Copyright
©The Author(s) 2015.
World J Hepatol. Jul 28, 2015; 7(15): 1921-1935
Published online Jul 28, 2015. doi: 10.4254/wjh.v7.i15.1921
Published online Jul 28, 2015. doi: 10.4254/wjh.v7.i15.1921
Table 1 Hepatitis C and pain related diagnoses
| Ref. | n | Design | Assessments | Outcome |
| Whitehead et al[13] | 8224 | Retrospective chart review | Clinical data, diagnoses, and medical history | Pain and SUD diagnoses were common among HCV patients, and opioids were frequently prescribed |
| Morasco et al[14] | 49 | Subjective assessment | Clinical interview, medical records BDI-II, SDS, HRQOL SF-36 | Psychosocial variables, particularly depression severity, account for variance in pain intensity and pain functioning |
| Rogal et al[17] | 1286 | Retrospective cohort study | Self-report, symptom checklist and medical record | There is a high prevalence of pain and opioid use in patients with chronic liver disease |
| Morasco et al[15] | 119 | Subjective assessment | TLFB, self-report; MPI, BDI-II, PCS, CPSS, CPCI, SCID | Biopsychosocial factors significantly affected pain severity and pain interference in patients with HCV |
Table 2 Hepatitis C and psychiatric comorbidities
| Ref. | n | Design | Assessments | Outcome |
| Lehman et al[20] | 120 | Subjective assessment | BDI-II, ASI, PCL, AUDIT, medical records | Clinically significant levels of depression anxiety, PTSD and alcohol-related problems were observed in patients with HCV |
| Fireman et al[19] | 293 | Prospective assessment | AUDIT-C, BDI-II | Psychiatric and substance use disorders are highly prevalent among veterans with chronic HCV |
| Rowan et al[21] | 62 | Subjective assessment | HRQOL SF-36 | Psychosocial factors, especially depression, are strong indicators of impaired HRQOL for HCV-infected Veterans |
| Bini et al[41] | 4084 | Prospective cohort study | Eligibility for IFN therapy based on medical chart review of psychiatric and SUDs | The majority of veterans were not considered suitable candidates for HCV treatment because of substance use disorders, psychiatric disease, and comorbid medical disease |
| Mikocka-Walus et al[10] | 139 | Cross-sectional assessment | HADS, SCL-90, HRQOL SF-12, disease severity assessments | Patients with HCV had significantly higher prevalence of depression and lower HRQOL than patients with IBD and IBS, and the general population |
| Nelligan et al[22] | 881 | Subjective assessment | BDI-II; medical records | Rates of depression are high among veterans with HCV and persist among those with antidepressant prescriptions |
| Weinstein et al[11] | 878 | Retrospective chart review | Clinical and demographic data, medical history | Individuals with HCV have a higher prevalence of depression than HBV and NAFLD patients and the general population |
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 |
Table 4 Antiviral treatment response rates in patients with psychiatric and substance use disorders comorbidities
| Ref. | n | Design | Treatment | Outcomes |
| Dalgard et al[31] | 27 | Longitudinal assessment | IFN-α-2a | Rate of reinfection was not significantly different among IVDUers treated for HCV as compared to non IVDUers despite reinitiation of injection drug use in 33% of IVDUers |
| Loftis et al[27] | 39 | Prospective cohort study | IFN-α-2b/RBV | Gender, past history of MDD, and past history of SUD were not significantly associated with response rates |
| Backmund et al[47] | 18 | Longitudinal assessment | IFN-α-2a, IFN-α-2a/RBV | IVDUers can be reinfected after treatment for HCV infection, but the reinfection rate is minimal and should not jeopardize the potential benefit for most patients |
| Chainuvati et al[40] | 647 | Retrospective database review | Eligibility/treatment rates for Interferon therapy | Therapy completion and SVR rates are similar among Veterans with and without psychiatric or SUDs, challenging the perception that adherence is worse as a result of psychiatric co-morbidities |
| Anand et al[42] | 4061 | Longitudinal assessment | IFN-α-2b/RBV | Patients with and without mild to moderate alcohol use had comparable completion and SVR rates to antiviral treatment |
| Hauser et al[38] | 55 | Retrospective chart review | PEGIFN/RBV, IFN/RBV | People with MDD had completion and SVR rates similar to those without psychiatric illness. Patients with MDD can be safely and effectively treated with antiviral therapy provided that they are on antidepressant medications during antiviral therapy |
| Huckans et al[43] | 60 | Retrospective chart review | PEGINF/RBV, IFN/RBV | Patients with schizophrenia experience similar rates of psychiatric symptoms on and off antiviral therapy |
| Grebely et al[48] | 58 | Prospective longitudinal follow up | IFN-α-2b/RBV, PEGIFN-α-2a, PEGIFN-α-2b | Rate of reinfection following treatment for HCV infection among current and former IVDUers engaged in a multidisciplinary program is low |
Table 5 Antidepressant treatment of interferon-induced depression
| Ref. | n | Design | Antidepressant | Outcomes |
| Gleason et al[54] | 15 | Open-label clinical trial | Citalopram | IFN-induced MDD in patients with HCV may be effectively and safely treated with citalopram |
| Hauser et al[24] | 39 | Prospective cohort study | Citalopram and buproprion | 33% of patients receiving IFN therapy develop IFN-induced MDD. There were no differences in age, gender, past history of MDD, or substance use between those who became depressed and those who did not. Of those who developed IFN-induced depression most responded to antidepressant treatment allowing continuation of antiviral therapy. Also the group who developed IFN-induced depression had significantly higher baseline BDI scores than the group who did not develop IFN- induced depression |
| Loftis et al[27] | - | Various antidepressants | IFN-α, IFN-β, and IFN-γ | Depression induced by IFN therapy is common and can limit treatment utility and necessitate discontinuation of antiviral treatment. However, the use of psychopharmacologic agents allows treatment continuation |
| Angelino et al[36] | - | Various antidepressants | IFN-α | Treatment with IFN may provoke episodes of depression however, several standard treatments for depression can mediate these symptoms, suggesting that depression may not be a barrier to effective treatment |
| Gleason et al[55] | 18 | Open-label clinical trial | Escitalopram | IFN-induced MDD in patients with HCV may be effectively and safely treated with escitalopram |
Table 6 Antidepressant prophylaxis
| Ref. | n | Design | Antidepressant | Outcomes |
| Angelino et al[36] | - | Retrospective literature review | Citalopram; fluvoxamine | Prophylactic antidepressants might be well-considered for patients with a family history of - or previous episodes of - depression |
| Schaefer et al[57] | 33 | Prospective clinical trial | Citalopram | Pre-treatment of psychiatric patients with citalopram significantly reduced the incidence of IFN-induced MDD during the first 6 mo of antiviral treatment |
| Raison et al[59] | 61 | Double-blind, placebo-controlled clinical trial | Paroxetine | Data support the use of antidepressant pre-treatment in HCV patients with elevated depressive symptoms at baseline |
| Morasco et al[58] | 33 | Double-blind, placebo-controlled clinical trial | Paroxetine | A prophylactic approach to reduce IFN-α-induced depression may not be indicated in patients with HCV |
| Galvão-de Almeida et al[56] | - | Retrospective literature Review | Citalopram, paroxetine, escitalopram | Antidepressant prophylaxis may blunt the magnitude of depressive symptoms in HCV patients and raise the rates of treatment completion in those with psychiatric diagnosis |
| Morasco et al[60] | 39 | Double-blind, placebo-controlled clinical trial | Citalopram | Citalopram is not superior to placebo in preventing IFN-induced MDD |
Table 7 Telaprevir
| Ref. | n | Design | Treatment | Population | Outcome |
| Hézode et al[73] | 334 | Phase 2 randomized clinical trial | Telaprevir PEGIFN/RBV | HCV genotype 1 - treatment naïve | Telaprevir groups had significantly higher rates of SVR than PEGIFN/RBV alone. Depression occurred in 20%-23% of patients and was not significantly different across groups |
| McHutchison et al[68] | 115 | Randomized clinical trial | Telaprevir | HCV genotype 1 - previous non-responders to PEGINF/RBV | Re-treatment with telaprevir was more effective than PEGIFN-α/RBV alone. Depression occurred in 11%-17% of participants |
| Zeuzem et al[69] | 663 | Phase III randomized clinical trial | Telaprevir, PEGIFN- α-2a/ RBV | HCV genotype 1 - previous non responders, partial responders and relapsers | Telaprevir in combination with PEGIFN/RBV significantly improved rates of SVR and, as compared with PEGIFN/RBV alone showed no increase in neuropsychiatric side effects |
| Kumada et al[72] | 1126 | Multicenter randomized clinical trial | Telaprevir, PEGIFN-α-2b/RBV | HCV genotype 1 - treatment naive | Triple therapy with telaprevir-based regimen resulted in higher SVR with shorter duration. Depression was not listed as an adverse event |
| Sherman et al[74] | 540 | Randomized clinical trial | Telaprevir PEGIFN-α-2a/RBV | HCV genotype 1 - treatment naïve | Combination therapy with telaprevir for 24 wk was non inferior to standard therapy for 48 wk. Fifty-three percent of patients experienced psychiatric symptoms |
Table 8 Boceprevir
| Ref. | n | Design | Treatment | Population | Outcome |
| Kwo et al[77] | 520 | Two part randomized clinical trial | Boceprevir | chronic HCV genotype 1 - treatment naïve | Boceprevir has the potential to double the SVR rate compared with standard treatment alone. Insomnia was the only psychiatric illness documented |
| Bacon et al[75] | 403 | Placebo controlled, randomized clinical trial | PEGIFN-α-2b/RBV boceprevir, PEGIFN-α-2b/RBV | Retreatment of patients with chronic HCV genotype 1 infection | Boceprevir resulted in significantly higher rates of SVR. Significant onset of depression was not indicated |
| Poordad et al[76] | 1097 | Double blind, placebo controlled randomized clinical trial | Boceprevir PEGIFN-α-2b/RBV | Chronic HCV genotype 1 - treatment naïve | Boceprevir significantly increased the rates of SVR. Insomnia was the only psychiatric condition identified as an adverse event |
Table 9 Simeprevir
| Ref. | n | Design | Treatment | Population | Outcome |
| Fried et al[80] | 338 | Phase 2b double blind, placebo controlled randomized clinical trial | Simeprevir PEGIFN-α-2a/RBV | Treatment-naıve patients with HCV genotype 1 infection. | Simeprevir in combination with PEGIFN/RBV significantly improved SVR rates and shortened therapy duration. Depression occurred in 10.4% of patients on simeprevir and 18.2% on standard treatment |
| Zeuzem et al[79] | 396 | Placebo controlled, randomized clinical trial | Simeprevir, PEGIFN-α-2a/RBV | patients with HCV genotype-1 infection previously treated with PEGIFN/RBV | 12, 24, or 48 wk simeprevir with 48 wk PEGIFN/RBV significantly increased rates of SVR and was generally well tolerated. Depression occurred in 2/396 simeprevir patients |
| Jacobson et al[81] | 394 | Phase 3, randomized, double blind, placebo controlled multicenter clinical trial | Simeprevir, PEGIFN-α-2a/RBV | Treatment naïve patients with HCV genotype 1 | Simeprevir with PEGIFN-α-2a/RBV shortens therapy without worsening the adverse event profiles associated with PEGIFN |
| Manns et al[82] | 257 | Phase 3 multicenter randomized, placebo controlled clinical trial | Simeprevir PEGIFN-α-2a or 2b/RBV | Treatment-naive patients with HCV genotype 1 infection | Addition of simeprevir to PEGIFN-α-2a or PEGIFN-α-2b plus RBV improved SVR without worsening the known adverse events associated with peginterferon |
| Kumada et al[83] | 79 | Open label non comparative multicenter trial | Simeprevir PEGIFN-α-2b/RBV | HCV genotype 1 - treatment-naïve or had previously received IFN-based therapy | Simeprevir combined with PEGIFN-α-2b/RBV was effective across both groups. One patient in the control group receiving standard therapy alone discontinued due to grade 2 depression |
Table 10 Sofosbuvir
| Ref. | n | Design | Treatment | Population | Outcome |
| Kowdley et al[86] | 316 | Multicenter, open label, phase 2 clinical trial | Sofosbuvir-2a PEGIFN-α-2a/RBV | HCV genotype 1 - non-cirrhotic treatment-naive, patients | SVR occurred in 90% of patients treated with sofosbuvir and PEGIFN/RBV for 12 wk. Depression occurred in 8%-16% of patients across all groups but was not a primary reason for discontinuation |
| Lawitz et al[87] | 147 | Two-cohort, phase 2, placebo controlled, clinical trial | Sofosbuvir PEGIFN/RBV | Treatment-naive patients with genotype 1-3 HCV infection | SVR occurred in 90% of patients treated with sofosbuvir and PEGIFN/RBV and the side effects profile was similar to that of PEGIFN/RBV and did not include depression. Depression was not a significant adverse event in this study |
| Jacobson et al[85] | 240 | Phase 3 randomized placebo controlled clinical trials | Sofosbuvir RBV | Chronic HCV genotype 2 or 3 previously unable to be treated with IFN, or previously treated with IFN-based therapies | Sofosbuvir and RBV was effective at 12 wk for genotype 2 and 16 wk for genotype 3. Premature discontinuation of the study drug due to adverse events was uncommon in all groups. Depression was not a significant adverse event in this study |
| Gane et al[84] | 75 | Open label randomized clinical trial | Sofosbuvir, RBV | HCV genotype 2 or 3 infection. with no response to prior treatment or with no prior treatment | Sofosbuvir plus RBV for 12 wk was effective for patients with genotype 1, 2, or 3 infections. Insomnia occurred in 30%-67% of participants across groups and was the only significant psychiatric symptom to develop during treatment |
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 |
- Citation: Hauser P, Kern S. Psychiatric and substance use disorders co-morbidities and hepatitis C: Diagnostic and treatment implications. World J Hepatol 2015; 7(15): 1921-1935
- URL: https://www.wjgnet.com/1948-5182/full/v7/i15/1921.htm
- DOI: https://dx.doi.org/10.4254/wjh.v7.i15.1921