Psychiatry/Second-generation antipsychotic

Second-generation (atypical) antipsychotics

also: olanzapine · risperidone · quetiapine · atypical antipsychotic

Overview

The "atypical" antipsychotics — first-line for schizophrenia. Fewer extrapyramidal effects than typicals, but metabolic syndrome is the dominant problem.

Mechanism

Block D₂ AND 5-HT₂A receptors. The added serotonergic action means relatively less nigrostriatal D₂ blockade → fewer EPSEs, but H1/5-HT2C and metabolic effects cause weight gain and dysglycaemia.

Indications

Schizophrenia / psychosis (first-line)
Bipolar — acute mania + prophylaxis (quetiapine/olanzapine)
Severe agitation; adjunct in depression

The agents

Olanzapinesedating

Greatest weight gain / metabolic effect.

Risperidone

depot available

Raises prolactin most of the atypicals; EPSEs at higher dose.

Quetiapinesedating

Low EPSE/prolactin; used in bipolar + as PRN; postural hypotension.

Adverse effects

Metabolic syndrome (weight gain, diabetes, dyslipidaemia)serious

The key atypical drawback — monitor weight/glucose/lipids.

Sedation, postural hypotensioncommon

EPSEs (less than typicals; dose-related, esp. risperidone)common

↑stroke/VTE/mortality in elderly dementia; NMS; QTserious

Cautions & contraindications

Elderly with dementia (unless severe distress)elderly

↑stroke + mortality.

Caution: cardiovascular/metabolic diseaseall

Interactions

QT-prolonging drugs; sedatives

Monitoring & kinetics

Weight/BMI, HbA1c/glucose, lipids, prolactin, ECG (baseline, 3 mo, then yearly)

Oral / depot. First-line class for schizophrenia.

Source: NICE NG178 — Schizophrenia · BNF — Antipsychotics