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Effect of sodium valproate on mania

The GABA-hypothesis of affective disorders

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Summary

A possible antimanic property of the GABA-ergic anticonvulsant valproate was examined by use of a double-blind placebo-controlled ABA design in 5 acutely ill manic patients. In 4 cases a marked improvement was observed after valproate medication whereas one patient showed no response. Seven further patients with frequently recurrent episodes of a manic or maniform schizoaffective psychosis, irresponsive to lithium prophylaxis, were chronically treated with valproate in combination with low doses of lithium (one case only with valproate). Over an observation period of 1 1/2–3 years none of the patients exhibited a relapse. It is proposed that, in general, GABA-ergic anticonvulsants possess antimanic properties and that the specific antimanic effect of lithium is due to a GABA-ergic mode of action. The possible role of GABA-systems in affective disorders and in organic types of psychoses (e.g., porphyria-psychosis, delirium tremens) is discussed on the basis of pharmacopsychiatric considerations.

Zusammenfassung

Unter Verwendung eines doppel-blinden ABA-Designs mit Placebo-Kontrolle wurde bei 5 Patienten mit akuter Manie eine mögliche antimanische Wirkung des GABA-ergen Anticonvulsivums Valproat untersucht. Bei 4 Patienten wurde eine deutliche Besserung beobachtet, während ein Patient auf Valproat nicht reagierte. Bei 7 weiteren Patienten mit häufig wiederkehrenden Phasen einer manischen oder maniformen schizoaffektiven Psychose, die auf die Lithium-Prophylaxe nicht ansprachen, wurde eine Dauerbehandlung mit Valproat in Kombination mit kleinen Lithium-Dosen durchgeführt. (In einem Fall wurde nur Valproat, ohne Lithium, gegeben.) Im Verlauf einer Beobachtungsphase von 1 1/2–3 Jahren wurde bei keinem dieser Patienten ein Rückfall beobachtet. Es wird die Hypothese vorgeschlagen, daß grundsätzlich GABA-erge Anticonvulsiva antimanische Eigenschaften aufweisen und daß auch der spezifische antimanische Effekt von Lithium auf einer GABA-ergen Wirkungskomponente beruht. Eine mögliche pathophysiologische Bedeutung zentraler GABA-Systeme bei affektiven und organischen Psychosen (z.B. Porphyrie, Delirium tremens) wird auf der Basis pharmakopsychiatrischer Überlegungen diskutiert.

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Authors and Affiliations

  1. Max-Planck-Institut für Psychiatrie, Kraepelinstr. 10, D-8000, München 40, Federal Republic of Germany

    H. M. Emrich, D. v. Zerssen, W. Kissling & H. -J. Möller

  2. Kinderklinik und Poliklinik der Technischen Universität, Munich, Federal Republic of Germany

    A. Windorfer

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  1. H. M. Emrich
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  2. D. v. Zerssen
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  3. W. Kissling
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  4. H. -J. Möller
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  5. A. Windorfer
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Supported by the Heisenberg-grant of the Deutsche Forschungsgemeinschaft

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Emrich, H.M., v. Zerssen, D., Kissling, W. et al. Effect of sodium valproate on mania. Arch. Psychiat. Nervenkr. 229, 1–16 (1980). https://doi.org/10.1007/BF00343800

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  • DOI: https://doi.org/10.1007/BF00343800

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