Pathologic gambling with dopamine agonist therapy in patients with Parkinson disease

Introduction
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By Douglas J Lanska MD MS MSPH

Reports of pathologic gambling in patients with Parkinson disease surfaced in 2000 (Molina et al 2000; Seedat et al 2000) with a considerable number of subsequent reports elaborating the association between gambling or other impulse control disorders with dopaminergic medications in patients with Parkinson disease.

Molina and colleagues reported 12 patients with Parkinson disease and pathologic gambling (Molina et al 2000). Ten patients started gambling after treatment with levodopa. Gambling was exclusively present or was much worse during "on" periods in 11 patients. Molina and colleagues suggested that gambling behavior could represent a "behavioral manifestation of pharmacologic treatment" (Molina et al 2000). Seedat and colleagues reported a case in which low-dose risperidone was helpful in controlling pathologic gambling attributed to dopamine agonist treatment of Parkinson disease (Seedat et al 2000).

In a convenience sample of 272 patients studied at 2 university-affiliated movement disorder clinics, Weintraub and colleagues reported that 7% of patients with Parkinson disease met criteria for an impulse control disorder at some point during the course of their illness (with 4% active), with compulsive gambling and sexual behavior being equally common (Weintraub et al 2006). Independent predictors of a current impulse control disorder in patients with Parkinson disease included treatment with a dopamine agonist and a history of impulse control disorder symptoms prior to Parkinson disease onset (Weintraub et al 2006).

Voon and colleagues similarly reported that the lifetime prevalence of pathologic gambling was 3%, but was 7% in those on dopamine agonist treatment (Voon et al 2006). Pathologic gambling was associated with earlier onset of Parkinson disease and with dopamine agonist treatment.

In some cases, compulsive behaviors (eg, pathologic gambling or pathologic eating) developed with either the institution of dopaminergic therapy or an increase in dose of the dopamine agonist (Driver-Dunckley et al 2003; Avanzi et al 2004; Dodd et al 2006; Nirenberg and Waters 2006). Typically, these behaviors resolved or improved when the dose was lowered or the dopamine agonist was discontinued (Driver-Dunckley et al 2003; Dodd et al 2006; Nirenberg and Waters 2006). Unfortunately, in many cases recognition and treatment of pathologic gambling behavior occurred only after subjects sustained substantial financial losses (Driver-Dunckley et al 2003).

Compulsive behaviors in patients with Parkinson disease:

  • Gambling
  • Hypersexuality
  • Hobbyism
  • Buying
  • Punding (ie, repetitive motor activity such as incessant handling, sorting, or arranging of objects)
  • Eating

Proposed risk factors for development of impulse control disorders in Parkinson disease:

  • Antiparkinsonian combination therapy (levodopa/carbidopa plus dopamine agonist) (Imamura et al 2006)
  • Dopamine agonist or amantadine therapy (Voon et al 2006; Weintraub et al 2006)
  • Higher dosages of dopamine agonists (Weintraub et al 2006)
  • History of impulse control disorder symptoms prior to Parkinson disease onset (Weintraub et al 2006)
  • History of recreational gambling (Weintraub et al 2006)
  • Younger age (Dodd et al 2005; Klos et al 2005)
  • Earlier Parkinson disease onset (Voon et al 2006)
  • Longer Parkinson disease duration (Weintraub et al 2006)
  • Advanced Parkinson disease (Imamura et al 2006)
  • Male (Dodd et al 2005; Klos et al 2005)
  • Personal or family history of alcoholism (Voon et al 2006)
  • Family history of bipolar disorder (Voon et al 2006)

Although some studies (based on anecdotal material) suggested that pramipexole was the dopamine agonist typically responsible for development of pathologic gambling (Dodd et al 2006), other reports have implicated ropinirole and pergolide and less commonly levodopa. Other studies using case-control methodology found no differences between dopamine agonists in their associations with impulse control disorders (Voon et al 2006; Weintraub et al 2006).

Evidence supporting a causal role for dopamine agonists in impulse control disorders in Parkinson disease:

  • Strong association of impulse control disorders with dopamine agonist therapy in multiple studies
  • Temporal onset after initiation or escalation in dose of dopamine agonist
  • Resolution after dose reduction or discontinuation of dopamine agonist

The mechanism of development of impulse control disorders following initiation or dose escalation of dopamine agonists in patients with Parkinson disease is not known. A variety of speculative mechanistic explanations have been proposed. Some have proposed a predisposition in Parkinson disease patients associated with cognitive and emotional dysfunction, including impaired executive function. In addition, many authors have postulated an alteration of dopamine function in mesocorticolimbic pathways involved in mediating reward and reinforcement behaviors.

Regardless of the mechanism, patients with Parkinson disease should be informed of the risk of developing an impulse control disorder prior to initiating treatment with a dopamine agonist, particularly in the presence of putative risk factors for the development of such disorders. Patients should also be regularly monitored for the development of impulse control disorder symptoms after starting such agents. If an impulse control disorder develops in a patient with Parkinson disease, consider (1) reducing the dose of an existing dopamine agonist, (2) switching to a different agonist, (3) discontinuing dopamine agonist therapy entirely, or (4) trying an atypical antipsychotic (eg, quetiapine or risperidone) based on a single anecdotal report (Dodd et al 2005).