Nonmotor symptoms of Parkinson's disease (PD) may emerge secondary to the underlying pathogenesis of the disease, while others are recognized side effects of treatment. Inevitably, there is an overlap as the disease advances and patients require higher dosages and more complex medical regimens. The non-motor symptoms that emerge secondary to dopaminergic therapy encompass several domains, including neuropsychiatric, autonomic, and sleep. These are detailed in the paper. Neuropsychiatric complications include hallucinations and psychosis. In addition, compulsive behaviors, such as pathological gambling, hypersexuality, shopping, binge eating, and punding, have been shown to have a clear association with dopaminergic medications. Dopamine dysregulation syndrome (DDS) is a compulsive behavior that is typically viewed through the lens of addiction, with patients needing escalating dosages of dopamine replacement therapy. Treatment side effects on the autonomic system include nausea, orthostatic hypotension, and constipation. Sleep disturbances include fragmented sleep, nighttime sleep problems, daytime sleepiness, and sleep attacks. Recognizing the non-motor symptoms that can arise specifically from dopamine therapy is useful to help optimize treatment regimens for this complex disease. 1. Neuropsychiatric Hallucinations and psychosis have long been known to be associated with dopaminergic therapy. Psychosis in PD refers to the combination of chronic hallucinations and delusions occurring in the setting of otherwise clear senses. Hallucinations can involve various sensory modalities; however, visual hallucinations are the most common. Some may be benign and nonbothersome, while others can be terribly frightening to patients. Risk factors for developing hallucinations include older age, longer duration of PD, history of sleep disorder, depression, and coexisting cognitive impairment [1, 2]. Interestingly, there has been no evidence that increased dose or specific dopaminergic drug class (agonists versus L-dopa) is related to this problem [1, 3], and it is clear that hallucinations and psychosis are not just mere side effects of treatment. The likely pathogenesis is multifactorial involving pharmacologic mechanisms in conjunction with disease-related elements. Treatment for chronic hallucinations includes reduction of dopaminergic medications and discontinuation of anticholinergics or other drugs. If needed, antipsychotic medications may be used. Clozapine has demonstrated efficacy in a double-blind placebo-controlled trial [4]; however, in clinical practice
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