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Stressful reactions and panic attacks induced by flumazenil in chronic benzodiazepine users

Ambulatório de Ansiedade, Instituto de Psiquiatria, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo

C. Gorenstein

Departamento de Farmacologia, Instituto de Ciências Biomédicas and LIM-23, Faculdade de Medicina, Universidade de São Paulo, Brazil

A.H.G. Vieira Filho

Ambulatório de Ansiedade, Instituto de Psiquiatria, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo

The acute effects of flumazenil, a benzodiazepine (BZD) receptor antagonist in long-term BZD users were used as a possible test to detect physiological dependence. Thirty-four subjects (20 females, 14 males) aged 26-48 years (mean ± SD, 42.4 ± 8.5 years), all chronic users of low doses of diazepam (5-20 mg/day,14.2 ± 4.8 mg/day) for 5 to 28 years (10.5 ± 6 years), received a single 1-mg i.v. flumazenil dose or saline, infused slowly under double-blind conditions. Physiological dependence was suggested as all patients receiving flumazenil developed an anxiety reaction while the placebo group did not. Flumazenil triggered a qualitatively different reaction amounting to a panic attack during infusion in nine out of 15 patients. These patients had a diagnosis of panic disorder or a history of panic attacks. Caution should be exercised when giving flumazenil to panic patients who are taking BZDs as maintenance treatment.

Key Words: benzodiazepines • dependence • flumazenil • humans • panic attacks

Journal of Psychopharmacology, Vol. 12, No. 2, 146-150 (1998)
DOI: 10.1177/026988119801200205


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