Antipsychotics

Extrapyramidal symptoms are a time-ordered family of movement disorders caused by dopamine D2 receptor blockade from antipsychotics or antiemetics: acute dystonia within hours to days, akathisia within days to weeks, drug-induced parkinsonism within days to months, and tardive dyskinesia after months to years. Diagnosis is clinical; treatment is syndrome-specific, from intramuscular benztropine for dystonia to a vesicular monoamine transporter 2 (VMAT2) inhibitor such as valbenazine for tardive dyskinesia.

Neuroleptic malignant syndrome is a rare, life-threatening idiosyncratic reaction to dopamine-blocking agents, presenting days to weeks after starting or raising the dose, with fever, lead-pipe rigidity, autonomic instability, altered mental status, and a markedly elevated creatine kinase. Diagnosis is clinical. First-line management is stopping the offending drug, aggressive cooling, and IV fluid resuscitation, escalating to lorazepam, dantrolene, and bromocriptine.

Bipolar I disorder is a chronic mood disorder defined by at least one manic episode lasting a week or requiring hospitalization, with three or more DIG FAST symptoms causing marked impairment. Diagnosis is clinical after substances and medical mimics are excluded. Acute mania is treated with lithium or valproate, often with an atypical antipsychotic, and most patients need lifelong mood-stabilizer maintenance.

Major depressive disorder is a mood disorder defined by 5 or more of 9 major depressive episode symptoms, including depressed mood or anhedonia, present nearly every day for at least 2 weeks and causing significant functional impairment. Diagnosis is clinical, screened with the Patient Health Questionnaire. First-line treatment is cognitive behavioral therapy, a selective serotonin reuptake inhibitor (SSRI) such as sertraline, or both, escalating to augmentation, esketamine, or electroconvulsive therapy for refractory or acutely suicidal presentations.

Lithium carbonate is the reference mood stabilizer for bipolar disorder, first-line for acute mania and long-term maintenance, and the only mood stabilizer credited with reducing suicide risk. Dosing is titrated to a trough serum level, targeting 0.8 to 1.2 mEq/L for acute mania and 0.6 to 1.0 mEq/L for maintenance. Its narrow therapeutic index and near-total renal clearance make dehydration, renal impairment, and interacting drugs the leading triggers of toxicity, which is treated with isotonic fluids and, when severe, hemodialysis.

Valproate/divalproex, lamotrigine, carbamazepine, oxcarbazepine, and second-generation antipsychotics are the mood stabilizers used for bipolar disorder when lithium is ineffective, poorly tolerated, or contraindicated. Valproate treats acute mania, mixed episodes, and rapid cycling with an oral loading dose; lamotrigine, titrated slowly to limit serious rash, treats bipolar depression and maintenance but not acute mania; carbamazepine is second-line, limited by agranulocytosis.

Hyperprolactinemia is an elevated serum prolactin level with causes ranging from physiologic states and medications to hypothyroidism, renal failure, and a prolactin-secreting pituitary tumor. Diagnosis requires a confirmed elevated prolactin with exclusion of pregnancy, medication effect, and hypothyroidism before attributing the finding to a pituitary adenoma, and first-line treatment for a symptomatic pituitary cause is a dopamine agonist such as cabergoline.

Torsades de pointes is a polymorphic ventricular tachycardia occurring on a background of QT prolongation, with a characteristic twisting of QRS complexes around the baseline. Management is intravenous magnesium, correction of the underlying QT-prolonging cause, and rate acceleration by pacing or isoproterenol; unstable episodes are defibrillated.

Dementia with Lewy bodies is a synuclein-related neurodegenerative dementia defined by dementia plus parkinsonism, fluctuating attention, visual hallucinations, and REM sleep behavior disorder arising within about two years of each other. Diagnosis is clinical; acetylcholinesterase inhibitors treat cognitive symptoms and first-generation antipsychotics must be avoided because of severe neuroleptic sensitivity.

Acute antipsychotic overdose produces central nervous system depression, anticholinergic signs, alpha-1 blockade hypotension, and agent-specific cardiac conduction abnormalities, and is usually survivable with airway protection, cardiac monitoring, and isotonic crystalloid; sodium bicarbonate treats QRS widening, magnesium treats torsades, and norepinephrine treats refractory hypotension.

Dystonia is a movement disorder of sustained or intermittent muscle contractions causing repetitive, directional twisting postures; adult-onset focal forms (cervical dystonia, blepharospasm) are treated with botulinum toxin injection, while young-onset or progressive cases warrant a levodopa trial and screening for Wilson disease.

Parkinsonism is the clinical syndrome of bradykinesia plus rest tremor, rigidity, or postural instability, produced by idiopathic Parkinson disease or by secondary/atypical causes (drug-induced, vascular, Parkinson-plus syndromes, normal pressure hydrocephalus). Management treats the identified cause: stop the offending drug, shunt confirmed normal pressure hydrocephalus, or start levodopa for idiopathic disease.