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What Happens When Antidepressant Drugs Stop Working?

September 26, 2002

In this review Dr Nicoletta Sonino (Department of Statistical Sciences, University of Padava) and Dr Giovanni Fava (Department of Psychology, University of Bologna) discuss an issue that is seldom analyzed in the literature: the fact that after 2-3 months, in 10-50% of cases (depending on the series) antidepressant drugs stop working. They postulate that this tolerance have a homonal basis and discuss potential remedies which are suggested by research on Cushing's disease. The pharmaceutical industry - comments Dr Fava - does not want to talk about tolerance in antidepressant treatment. The problem affects a lot of patients, but there is little research about it.

Comorbid conditions may add to the burden of depressed patients and hamper their treatment. We therefore investigated the impact of anxiety disorders and somatic comorbidity in a group of depressed chronic benzodiazepine users on disease status, treatment, benzodiazepine history and discontinuation outcome.

At screening for a discontinuation programme, full psychiatric status was determined using the MINI-interview and psychopathology was assessed using several rating scales. Relevant medical history, including surgeries, was recorded as well. Patients with comorbid anxiety disorders were 8 years younger (p < 0.001), more anxious (p = 0.004) and reported more benzodiazepine withdrawal symptoms (p = 0.011) than depressed patients without comorbid anxiety disorders. They also had been using more long-acting benzodiazepines (p = 0.003), in higher dosages (p = 0.019). However, this did not result in more difficulty in tapering off benzodiazepines, either at post-test, or at follow-up 2.3 years later.

Somatic comorbidity was not associated with the level of psychopathology and not related to the outcome of the discontinuation programme. Comorbid anxiety disorders are associated with a more severe disease status in depressed chronic benzodiazepine users, but have no influence on the benzodiazepine discontinuation. Somatic comorbidity has no impact on the severity of the psychopathology, or on benzodiazepine discontinuation.

Psychotherapy and Psychosomatics, Journal of

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