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

Abstract

Background: Major depression affects one in two patients with multiple sclerosis (MS) during the course of their lifetime. This adds to the morbidity associated with the disorder and may contribute to an increased mortality rate 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 depression or the worsening of a depressive illness. Methodology: A MEDLINE and PSYCHLIT 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 provided of treatment modalities for the depressed MS patient. Results: There are conflicting data that depression may occur with some disease modifying drugs, particularly interferon beta-1b. However, all studies reveal limitations with respect to the assessment of mood. Some reports, despite omitting details of how mentation was assessed, still comment on the presence or absence of depression. Others suffer from one or more of the following shortcomings: a failure to assess premorbid risk factors for mood disorder; a reliance on one question to assess depression; the utilisation of self report mood rating scales of questionable validity; neglecting to distinguish depression as a symptom from depression as a syndrome (i.e. major depression as defined by the DMS-1V). Conclusions: Given the many methodological pitfalls inherent in all studies to date, it is premature to conclude that disease modifying drugs are associated with depression. Evidence suggests that treatment of depression, irrespective of a putative association with a disease modifying agent, is frequently effective. This applies to pharmacotherapy or psychotherapy, although the former may be preferred should depression arise during a course of treatment with a disease modifying agent.