The Effect of Nortriptyline on Cognition

Abstract

Despite widespread belief that antidepressants cause cognitive dysfunction, there has been surprisingly little systematic research that supports this view. With this in mind, our group sought to evaluate the effects of the tricyclic antidepressant nortriptyline on a variety of cognitive and psychomotor tasks. For the purposes of this report, we will focus on Buschke Total Recall. Seventy-eight patients (age range 21-81, mean age 49.95) who met RDC and DSM-III criteria for major depression (mean Hamilton score 20.82) voluntarily agreed to participate in a 6 week double-blind trial whereby they received either notriptyline (NT) or placebo (PBO) following a 1 week single-blind placebo. At each weekly visit the patient received a comprehensive neuropsychological battery which included the Buschke Selective Reminding Task. In addition at baseline, the patient was acutely challenged with the medication to which he was randomized (either PBO or 50 mg NT) and the neuropsychological battery including Buschke selective reminding test was repeated at 1.5 and 4 hrs. All patients received another acute challenge (either placebo or 50 mg nortriptyline) after 6 weeks of chronic treatment. Doses of NT were adjusted weekly to maintain therapeutic plasma levels. Data were analyzed by an analysis of variance with age group (young vs old-55 was the cutoff) and drug status (drug vs PBO) the between subject factors and time of assessment (weekly for the chronic effect and 1.5 & 4 hrs for the acute effect) as the within subject factor. In view of the effect of depression on memory, we used weekly Hamilton depression score as a covariate. The results indicated that there was no statistically significant difference between the NT (mean plasma level 87.94 ng/ml at wk6) vs PBO group with respect to the chronic effects on Buschke Total Recall. There was also no difference between NT vs PBO with respect to Buschke Total Recall after acute challenge at baseline and after acute rechallenge following 6 weeks chronic treatment with either NT or PBO.