine, quetiapine, chlorpromazine, and fluoxetine do not typically produce ataxia.

32. Answer: D. Hyperawareness of senses, dysphoria, tremors, and tongue fasciculations are more suggestive of benzodiazepine withdrawal. Difficulty to stop worrying and the inability to relax are more commonly seen in patients with anxiety disorder.

33. Answer: C. Acute dystonia is associated with dopamine receptor antagonists, and benzodiazepines are one of the classes of drugs used to treat acute dystonia. Ataxia, confusion, drowsiness, and aggression (especially in individuals with traumatic brain injury) are recognized side effects of benzodiazepines.

34. Answer: E. Benzodiazepines act at the GABA-BDZ receptor complex and potentiate the effects of GABA. They increase the frequency of opening of chloride ion channels and cause hyperpolarization of the cells. Flumazenil, a benzodiazepine receptor antagonist is used to reverse the effects of benzodiazepines. Naloxone is used in patients with opiate toxicity.

35. Answer: B. Amitriptyline, lithium, haloperidol, and phenelzine are all associated with tremors. Diazepam is not associated with tremors.

36. Answer: E. Tricyclic antidepressants have anticholinergic effects that result in blurred vision, dry mouth, urinary hesitancy, delirium, and constipation. Paralytic ileus may occasionally occur. Desipramine and nortriptyline have a lower incidence of anticholinergic effects compared with other tricyclics.

37. Answer: B. Nortriptyline is the only tricyclic antidepressant that has good evidence for an effective therapeutic window. Blood levels in the range of 50 to 150 ng/mL are considered to be therapeutic, whereas levels >500 ng/mL are considered toxic.

38. Answer: E. Tricyclics have a low therapeutic index, that is, the therapeutic dose is close to the toxic dose. Tricyclic overdose (deliberate or accidental) can be lethal. Intravenous sodium bicarbonate is often used as an antidote to neutralize metabolic acidosis.

39. Answer: B. Tricyclics are sometimes classified as tertiary amines and secondary amines. In general, the tertiary amines inhibit reuptake of serotonin as well as norepinephrine and produce more sedation, anticholinergic effects, and orthostatic hypertension. The secondary amines act primarily on norepinephrine and tend to have a lower side effect profile. Secondary amine tricyclics include nortriptyline, desipramine, and protriptyline.

40. Answer: B. Of all the tricyclics, amitriptyline has the most anticholinergic effects, and desipramine has the least anticholinergic effects.

41. Answer: C. Nortriptyline, a secondary amine tricyclic, which predominantly inhibits the reuptake of norepinephrine, is least likely to cause postural hypotension.

42. Answer: C. Nortriptyline is the only tricyclic antidepressant that has good evidence for an effective therapeutic window. Blood levels in the range of 50 to 150 ng/mL are considered to be therapeutic, whereas levels >500 ng/mL are considered toxic.

43. Answer: D. The symptoms suggest seasonal affective disorder. Bupropion has been found to be more effective in these patients. SSRIs are also useful but lack the activating effects of bupropion. Mirtazapine is not a good choice, as it is likely to worsen hypersomnia and enhance appetite further.

44. Answer: C. Tyramine, a substrate of MAO enzymes is present in certain fermented foodstuffs such as red wine, cheese, yeast extracts, and pickled fish. Patients taking MAOIs are unable to deaminate tyramine, normally broken down by MAO-A in the gut. This results in the displacement of intracellular stores of norepinephrine and can cause a pressor response resulting in hypertensive crisis.

45. Answer: B. Tyramine, a substrate of MAO enzymes is present in high concentrations in certain foods such as cheese, red wine, and yeast extracts. Ingestion of these foods results in hypertensive crisis. Bananas do not cause a hypertensive crisis with MAOIs, although the skin of banana can.

46. Answer: E. The symptoms described are typical of serotonin syndrome. The combination of sumatriptan and MAOIs can result in serotonin syndrome. This reaction is commonly seen when MAOIs are combined with SSRIs or other tricyclic antidepressants. For this reason, when switching from MAOIs to SSRIs or tricyclics or vice versa, a minimum of a 2-week washout period is required.