Second-generation antipsychotics

Most second-generation antipsychotics block dopamine D2 receptors together with serotonin 5-HT2A receptors, though exactly how they work is unclear; aripiprazole instead is a partial agonist at D2 receptors. As a group they cause fewer extrapyramidal effects than first-generation drugs, but many also block H1, α1 or muscarinic receptors, and weight gain with raised glucose and lipids is common.

• RisperidoneIts label states it raises prolactin more than other antipsychotics, and its extrapyramidal effects are dose-related; paliperidone is its active metabolite.
• OlanzapineWeight gain and raised glucose and lipids are prominent, and adolescents are more prone to them than adults, so other drugs may be tried first in teenagers.
• QuetiapineIts strongest binding is to H1 and α1 receptors rather than D2, and it is licensed for bipolar depression as well as mania; its label asks for regular lens checks.
• ClozapineKept for schizophrenia that has not responded to other antipsychotics because of its risks of severe neutropenia and seizures; it causes few movement side effects.
• AripiprazoleUnlike most antipsychotics, it partly stimulates D2 receptors instead of simply blocking them; akathisia and restlessness are among its commonest effects.

• Schizophrenia
• Bipolar disorder: mania, depression, maintenance
• Depression, as add-on treatment
• Irritability in autism

• Weight gainKnown for
• Raised blood sugar and lipids (metabolic changes)Known forSerious
• Drowsiness
• Dizziness on standing (orthostatic hypotension)
• Extrapyramidal effects, more at higher doses
• Raised prolactin, most with risperidone
• Tardive dyskinesiaSerious
• Neuroleptic malignant syndromeSerious
• Higher death rate in older people with dementiaSerious
• Low white cell count; severe neutropenia with clozapineSerious

What the class has in common. Each drug's card has its own, and Known for marks what an exam expects you to know.

• Check weight, blood glucose and lipids before starting and regularly during treatment.
• Older people with dementia-related psychosis have a higher death rate and more strokes on these drugs.
• Clozapine needs neutrophil counts before and during treatment because it can cause severe neutropenia.
• Stop at once and treat urgently if fever, rigidity and confusion suggest neuroleptic malignant syndrome.

Written for biofideX in plain words, after checking these references:

• Treatment: schizophrenia (NHS)
• Risperidone tablets: label (DailyMed)
• Aripiprazole tablets: label (DailyMed)
• Clozapine 25 mg tablets: SmPC (emc)

For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.