Pramipexole (Mirapex)

What pramipexole is

Pramipexole was first sold under the brand name Mirapex, and the regular tablet is now dispensed as a generic. It acts on the receptors for dopamine, one of the chemical messengers nerve cells use to communicate, and medicines that work this way are called dopamine agonists. It comes as a regular tablet and as an extended-release tablet. In psychiatry it is used for a particular purpose: as an add-on for depression that has not improved enough with other treatment.

What it treats

Your clinician might suggest pramipexole off-label for depression, including the depressive phase of bipolar disorder, when other treatment has not helped enough. This is an off-label use, meaning it is not a use the medication is approved for. In most of the clinical trials it was added to the treatment a person was already taking rather than replacing it.

The research is still limited. Earlier small trials gave mixed results, and a larger, more recent trial found a clear benefit when pramipexole was added to ongoing treatment, though side effects led some people to stop it. For bipolar depression the trials are smaller and the picture is less settled, and pramipexole can bring on symptoms of an abnormally elevated mood. It does not help everyone, and we would watch together to see whether it helps you.

Pramipexole is approved for Parkinson's disease and, as the regular tablet, for moderate to severe primary restless legs syndrome. Those are general medical uses rather than something our practice manages.

Whether it is a good fit depends on several factors, including your history, your other medications, and what you are working on. As with everything in psychiatry, that is decided case by case.

Who should not take pramipexole. FDA labeling lists no absolute exclusions for pramipexole. It does say that people with a major psychotic disorder should ordinarily not take medicines of this kind, because they can make psychosis worse, and it advises caution with kidney disease, because the kidneys clear pramipexole from the body. Make sure your clinician knows your full history and has your full medication list.

How it works

Honestly, no one knows with complete certainty how pramipexole eases depression. What research suggests is that it activates dopamine receptors, with a particular preference for one type called D3. Dopamine is involved in motivation, reward, and the ability to feel pleasure, and one idea is that strengthening that signal may help with the low drive and loss of enjoyment that can come with depression. The biology is only part of the picture: how much a medication helps, and how it feels, is individual. Two people on the same medication can have very different experiences.

How to take it

There is no single right way to take pramipexole; it depends on you and your clinician. It is started at a low dose and increased gradually, and it can take several weeks to reach a dose that helps. The plan you and your clinician make together is the one to follow, not a number you read online. A few points matter here:

• Take it the way you and your clinician agreed. It can be taken with or without food, and taking it with food can help if it causes nausea.
• Because it can make you sleepy, and some people have fallen asleep suddenly without warning, do not drive or do anything that needs full alertness until you know how it affects you.
• Alcohol and other medicines that cause drowsiness can add to the sleepiness.
• When you get up from sitting or lying down, rise slowly, especially early on and after a dose increase, so you do not get dizzy or faint.
• If you miss a dose, ask your clinician or pharmacist what to do rather than doubling up.
• Do not stop it suddenly. Stopping or lowering it, especially quickly, can cause withdrawal symptoms such as anxiety, low mood, loss of interest, tiredness, trouble sleeping, sweating, or pain. These can happen even during a gradual taper, so tell your clinician if they do. Your clinician can lower it gradually if and when that makes sense.
• If you have been off it for a while, do not restart on your own. It usually needs to be built back up gradually.
• Tell your clinician about everything you take. The heartburn medicine cimetidine (Tagamet) can raise pramipexole levels, and medicines that block dopamine, including some used for psychosis and the nausea medicine metoclopramide, may make it less effective.

What to expect

This varies from person to person. Nausea and sleepiness, if they happen, vary in how strong they are, and sleepiness can also start later. In the clinical trials, the main measure of the effect on depression was taken at about 6 to 12 weeks. If nothing has shifted after a fair trial, that is useful information, not a dead end, and there are other options. As always, this is case by case.

Side effects

Not everyone gets side effects, and some, like nausea, often ease as your body settles. Sleepiness can also appear later, even months into treatment. The lists below are possibilities, not certainties.

Possible more common side effects:

• Nausea, sometimes with vomiting
• Sleepiness or tiredness
• Dizziness or lightheadedness, especially when standing up
• Trouble sleeping, or unusual dreams
• Headache
• Constipation or dry mouth

If any of these stick around or bother you, they are worth raising. Send a non-urgent message through the patient portal or bring it up at your next visit; often a small change helps.

New or stronger urges. Medicines that act on dopamine have been linked to intense urges that are hard to control: gambling, spending money, sexual urges, binge eating, or other behaviors that are unusual for you. People may not recognize the change in themselves, so it helps to tell a family member or someone close to you about this possibility and ask them to speak up if they notice it. If it happens, it can be a side effect of the medication, not a personal failing. Send your clinician a message through the patient portal as soon as you or they notice it, rather than waiting for your next visit. In some cases the urges have stopped after the dose was lowered or the medication was stopped.

Falling asleep during the day. If you become very drowsy, or fall asleep during an activity such as a conversation, a meal, or a drive, tell your clinician, and do not drive or do anything that could be dangerous until you have talked with them. They may decide to stop it.

Less common, but concerning side effects that could require emergency care:

• Seeing or hearing things that are not there, severe confusion, or feeling paranoid, agitated, or aggressive in a way that is not like you
• Feeling abnormally high, wired, or irritable, with racing thoughts and far less need for sleep than usual
• Fainting or passing out
• A fever with stiff muscles or confusion, especially after the dose was lowered or the medication was stopped
• Muscle pain, tenderness, or weakness with no clear cause, especially with dark urine
• Changes in vision
• Movements you cannot control, or a new bend or tilt in your neck or trunk when you sit, stand, or walk
• Signs of an allergic reaction. Call 911 right away for swelling of the face, lips, tongue, or throat, or trouble breathing. Contact your clinician promptly about a new rash or hives.
• Any new or worsening thoughts of harming yourself, whether or not you think the medication is behind it

For any of these, use the help options at the top of this page: call 911 or go to the nearest emergency department for a medical emergency or severe reaction, or call or text 988 for a mental health crisis.

If hallucinations or severe confusion are the concern, tell the clinicians treating you everything you take, including this medication. They may decide to stop it.

Pregnancy and breastfeeding

If you are pregnant, thinking about it, or breastfeeding, this is worth going through together rather than settling from a page. There is little information about pramipexole in pregnancy or breastfeeding. Tell your clinician before changing anything, and do not stop suddenly on your own.

In pregnancy

FDA labeling says there are no adequate data on the developmental risk of pramipexole in human pregnancy, and that, based on animal data, it may cause fetal harm. In animal studies, no harmful effects on development were seen in rabbits. In rats, early pregnancies were lost at the highest dose tested. The label says those losses are thought to result from pramipexole lowering prolactin, a hormone that early pregnancy depends on in rats but not in rabbits or humans. Because of those losses, the effect on early development in rats could not be properly assessed, and the growth of the offspring after birth was slowed. For scale, the label notes that in the general population about 2 to 4 in 100 recognized pregnancies involve a major birth defect and about 15 to 20 in 100 end in miscarriage, before any particular exposure is considered.

While breastfeeding

There are no studies of pramipexole in human milk or in breastfed babies. Pramipexole lowers prolactin, the hormone that supports milk production, and FDA labeling says a drop in milk supply is expected for that reason. LactMed, the National Institutes of Health lactation database, says that pramipexole may interfere with breastfeeding and that another medication may be preferred, especially while nursing a newborn or a baby born early. It also notes that the prolactin level of a mother whose milk supply is already established may not affect her ability to breastfeed.

When to reach out, and where

For routine questions, side effects that can wait, or how things are going, send your clinician a message through the patient portal. These are part of your ongoing care and are answered in the normal course of a few business days, so they are best for things that are not urgent.

If something feels urgent, you do not need to wait for a reply. The help options at the top of this page are the fastest way to get care: 911 or the nearest emergency department for a medical emergency or severe reaction, or 988 any time for a mental health crisis or thoughts of self-harm.

Questions to ask your clinician

• What are you hoping pramipexole will help with in my case?
• How and when will we know if it is working?
• What should I, and the people close to me, watch for with urges or sleepiness?
• How does this fit with the other medications I take?
• What is the plan if this one turns out not to be the right fit?
• How will we handle stopping it, if and when we get there?