Pharmacotherapy of Psychiatric and Substance Use Disorders
First-line logic by disorder
SSRIs are first-line for major depression, generalized anxiety, panic, OCD, and PTSD; escitalopram and sertraline are the usual starting points. Alternatives include SNRIs, mirtazapine, and bupropion. Treatment-resistant depression conventionally means failure of two adequate trials (adequate dose AND duration, typically 6 to 8 weeks); augmentation options include lithium, aripiprazole, quetiapine, and liothyronine.
Bipolar disorder: lithium remains a first-line agent for mania and maintenance, valproate is useful in mixed states and rapid cycling, and lamotrigine targets bipolar depression with slow titration. Antidepressant monotherapy in bipolar disorder is a classic trap. Schizophrenia: clozapine is indicated after two failed antipsychotic trials and for persistent suicidality; long-acting injectables address adherence.
ADHD: stimulants first-line, with atomoxetine or alpha-2 agonists as alternatives. Substance use disorder: buprenorphine, methadone, or extended-release naltrexone for opioid use disorder; naltrexone or acamprosate for alcohol use disorder; varenicline, nicotine replacement, or bupropion for tobacco.
Traps
Watch dose ceilings in special populations (citalopram 20 mg in older adults, hepatic impairment, or CYP2C19 poor metabolizers; escitalopram 10 mg), fluoxetine's long half-life and CYP2D6 inhibition, paroxetine's anticholinergic burden and discontinuation syndrome, bupropion's contraindications (seizure disorder, bulimia/anorexia, MAOI use), and combined benzodiazepine-opioid risk.
Rule of thumb
Reassess 4 to 6 weeks after starting an antidepressant. Partial response at 4 to 8 weeks argues for optimizing the dose first; true nonresponse at 4 weeks on an adequate dose justifies switching sooner.