Dopamine Partial Agonists: An Overview

February 5, 2016 · Posted in Current Treatments · Comment 

pillsSeveral atypical antipsychotic drugs are partial agonists of dopamine. They provide weak stimulation of dopamine receptors in the brain and prevent dopamine from overstimulating the receptors by binding to them in its place.

In contrast, most antipsychotic and antimanic drugs are dopamine antagonists, which also bind to dopamine receptors but prevent any stimulation from occurring there.

A.    Aripiprazole (Abilify) was the first partial dopamine agonist approved by the Food and Drug Administration for the treatment of schizophrenia, and mania, and as an add-on treatment to antidepressants for the treatment of unipolar depression, but not bipolar depression.

B.    Brexpiprazole (Rexulti) received FDA approval for the treatment of schizophrenia and as an add-on treatment to antidepressants for the treatment of unipolar depression in 2015. It is similar to aripiprazole but has weaker activity at the dopamine D2 receptor. Brexpiprazole is associated with small increases in the hormone prolactin, as opposed to the small decreases in prolactin seen with aripiprazole.

C.    Cariprazine (Vraylar) is FDA-approved for schizophrenia and mania, and it also has positive placebo-controlled data in bipolar depression and as an adjunct to antidepressants in unipolar depression.  It differs from the others in that it is more potent at dopamine D3 receptors than at D2 receptors. It is thought that effects on D3 receptors may provide better antidepressant effects, but this proposition has not yet been tested.

New Atypical Antipsychotic Drug Brexpiprazole Improves Depression When Added to Antidepressants

January 25, 2016 · Posted in Peer-Reviewed Published Data, Potential Treatments · Comment 

brexpiprazoleTwo studies published in the Journal of Clinical Psychiatry in 2015 suggest that the new atypical antipsychotic brexpiprazole (trade name Rexulti) safely improves depression when added to antidepressant treatment. The 6-week studies, both by Michael E. Thase and colleagues, compared brexpiprazole to placebo in people who had not responded adequately to one to three antidepressants and were taking at least one antidepressant at the time of the study.

The studies examined the effectiveness of different doses of brexpiprazole. Doses of 2mg/day and 3mg/day were more effective than placebo, while a dose of 1mg/day was not. The drug was well-tolerated by patients at each of these doses, although those taking the 3mg/day reported more side effects than those taking 2mg/day. The side effects included restless legs, weight gain, and headaches.

Like the atypical antipsychotic aripiprazole (Abilify), brexpiprazole partially blocks and partially stimulates dopamine receptors. While aripiprazole allows 61% activity at dopamine D2 receptors, brexpiprazole allows 43%. It is not yet clear how the new drug’s effects may differ from those of aripiprazole.

Another relatively new atypical antipsychotic drug, cariprazine (Vraylar) is approved by the Food and Drug Administration for schizophrenia and mania, but not yet for bipolar depression or as an add-on treatment to antidepressants in unipolar depression, although there are placebo-controlled trials showing that cariprazine can also treat these conditions.

Like aripiprazole and brexpiprazole, cariprazine also partially blocks and partially stimulates dopamine receptors. Unlike them, cariprazine is more potent at dopamine D3 receptors, which are linked to mood, motivation, and drug reward, than at D2 receptors, which are linked to motor control. It is not yet clear how these differences may change treatment outcomes or side effects.