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Difficulty: Very hardBipolar and Related Disorders

Match each clinical presentation of an adverse drug reaction in a patient treated for bipolar disorder to the most likely responsible psychotropic medication.

  • A 34-year-old woman evaluated in the ED for severe polyuria and weakness. Past psychiatric history is significant for bipolar I disorder on maintenance therapy. Physical exam shows dry mucous membranes. Labs reveal a non-anion gap metabolic acidosis and a urine osmolality of 150 mOsm/kg that remains unchanged after exogenous desmopressin administration.Lithium carbonate
  • A 28-year-old man presents to urgent care with acute nystagmus, diplopia, and severe ataxia. He has bipolar disorder stable on a mood stabilizer but was prescribed clarithromycin three days ago for atypical pneumonia. Mental status exam shows slurred speech. This toxicity is due to profound CYP3A4 enzyme inhibition.Carbamazepine
  • A 22-year-old woman evaluated in the outpatient clinic for new-onset oligomenorrhea, hirsutism, and a 10-kg (22-lb) weight gain. She is treated for acute mania. Physical exam shows significant facial acne. Labs reveal asymptomatic hyperammonemia and elevated serum free testosterone.Valproic acid
  • A 45-year-old man presents to the ED with exertional dyspnea and orthopnea two months after starting a new agent for treatment-refractory bipolar disorder. Past psychiatric history includes multiple failed medication trials. Physical exam reveals crackles at lung bases. Labs show elevated troponins. The medication requires strict registry monitoring for severe neutropenia.Clozapine
  • A 31-year-old woman is evaluated in the psychiatric clinic for an intense, distressing urge to pace and inability to sit still. She was recently started on an agent for bipolar depression. Mental status exam reveals severe agitation and continuous leg tapping. This medication uniquely requires co-administration with at least 350 calories.Lurasidone

Answer

The correct matches are: 1 with Lithium carbonate; 2 with Carbamazepine; 3 with Valproic acid; 4 with Clozapine; 5 with Lurasidone.
Each correct match relies on highly specific pathognomonic features of psychiatric medication toxicity: Lithium causes both NDI and Type 1 RTA; Carbamazepine is uniquely susceptible to CYP3A4 inhibitors like clarithromycin; Valproic acid induces hyperammonemia and PCOS-like changes; Clozapine requires absolute neutrophil count monitoring and causes myocarditis; and Lurasidone has a specific 350-calorie requirement along with a high risk of akathisia.

Step-by-Step Solution

1
Analyze the first presentation regarding non-anion gap metabolic acidosis and ADH-resistant polyuria.
Identifies nephrogenic diabetes insipidus (NDI) and distal renal tubular acidosis (RTA), pointing to Lithium carbonate.
Lithium interferes with aquaporin-2 channels causing NDI, and impairs distal tubular hydrogen secretion causing type 1 RTA.
2
Evaluate the second presentation involving clarithromycin administration and subsequent neurologic toxicity.
Identifies a CYP3A4 drug-drug interaction leading to toxicity, pointing to Carbamazepine.
Carbamazepine is a CYP3A4 substrate; macrolides like clarithromycin inhibit this enzyme, precipitating carbamazepine toxicity (nystagmus, ataxia).
3
Assess the third presentation featuring oligomenorrhea, hyperandrogenism, and hyperammonemia.
Recognizes medication-induced PCOS-like syndrome and hyperammonemia, pointing to Valproic acid.
Valproic acid uniquely causes both hyperammonemia (often asymptomatic) and reproductive endocrine abnormalities mimicking polycystic ovary syndrome.
4
Examine the fourth presentation involving heart failure, elevated troponins, and strict neutropenia monitoring.
Identifies drug-induced myocarditis in the setting of REMS monitoring, pointing to Clozapine.
Clozapine requires strict monitoring for absolute neutrophil count (ANC) due to agranulocytosis risk and is notoriously associated with myocarditis.
5
Analyze the fifth presentation involving a 350-calorie requirement and severe akathisia in bipolar depression.
Identifies the unique pharmacokinetic requirement and adverse effect profile of Lurasidone.
Lurasidone must be taken with at least 350 calories for adequate absorption and has a high incidence of extrapyramidal symptoms, particularly akathisia.

Key Concept

The pharmacodynamics, pharmacokinetics, and highly specific adverse effect profiles of mood stabilizers and atypical antipsychotics used in bipolar disorder.
Estimated Time:3m 0s
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Topics

Bipolar and Related Disorders

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