Psychiatric and substance use disorders co-morbidities and hepatitis C: Diagnostic and treatment implications

Table 11 Newer medications and interferon free therapies

Ref.	n	Design	Treatment	Population	Outcome
Pol et al[92]	48	Double blind parallel group, dose finding phase 2a randomized, placebo controlled clinical trial	Daclatasvir PEGIFN-α-2a/RBV	HCV genotype 1 - treatment-naive (without cirrhosis)	Daclatasvir increases the antiviral potency of PEGIFN/RBV without increasing the side effects profile. Psychiatric adverse events were not significant in this study
Chayama et al[91]	10	Open label phase 2a clinical trial	Daclatasvir asunaprevir	Chronic HCV genotype 1b - previous null responders to PEGINF/RBV	Dual therapy with daclatasvir and asunaprevir alone can achieve high rates of SVR in difficult-to-treat patients and has minimal side effects
Herbst et al[90]	-	Retrospective literature review of phase 1 to phase 3 clinical trials	Daclatasvir	All genotypes; treatment naive and experienced cohorts	Daclatasvir has a potent antiviral effect and clinical efficacy across genotypes and in both treatment naive and experienced cohorts with no evidence of psychiatric adverse events
Suzuki et al[94]	43	Open label phase 2a clinical trial	Daclatasvir asunaprevir	HCV genotype 1b for patients with limited treatment options including those with complications of depression	Dual therapy with daclatasvir and asunaprevir was well tolerated and achieved high SVR rates. The adverse event profile was favorable; no psychiatric abnormalities were reported
Zeuzem et al[88]	394	Phase 3 placebo controlled randomized clinical trial	ABT-450 ritonavir (ABT-450/r), ombitasvir (ABT-267) dasabuvir (ABT-333) RBV	Retreatment of HCV in patients who were previously treated with peginterferon-ribavirin	Rates of response to a 12-wk IFN-free combination regimen were more than 95%. Psychiatric adverse events were not reported
Andreone et al[89]	179	Phase 3 open label randomized clinical trial	ABT-450, ritonavir, ombitasvir, dasabuvir RBV	HCV genotype 1b - treatment experienced patients	ABT-450, ritonavir, ombitasvir, and dasabuvir, with or without RBV, produced a high rate of SVR. Both regimens were well tolerated with minimal adverse events
Sulkowski et al[93]	167	Two part, open label clinical trial	Daclatasvir sofosbuvir	HCV genotype 1, 2, or 3	Daclatasvir plus sofosbuvir was associated with high rates of SVR. Psychiatric problems were not listed as significant adverse events
Afdhal et al[96]	865	Phase 3, open-label randomized clinical trial	Ledipasvir sofosbuvir RBV	HCV genotype 1 - treatment naive	Ledipasvir–sofosbuvir with or without RBV for 12 or 24 wk was highly effective. The most common adverse events were fatigue, headache, Insomnia, and nausea
Lawitz et al[98]	100	Open label randomized clinical trial	Sofosbuvir ledipasvir RBV	HCV genotype 1 - treatment-naive or previously treated with a protease-inhibitor regimen	Sofosbuvir-ledipasvir alone or with RBV has the potential to cure most patients with genotype-1. Psychiatric symptoms were not a listed as significant adverse events
Afdhal et al[95]	440	Phase 3, randomized, open-label clinical trial	Ledipasvir sofosbuvir RBV	HCV genotype 1 - previously treated	Treatment with ledipasvir and sofosbuvir resulted in high rates of SVR. Neuropsychiatric side effects were minimal, but were observed more frequently among groups with the RBV-containing regimen than ledipasvir sofosbuvir alone
Kowdley et al[97]	647	Phase 3, open label clinical trial	Sofosbuvir ledipasvir	HCV genotype 1 - treatment naive	Ledipasvir-sofosbuvir was associated with a high rate of SVR. Adverse events were more common in the group that received RBV. No additional benefit was associated with the inclusion of RBV

PEGIFN: Pegylated interferon (peginterferon); RBV: Ribavirin; HCV: Hepatitis C virus; SVR: Sustained virologic response; IFN: Interferon.