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A meta-analysis of the response to chronic l-dopa in patients with schizophrenia: therapeutic and heuristic implications

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Abstract

Rationale

While it is generally believed that administration of the dopamine precursor levodopa (l-dopa) exacerbates symptoms of schizophrenia, numerous reports suggest that adjunctive l-dopa may be beneficial. This body of literature has not been critically reviewed.

Objectives

On the basis of published studies, to determine whether l-dopa administered concomitantly with antipsychotic drugs provides a beneficial response in patients with schizophrenia.

Methods

This review examined 30 studies involving 716 patients. Due to wide methodological variability and limited statistical information, only five studies encompassing 160 patients could be included in a meta-analysis. The others were evaluated qualitatively.

Results

When l-dopa was added to antipsychotic drugs, the overall improvement was moderate (d=0.71) and highly significant (P<0.0001). There were 16 other studies in which l-dopa was added to antipsychotic drugs, but which did not meet criteria for inclusion in the meta-analysis. In these, worsening occurred in less than 20% of patients; the percentage of improved patients varied widely but had a central tendency around 50%.

Conclusions

In patients already on antipsychotic drugs, the addition of l-dopa can be beneficial. Dopamine agonists merit further consideration as adjuncts to antipsychotic drugs in the treatment of schizophrenia.

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Acknowledgements

The authors thank Dr. Lee Friedman for his invaluable statistical consultation and Dr. Milton Strauss for his constructive review of the manuscript.

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  1. Anand P. Popli

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Authors and Affiliations

  1. Psychiatry Service 116 A(B), Louis Stokes Cleveland VAMC, 10000 Brecksville Road, Brecksville, OH, 44141, USA

    George E. Jaskiw

  2. Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio, USA

    George E. Jaskiw

  3. Indiana University School of Medicine, Indianapolis, Ind., USA

    Anand P. Popli

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Correspondence to George E. Jaskiw.

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This research was conducted at and supported by the Louis Stokes Cleveland Department of Veterans Affairs Medical Center. Dr. Jaskiw has conducted clinical trials and/or received lecture sponsorship from the following: Abbot, Bristol-Myers-Squibb, Janssen, Lilly, Novartis, Pfizer, Zeneca. These data were first presented in preliminary form at the 5th International Congress for Schizophrenia Research, Warm Springs, Va., USA 1995.

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Jaskiw, G.E., Popli, A.P. A meta-analysis of the response to chronic l-dopa in patients with schizophrenia: therapeutic and heuristic implications. Psychopharmacology 171, 365–374 (2004). https://doi.org/10.1007/s00213-003-1672-y

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