Multiple sclerosis, disease modifying treatments and depression: a critical methodological review

Background: Major depression affects one in two patients with multiple scle rosis (MS) during the course of their lifetime. This odds to the morbidity associated with the disorder and may contribute to an increased mortality r ate because of suicide. Over the past few years, with the advent of disease modifying treatments for MS, a new concern with respect to mood has arisen , namely the Possibility that some of these drugs may have depression as a clinically significant side effect. Objective: To ascertain whether disease modifying treatments in MS are associated with the development of depressi on or the worsening of a depressive illness. Methodology: A MEDLINE and PSY CHLIT search focusing on depression and disease modifying treatments going back to 1993 (the Publication date of the results of the first randomised, placebo controlled trial). The methodology pertaining to the assessment of depression is critically reviewed. Furthermore, a critical summary is provi ded of treatment modalities for the depressed MS patient Results: There ore conflicting data that depression may occur with some disease modifying dru gs, particularly interferon beta-1b. However, all studies reveal limitation s with respect to the assessment of mood. Some reports, despite omitting de tails of how mentation was assessed, still comment on the Presence or absen ce of depression. Others suffer from one or more of the following shortcomi ngs: a failure to assess premorbid risk factors for mood disorder; a relian ce on one question to assess depression; the utilisation of self report moo d rating scales of questionable validity; neglecting to distinguish depress ion as a symptom from depression as a syndrome (i.e. major depression as de fined by the DMS-IV). Conclusions: Given the many methodological Pitfalls i nherent in all studies to date, it is premature to conclude that disease mo difying drugs ore associated with depression. Evidence suggests that treatm ent of depression, irrespective of a putative association with a disease mo difying agent is frequently effective. This applies to pharmacotherapy or p sychotherapy although the former may be Preferred should depression arise d uring a course of treatment with a disease modifying agent.