Pramipexole has been available since 1997 and is used to treat Parkinson’s disease and restless legs syndrome. It is available as a generic in tablets of 0.125mg, 0.25mg, 0.5mg, and 1.5mg.

Mechanism of Action

Pramipexole is a dopamine agonist, especially targeting the D-3 receptor. Thus, it increases the level of dopamine, which is why it is useful for treating Parkinson’s disease. It is also thought to have neuroprotective properties.

Use in Schizophrenia

Two open-label and two placebo-controlled, double-blind studies have been carried out. The former included a study of 37 patients, of which only 8 completed 3 weeks on the drug; 4 were said to be responders.77 The other open-label study included 15 patients and used up to 10.25mg for 6 days; 4 patients dropped out (2 due to worsening of symptoms), and 5 others were said to be “much improved.”78 In a double-blind trial, 41 patients with residual schizophrenia were randomized to pramipexole up to 5 mg/d or placebo for 10 weeks; 7 pramipexole patients dropped out, and 9 were said to improve on the PANSS total score.77 In the other trial, 24 patients were treated with pramipexole 0.375–4.5mg/day or placebo for 12 weeks; 2 out of 11 pramipexole patients dropped out, but the others showed a significant decrease in PANSS positive (P=0.006) and PANSS total scores.79 SMRI is supporting a large (n=200) double-blind study in progress.

Use in Bipolar Disorder

Two small double-blind trials have been published involving 22 bipolar I and II depressed patients and 21 bipolar II depressed patients, respectively. In the first, 8 of 12 patients on pramipexole had “an improvement of at least 50% in their Hamilton depression scale scores.”80  In the second study, 6 of 10 patients on pramipexole had “a significant treatment effect.”81 A third study, publicly reported but not yet published, randomized 35 patients with bipolar I to pramipexole 1.5 mg/d or placebo; those on pramipexole had significant cognitive improvement on processing speed and working memory.82 An open-label study of 21 bipolar depressed patients also reported that two-thirds improved on pramipexole.83 In addition, two retrospective chart studies both reported evidence of pramipexole’s efficacy for bipolar depression,84,85 and a large (n=174) study of unipolar depression reported pramipexole to be efficacious.86 Many of these studies are summarized in a review by Aiken.87 Pramipexole is listed as an alternate treatment for bipolar depression by the Texas Implementation of Medication Algorithms for Bipolar Disorder and by the Canadian Network for Mood and Anxiety Treatments.


Pramipexole may have a therapeutic role in schizophrenia for a subset of patients if they can be identified. However, the risk of exacerbation of symptoms appears to be substantial. By contrast, pramipexole appears to be potentially useful as an adjunct drug for bipolar depression. The main problem is side effects, the most common of which are headache, nausea, and somnolence. Of greater concern are rare but serious side effects: compulsive behaviors such as pathological gambling; sleep attacks; and, psychotic symptoms. Side effects appear to be dose-related, and all patients being put on pramipexole should be very slowly titrated upward (e.g., 0.125mg per week).