Psychiatric-Medical Comorbidity and Psychopharmacology in the Medically Ill
Pharmacokinetics in organ disease
Start low and go slow, but titrate to effect. In renal impairment, avoid or dose-adjust drugs with active metabolites: venlafaxine (desvenlafaxine accumulates), lithium (nephrotoxic and renally cleared), gabapentin and pregabalin; consider dialyzability in overdose. In hepatic impairment, prefer low-extraction drugs and reduce doses of hepatically metabolized agents; avoid nefazodone and use caution with valproate, duloxetine and tricyclics.
Interactions and cardiac risk
Map the CYP interactions examiners favor: fluoxetine and paroxetine inhibit 2D6 (reducing tamoxifen's active metabolite, raising risperidone and tricyclics, and impairing codeine analgesia); fluvoxamine inhibits 1A2 and 3A4 (clozapine, theophylline); carbamazepine induces 3A4 (oral contraceptives, tacrolimus, cyclosporine). QT matters for haloperidol, ziprasidone, citalopram (maximum 20 mg/day in older adults, hepatic impairment or with CYP2C19 inhibitors), methadone and droperidol. Check potassium and magnesium before adding a QT-prolonging agent.
Serotonergic and other syndromes
Serotonin syndrome (clonus, hyperreflexia, agitation, diarrhea) differs from neuroleptic malignant syndrome (rigidity, hyperthermia, elevated CK, autonomic instability, slower onset). Lithium levels rise with NSAIDs, thiazides and ACE inhibitors; monitor renal function and TSH.
Somatic treatments
ECT is often safer than untreated severe illness. Risks include recent myocardial infarction, unstable angina, arrhythmia, intracranial mass with raised pressure and pheochromocytoma; pacemakers require coordination, not prohibition. In transplant patients, coordinate with the transplant team about 3A4 interactions and immunosuppressant levels.
Trap
Adding standard antidepressant doses in renal or hepatic failure, or starting fluoxetine or paroxetine in a woman taking tamoxifen.
Rule of thumb
Before prescribing, check: creatinine clearance, liver function, QT, CYP interactions, and what else is on the medication list.