SUMMARY A six‐week, double‐blind, randomised study was used to compare the efficacy, tolerability, safety and effect on cognitive function of paroxetine with that of lofepramine in the treatment of 138 patients with major depression in general practice. Efficacy was assessed using the Montgomery and Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) scale. Effect on cognitive function was assessed using the paired associate learning test and the serial ‘E’ cancellation test. The results showed that the antidepressant efficacy of paroxetine was comparable to that of lofepramine in the treatment of depressed patients. Similar improvements in mean total MADRS scores were observed in both treatment groups, but a significantly greater improvement was seen in the CGI with paroxetine at weeks 2 and 4. The effect of treatment on cognitive function did not differ significantly across the two treatment groups, nor did the number of adverse events reported nor the overall tolerability.
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