Psychiatry Flashcards

A 34-year-old woman with bipolar I disorder maintained on lithium for 3 years presents with a 6-week history of depressive episodes. Her lithium level is 0.9 mEq/L. She also reports polyuria and polydipsia. TSH is 8.2 mIU/L. Which of the following is the MOST appropriate next step?

Answer: Add levothyroxine and continue lithium

Lithium-induced hypothyroidism occurs in up to 40% of long-term users and can precipitate depressive breakthrough. The correct approach is to treat the hypothyroidism with levothyroxine while continuing lithium, which remains effective for bipolar I maintenance. Switching to valproate is not indicated for a therapeutic lithium level; reducing the dose risks destabilizing mood without addressing the hypothyroidism; lamotrigine addition does not address the root hormonal cause of the depression.

A 52-year-old man with schizophrenia has been stable on clozapine 450 mg/day for 8 years. He is admitted to the hospital and started on ciprofloxacin for a urinary tract infection. On day 3, he develops drooling, sedation, and a clozapine level of 920 ng/mL (therapeutic 250–450 ng/mL). What is the MOST likely mechanism?

Answer: Ciprofloxacin inhibits CYP1A2, reducing clozapine metabolism

Clozapine is primarily metabolized by CYP1A2. Ciprofloxacin (a fluoroquinolone) is a moderate inhibitor of CYP1A2, which dramatically slows clozapine clearance and causes toxic accumulation. This is a clinically significant drug interaction. CYP3A4 plays a minor role in clozapine metabolism; protein binding displacement is not the mechanism; P-glycoprotein is not involved in this interaction.

A 28-year-old male veteran presents with nightmares, hypervigilance, and emotional numbing 14 months after a combat deployment. He has failed two adequate SSRI trials. He now reports passive suicidal ideation without plan or intent. Which pharmacologic agent has the STRONGEST evidence as an augmentation strategy specifically targeting PTSD nightmares?

Answer: Prazosin

Prazosin, an alpha-1 adrenergic antagonist, has the most robust randomized controlled trial evidence specifically for PTSD-related nightmares and sleep disturbance. It reduces noradrenergic activity during REM sleep. Quetiapine has limited evidence as augmentation. Topiramate has some data but is not FDA-indicated and evidence is mixed. Nabilone (a cannabinoid) has preliminary data in treatment-resistant PTSD nightmares but far less evidence than prazosin.

A 19-year-old college student is brought to the ED after being found confused and agitated at a party. She has diaphoresis, mydriasis, tachycardia (HR 128), and bilateral lower extremity clonus. Temperature is 38.9°C. Reflexes are brisk throughout. A friend states she was prescribed phenelzine for atypical depression and may have taken 'something else' at the party. What is the MOST likely diagnosis?

Answer: Serotonin syndrome

The combination of an MAOI (phenelzine) plus a serotonergic substance (likely MDMA/ecstasy, common at parties) produces serotonin syndrome, characterized by the Hunter Criteria triad: cognitive/behavioral changes, autonomic instability, and neuromuscular abnormalities (clonus is the most specific finding). NMS has lead-pipe rigidity and occurs with antipsychotics. Anticholinergic toxidrome causes anhidrosis and absent bowel sounds. Sympathomimetics don't cause clonus. The presence of clonus strongly favors serotonin syndrome.

A 67-year-old woman with major depressive disorder is started on nortriptyline. Two weeks later she complains of blurred vision and difficulty urinating. Her ECG shows a QTc of 478 ms (baseline 412 ms). She is otherwise medically stable. Which of the following is the MOST appropriate management?

Answer: Discontinue nortriptyline and switch to mirtazapine

A QTc prolongation from 412 to 478 ms (>60 ms increase) on a TCA raises significant cardiac risk for torsades de pointes, particularly in a 67-year-old. The anticholinergic symptoms (urinary retention, blurred vision) further indicate toxicity. The safest course is discontinuation. Mirtazapine is a reasonable alternative as it has minimal QTc effect and no anticholinergic burden. Reducing the dose does not sufficiently address the QTc risk. Bethanechol manages symptoms but not the cardiac danger. Bupropion lowers the seizure threshold and is relatively contraindicated in older patients with cardiac history.

A 45-year-old man with treatment-resistant OCD has failed three adequate SSRI trials at maximum doses. He is currently on fluvoxamine 300 mg/day with partial response. His psychiatrist considers augmentation. Which of the following augmentation strategies has the BEST evidence base for treatment-resistant OCD?

Answer: Low-dose risperidone

Low-dose antipsychotic augmentation, particularly with risperidone (0.5–2 mg/day), has the strongest evidence for SSRI-refractory OCD in multiple randomized controlled trials and is endorsed by treatment guidelines. The mechanism may involve combined serotonin and dopamine modulation. Clonazepam has limited and inconsistent evidence. Buspirone showed early promise but has not replicated well in controlled trials. Lithium augmentation lacks consistent evidence in OCD and is better established in major depressive disorder.