Dopamine Partial Agonist
How it works:
Aripiprazole is a partial dopamine receptor 2 agonist. This theoretically increases dopamine when concentrations are low (helpful for depression) and decreases dopamine when concentrations are high (helpful for psychosis). Aripiprazole blocks a type of serotonin, called serotonin-2A. This may help with dopamine release. Additionally, it blocks serotonin-2C and 7 receptors, which may be helpful in depression. It is a partial agonist of a type of serotonin called 5HT-1A, which is found in other antidepressant medications. Long story short, the mechanism is complicated and not completely understood.
What makes it unique:
This was the first partial dopamine agonist. It is sometimes called a “third-generation antipsychotic” because of its differences from other antipsychotics. This medication is only approved for use in depression as an add on to another medication such as an SSRI or SNRI. There are now a few more medications in this class.
Blockage of alpha 1 can cause dizziness, sedation, and a decrease in blood pressure. Partial agonism of Dopamine 2 can cause the side effect called Akathisia. This is a feeling of internal restlessness. When I have seen this in patients, it shows up as the patient not being able to sit for a treatment session. They stand up, walk around, sit back down, and stand up again. Over and over. Weight gain and metabolic issues can occur. It can also cause pathological gambling and other compulsive behaviors.
This medication carries a risk of suicidal thinking and behavior in people age 24 and younger when used with an antidepressant medication.
How effective is it:
(1) A trial compared the addition of either Aripiprazole or Bupropion to another antidepressant medication to see if additional benefits would be seen. The QIDS score was used to assess for improvements. At the end of the observation period, 50% of patients receiving Aripiprazole achieved remission from depression as compared to 33% of patients in the Bupropion group. Both Aripiprazole and Bupropion can be helpful when added to another antidepressant.
(2) A trial from Japan compared Aripiprazole at 3mg/day with Aripiprazole 3-15mg/day and placebo as an addition to depression treatment. 586 patients were assessed using the MADRS. The score was improved by 10.5 points in the fixed-dose group, 9.6 in the flexible-dose group, and 7.4 in the placebo group.
Patients may feel some improvement with the standard antidepressants but still look for more improvement. Aripiprazole may play a role as an add on medication. It is usually used at lower doses for depression. Watch out for feelings of restlessness that this medication can cause! Pharmaceuticals should never be used as the sole treatment for mental illnesses. Therapy, exercise, meditation or other treatments should always accompany prescriptions.
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1. Nasr S, Wendt B, Popli A, et al. Comparing outcomes of adjunctive treatment in depression: aripiprazole versus bupropion. J Affect Disord. 2014 Jun;162:50-4.
2. Kamijima K, Higuchi T, Ishigooka J. et al. Aripiprazole augmentation to antidepressant therapy in Japanese patients with major depressive disorder: a randomized, double-blind, placebo-controlled study (ADMIRE study). J Affect Disord. 2013 Dec;151(3):899-905.