Prevention studies of IFN-MDD A few prophylactic trials using selective serotonin reuptake inhibitors (SSRIs) have transpired. These prevention studies initiated SSRIs in patients who were not currently experiencing any MDE prior to beginning the IFN-a therapy (Table II)80,83,85,104-107. The first randomized placebo-controlled trial (RCT) was done in patients with metastatic melanoma, using very high doses of intravenous IFN-a. This initial study found strong evidence for prevention of IFN-MDD, with only 2/18 par oxe tinetreated patients (11%) developing Inhibitors,research,lifescience,medical IFN-MDD, as compared with 45% of the placebo-treated group.80 Similarly, in three open-label

trials of prophylactic SSRIs given Inhibitors,research,lifescience,medical to nondepressed HCV patients, only 3/32 patients

(9%) developed IFN-MDD, GDC-0449 mw despite all 32 patients having a prior history of affective disorder. These open-label studies are thus consistent with this RCT study, supporting the conclusion that preventative treatment with SSRIs may be useful. Table II. Studies examining prevention of IFN-MDD using antidepressants. Three randomized placebo-controlled trials (RCT), and four open-label studies examining the prevention of major depressive disorder (MDD), diagnosed using criteria from the Diagnostic Inhibitors,research,lifescience,medical and … However, two small RCT studies have now been completed in patients with HCV (Table II). Neither study found IFN-MDD prevention.85,106 Prophylactic SSRIs may therefore not be universally effective. Despite Inhibitors,research,lifescience,medical these two negative findings, one of these studies did report that 24/29 patients

in the placebo group developed elevated depression symptoms compared with 10/23 in the paroxetine group.106 Additionally, further exploratory analyses indicated that prevention may have been most successful for those subjects who already had high pretreatment baseline levels of depressive symptoms.106 This would be an example of “indicated prevention” whereby treating “subthreshold” depression symptoms may prevent subsequent worsening to full categorical MDD.108-111 It has been well-replicated Inhibitors,research,lifescience,medical that higher levels of pretreatment depression symptoms are associated with the development of IFN-MDD,18,112-115 and these subthreshold symptoms may be an appropriate target for using preventive SSRIs. Another open possibility is that prophylactic SSRIs specifically prevented IFN-MDD not in those with past histories of MDD in remission. This type of prevention would be consistent with the use of antidepressants to prevent recurrence of remitted MDD.116-119 To explore this latter possibility, we prospectively followed 31 patients who were not depressed at the onset of IFN-α therapy (as determined using a Structured Clinical Interview of DSM-IV Axis I diagnoses). All of these patients had no MDEs within 6 months prior to starting IFN-α, but they did have a history of past MDD.