Antidepressant-induced undesirable weight gain: Prevention with rimonabant without interference with behavioral effectiveness

Nikolai Gobshtis, Shimon Ben-Shabat, Ester Fride

    Research output: Contribution to journalArticlepeer-review

    28 Scopus citations


    Antidepressant pharmacotherapy has dramatically improved the quality of life for many patients. However, prolonged use may induce weight gain, resulting in enhanced risk for treatment noncompliance. Cannabinoid CB1 receptor antagonists decrease food intake and body weight, but may also affect mood. We investigated in female Sabra mice first, whether acute treatment with the cannabinoid receptor antagonist rimonabant (5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, SR141716, 5 mg/kg) interfered with the tricyclic antidepressant desipramine (15 mg/kg) or the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg) in the Porsolt forced swimming test. Second, whether chronic treatment (3 months) with desipramine (5 mg/kg) enhanced weight gain and whether cotreatment with rimonabant (2 mg/kg), prevented the excessive weight gain, while retaining antidepressant effectiveness. Motor activity and anxiety-like behavior were also investigated. The acute studies indicated that rimonabant did not influence 'antidepressant' activity of desipramine or fluoxetine. In the chronic studies, desipramine enhanced weight gain, despite the observation that the injection procedure reduced weight gain. The enhanced weight gain continued at least 35 days after treatment ended. Rimonabant reduced weight gain to which no tolerance developed and which persisted at least 30 days beyond treatment. Mice cotreated with rimonabant and desipramine had body weights closer to controls or to those receiving rimonabant alone than to those treated with desipramine alone. The antidepressant effects of desipramine were maintained throughout treatment; this was not altered by the chronic rimonabant treatment at any time, although rimonabant together with desipramine transiently enhanced anxiety-like behavior. These observations suggest that combined treatment with antidepressants and cannabinoid CB1 receptor antagonist to prevent undesirable weight gain, should be further investigated.

    Original languageEnglish
    Pages (from-to)155-163
    Number of pages9
    JournalEuropean Journal of Pharmacology
    Issue number2-3
    StatePublished - 12 Jan 2007


    • (Mouse)
    • Antidepressant
    • CB receptor
    • Cannabinoid
    • Desipramine
    • Endocannabinoid
    • Fluoxetine
    • Obesity
    • Rimonabant
    • Weight gain

    ASJC Scopus subject areas

    • Pharmacology


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