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Recommendations on the Drug Treatment of Psychosis in Parkinson's Disease

      To the Editor:
      In an otherwise excellent and balanced summary of the problem of psychosis in parkinsonian patients, Hasnain et al
      • Hasnain M.
      • Vieweg W.V.R.
      • Baron M.S.
      • et al.
      Pharmacological management of psychosis in elderly patients with Parkinsonism.
      make the unfortunate recommendation of equating quetiapine and risperidone for the treatment of psychotic symptoms in non-demented patients with Parkinson's disease. They also fail to note that in the trials of clozapine for treating Parkinson's disease psychosis, demented patients were included, and in one subgroup analysis there were no differences in efficacy between demented and non-demented subjects with Parkinson's disease.
      Parkinson Study Group
      Low dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease.
      Although the authors are clearly correct in noting that the only double-blind, placebo-controlled trials of quetiapine for the treatment of Parkinson's disease psychosis showed no benefit,
      • Ondo W.G.
      • Tintner R.
      • Young K.D.
      • et al.
      Double blind placebo controlled unforced titration parallel trial of quetiapine for dopamine-induced hallucinations in Parkinson's disease.
      • Rabey J.M.
      • Prokhorov T.
      • Minovitz A.
      • et al.
      Effect of quetiapine in psychotic Parkinson disease patients: a double blind labeled study of 3 months duration.
      • Shotbolt P.
      • Samuel M.
      • Fox C.
      • David A.S.
      A randomized controlled trial of quetiapine for psychosis in Parkinson's disease.
      these trials also concluded that the drug caused no worsening of motor symptoms. All open-label trials of quetiapine have been positive,
      • Chou K.L.
      • Borek L.L.
      • Friedman J.H.
      Management of psychosis in movement disorder patients.
      whereas risperidone's motor side effects have often been extreme.
      • Ford B.
      • Lynch T.
      • Greene P.
      Risperidone in Parkinson's disease.
      • Rich S.S.
      • Friedman J.H.
      • Ott B.R.
      Risperidone versus clozapine in the treatment of psychosis in six patients with Parkinson's disease and other akinetic-rigid syndromes.
      It is true that the published reports on risperidone have been mixed in terms of the motor side effects,
      • Chou K.L.
      • Borek L.L.
      • Friedman J.H.
      Management of psychosis in movement disorder patients.
      but The American Academy of Neurology's task force on practice parameters in the treatment of Parkinson's disease published its recommendations in 2006
      • Miyasaki J.
      • Shannon K.
      • Voon V.
      • et al.
      Practice Parameter: evaluation and treatment of depression, psychosis and dementia in Parkinson disease (an evidenced-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
      recommending quetiapine as the drug of first choice for treating psychosis in Parkinson's disease, although noting that there are no level 1 data to support its use, with clozapine as the second-line choice. I think it highly unlikely that any Parkinson's disease specialist would recommend risperidone until quetiapine, clozapine, aripiprazole, and cholinesterase inhibitors had failed.
      We suggest that risperidone, which causes all the extrapyramidal side effects of the first generation of antipsychotics, be removed as a recommended treatment for patients with Parkinson's disease psychosis.

      References

        • Hasnain M.
        • Vieweg W.V.R.
        • Baron M.S.
        • et al.
        Pharmacological management of psychosis in elderly patients with Parkinsonism.
        Am J Med. 2009; 122: 614-622
        • Parkinson Study Group
        Low dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease.
        N Engl J Med. 1999; 340: 757-763
        • Ondo W.G.
        • Tintner R.
        • Young K.D.
        • et al.
        Double blind placebo controlled unforced titration parallel trial of quetiapine for dopamine-induced hallucinations in Parkinson's disease.
        Mov Disord. 2005; 20: 958-963
        • Rabey J.M.
        • Prokhorov T.
        • Minovitz A.
        • et al.
        Effect of quetiapine in psychotic Parkinson disease patients: a double blind labeled study of 3 months duration.
        Mov Disord. 2007; 22: 313-318
        • Shotbolt P.
        • Samuel M.
        • Fox C.
        • David A.S.
        A randomized controlled trial of quetiapine for psychosis in Parkinson's disease.
        Neuropsychiatr Dis Treatment. 2009; 5: 327-332
        • Chou K.L.
        • Borek L.L.
        • Friedman J.H.
        Management of psychosis in movement disorder patients.
        Exp Opin Pharmacother. 2007; 8: 935-943
        • Ford B.
        • Lynch T.
        • Greene P.
        Risperidone in Parkinson's disease.
        Lancet. 1994; 344: 681
        • Rich S.S.
        • Friedman J.H.
        • Ott B.R.
        Risperidone versus clozapine in the treatment of psychosis in six patients with Parkinson's disease and other akinetic-rigid syndromes.
        J Clin Psychiatry. 1995; 56: 556-559
        • Miyasaki J.
        • Shannon K.
        • Voon V.
        • et al.
        Practice Parameter: evaluation and treatment of depression, psychosis and dementia in Parkinson disease (an evidenced-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
        Neurology. 2006; 66: 996-1002

      Linked Article

      • Pharmacological Management of Psychosis in Elderly Patients with Parkinsonism
        The American Journal of MedicineVol. 122Issue 7
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          Parkinsonism is a characteristic feature of Parkinson's disease and dementia with Lewy bodies and is commonly seen in Alzheimer's disease. Psychosis commonly appears during the course of these illnesses. Treatment of parkinsonism with antiparkinsonian medications constitutes an additional risk factor for the appearance or worsening of psychosis. Conversely, treatment of psychosis with antipsychotic drugs in patients with parkinsonism might worsen the underlying movement disorder, especially in the elderly.
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      • The Reply
        The American Journal of MedicineVol. 123Issue 4
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          We agree with Friedman that quetiapine and risperidone are not comparable in terms of their potential to worsen motor features of parkinsonism. In Table 1 of our publication,1 we stated that quetiapine has a “low” potential and risperidone has a “medium to high” potential to cause extrapyramidal side effects in the 3 parkinsonian conditions we discussed. This difference also is specified within the text. Specifically in regard to psychosis associated with Parkinson's disease, we noted, “Several open-label studies reported that quetiapine possesses modest efficacy against psychosis with few motor side effects in a heterogenous group of patients with psychosis and parkinsonism” and “Although risperidone can improve psychosis associated with Parkinson's disease, information about its side effects is limited and mixed.” Both these statements are substantiated in the literature.
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