Drug Class Guide
Atypical Antipsychotics
Second-generation medicines for schizophrenia and bipolar disorder, several of which are also approved as add-on treatment for depression.
How Atypical Antipsychotics Work
Atypical, or second-generation, antipsychotics block dopamine D2 receptors in brain circuits linked to psychosis and also act on serotonin receptors, especially 5-HT2A. That combination quiets hallucinations and delusions and steadies mood, with less of the stiffness and tremor caused by older antipsychotics. Aripiprazole, brexpiprazole and cariprazine are partial agonists: they turn dopamine signaling down where it is too high rather than blocking it outright.
What Atypical Antipsychotics Treat
- Schizophrenia
- Bipolar disorder, including bipolar depression
- Depression, as an add-on to an antidepressant
- Agitation in Alzheimer dementia (brexpiprazole)
- Irritability with autism (aripiprazole, risperidone)
Atypical Antipsychotics in Our Medication Guide
- AripiprazoleAbilifySchizophrenia, bipolar mania and add-on treatment for depression; less weight gain than many in the class.
- BrexpiprazoleRexultiSchizophrenia, add-on for depression, and agitation associated with Alzheimer dementia.
- CariprazineVraylarSchizophrenia, bipolar mania and bipolar depression, and add-on treatment for depression.
- LurasidoneLatudaSchizophrenia and bipolar depression; taken with a meal of at least 350 calories.
- QuetiapineSeroquelSchizophrenia and bipolar disorder, including bipolar depression; one of the more sedating options.
- RisperidoneRisperdal, Risperdal ConstaSchizophrenia and bipolar mania; also available as long-acting injections. Raises prolactin more than most.
- PaliperidoneInvegaThe active form of risperidone; long-acting injections can be given monthly or less often.
- AsenapineSaphris, SecuadoDissolves under the tongue; nothing to eat or drink for 10 minutes afterward.
- IloperidoneFanaptSchizophrenia and bipolar mania; the dose is raised slowly to avoid dizziness on standing.
Common Side Effects
Weight gain and rises in blood sugar and cholesterol are the main long-term concerns; how much varies widely between drugs. Others include drowsiness, dizziness on standing, restlessness (akathisia), and, less often than with older antipsychotics, stiffness, tremor or involuntary movements (tardive dyskinesia). Risperidone and paliperidone can raise prolactin, which may cause breast changes or missed periods.
Important Cautions
- The whole class carries an FDA boxed warning: older adults with dementia-related psychosis have a higher risk of death when treated with antipsychotics.
- Those approved for depression carry the antidepressant boxed warning about suicidal thoughts in children and young adults.
- Weight, blood pressure, blood sugar and cholesterol should be checked before starting and regularly afterward.
- High fever with rigid muscles and confusion can signal neuroleptic malignant syndrome, a rare emergency.
- Do not stop suddenly; relapse is common when these medicines are stopped without a plan.
Common Questions About Atypical Antipsychotics
Why would an antipsychotic be prescribed for depression?
When an antidepressant alone has not worked well enough, adding a low dose of certain atypical antipsychotics can help. Aripiprazole, brexpiprazole, cariprazine and extended-release quetiapine are FDA-approved for this. Lurasidone, quetiapine and cariprazine are also approved for the depressive phase of bipolar disorder. It does not mean a person has psychosis.
Which antipsychotics cause the most weight gain?
Olanzapine and clozapine cause the most, followed by quetiapine, risperidone and paliperidone. Aripiprazole, lurasidone, cariprazine and brexpiprazole tend to cause less. Because the effect varies from person to person, weight and metabolic labs are tracked over time, and switching to a different drug is an option if weight climbs.
What is the difference between typical and atypical antipsychotics?
Older, typical antipsychotics such as haloperidol mainly block dopamine and more often cause stiffness, tremor and tardive dyskinesia. Atypical antipsychotics also act on serotonin receptors, cause fewer movement problems and help with mood, but are more likely to affect weight, blood sugar and cholesterol.
This guide is general information, not a substitute for advice about your own medicines. Do not start, stop or switch a medication without talking with your doctor. Questions about a prescription? Our internal medicine team can help.
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