Table 3.

Neuropsychiatric side effects of interferon and interferon-induced depression

Ref.	n	Design	Treatment	Outcomes
Fried et al[32]	-	Retrospective literature review	PEGIFN-α-2a and 2b with RBV, IFN-α -2b/RBV	Across studies, depression occurred in 22% of those treated with PEGIFN-α-2a/RBV, 31% with PEGIFN-α-2b/RBV and 30%-34% of those treated with standard IFN treatment (PEGIFN-α-2b/RBV)
Fried et al[33]	1121	Randomized clinical trial	PEGIFN-α-2a/RBV, IFN-α-2b/RBV, PEGIFN-α-2a	Patients treated with PEGIFN-α-2a plus RBV or placebo had a lower incidence of depression than those treated with IFN-α-2b plus RBV (22% and 20% vs 30%)
Loftis et al[16]	-	Retrospective literature review	IFN-α, IFN-β, and IFN-γ	Symptoms of depression induced by IFN therapy is common and can limit the treatment utility, often necessitate discontinuation of IFN treatment or the use of psychopharmacologic agents. Depression is also a suspected side effect of therapy with IFN-β and IFN-γ; however, the association has not been as convincingly confirmed
Hauser et al[34]	-	Retrospective literature review	IFN-α	Neuropsychiatric side effects such as depression, may develop as a result of IFN therapy and lead to lower HRQOL, dose reductions or discontinuation
Raison et al[35]	162	Longitudinal assessment	PEGIFN-α-2b	Moderate to severe depressive symptoms occurred frequently during PEGIFN/RBV treatment and was predicted by baseline depression scores and higher doses of RBV
Inder et al[37]	1	Retrospective case report	IFN-α-2a/RBV	Suicide attempt occurred during IFN-α treatment, improvements were only seen with drug discontinuation. Following re-challenge with combination therapy, patient again experienced suicidal ideation
Loftis et al[18]	32	Prospective cohort study	PEGIFN-α-2a and 2b/RBV	IFN therapy results in a significant increase in depressive symptoms over time, with neuro-vegetative and somatic symptoms of depression increasing more than other depressive symptoms

PEGIFN: Pegylated interferon (peginterferon); RBV: Ribavirin; IFN: Interferon; HRQOL: Health related quality of life.