Only 20% (2/10) of the patients on SSRIs developed IFN-MDD, while 47.6% (10/21) not on antidepressants did. These results are numerically similar to the RCTs reviewed above. This very limited analysis suggests a more targeted use of SSRIs to prevent recurrence, limiting prophylactic SSRI to those patients who are known to have past MDD histories. However, all of these studies have been very limited in size, and therefore power. Assessing all of the six published prevention studies and our open-label data combined – in a very exploratory type of meta-analysis

– 15/97 (15%) patients receiving SSRIs prior to starting IFN-α developed IFN-MDD, compared with 36/99 (36%). This is a Inhibitors,research,lifescience,medical significant difference, χ2=8.2;P<0.001. However, limiting the meta-analysis to the three RCTs, 10/55 (18%) subjects randomized to pretreatment paroxetine developed IFN-MDD while 21/68 Inhibitors,research,lifescience,medical (31%) randomized to placebo did. The trend is numerically similar to the larger meta-analysis, but does not have the power to be significant in a chi-square test (χ2=1.98). At this point, only tentative conclusions are possible: (i) Prophylactic SSRIs may plausibly cut in half the incidence of IFN-MDD. To conclusively determine this, however,

will require a larger-size trial than those performed to date; (ii) SSRIs Inhibitors,research,lifescience,medical may specifically benefit subjects with Belinostat buy either pre-existing depressive symptoms (ie, subthreshold depression) and/or a history of prior MDD. This is consistent either with studies of “indicated prevention” in which patients with subthreshold depression are prevented from worsening to full categorical MDD by about Inhibitors,research,lifescience,medical 30%,108-110 or with studies preventing recurrence of MDD.116-119 A more targeted prevention RCT would be valuable to examine these two possibilities; (iii) Even if Inhibitors,research,lifescience,medical SSRIs are found to be effective prophylactics for some people, about 15% to 20% of patients still developed IFN-MDD even when prescribed SSRIs, there fore antidepressants may not be universally effective. Other targets and approaches for prevention

are needed; (iv) Most importantly, about half of the patients with a history of MDD remain resilient even during IFN-α treatment. Identifying the source of this resilience for potential replication in other patients Dacomitinib would be beneficial. Modifiable risk factors for IFN-MDD The goal for this work is preventative treatments that can be targeted towards specifically mitigating those mechanisms underlying vulnerability. Poor sleep quality prior to IFN-α treatment may be one such risk factor.121,122 Patients with scores greater than 10 on the Pittsburgh Sleep Quality Index, a validated self-report assessment of sleep quality,123 were ten times more like to subsequently develop IFN-MDD than patients sleeping better than this.122 This large effect size was evident even when controlling for other depression symptoms.