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Studies have long suggested that agents that enhance dopamine neurotransmission may be particularly useful in reducing treatment-resistant depression. A previous study comparing pramipexole with placebo in an 8-week randomized, double-blind trial with 60 outpatients with major depression for whom at least one adequate antidepressant medication trial (mean, two trials) had failed reported a modest statistically significant benefit of pramipexole (mean= 1.35 mg/day) over placebo, but neither the response rates (40% compared with 33%) nor the remission rates (27% compared with 23%) differed significantly between groups.
For the current treatment series, Jan Fawcett, M.D. (pictured above), a professor of psychiatry at the at the University of New Mexico School of Medicine, and colleagues administered pramipexole (0.25 mg to 5.0 mg/day) to 42 patients aged 25 to 84 with treatment-resistant depression for 2 weeks to 60 months. All patients took pramipexole while maintaining their treatment regimen for depression, which included selective serotonin reuptake receptor inhibitors, tricyclics, and monoamine oxidase inhibitors, as well as electroconvulsive therapy (ECT).
Overall, 76% of the patients showed a meaningful clinical response (achieving remission or a reduction of symptoms), which persisted over a 16-month follow-up period, while 24% were intolerant or nonresponsive to pramipexole. Effective pramipexole dosages ranged from 0.75 mg/day to 5.0 mg/day, with a mean effective dosage of pramipexole in responders and remitters of 2.46 mg/day. Intolerance was encountered early, often at a low dosage and usually due to nausea.
“To our knowledge, this is the first case series of adjunctive pramipexole in patients with treatment-resistant depression,” the authors wrote. They added that although the case series was not a planned study, with patients being managed and evaluated clinically without rating scales or structured interviews, the results “support the notion that pramipexole—and potentially other dopamine agonists—are of value for patients in a treatment-resistant depressive episode. Appropriate precautions, careful patient monitoring, and gradual dosage escalation are advised.”
Pramipexole has not been approved by the Food and Drug Administration for the treatment of depression.
To read more about potential therapies for depression, see the Psychiatric News article “The Ketamine Challenge: When Practice Leaps Ahead of Science.”
(Photo Courtesy of UNMSM)