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Dipyridamole monotherapy in schizophrenia

Pilot of a novel treatment approach by modulation of purinergic signaling

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Abstract

Background

Emerging data indicate the neuromodulator adenosine may play a role in the therapeutics of schizophrenia. Adenosine A2A receptor stimulation exerts a functional antagonism at postsynaptic D2 receptors. Data from animal models relevant to schizophrenia support a therapeutic effect of modulating adenosinergic transmission in the ventral striatum. One previous clinical trial showed superiority of adjunctive dipyridamole, an adenosine reuptake inhibitor, compared to placebo in ameliorating positive symptoms in schizophrenia patients.

Objectives

The aim of this study was to examine the effects of dipyridamole monotherapy of 200 mg/day on positive and negative symptoms, with the goal of determining dosing for future adjunctive studies in schizophrenia.

Methods

Twenty symptomatic schizophrenia participants were randomized to a 6-week double-blind trial comparing olanzapine (20 mg/day) to dipyridamole monotherapy (200 mg/day). Thirteen participants completed the treatment phase (eight on dipyridamole; five on olanzapine).

Results

The olanzapine group showed a trend (p = 0.08) for superiority on BPRS total scores (mean ± SD: total BPRS score decreasing from 36.8 ± 2.3 at week 1, to 33.2 ± 5.5 at the end of the study). The mean total BPRS scores decreased from 36.4 ± 5.3 to 34.0 ± 7.7 in the dipyridamole group.

Conclusions

Although these pilot data do not support a significant antipsychotic effect of dipyridamole monotherapy, the results provide some evidence for examining dipyridamole (200 mg/day) as adjunct to symptomatic antipsychotic-treated schizophrenia patients.

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Acknowledgement

This work was supported by a grant from the Stanley Medical Research Institute.

Registration at clinicaltrials.gov

This study is registered at clinicaltrials.gov.

Authors’ disclosure

The authors declare no conflict of interest in the preparation of this manuscript.

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Authors and Affiliations

  1. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA

    Ikwunga Wonodi, Hirekatur V. Gopinath, Judy Liu, Helene Adami, L. Elliot Hong, Robert Allen-Emerson, Robert P. McMahon & Gunvant K. Thaker

Authors
  1. Ikwunga Wonodi
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  2. Hirekatur V. Gopinath
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  3. Judy Liu
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  4. Helene Adami
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  5. L. Elliot Hong
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  6. Robert Allen-Emerson
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  7. Robert P. McMahon
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  8. Gunvant K. Thaker
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Correspondence to Ikwunga Wonodi.

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Wonodi, I., Gopinath, H.V., Liu, J. et al. Dipyridamole monotherapy in schizophrenia. Psychopharmacology 218, 341–345 (2011). https://doi.org/10.1007/s00213-011-2315-3

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  • DOI: https://doi.org/10.1007/s00213-011-2315-3

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