Abstract

Parkinson’s disease (PD) patients using dopamine agonists can develop withdrawal symptoms, referred to as dopamine agonist withdrawal syndrome (DAWS), under dose tapering or discontinuation of these drugs. DAWS includes a severe stereotypical cluster of psychiatric and psychological symptoms encompassing severe mood and anxiety disturbances, autonomic symptoms, as well as generalized pain and drug cravings. However, symptoms of withdrawal of dopamine replacement therapies (DRT) are not simply limited to dopamine agonists tapering, as observed in PD patients on deep brain stimulation after dopaminergic drugs withdrawal related to surgery. To date, no DRT-related withdrawal syndrome has been described in PD patients who discontinue rasagiline, an irreversible inhibitor of monoamine oxidase-B (MAO-B). Here we report three PD patients who developed a severe withdrawal syndrome after rasagiline suspension. The syndrome was mainly characterized by prominent psychiatric disorders (depression, anxiety with panic attacks, dysphoria, and agitation) associated with fatigue, generalized pain, and autonomic manifestations (closely resembling symptoms of DAWS). In our opinion, this report suggests the importance of closely monitoring PD patients undergoing rasagiline suspension for withdrawal symptoms and provides interesting points of reflection on the role of rasagiline and other MAO-B inhibitors in mood disorders.

Highlights

  • Parkinson’s disease (PD) patients using dopamine agonists can develop symptoms similar to addictive drug withdrawal

  • The withdrawal symptoms that we have described in this study were highly stereotyped and mainly characterized by prominent psychiatric disorders

  • dopamine agonist withdrawal syndrome (DAWS) is a disabling complication related to DA tapering which encompasses a severe stereotypical cluster of psychiatric and psychological symptoms, such as anxiety, agitation, depression and drug craving, causing clinically significant distress or social/occupational dysfunction, very similar to those observed in patients with rasagiline withdrawal, and strongly linked with impulse control disorders (ICD) [2,3]

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Summary

Introduction

Parkinson’s disease (PD) patients using dopamine agonists can develop symptoms similar to addictive drug withdrawal. Neurological examination showed enhanced resting tremor, hypomimia, bilateral bradykinesia, rigidity, and associated postural instability (UPDRS-III score equal to 39, Hoehn and Yahr stage was 3) This disabling impairment required the prompt introduction of levodopa at 300 mg/daily. One month after the introduction of levodopa, the PD motor symptomatology was clearly improved (UPDRS-III score equal to 22), the affective disturbances were always persistent and severe She complained that levodopa treatment did not alleviate her symptoms since she was unable to perform any kind of daily activity, with repeated requests of increasing her DRT. Severe affective symptoms were present for other six months with the need to further increase dopaminergic treatment, with following spontaneous amelioration

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