Lack of Beneficial Effects of L-Baclofen in Affective Disorder

Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.
International Clinical Psychopharmacology (Impact Factor: 2.46). 02/1991; 6(4):197-207. DOI: 10.1097/00004850-199100640-00001
Source: PubMed


GABAB mechanisms have been implicated in the antinociceptive, but not anticonvulsant effects of carbamazepine. A variety of antidepressants have been reported to upregulate GABAB receptors after chronic administration. The GABAB agonist l-baclofen was studied in depressed patients based on two separate rationales. l-Baclofen, in doses ranging from 10-55 mg/day, was administered to five patients with primary affective disorder. No patient showed a positive clinical response, while three patients showed a pattern of increasing depression or cycling during treatment and improvement during withdrawal. These preliminary data suggest that GABAB agonism is unlikely to produce antidepressant effects and may be unrelated to the mechanism of carbamazepine's antidepressant action. These data, taken with a reinterpretation of other findings that antidepressant modalities upregulate GABAB receptors in brain following chronic administration, suggest that GABAB antagonism rather than agonism may be a fruitful clinical strategy to explore in depression.

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    • "GABA B receptor antagonists have been found to produce antidepressant properties in animal models, as have GABBR1 deletion studies (Nakagawa et al., 1999; Heese et al., 2000; Mombereau et al., 2005). Moreover, a study found that treatment of subjects with major depression with baclofen resulted in a worsening of symptoms (Post et al., 1991). These findings have led some to believe that an overactive GABA system contributes to major depression (Ghose et al., 2011). "
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    • "However, regarding the GABA B system, only one small study with five patients, to date, has been performed, which employed baclofen. In agreement with the recent preclinical evidence, baclofen was reported in three out of the five patients to worsen their symptoms but clearly such a small sample size means that the findings are questionable (Post et al., 1991). While studies examining the direct effect of baclofen on depressive symptomology have not been extensively performed, a number of studies have assessed the impact of acute baclofen administration on endocrine parameters in depressed patients. "
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