Pramipexole in Unipolar and Bipolar Depression

Peter ForsterBipolar Treatment, Treatments of Depression

For many years we’ve been impressed with the response in some patients with bipolar depression to relatively high doses of pramipexole. Pramipexole is an agent that enhances dopamine neurotransmission and has been approved for the treatment of Parkinson’s disease. There are relatively few medications that significantly affect dopamine, one of the three monoamine neurotransmitters associated with depression and pramipexole is one of those medications.

Other medications that affect dopamine and that seem to be useful in the treatment of patients with treatment resistant depression include monoamine oxidase inhibitors and stimulants. It has been noted that patients with treatment resistant depression often have significant deficits in interest, motivation, and the ability to experience pleasure and that all of these have been linked to reduced dopamine function.

Pramipexole is a relatively selective dopamine three receptor agonist, and dopamine three receptors are found in the mesolimbic system, which has been implicated in the motivational and pleasure deficits found in depression.

We read with interest the results of a large case series published by Jan Fawcett, John Rush, et al. in the February 2016 issue of the American Journal of Psychiatry. They report a relatively aggressive approach to dosing. In patients under age 45, dosing started at 0.25 mg a day and was raised every three days in 0.25 mg increments with an initial goal of 2 mg a day. Moreover they gave the medication entirely at night.

In patients over the age of 45, they were even more aggressive with dosing and cite “clinical observation and evidence of decreasing dopamine three receptors with the age.” In this older group dosing started at 0.5 mg a day and increased in 0.5 mg increments but otherwise followed the same approach. In their study the mean dosage of pramipexole for those who responded or remitted was 2.5 mg a day. They report a therapeutic dose range of 1 to 5 mg a day. Common adverse of vents include nausea, sleepiness, dizziness, tremors, compulsive behaviors and sleep attacks. They feel that depressive episodes associated with severe lack of pleasure, lack of motivation, inability to initiate behaviors, and un-reactive mood are predictors of a better response. They report that the expected benefit, if it occurs, should take place by four weeks at the maximally tolerated dose. They caution against abrupt discontinuation because the risk of dopamine agonist withdrawal syndrome may be as high as 15%. Finally they note that only one of 42 patients had in activating responsive irritability to pramipexole. Two patients reported hypersexuality, both young men with bipolar two disorder. In their case series 20 of 42 patients or nearly 50% of patients remitted.

Case series are useful for generating hypotheses and suggesting experimental treatments but not particularly helpful at evaluating how different medications stack up in terms of effectiveness.


Clinical Experience With High-Dosage Pramipexole in Patients With Treatment-Resistant Depressive Episodes in Unipolar and Bipolar DepressionJan Fawcett, A. John Rush, John Vukelich, Shanna H. Diaz, Lucas Dunklee, Paul Romo, Brandon C. Yarns, and Rodrigo Escalona. American Journal of Psychiatry 2016 173:2, 107-111