An antipsychotic that turns dopamine up when it's low and down when high
Most older antipsychotics simply block dopamine. Aripiprazole, sold as Abilify, behaves more like a thermostat: as a partial agonist it boosts dopamine signalling where levels run low and damps it where they run high. That unusual trick made it the first of a third generation and reshaped how such drugs are designed.
Otsuka Pharmaceutical discovered the compound in 1988, and it won approval in the United States in 2002. It is now generic, counts among the WHO's essential medicines, and in 2023 ranked 95th among American prescriptions with more than 7 million filled. Its main uses are schizophrenia and the manic phase of bipolar disorder, plus irritability in autism; it is also added to other treatments for depression, obsessive-compulsive disorder and tic disorders. It comes as tablets or as an injection into muscle.
Pharmacologically, its central action is at dopamine D2 receptors, with partial agonism at D3 and D4 receptors and at two serotonin receptor types as well. A 2013 comparison of 15 antipsychotics placed it mid-table for effectiveness, roughly level with haloperidol and quetiapine, but near the top for tolerability. It ranked best for keeping prolactin levels down, which is why doctors sometimes switch to it or add it when another drug has raised prolactin. Guidance from biological psychiatry societies also suggests moving to it when other antipsychotics cause heavy weight gain.
Evidence quality is a recurring caveat. Cochrane reviews in 2011 and 2014 found high dropout rates and poor data, making it hard to confirm relapse prevention or to separate it clearly from rivals, and rated the evidence for schizophrenia as low quality. As an add-on for depression, the benefit is small to moderate, with no clear gain in quality of life or everyday functioning. In bipolar disorder it helps with mania but not with the depressive phase.
Side effects commonly include restlessness, insomnia, nausea, dizziness and mild sedation, with rarer serious reactions such as tardive dyskinesia. It carries a higher death risk in older people with dementia-related psychosis, is not advised during breastfeeding, and may harm a fetus. Some antidepressants that block the liver enzyme CYP2D6 can roughly double blood levels, so prescribers adjust doses.
Source: Aripiprazole
