Wednesday, July 16, 2008

Pramipexole and Compulsive Masturbation

September 2007

by Randy A. Sansone, MD; and Mark Ferlan, DO

Dr. Sansone is a Professor in the Departments of Psychiatry and Internal Medicine at Wright State University School of Medicine in Dayton, Ohio, and Director of Psychiatry Education at Kettering Medical Center in Kettering, Ohio. Dr. Ferlan is a resident in the Department of Internal Medicine at Kettering Medical Center in Kettering, Ohio.

Abstract

Objective: Exploration of a possible relationship between pramipexole and compulsive masturbation.
Methods: We present a case report.
Results: Given the temporal overlap between pramipexole prescription and its discontinuation, and the onset and cessation of the patient’s hypersexual behavior, there appears to be a strong likelihood of association.
Conclusions: Like other dopamine agonists, pramipexole may precipitate compulsive behaviors, including hypersexual behavior in the form of compulsive masturbation.

Key Words: dopamine agonists, hypersexual behavior, compulsive sexual behavior, masturbation, adverse effects

Introduction

Pramipexole is a non-ergot dopamine agonist that binds to D2 and D3 dopamine receptors in the striatum and substantia nigra. This drug is a full dopamine agonist (bromocriptine and pergolide are partial agonists) and is more selective for the D3 receptor than either bromocriptine or pergolide. Pramipexole has no significant effects on adrenergic or serotonergic receptor sites and is primarily prescribed for the treatment of Parkinson’s disease and restless legs syndrome.

In the empirical literature, there are a number of reports of compulsive behaviors in association with dopamine agonist therapy. For example, there are several case reports of dopamine agonist therapy and pathological gambling.[1-9] In one series of 388 patients, 4.4 percent developed pathological gambling.[2] In a sample of Italian patients, the prevalence of pathological gambling was 6.1 percent, compared with 0.25 percent among controls.[3]

In addition to pathological gambling, other compulsive behaviors have been reported with the use of dopamine agonists. For example, there are several case reports of patients compulsively using dopamine agonist drugs, a phenomenon that is identified as “dopamine dysregulation syndrome”[10] or “hedonistic homeostatic dysregulation.”[11] Pezzella and colleagues describe this behavior as “self-medication and addiction to dopaminergic drugs.”[11] Punding, a stereotypic behavior characterized by the repetitive handling and examination of mechanical objects, has also been reported in association with dopamine agonist therapy.[12,13] In one case, punding manifested as “computer addiction.”[13] There have also been case reports of compulsive eating with dopamine agonist therapy.[14]

Although infrequently reported, hypersexual behavior has also been described in patients on dopamine agonists. Weintraub and colleagues found that 2.6 percent of their patient series reported compulsive sexual behaviors while on dopamine agonist therapy.[7] In their discussion of findings, the authors never explicitly describe these behaviors. However, pramipexole was the most frequently implicated drug. In a retrospective review of medical records, Klos and colleagues described 15 cases of hypersexuality associated with dopamine agonist therapy.[15] These hypersexual behaviors included the compulsive use of pornography, extramarital affairs, and delusions of spouse infidelity. One-third of the patients were prescribed pramipexole.

While all dopamine agonists are generally associated with diverse compulsive behaviors, some investigators believe that pramipexole is more likely to be causative.[8,9] Some studies support this suspicion. For example, while the precise neurophysiology of this association remains unknown, rats treated chronically with a D2/D3 agonist developed compulsive checking of specific locations.[16] By being a full and selective D3 agonist, pramipexole may pose a heightened risk for the development of compulsive behaviors. These behaviors may be mediated through ventral-striatal over-stimulation, and manifest as novelty and reward-seeking.17 While compulsive behaviors associated with dopamine agonists may appear to have overtones of obsessive-compulsive disorder, comparative examination does not appear to support a relationship between the two.[18]

In the following case report, we describe a male patient who was treated with pramipexole for restless legs syndrome. While on treatment with dopamine agonist therapy, he developed relentless compulsive masturbation.

Case Report

Mr. T. was a 67-year-old white man with medical diagnoses of hypertension, complex-partial epilepsy, liver cancer (status-post resection), hemochromatosis, gastroesophageal reflux, sleep apnea, restless legs syndrome, and major depression. His medications were lisinopril 10mg daily, clonidine transdermal 0.2mg daily, amlodipine 10mg daily, oxcarbazepine 600mg twice per day, clopidogrel 75mg daily, allopurinol 100mg daily, aspirin daily, hydrochlorothiazide 25mg daily, ranitidine 75mg daily, pramipexole 0.5mg at bedtime, and escitalopram 10mg daily.

During an appointment, Mrs. T. voiced her concern about her husband’s hypersexuality. She stated that for the past 3 to 4 years, Mr. T. had experienced a very high libido and was masturbating approximately 6 to 8 times a day. Mrs. T. explained that he would also wake her up in the middle of the night to satisfy his needs. In addition, he would excuse himself from the dinner table at home, in restaurants, or at the homes of friends to masturbate. The patient acknowledged these behaviors but was unable to explain them. Upon careful inquiry, the patient affirmed that his symptoms began shortly after starting pramipexole for restless legs syndrome. A literature search indicated a possible relationship between compulsive behaviors and pramipexole, and the temporal association was convincing. The patient was advised to discontinue the pramipexole. Mr. T. and his wife returned for a follow-up encounter two weeks later and indicated that since the discontinuation of the pramipexole, there had been a marked decrease in his masturbatory behavior, which was no longer daily.

Conclusions

It appears that dopamine agonists may, in susceptible patients, result in various types of compulsive behaviors. We have previously discussed some possible neurophysiological substrates that may account for these unusual behaviors. However, a number of questions remain unanswered. For example, are there specific dopamine subreceptors that, when stimulated, are more likely to cause compulsive behaviors (e.g., D3 receptors)? Will the various dopamine agonists evidence differing rates of risk for compulsive behaviors based upon their dopamine receptor profiles? Are there any predisposing factors in the patient’s premorbid history that partially account for the specific type of compulsive behavior manifested? Only further investigation will clarify these intriguing issues. For the time being, however, it seems prudent to recommend that clinicians who see patients on dopamine agonists routinely inquire about the unusual side effect of compulsive behavior, including hypersexuality and masturbation. In addition, these drugs should be used very cautiously and with great discretion in sex offenders.

References

1. Voon V, Thomsen T, Miyasaki JM, et al. Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease. Arch Neurol 2007;64:212–6.
2. Grosset KA, Macphee G, Pal G, et al. Problematic gambling on dopamine agonists: Not such a rarity. Mov Disord 2006;21:2206–8.
3. Avanzi M, Baratti M, Cabrini S, et al. Prevalence of pathological gambling in patients with Parkinson’s disease. Mov Disord 2006;21:2068-72.
4. Quickfall J, Suchowersky O. Pathological gambling associated with dopamine agonist use in restless legs syndrome. Parkinsonism Relat Disord Jan 29 2007 (Epub ahead of print).
5. Spengos K, Grips E, Karachalios G, et al. Reversible pathological gambling under treatment with pramipexole. Nervenarzt 2006;77:958–60.
6. Weintraub D, Siderowf AD, Potenza MN, et al. Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol 2006;63:969-73.
7. Molina JA, Sainz-Artiga MJ, Fraile A, et al. Pathological gambling in Parkinson’s disease: A behavioral manifestation of pharmacologic treatment? Mov Disord 2000;15:869–72.
8. Driver-Dunckley E, Samanta J, Stacy M. Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease. Neurol 2003;61:422–3.
9. Dodd ML, Klos KJ, Bower JH, et al. Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 2005;62:1377–81.
10. Evans AH, Lawrence AD, Potts J, et al. Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease. Neurol 2005;65:1570–4.
11. Pezzella FR, Colosimo C, Vanacore N, et al. Prevalence and clinical features of hedonistic homeostatic dysregulation in Parkinson’s disease. Mov Disord 2005;20:77–81.
12. Shapiro MA, Chang YL, Munson SK, et al. Hypersexuality and paraphilia induced by selegiline in Parkinson’s disease: Report of 2 cases. Parkinsonism Relat Disord 2006;12:392–5.
13. Fasano A, Elia AE, Soleti F, et al. Punding and computer addiction in Parkinson’s disease. Mov Disord 2006;21:1217–8.
14. Nirenberg MJ, Waters C. Compulsive eating and weight gain related to dopamine agonist use. Mov Disord 2006;21:524–9.
15. Klos KJ, Bower JH, Josephs KA, et al. Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 2005;11:381–6.
16. Dvorkin A, Perreault ML, Szechtman H. Development and temporal organization of compulsive checking induced by repeated injections of the dopamine agonist quinpirole in an animal model of obsessive-compulsive disorder. Behav Brain Res 2006;169:303–11.
17. Voon V. Repetition, repetition, and repetition: Compulsive and punding behaviors in Parkinson’s disease. Mov Disord 2004;19:367–70.
18. Harbishettar V, Pal PK, Janardhan Reddy YC, Thennarasu K. Is there a relationship between Parkinson’s disease and obsessive-compulsive disorder? Parkinsonism Relat Disord 2005;11:85–8.

3 comments:

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