A Cross-Sectional Study of the Prevalence of Cognitive and Physical Symptoms During Long-Term Antidepressant Treatment

Background: Antidepressant therapies have been associated with a variety of side effects of both physical and psychological nature. Until recently, however, the majority of the studies focusing on side effects of antidepressants have not routinely included assessment of cognitive side effects. The purpose of the present work is to examine cross-sectionally the prevalence of cognitive and physical side effects of antidepressants during long-term treatment of depression.

Method: Patients at least 18 years of age who were deemed responders to antidepressant therapy following at least 3 months of treatment for major depressive disorder (MDD) (diagnosed according to DSM-IV criteria) and whose MDD was considered to be in partial or full remission were eligible for inclusion in this study. Eligible patients were enrolled between January 2003 and December 2004. Study participants were administered the Harvard Department of Psychiatry/National Depression Screening Day (HANDS) scale, the Epworth Sleepiness Scale, the Brief Fatigue Inventory, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), and a study-specific questionnaire inquiring about the emergence of specific side effects such as apathy, fatigue, and inattentiveness.

Results: 117 MDD patients (mean ± SD age: 43.4 ± 12.6 years; women: N = 78 [66.7%]) met criteria for response according to the HANDS (score < 9). Cognitive symptoms (apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowing) were each reported on both the CPFQ and the study-specific questionnaire by more than 30% of the responders on antidepressants. The physical symptoms of fatigue and sleepiness/sedation were reported by over 40% of the responders on both the CPFQ and the study-specific questionnaire. A significant, positive relationship was found between the CPFQ and the severity of residual depressive symptoms as measured by the HANDS total score (F = 15.3, p = .0002).

Conclusion: Physical and cognitive symptoms are frequently reported by MDD patients who have responded to antidepressants and are treated in the long term with these agents. It is likely that these symptoms are both side effects of the antidepressants as well as residual symptoms of MDD.