37,38 In sum, there is a strong, bidirectional relationship between depression

and migraine headaches. In patients with a history of depression or who are currently depressed, topiramate and flunarizine should be avoided when possible; if treatment with these medications is required, depressive symptoms should be monitored. For these patients, acute treatment with serotonin agonists and prophylactic treatment with TCAs might be considered, as such treatment could alleviate symptoms of both depression and migraine headaches. Medications for the treatment of multiple sclerosis Patients with multiple sclerosis (MS) are at significantly increased Inhibitors,research,lifescience,medical risk for depression; Inhibitors,research,lifescience,medical one study found a 2.3-fold increase in depression risk, even after controlling for age and gender.39 At present there is no consensus regarding the pathophysiological link between depression and MS; while some researchers suggest increased rates of depression in patients with lesions in specific areas of the brain (eg, right temporal lobe, superior frontal or parietal regions), others have found no such relationship.40 In patients with MS, depression has been associated with worse quality of life,41 increased levels of disability,42 worse adherence to MS treatment,43,44 and an increased risk of suicide Inhibitors,research,lifescience,medical in some studies.45 Interferon (IFN)-ß-1a and IFN-ß-1b

are two of the most common disease-modifying agents used to treat MS. Given the risk of depression using IFN-α in patients with HCV infection (see Inhibitors,research,lifescience,medical Anti- infective agents section), there has been significant concern that IFN-ß similarly causes depressive symptoms. Although a few early studies found that IFN-ßBI 6727 concentration -1b-treated patients suffered from high rates of depression and suicidal ideation,43,46 these findings have not Inhibitors,research,lifescience,medical been replicated. In a secondary

analysis of a double-blind, placebo-controlled study evaluating the efficacy of IFN-ß-1a in 365 MS patients, Patten and associates47 found no significant differences in depression between IFN-ß-1a and placebo at 36-month follow-up. Others similarly found no increased risk of depression with IFN-ß treatment in patients with MS who were re-evaluated at 65 months; they suggested that pretreatment depression and disability were the biggest predictors of depression at follow-up.48 Other agents used in the treatment of MS include 4aminopyridine, glatiramer, Non-specific serine/threonine protein kinase fingolimod, mitoxantrone, and natalizumab. Unfortunately, few data exist regarding the rates of depression in patients taking these medications. Depression, specifically, has been studied for only two of these medications: natalizumab and fingolimod. Two randomized controlled trials (RCTs) of natalizumab found no increased risk of depression.49,50 A randomized trial of fingolimod similarly found no increase in depression compared with placebo.