Atypicals

Atypicals, in medical usage, refer to atypical antipsychotics, a class of second-generation antipsychotic drugs developed to treat schizophrenia and related disorders with a lower risk of extrapyramidal side effects than earlier, first-generation antipsychotics. The term is commonly used to describe several agents approved since the 1990s, including clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, lurasidone, asenapine, and cariprazine.

Pharmacology and differences from typical antipsychotics are a key feature of atypicals. Most act as antagonists at dopamine D2 receptors and serotonin 5-HT2A receptors, while some have partial agonist activity at D2 or other receptor sites. This broader receptor profile helps reduce extrapyramidal symptoms but can introduce metabolic risks and other adverse effects. Some agents also influence histamine or adrenergic receptors, contributing to sedation and orthostatic effects.

Indications for atypicals include schizophrenia and schizoaffective disorder, and many are used in bipolar disorder (manic, mixed, or depressive episodes). They are also employed as adjunctive therapy for major depressive disorder and, in some cases, for irritability or behavioral disturbances associated with autism. Long-acting injectable formulations exist for several agents, aiding adherence in certain patients.

Common adverse effects vary by drug but often include weight gain, metabolic changes (glucose and lipid abnormalities), sedation, and dizziness. Prolactin elevation may occur with some agents, notably risperidone and paliperidone. Serious but rare risks include agranulocytosis with clozapine and myocarditis, or QT prolongation with certain others. Monitoring typically covers metabolic risk, movement disorders, and, when applicable, blood counts and cardiac safety.