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  • Writer's pictureDr. Harold Pierre

Can Adding Pramipexole to Buprenorphine Therapy Improve Outcomes in Opioid Addiction Treatment?

Updated: Dec 7, 2023

Introduction


Buprenorphine has become a cornerstone medication in treating opioid use disorder (OUD). As a partial opioid agonist, it helps reduce cravings and withdrawal symptoms without creating the same “high” as full opioids like heroin or oxycodone. However, some patients struggle with lingering effects of addiction even while taking buprenorphine as prescribed.


I am Dr. Harold Pierre. For the past 20 years, I have been on a quest to uncover innovative solutions that can boost treatment outcomes. I make a daily practice of reading the newly released medical literature to discover and implement the most promising advances into my practice. One promising addition is pramipexole, a dopamine agonist medication. Research indicates combining pramipexole with buprenorphine may enhance its effectiveness by targeting the dopamine deficiency characteristic of OUD. My hope is that by improving buprenorphine therapy in this way, I can give patients the best chance at overcoming addiction.


This article will explore the potential therapeutic role of combining pramipexole with buprenorphine therapy for OUD. We’ll cover:


  • How pramipexole works as a dopamine agonist.

  • Ways it may complement buprenorphine pharmacologically.

  • Possible benefits in alleviating withdrawal, cravings, anhedonia, pain.

  • Risks and side effects requiring consideration.

  • Current level of evidence and need for further research.

  • Key takeaways for patients and providers considering this approach.


With opioid addiction continuing to impact communities, identifying better treatment options remains crucial. While not a silver bullet, pramipexole could be a promising adjunct to augment buprenorphine therapy.


How Pramipexole Works in the Brain


Pink prescription pills on blue pastel coloured background

Pramipexole is approved for treating Parkinson’s disease and restless leg syndrome. This prescription medication activates dopamine receptors in the brain. Understanding dopamine’s role provides insight into how pramipexole may help OUD.


Dopamine is a neurotransmitter essential for motivation, pleasure, learning, motor control and more. It activates reward pathways and reinforces behaviors. Many addictive drugs flood the brain’s dopamine system. With repeated use, the reward circuitry adapts, leading to decreased dopamine activity and a higher need for the drug to achieve effects.


This dopamine deficiency contributes to withdrawal symptoms and cravings when opioid use stops. As a dopamine agonist, pramipexole stimulates dopamine activity independent of the impaired neurotransmitter system.


Researchers hypothesize this mechanism may enhance buprenorphine’s effects for OUD in several ways:


Potential Benefits of Adding Pramipexole to Buprenorphine Therapy


Reducing Withdrawal and Cravings


  • Buprenorphine alleviates opioid withdrawal and cravings by partially activating opioid receptors. But some patients struggle with residual symptoms, raising their relapse risk.


  • Pramipexole offers a complementary approach. Rather than acting on the opioid system, it targets the disrupted dopamine system underlying addiction.


  • Increasing dopamine activity could ease withdrawal and reduce cravings. A small study found a significant drop in opioid cravings for patients on buprenorphine/naloxone therapy after 6-8 weeks on pramipexole. Larger trials are still needed.


Lessening Anhedonia and Depression


Many individuals with OUD also suffer from anhedonia – inability to experience pleasure. This depression-like symptom relates to dopamine dysfunction. By stimulating dopamine pathways, pramipexole may augment buprenorphine’s mood effects and help address anhedonia.


One notable case report described a patient on a stable buprenorphine/naloxone dose still experiencing significant anhedonia and low motivation. After adding pramipexole, he reported "improved mood and motivation" within one week. The patient also reengaged in hobbies he had lost interest in. His Montgomery-Åsberg Depression Rating Scale (MADRS) score improved from the mild depression range to remission within 6 weeks of starting pramipexole. While only anecdotal evidence, this case provides valuable real-world insight into how rapidly pramipexole augmented buprenorphine's effects on mood and anhedonia symptoms when antidepressant therapy alone was insufficient. More research is needed, but this offers encouraging indicators about the potential role of pramipexole as a fast-acting additive agent.


Alleviating Restless Legs and Pain


A significant portion of OUD patients entering treatment also have chronic pain. Pramipexole is known to reduce restless leg symptoms, which involve abnormal dopamine signaling. Through its dopamine agonist effects, it may also decrease opioid withdrawal-related leg restlessness.


  • A case report by Makhinson and Gomez-Makhinson detailed a patient with severe opioid withdrawal symptoms including anxiety and leg restlessness when tapering off buprenorphine. Symptoms did not improve with clonidine or benzodiazepines. After a single 0.25mg dose of pramipexole, the patient experienced rapid resolution of the leg restlessness and withdrawal symptoms. This case illustrates pramipexole's potential efficacy in alleviating difficult opioid withdrawal symptoms.


Additionally, some evidence suggests pramipexole can lessen chronic pain by modulating dopamine’s role in pain perception. This could provide further symptom relief off opioids.


Augmenting Buprenorphine Efficacy


On a pharmacological level, pramipexole may strengthen buprenorphine’s effectiveness by restoring dopamine system functioning. This combination could allow lower buprenorphine doses to achieve desired outcomes.


One study saw patients on both medications require 50 to 70% less buprenorphine, while still reporting reduced cravings and withdrawal. But larger placebo-controlled studies are needed to corroborate this early finding.


Risks and Side Effects of Pramipexole


While holding promise, pramipexole also comes with potential side effects and risks that require careful consideration:


  • Nausea, dizziness, sleepiness - common early side effects that often resolve with continued use.

  • Increased risk of compulsive behaviors like gambling, shopping or internet use. Mainly observed in Parkinson’s patients on higher doses.

  • May exacerbate psychosis, mania symptoms in vulnerable individuals.

  • Dosing requires gradual titration and monitoring to avoid adverse effects.

  • Safety and efficacy in OUD is not yet fully established through large trials. Interactions with buprenorphine need further study.

  • Not recommended for pregnant or breastfeeding women due to lack of research in these populations.


The decision to add pramipexole should involve carefully weighing possible benefits against these potential risks. OUD patients considering this approach should have an in-depth discussion with their doctor.


Current Evidence and Need for Further Research

Attractive young scientist team in lab coat and safety goggles working with analysing test trial or investigations with test tubes in laboratory (1)

Most data on using pramipexole for OUD comes from small pilot studies, case reports, and theories about its dopamine effects. But larger double-blind randomized controlled trials are still needed to truly demonstrate efficacy and safety.


Some key questions requiring further research include:


  • What is the optimal pramipexole dosage when combined with buprenorphine?

  • How does pramipexole affect buprenorphine’s pharmacological properties?

  • What is the long-term safety profile of this medication combination?

  • How does effectiveness compare to buprenorphine monotherapy or buprenorphine with other antidepressants?


While initial results are promising, pramipexole for OUD remains an off-label use lacking robust clinical evidence. Patients and doctors should carefully weigh its experimental nature.


Key Takeaways on Pramipexole and Buprenorphine


The potential synergistic effects of adding pramipexole to buprenorphine therapy show preliminarily promise for difficult-to-treat OUD. But considerable research is still needed to confirm benefits and establish safety guidelines. Key points for patients and providers considering this experimental approach include:


  • Pramipexole is not FDA-approved for OUD; current use is off-label.

  • May augment buprenorphine treatment by stimulating dopamine pathways.

  • Could possibly reduce withdrawal, cravings, anhedonia, and pain.

  • Carries risks like compulsive behaviors; careful monitoring required.

  • Large controlled trials still needed to demonstrate efficacy and ideal dosing.

  • Patients and doctors should have an in-depth discussion weighing pros and cons.


While an exciting prospect, pramipexole for OUD requires cautious, evidence-based consideration at this preliminary stage. Ongoing research will continue shining light on if and how this dopamine agonist could best improve buprenorphine’s benefits for addiction recovery.


Laubenthal, C. E., Escalona, R., & Welch, J. E. (2023). Rapid treatment of anhedonia with pramipexole as adjunct to buprenorphine in opioid use disorder. Primary Care Companion to the Journal of Clinical Psychiatry, 25(5), 22cr03535. https://doi.org/10.4088/PCC.22cr03535


Makhinson, M., & Gomez-Makhinson, J. (2014). A successful treatment of buprenorphine withdrawal with the dopamine receptor agonist pramipexole. The American Journal on Addictions, 23(5), 475-477. https://doi.org/10.1111/j.1521-0391.2014.12133.x


About the author:

Dr. Harold Pierre is a board-certified anesthesiologist and addiction medicine specialist with over 20 years of experience. He is board-certified by the American Board of Anesthesiology and the American Board of Preventive Medicine.


This website is provided for educational and informational purposes only and does not constitute providing medical advice or professional services. The information provided should not be used for diagnosing or treating a health problem or disease, and those seeking personal medical advice should consult with a licensed physician or another qualified medical professional. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.





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