Table 4.

Studies reviewed to assess whether treatment-related risk factors can be associated with development of depression in patients prescribed IFN-α

Risk factor	Evidence for	Evidence against
Dose of interferon	Fried et al108 Of those patients taking 180 μg PEG–IFN, 20%–22% became depressed; however, 30% of those patients taking 3 MU of IFN-α b became depressed. (However, this was not reported to be significant). Mulder et al109 Ascribe the fact that they found no significant changes in depressive symptamology to lower doses of interferon used Renault et al110 Those patients taking a higher dose of IFN-α (10 MU every other day) were more likely to develop what the authors termed an ‘affective syndrome’ than those patients taking 5 MU every day Malaguarnera et al111 When different types of interferon were compared, mean scores on SDS were higher in those patients taking recombinant interferon-α-2a or lymphoblastoid interferon-α than recombinant interferon-α-2b or leukocyte interferon-α	Horikawa et al98 No evidence that type and dose of interferon impacted on depression rates Iino112 In patients taking three regimens of high-dose IFN treatment (10 MU over varying periods up to 14 weeks to a total of 480 MU). Rates of reported depression ranged from 4.8% to 7.1% Kraus et al113 There was no significant difference in reported rates of depression between those patients taking 5 MU IFN-α (33.3%) and those taking 80–150 μg PEG–IFN-α (40%) Manns et al114 In a comparison of different dosing regimes of interferon, there was no significant difference in rates of depression between higher dose peginterefron plus ribavirin (31%), lower dose peginterefron + ribavirin (29%), and interferon plus ribavirin (34%) Okanoue et al107 In a clinical study where patients were taking 6–10 MU of interferon, only 3.5% became clinically depressed Zeuzem et al115 There was no significant difference in reported rates of depression between those patients taking 180 μg/week of PEG–IFN-α (16%) and those patients taking 3 MU IFN-α (23%). Clinically depressed
Length of treatment	–	Castera et al97 There was no significant difference in rates of depression between those on treatment for 24 weeks (53%) and those on treatment for 48 weeks (47%) Hauser et al99 Median time to depression in those patients who developed it was 12 weeks Horikawa et al98 73.9% of patients developed depression within first 8 weeks Robaeys et al116 Depression occurred in patients between 4 and 26 weeks, with the mean time to depression 10 weeks
Retreatment following nonresponse	–	Quarantini et al117 In nonresponder patients, rates of IFN-α-induced depression were comparable to studies in treatment naïve patients with 10% of 30 patients being diagnosed with depression during treatment
Ribavirin	Raison et al62 Patients who received weight-based dosing of ribavirin (800–1400 μg/day) were significantly more likely to develop moderate to severe depressive symptoms than those people who received a standard dose (800 μg/day)	Davis et al12 No significant difference between development of depression in those patients taking IFN (11%) and those patients taking IFN + ribavirin (16%) Fried et al108 No difference in rates of depression between two groups both receiving PEG–IFN-α with either ribavirin (22%) or Placebo (20%) McHutchison et al21 There were no significant differences between the rates of depression in those people taking a standard dose of IFN (25%–37%) and those patients taking interferon and ribavirin (32%–36%)