Treatment options for depression and psychosis in Parkinson's disease

Neuropsychiatric symptoms are a frequent feature of advancing Parkinson's disease (PD). The reported prevalence of depression varies greatly between different studies but there is general consensus that between 40 and 50% of patients will be affected. Depression may antedate motor manifestations of Parkinson's disease and is usually of moderate or mild intensity. However, depression is of major impact on the quality of life in PD patients according to a recent survey. Drug-induced psychosis is one of the major therapeutic challenges in Parkinson's disease and may occur in up to 6% in otherwise uncomplicated de novo patients when first receiving dopaminergic therapy. It increases in frequency, in advanced disease and particularly in patients with dementia where up to 22% may be affected. There is an amazing lack of controlled clinical trials assessing the effects of antidepressants in clinical trials including more than 20 patients and assessing efficacy of antidepressants specifically in the context of mood changes in Parkinson's disease. A comprehensive literature search yielded only a total of 17 articles of which a majority included less than 20 patients and/or did not use valid depression ratings. The only randomized controlled trial was conducted more than 20 years ago using nortryptiline while no controlled trials were available on the use of serotonin reuptake inhibitors. Studies assessing the antidepressant action of dopaminergic therapies are few and inconclusive. Thus, while tricyclic antidepressants or SSRIs are widely used in clinical practice, there is still a need for controlled clinical trials proving their efficacy specifically in parkinsonian depression. Three randomized controlled trials are now available assessing the efficacy of the atypical neuroleptics clozapine and olanzapine in the treatment of drug-induced psychosis. While clozapine is of proven efficacy at least in the short-term management of this complication without negative impact on the motor symptoms, olanzapine in currently used doses of 2.5 to 15 mg/d seems to aggravate motor symptoms with lesser effect on psychosis compared to clozapine. Currently, clozapine is the atypical neuroleptic of choice for the treatment of drug-induced psychosis in Parkinson's disease.