1. A 22-year-old man with no prior psychiatric or antipsychotic history is brought to the emergency department with acute agitation and receives intramuscular haloperidol. About four hours later he develops a forced sustained upward deviation of both eyes and painful twisting of his neck to one side. He is alert, afebrile, and hemodynamically stable, with no rigidity elsewhere. What is the most appropriate immediate management?
A) Administer intravenous dantrolene and begin external cooling
B) Increase the haloperidol dose to control what is likely breakthrough agitation
C) Administer intramuscular benztropine or diphenhydramine, anticipating relief within 15 to 30 minutes
D) Start oral propranolol and observe over the next several days
E) Begin a vesicular monoamine transporter 2 (VMAT2) inhibitor such as valbenazine
ANSWER: C
Rationale:
A young, antipsychotic-naive man developing oculogyric crisis and torticollis within hours of a first high-potency dose has acute dystonia, the earliest extrapyramidal syndrome and one most common in exactly this demographic. The mechanism is an acute reduction in striatal dopamine tone that unmasks a relative cholinergic excess, so an intramuscular anticholinergic such as benztropine or the antihistamine diphenhydramine reverses it rapidly, typically within 15 to 30 minutes.
Option A: Option A is incorrect because dantrolene and cooling treat neuroleptic malignant syndrome, and this patient has no fever, generalized rigidity, or autonomic instability.
Option B: Option B is incorrect because increasing the dose deepens the dopamine blockade and worsens dystonia.
Option D: Option D is incorrect because propranolol over days is the treatment for akathisia, not an acute dystonic reaction requiring immediate relief.
Option E: Option E is incorrect because VMAT2 inhibitors treat tardive dyskinesia, which develops after months to years, not within hours.
2. A 74-year-old woman started on haloperidol three weeks ago for late-onset psychosis develops bradykinesia, limb rigidity, and a mild resting tremor that are bilateral and roughly symmetric from the outset, along with reduced facial expression. She has no prior movement disorder. Which interpretation and management plan is most appropriate?
A) This is drug-induced parkinsonism; the bilateral symmetric onset and temporal relationship favor it over idiopathic Parkinson disease, and management favors reducing the dose or switching to a lower-extrapyramidal-risk agent, with amantadine preferred over an anticholinergic in an elderly patient because of its more favorable cognitive profile
B) This is idiopathic Parkinson disease unmasked by the drug and should be treated with levodopa while continuing haloperidol unchanged
C) This is tardive dyskinesia and should be treated with a VMAT2 inhibitor
D) This is acute dystonia and warrants immediate intramuscular diphenhydramine
E) This is akathisia and the haloperidol dose should be increased to control it
ANSWER: A
Rationale:
Drug-induced parkinsonism produces bradykinesia, rigidity, and tremor emerging over days to weeks and is typically bilateral and symmetric from the outset, in contrast to the characteristically asymmetric onset of idiopathic Parkinson disease; the elderly are at higher risk because of reduced nigrostriatal reserve. Management favors dose reduction or a lower-extrapyramidal-risk agent, and when a pharmacologic agent is needed, amantadine is preferred over an anticholinergic in an elderly patient because anticholinergics carry significant cognitive and peripheral burden in this group.
Option B: Option B is incorrect because the symmetric onset and clear temporal link to the drug point to a drug-induced and reversible process, not idiopathic disease to be treated while continuing the offending agent.
Option C: Option C is incorrect because tardive dyskinesia involves involuntary orofacial movements after months to years, not subacute parkinsonism.
Option D: Option D is incorrect because acute dystonia is sudden sustained spasm within hours to days, not evolving bradykinesia and rigidity.
Option E: Option E is incorrect because this is not akathisia, and raising the dose would worsen the parkinsonism.
3. A 45-year-old man with schizophrenia has been stable for years on chlorpromazine as an outpatient and smokes one and a half packs of cigarettes daily. He is admitted to a smoke-free inpatient medical unit for pneumonia and stops smoking on admission. Over the next several days he becomes increasingly sedated, with dry mouth and mild confusion, although no new medication has been started. What is the most likely explanation and appropriate response?
A) The sedation is an early sign of neuroleptic malignant syndrome and the chlorpromazine should be stopped and dantrolene started
B) The new symptoms reflect worsening pneumonia with no relationship to the antipsychotic, so no change to chlorpromazine is needed
C) Smoking cessation has lowered chlorpromazine levels, so the dose should be increased
D) Stopping smoking has removed the induction of the metabolizing enzyme CYP1A2, slowing chlorpromazine clearance and raising its plasma level over several days, producing dose-related sedation and anticholinergic effects; the chlorpromazine dose should be reduced
E) The symptoms indicate the patient was never adherent as an outpatient and is now experiencing first-dose effects
ANSWER: D
Rationale:
Cigarette smoke induces CYP1A2, the enzyme that clears chlorpromazine, so chronic smokers run lower plasma levels; when this patient stops smoking on a smoke-free unit, the induction is lost over several days, clearance slows, and chlorpromazine accumulates, producing dose-related sedation and anticholinergic effects exactly as described, and the appropriate response is to reduce the dose.
Option A: Option A is incorrect because there is no fever, rigidity, autonomic instability, or elevated creatine kinase to suggest neuroleptic malignant syndrome.
Option B: Option B is incorrect because the timing and the anticholinergic-sedative pattern point to rising drug levels rather than the pneumonia alone.
Option C: Option C is incorrect because cessation removes the inducer and raises rather than lowers levels, so increasing the dose would worsen toxicity.
Option E: Option E is incorrect because the picture is one of new dose-related toxicity from de-induction in a previously stable patient, not first-dose effects from prior non-adherence.
4. A 38-year-old man hospitalized for psychosis has had his haloperidol rapidly escalated over two days. He now has a temperature of 40 degrees Celsius, generalized lead-pipe rigidity, blood pressure and heart rate that fluctuate widely, and a fluctuating level of consciousness. His creatine kinase is 18,000 units per liter and his reflexes are reduced. Which assessment and management is most appropriate?
A) This is serotonin syndrome; the hyperreflexia and rapid onset are diagnostic, and treatment is a serotonin antagonist alone
B) This is neuroleptic malignant syndrome; the lead-pipe rigidity, reduced reflexes, gradual onset, and markedly elevated creatine kinase distinguish it from serotonin syndrome, and management is immediate discontinuation of the antipsychotic with supportive cooling and hydration, dantrolene to reduce rigidity and hyperthermia, and a dopamine agonist such as bromocriptine to restore central dopaminergic tone
C) This is severe akathisia and the haloperidol should be increased to control the agitation driving the fever
D) This is acute dystonia and intramuscular benztropine will resolve the entire presentation
E) This is uncomplicated drug-induced parkinsonism and only an oral anticholinergic is required
ANSWER: B
Rationale:
Fever, lead-pipe rigidity, autonomic instability, fluctuating consciousness, and a markedly elevated creatine kinase after rapid dose escalation constitute the defining tetrad of neuroleptic malignant syndrome; the lead-pipe rigidity, reduced reflexes, and onset over roughly 24 to 72 hours distinguish it from serotonin syndrome, which instead shows hyperreflexia and clonus with more rapid onset. Management is immediate discontinuation of the antipsychotic, supportive cooling and hydration with monitoring for rhabdomyolysis and acute kidney injury, dantrolene to reduce rigidity and hyperthermia, and a dopamine agonist such as bromocriptine to restore dopaminergic tone.
Option A: Option A is incorrect because this presentation shows reduced reflexes and a slower onset, the opposite of serotonin syndrome.
Option C: Option C is incorrect because this is not akathisia and escalating the antipsychotic would worsen a dopamine-blockade emergency.
Option D: Option D is incorrect because acute dystonia is an isolated sustained spasm without fever, autonomic instability, or markedly elevated creatine kinase.
Option E: Option E is incorrect because drug-induced parkinsonism does not produce high fever, autonomic instability, or creatine kinase of this magnitude.
5. A 56-year-old woman with treatment-refractory psychosis is maintained on thioridazine, which she has tolerated for years. She develops community-acquired pneumonia, and the admitting team plans moxifloxacin, a fluoroquinolone that prolongs the QTc interval. Her baseline electrocardiogram shows a high-normal QTc, and her serum potassium is 3.1 millimoles per liter. What is the safest management approach?
A) Continue thioridazine and start moxifloxacin without monitoring, since QTc effects from different drug classes do not combine
B) Continue thioridazine and start moxifloxacin, relying on the low potassium to shorten the QTc and offset the risk
C) Recognize that thioridazine, the fluoroquinolone, and the hypokalemia together compound the risk of torsades de pointes; switch to a different antipsychotic for the duration of the antibiotic course and correct the potassium before and during treatment
D) Double the thioridazine dose to maintain antipsychotic coverage during the acute illness and proceed with the antibiotic
E) Withhold antibiotic therapy entirely and treat the pneumonia supportively, since the antipsychotic must never be interrupted
ANSWER: C
Rationale:
Thioridazine is a potent blocker of the cardiac hERG potassium channel and produces the most severe QTc prolongation in the class; its effect is additive with other QTc-prolonging agents such as fluoroquinolones, and hypokalemia independently lowers the threshold for torsades de pointes, so all three factors here compound the arrhythmia risk. The safest approach is to switch to a different antipsychotic for the duration of the QTc-prolonging antibiotic and to correct the potassium, with electrolyte and electrocardiographic monitoring.
Option A: Option A is incorrect because QTc-prolonging effects from different drugs are additive, not independent.
Option B: Option B is incorrect because hypokalemia worsens, not offsets, the torsades risk.
Option D: Option D is incorrect because doubling thioridazine would increase the QTc and the danger.
Option E: Option E is incorrect because the pneumonia requires treatment and the antipsychotic can be substituted rather than the antibiotic withheld.
6. A 30-year-old man started on haloperidol three days ago for a first psychotic episode now paces the ward continuously, cannot remain seated, and describes a distressing inner sensation of needing to move, as if he is crawling out of his skin. The covering clinician documented worsening agitation yesterday and increased the haloperidol dose, after which the restlessness intensified. He is afebrile with no rigidity. What is the most appropriate management?
A) Continue increasing the haloperidol dose, since escalating restlessness signals undertreated psychosis
B) Start a vesicular monoamine transporter 2 (VMAT2) inhibitor for what is likely early tardive dyskinesia
C) Administer intramuscular diphenhydramine for an acute dystonic reaction
D) Begin dantrolene and discontinue all treatment for presumed neuroleptic malignant syndrome
E) Recognize akathisia worsened by the recent dose increase, reduce the haloperidol dose where feasible, and treat with propranolol, the most evidence-supported agent for the subjective restlessness
ANSWER: E
Rationale:
Motor restlessness with an intense subjective urge to move, appearing within days of starting an antipsychotic, is akathisia; because it is driven by the dopamine blockade, mistaking it for agitation and raising the dose worsens it, exactly the trajectory described. The appropriate management is to recognize the syndrome, reduce the dose where feasible, and treat with propranolol, the most evidence-supported agent for the subjective restlessness, reserving other measures if it persists.
Option A: Option A is incorrect because further escalation worsens akathisia rather than treating psychosis.
Option B: Option B is incorrect because tardive dyskinesia appears after months to years and consists of orofacial movements, not early restlessness.
Option C: Option C is incorrect because there is no sustained dystonic spasm; the picture is restlessness, not dystonia.
Option D: Option D is incorrect because there is no fever, rigidity, or autonomic instability to indicate neuroleptic malignant syndrome.
7. A 29-year-old woman has taken fluphenazine for 14 months for schizophrenia. She reports that her menstrual periods have stopped and that she has milky breast discharge. She is not pregnant. Which interpretation and management is most appropriate?
A) These symptoms reflect hyperprolactinemia from blockade of dopamine at the tuberoinfundibular pathway, where dopamine normally restrains prolactin release; beyond the immediate symptoms, sustained hyperprolactinemia over many months can reduce bone mineral density and raise fracture risk, particularly in a premenopausal woman, so prolactin should be measured and the antipsychotic regimen reconsidered
B) These symptoms are unrelated to fluphenazine, since first-generation antipsychotics lower rather than raise prolactin
C) The galactorrhea indicates an early prolactinoma unrelated to the medication and the fluphenazine can be continued unchanged
D) The amenorrhea reflects accelerated drug metabolism and will resolve without evaluation
E) The elevated prolactin is protective for bone, so reassurance alone is appropriate and no monitoring is needed
ANSWER: A
Rationale:
First-generation antipsychotics block dopamine at the tuberoinfundibular pathway, removing the normal dopaminergic brake on prolactin and producing hyperprolactinemia with amenorrhea and galactorrhea. Beyond these symptoms, sustained hyperprolactinemia over many months is associated with reduced bone mineral density and increased fracture risk, an underrecognized concern that is particularly relevant in a premenopausal woman, so the appropriate steps are to measure prolactin and reconsider the regimen.
Option B: Option B is incorrect because these agents raise, not lower, prolactin, and the symptoms are directly drug-related.
Option C: Option C is incorrect because the clinical picture is explained by the known prolactin-elevating effect of the drug rather than presuming an unrelated tumor while continuing the offending agent.
Option D: Option D is incorrect because the amenorrhea reflects prolactin elevation from D2 blockade, not accelerated metabolism, and warrants evaluation.
Option E: Option E is incorrect because sustained hyperprolactinemia is harmful to bone over time, not protective.
8. A 60-year-old woman maintained on haloperidol for several years develops involuntary lip-smacking, tongue protrusion, and chewing movements. When her clinician lowers the haloperidol dose hoping to help, the movements become more pronounced over the following weeks. Which interpretation and management is most appropriate?
A) The dose reduction caused a new movement disorder, so the haloperidol should be permanently returned to the higher dose to suppress it
B) This is acute dystonia and should be treated with a standing oral anticholinergic
C) This is tardive dyskinesia; the worsening on dose reduction reflects unmasking of dopamine-receptor supersensitivity that ongoing blockade had been concealing, and management includes minimizing the antipsychotic where feasible, considering a vesicular monoamine transporter 2 (VMAT2) inhibitor such as valbenazine, avoiding anticholinergics, and monitoring with the Abnormal Involuntary Movement Scale (AIMS)
D) This is akathisia and propranolol is the first-line treatment
E) This is neuroleptic malignant syndrome and requires dantrolene
ANSWER: C
Rationale:
Involuntary orolingual movements after years of antipsychotic exposure are tardive dyskinesia, and their worsening when the dose is lowered reflects the withdrawal-emergent or unmasking pattern, in which ongoing blockade had been partly concealing dyskinesia at supersensitive receptors. Management includes minimizing the antipsychotic dose where feasible, considering a VMAT2 inhibitor such as valbenazine, avoiding anticholinergics because they can worsen tardive dyskinesia, and monitoring with the AIMS.
Option A: Option A is incorrect because permanently raising the dose to mask the dyskinesia is the wrong strategy and does not address the underlying supersensitivity.
Option B: Option B is incorrect because acute dystonia is sudden sustained spasm seen early in treatment, and anticholinergics can aggravate tardive dyskinesia.
Option D: Option D is incorrect because akathisia is restlessness with an urge to move, not orofacial dyskinesia.
Option E: Option E is incorrect because there is no fever, rigidity, or autonomic instability to suggest neuroleptic malignant syndrome.
9. A 68-year-old man in the intensive care unit develops hyperactive delirium with agitation that threatens his lines and airway, and the team decides pharmacologic treatment is warranted after addressing reversible causes. Among first-generation antipsychotics, which choice and accompanying precaution is best supported for this setting?
A) Chlorpromazine, chosen specifically for its strong anticholinergic activity, which is advantageous in delirium
B) Haloperidol, which has the best evidence base among first-generation agents for delirium in the critically ill and whose limited anticholinergic activity is an advantage over low-potency agents, while recognizing that the intravenous route carries a higher QTc-prolongation risk and warrants cardiac monitoring
C) Thioridazine, chosen for its favorable cardiac profile in monitored settings
D) Trifluoperazine by long-acting injection, to provide sustained control over the coming weeks
E) Diphenhydramine alone, since an antihistamine fully treats the underlying delirium
ANSWER: B
Rationale:
Haloperidol has the best-established evidence base among first-generation agents for delirium in the medically ill and critically ill, and its limited anticholinergic activity is an advantage over low-potency agents, since anticholinergic burden can worsen delirium; the important precaution is that intravenous haloperidol carries a higher QTc-prolongation risk than the oral or intramuscular routes and should be used with cardiac monitoring.
Option A: Option A is incorrect because chlorpromazine's strong anticholinergic activity is a liability in delirium, not an advantage, and can worsen confusion.
Option C: Option C is incorrect because thioridazine has the worst cardiac profile in the class, not a favorable one.
Option D: Option D is incorrect because a long-acting injectable for sustained weeks-long control is inappropriate for acute, often reversible delirium requiring flexible titration.
Option E: Option E is incorrect because diphenhydramine does not treat the underlying delirium and its anticholinergic effect can worsen it.
10. A 41-year-old man with chronic schizophrenia has relapsed twice in the past year because he stops taking his oral medication. He has no prominent negative symptoms or cognitive deficits, and his care is delivered in a setting where cost is a genuine constraint and second-generation long-acting injectables are not affordable. A large effectiveness trial found the first-generation agent perphenazine comparable to several second-generation agents on all-cause discontinuation. Which plan is best supported for this patient?
A) Mandate an oral second-generation agent, because second-generation drugs are categorically superior and route does not matter
B) Lower the dose of his current oral agent, since reducing the dose is the most reliable way to solve non-adherence
C) Continue oral therapy and simply counsel him more intensively, deferring any change in formulation
D) Recognize that comparable-effectiveness data make a first-generation agent a defensible, cost-conscious choice in a patient without a specific second-generation indication, and use an established, inexpensive first-generation long-acting injectable such as haloperidol decanoate or fluphenazine decanoate to address the adherence problem directly
E) Avoid all long-acting injectables, since depot formulations cannot address non-adherence
ANSWER: D
Rationale:
The finding that perphenazine performed comparably to several second-generation agents supports using a first-generation agent as a defensible, cost-conscious choice in a patient without a specific indication for a second-generation drug, and the recurrent relapse from non-adherence is directly addressed by an established, inexpensive first-generation long-acting injectable such as haloperidol decanoate or fluphenazine decanoate, which converts daily adherence into a periodic clinical contact.
Option A: Option A is incorrect because second-generation superiority is not categorical and the effectiveness data are directly relevant here.
Option B: Option B is incorrect because lowering the dose does not solve non-adherence.
Option C: Option C is incorrect because counseling alone has already failed to prevent relapse and does not resolve the adherence barrier.
Option E: Option E is incorrect because long-acting injectables are specifically designed to address non-adherence and are the appropriate tool here.
11. A 35-year-old woman with schizophrenia and a history of poor adherence is being transitioned to haloperidol decanoate, the long-acting injectable form, to improve adherence. Her chart documents that on oral haloperidol she developed severe akathisia at a dose roughly equivalent to the planned monthly depot dose, which has not yet been addressed. A covering clinician is about to administer the equivalent depot dose. What is the most appropriate course of action?
A) Proceed with the equivalent depot dose, because the decanoate formulation changes the receptor-binding profile and will not reproduce the akathisia
B) Proceed with a higher depot dose, because depot formulations require supratherapeutic loading to overcome slow absorption
C) Proceed immediately, because any adverse effect from the depot can be reversed within hours if it occurs
D) Cancel any consideration of a long-acting injectable permanently, because prior akathisia is an absolute contraindication to all depot antipsychotics
E) Hold the equivalent-dose depot, because the depot delivers the same EPS-prone receptor occupancy with a long washout, so the akathisia would likely recur and resolve only slowly; first address the akathisia and confirm tolerability of the oral form, or select a different long-acting agent
ANSWER: E
Rationale:
A depot formulation changes only the delivery kinetics, not the receptor-binding profile, so a patient who experienced severe akathisia on oral haloperidol at an equivalent dose will encounter the same EPS-prone occupancy on haloperidol decanoate; because the depot has a long washout, any recurrent akathisia would resolve only slowly. Sound practice is therefore to hold the equivalent-dose depot, address the akathisia and confirm oral tolerability first, or select a different long-acting agent.
Option A: Option A is incorrect because the depot does not alter the receptor profile and would reproduce the akathisia.
Option B: Option B is incorrect because supratherapeutic loading would increase, not reduce, the adverse-effect risk.
Option C: Option C is incorrect because depot adverse effects resolve slowly over weeks, not within hours.
Option D: Option D is incorrect because prior akathisia is a caution prompting dose optimization or agent selection, not an absolute contraindication to every depot antipsychotic.
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