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Subject: Dopamine Agonist Withdrawal Syndrome in PD Patients with Impulse Control Disorder Date: 2/24/2010 Parkinson’s disease patients with impulse control disorders (ICD) are at risk for developing dopamine agonist withdrawal syndrome (DAWS) when tapering the DA, according to a new study. DAWS is defined as “a severe, stereotyped cluster of physical and psychological symptoms that correlate with DA withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other PD medications (and thus occur even in the on state), and cannot be accounted for by other clinical factors,” according to the authors. In a convenience sample of 93 PD patients at a tertiary movement disorders center, 40 patients had received treatment with a DA. Of these, 26 underwent tapering of the DA, including 15 with impulse control disorder. Twenty-one of the 26 successfully reduced or stopped DA treatment, with concomitant increase in levodopa or other PD drugs. Five of the 26 developed DAWS upon attempted DA reduction, despite an increase in levodopa. One-third (5/15) of patients with ICD, and no patient (0/11) without ICD, developed DAWS upon tapering. Compared to patients who did not develop DAWS, patients who developed DAWS were more likely to have a pre-existing ICD (5/5 vs 10/21), had higher cumulative exposure to dopaminergic drugs (approximately 2.5 fold), and had better on-state UPDRS motor scores (21 vs. 31). Symptoms of DAWS included “anxiety, panic attacks, depression, dysphoria, agitation, insomnia, dizziness, nausea, irritability, fatigue, orthostatic hypotension, diaphoresis, generalized pain, and drug cravings.” Symptoms were unresponsive to levodopa, antidepressants, benzodiazepines, or cognitive behavioral therapy, but improved rapidly and dramatically with reinstitution of the DA. Two DAWS patients recovered. Three required reinstitution of the DA, and continue to experience “chronic, disabling ICDs.” According to the authors, addiction to dopamine agonists is likely to be due to increased dopamine signaling in mesocorticolimbic circuits, the same circuits implicated in addiction to cocaine and amphetamines, which also increase dopamine signaling. “We postulate that there is a mesocorticolimbic variant of PD, characterized by the following: (1) disproportionate mesocorticolimbic (vs. nigrostriatal) dopaminergic dysfunction; (2) increased vulnerability to ICDs and DAWS; and (3) a relatively benign motor phenotype.” Based on the findings in the study, the authors recommend close monitoring of patients when DAs are withdrawn, and strong consideration of DA tapering as soon as ICDs develop, to increase the chances for successful dose reduction. Dopamine agonist withdrawal syndrome in Parkinson disease CA Rabinak, MJ Nirenberg Arch Neurol 2010;67:58-63 E-MOVE Editor: Richard Robinson, NASW, WE MOVE
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