Pramipexole for Depression

Pramipexole is a dopamine agonist that is very effective in treating both unipolar and bipolar depression. While it is FDA approved to treat Parkinson’s Disease & restless leg syndrome (RLS), it is no longer a branded medication, so drug companies don’t have financial incentive to get it FDA approved for depression treatment. That said, there are many studies and case reports of how powerful it is for depression, even in those with treatment resistant depression. It is also thought to be “neuroprotective”, which means it is thought to support neuronal health in the brain.  

What is the mechanism of Pramipexole?
It activates dopamine receptors in many parts of the brain, but especially the D3 receptors in the striatum. Despite working on dopamine, it is not considered an addictive medication as it doesn’t activate the dopamine cascade in the mesolimbic area of the brain in the same way addictive substances do.

What is the dosing of Pramipexole?
We always start at the lowest dose (0.125mg), given at bedtime, because it is usually sedating (in 1/15 cases it can be stimulating, in which case we would give it in the morning). We go up very slowly (every 3-5 days or slower), and this is even more important in younger patients who have more sensitive dopamine receptors than older patients. In fact, in patients over age 50 we can start at 0.25mg.
The goal dose is anywhere from 0.5mg to a maximum of 2.5mg at bedtime. Average doses are 1.4 to 1.7mg per day, but many people do very well at lower doses.
For those who feel its effects wear out too early each day, it can be given 2x per day. 
It is mostly excreted by the kidneys in the urine, so dosing should be more cautious in those with renal disease.

What are the potential side effects of Pramipexole?
For most, it is sedating, so it is given at bedtime. For 1/15 people, it is stimulating, so we give it in the morning.
1/10 people may experience nausea when they first start it or increase the dose. This usually gets better with time.
1/20 people can have constipation. For ways to help medication induced constipation, click here.
1/50 people experience diarrhea.
1/50 people experience dry mouth.

Is Pramipexole safe in Bipolar Depression?
Yes, it is thought to help depression without inducing mood swings or manic symptoms in patients with either bipolar 1 or 2.

Is Pramipexole safe to take with other medications that work on dopamine such as stimulants, wellbutrin, and/or antipsychotics?
Yes, from what the evidence shows as of February, 2022, it is thought to be safe when taken with the above medications.

Is Pramipexole safe in patients with schizophrenia?
There is not a lot of data but there is a study that looked at adding Pramipexole to haloperidol in patients with schizophrenia and the results were promising. There was no evidence for worsening of psychosis.

If this medication needs to be stopped, how should it be done?
The medication should be slowly tapered off to avoid symptoms such as panic, anxiety, worsening depression, sweating, fatigue, or lower blood pressure. 

Sources for the above information: 

• Studied in treatment resistant depression. 
• Studied in unipolar depression. 
• Studied in bipolar depression.
• Studied in treatment resistant depression.