Drugs used to treat Parkinson’s disease can worsen impulsivity

Parkinson’s disease (PD) commonly includes a variety of behavioral disturbances related to impulsivity.  Impulse control problems noted in PD includes hypersexuality, compulsive shopping, compulsive eating and pathological gambling.

These behavioral problems may be related to the pathophysiology of Parkinson’s disease.  However, drugs commonly used in Parkinson’s disease appear to increase the risk for impulsive behavioral problems.

Clinicians face a dilemma in drug-induced behavioral disturbances.  The drugs that may be effective for treating the motor symptoms may be causing behavioral problems.  Stop the drug and the behavioral symptoms improve but the motor symptoms return.

Dysregulation in brain glutamate has been hypothesized to contribute to dyskinesias and behavioral problems in PD.  Dopaminergic drugs may alter glutamate regulation as well as sensitizing dopamine and NMDA glutamtergic receptors.

Thomas and colleagues from Italy, recently published a clinical trial examining the effect of the antiglutamatergic drug amantadine for pathological gambling in PD.  The key elements of the study design included:

  • 17 subjects with PD
  • Double-blind crossover study
  • Amantadine 200 mg/day vs placebo (50 mg twice daily for two days then 100 mg twice daily)
  • Outcome variables: Yale-Brown Obsessive Compulsive Scale for Pathological Gambling, Gambling-Symptom Assessment Scale, South Oaks Gambling Screen, time and money spent gambling

All the subjects were gambling by purchasing scratch off lottery tickets and about a third also were gambling using slot machines.  Before the intervention, they were losing 2% of their salary per gambling day.

Amantadine treatment produced a significant reduction in the primary psychometric measures and in time and money spent gambling.  The effect appeared within two to three days of initiation.

Amantadine treatment resulted in five drop-outs during the study.  Main adverse effects included: insomnia, visual hallucination, orthostatic hypotension and confusion.  It appears that amantadine may not be tolerated by many with PD and this may limit its use.

This study needs replication before changing clinical practice approaches.  The study does highlight the potential role of glutamatergic drugs in impulse control disorders including pathological gambling.

Amantadine may be a promising research drug for clinical trials in pathological gambling in younger populations without PD.

William Yates is a family physician who blogs at
Brain Posts.

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