Placebo-controlled studies in acute schizophrenia — an issue of concern

Delini‐Stula, A.; Berdah-Tordjman, D

doi:10.1016/0924-977x(91)90705-y

European Neuropsychopharmacology

1991

DOI: 10.1016/0924-977x(91)90705-y

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Placebo-controlled studies in acute schizophrenia — an issue of concern

A. Delini‐Stula

D Berdah-Tordjman

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1995

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“…Essentially, such studies should be of the highest scientific value and should provide unequivocal results. Studies of BDZ coadministered with neuroleptics are not considered in the present review because, due to inherent methodological bias, they a priori do not provide conclusive evidence of drug efficacy (Delini-Stula and Berdah-Tordjman, 1994). Pertinent pharmacological findings on the role of GABA and BDZ in schizophrenia are also reviewed briefly in view of the problems in their interpretation.…”

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Benzodiazepines and GABA hypothesis of schizophrenia

Delini‐Stula

Berdah-Tordjman

1995

J Psychopharmacol

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Clinical and experimental studies pertinent for demonstrating the antipsychotic potential of benzodiazepines (BDZ) and the involvement of γ-aminobutyric acid (GABA) in the origin of schizophrenia are reviewed. It is shown that, due to severe methodological problems and pitfalls, placebo-controlled, double-blind studies do not permit unequivocal conclusions on the efficacy of BDZs, but neither do they completely disprove it. Furthermore, at first glance, confusing and controversial findings in animal models indicate a bi-directionality of effects of full BDZ agonists on dopamine-mediated functions, which may perhaps be explained by (i) anatomical and functional organization of the GABA-dopamine system in the nigro-striatal and ventro tegmental area, and (ii) the regional non-selectivity of action of these drugs. The recent demonstration of structural polymorphism of the GABA(A)-BDZ receptor complex and heterogeneous distribution of sets of subunits of the GABA( A)-BDZ receptor in the brain, suggests possibilities for development of partial BDZ agonists showing greater regional selectivity of action and thus potentially more specific antipsychotic action. Initial clinical results with bretazenil (Ro 16-6028), a partial BDZ agonist, in acute schizophrenia are, in this respect, an encouraging lead to be followed further.

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confidence: 99%

Benzodiazepines and GABA hypothesis of schizophrenia

Delini‐Stula

Berdah-Tordjman

1995

J Psychopharmacol

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Placebo-controlled studies in acute schizophrenia — an issue of concern

Cited by 1 publication

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Benzodiazepines and GABA hypothesis of schizophrenia

Benzodiazepines and GABA hypothesis of schizophrenia

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