Medication Safety, Adverse Effects, Interactions, and Laboratory Monitoring
Adverse effects with timelines
Extrapyramidal symptoms follow a predictable course: acute dystonia (hours to days), akathisia (days to weeks), parkinsonism (weeks), and tardive dyskinesia (months to years). Distinguish serotonin syndrome (clonus, hyperreflexia, agitation, hyperthermia; onset usually within 24 hours of a new or increased serotonergic agent) from neuroleptic malignant syndrome (lead-pipe rigidity, hyporeflexia, autonomic instability, rising CK; onset over days after a dopamine antagonist). Other high-yield effects: metabolic syndrome, QTc prolongation (ziprasidone, haloperidol IV, thioridazine, pimozide; citalopram capped at 40 mg and 20 mg in older adults), SIADH/hyponatremia, lithium-induced nephrogenic diabetes insipidus and hypothyroidism, clozapine agranulocytosis and myocarditis, and lamotrigine/carbamazepine severe rash.
Interactions
Smoking induces CYP1A2, lowering clozapine, olanzapine, and duloxetine exposure; smoking cessation can raise clozapine levels substantially. Fluvoxamine and ciprofloxacin inhibit 1A2. Fluoxetine, paroxetine, and bupropion inhibit 2D6, raising tricyclics, risperidone, aripiprazole, and affecting codeine and tramadol analgesia. Valproate inhibits glucuronidation and 2C9, raising lamotrigine levels; carbamazepine induces 3A4.
Therapeutic drug monitoring
Lithium 0.6 to 1.2 mEq/L (12-hour trough), valproate roughly 50 to 125 mcg/mL, clozapine above 350 ng/mL for response, and tricyclics in the presence of interacting drugs or adherence concerns.
Rule of thumb
Before attributing any new symptom to the illness, ask three questions: what changed in the regimen, what changed in the patient's physiology, and what is the level?