Benzodiazepines, but not antidepressants or neuroleptics, induce dose‐dependent development of tolerance to lorazepam in psychiatric patients

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Abstract
– Psychomotor effects of oral lorazepam 3 mg were studied in psychiatric patients stratified into four groups: 1) a group of six patients with no previous use of psychotrophic drugs (NoD), 2) a group of 12 patients treated with antidepressants and/or neuroleptics (PsyD), 3) a group of 10 patients treated with low doses of benzodiazepines (BZs) (lowBZ), and 4) a group of nine patients treated with high doses of BZs (highBZ). Similar objective psychomotor tests and subjective assessments were administered under single-blind conditions to all treatment groups at baseline, after intake of placebo, and after intake of 3 mg lorazepam. Both lorazepam (CGC) and total BZs (bioassay) in serum were assayed. The results demonstrate that treatment with BZs induce dose-dependent development of tolerance to psychomotor effects of lorazepam. Antidepressants and neuroleptics failed to induce cross-tolerance to lorazepam. The rise in serum lorazepam concentrations after lorazepam intake was similar (about 28 μg/1) in all treatment groups, suggesting a functional, not dispositional, tolerance. However, the initial learning effect in psychomotor performance was poorer among BZ users than among others.