Impulsive and Compulsive Behaviors During Dopamine Replacement Treatment in Parkinson’s Disease and Other Disorders

Abstract

Impulsive and compulsive behaviors, including pathologic gambling, hypersexuality, compulsive shopping, compulsive eating, excessive engagement in hobbies, punding, and Dopamine Dysregulation Syndrome (DDS), are increasingly reported serious side-effects of dopaminergic medication, used in the treatment of Parkinson's Disease (PD) and other disorders. Dopamine Agonists (DA) are strongly related with Impulse Control Disorders (ICDs), while L-dopa is associated with DDS. The present paper focuses on ICDs. The estimated prevalence of ICDs in PD patients treated with DA is as high as 14%. ICDs pathophysiology is complex, due to multiple contributing factors. Dopamine neurotransmission along the meso-cortico-limbic pathway is a modulator of risk behavior and can be altered in PD and in the course of dopaminergic treatment. Psychiatric complications, associated with treatment of PD are still underdiagnosed, although their consequences can be serious, even catastrophic. Physicians treating PD with DA should warn the patients and their relatives of the risk of inducing ICDs. Psychiatrists should be trained to recognize these side effects, that can mimic primary psychiatric conditions. The management of ICDs includes discontinuation of DA or switching from DA to other drugs for the treatment of PD. Cognitive behavior therapy, serotonin selective reuptake inhibitors, nalmefene, zonisamide, low dose of anti-dopaminergic drugs, as quetiapine or clozapine, can be effective. Psychological, spiritual, and ethical support (familial or individual) can help.

Cancer risks among the users of ergot-derived dopamine agonists for Parkinson's disease, a nationwide population-based survey

“…The work tiers from clinical, pathological to genetic and molecular efforts were intended to improve the accuracy of diagnosis for PD, especially for those with probable PD [4]. Although dopamine-replacing agents such as levodopa and dopamine agonists (DAs) improve motor function [5], they also have certain undesired side effects, such as neuropsychiatric symptoms [6] and valvular heart disease [7]. Epidemiologic discussions of this neurodegenerative disease have suggested that tea [8], caffeine and smoking [9] may exert protection against PD, whereas exposure to pesticides may contribute to it [10].…”

Recognizing off target drug effects in the gut and brain

“…Dopaminergic medications are known to provoke anxiety, sleep disturbance, compulsion, hypersexuality and restlessness [30,31] . The development of compulsion, such as the loss of control over gambling, alterations in sexual ideation, religious fervor, or craving of illicit substances may not be readily disclosed in the clinical setting and may require special sensitivity and targeted questioning [32,33] . Patients presenting with early drug induced neurotoxicity syndromes are exposed to a wide variety of medical specialists including neurologists, psychiatrists, primary care providers, gastroenterologists and dentists [34] .…”

The adenosine A2A receptor antagonist, istradefylline enhances the anti-parkinsonian activity of low doses of dopamine agonists in MPTP-treated common marmosets

“…However, motor complications (dyskinesia) can also appear that are provoked by all dopaminergic medications and these can become treatment limiting (Ahlskog and Muenter, 2001;Nutt, 2001). Dopamine agonists have lower efficacy than L-DOPA and dopamine agonist use is associated with the onset of compulsive behaviours, vascular change, hallucinations and psychosis (Perez-Lloret and Rascol, 2010;Raja and Bentivoglio, 2012). The frequent occurrence of dopaminergic side-effects means that raising the dose of a dopamine agonist when efficacy is insufficient, may not be an option.…”