Human Psychopharmacology of Second Generation Antidepressants.

Any compound which has the potential to disrupt cognitive and psychomotor performance will exacerbate the impairments which are a feature of depressive illness. The consequences of this include compromising the patient in terms of recovery from depression, reducing the quality of life and increasing the risk of accident. A critical review of the literature on the effects of antidepressants on performance in healthy volunteer and depressed patient populations showed that the older tricyclic antidepressants (TCAs) impaired cognitive and psychomotor performance, whereas the newer antidepressants appeared to have little or no effect. This review also revealed that there were tests which were sensitive to the effects of antidepressants on human information processing, but only when used in appropriately designed experiments. On the basis of these findings, seven experiments were carried out to investigate the effects of the second generation antidepressants moclobemide, brofaromine, paroxetine, litoxetine, fluvoxamine, citalopram and fengabine in healthy volunteers. These antidepressants either improved performance on the battery of tests or were no different to placebo, whereas the TCAs dothiepin and amitriptyline produced impairments throughout. The eighth experiment evaluated the effects of fluoxetine versus dothiepin in depressed patients treated in general practice. Although fluoxetine and dothiepin were equipotent in reducing clinical ratings of depression, the cognitive and psychomotor abilities of patients in the fluoxetine group were superior to those in the dothiepin group. It is generally accepted that there is little to choose between antidepressants in terms of efficacy, however, the data presented in this thesis suggest that there are differences in the extent to which these drugs affect performance. These factors should be taken into consideration in the management of depression in ambulant outpatients