By Liz Highleyman

Pre-existing psychiatric conditions have traditionally been considered a contraindication to interferon-based therapy for chronic hepatitis C, since the neuropsychiatric side effects of interferon - in particular depression - appear to be more common and more severe in this population.

Three studies presented at the recent Digestive Disease Week 2006 conference in Los Angeles, however, showed that with appropriate monitoring and management, such individuals can be successfully treated for hepatitis C.

Psychiatric and Substance Use History

In the first study, J. Nelligan and colleagues reviewed the medical records of 82 U.S. veterans (96% men; mean age 51 years) who received treatment with interferon-based regimens (conventional or pegylated) at the Portland Veterans Administration (VA) Medical Center between 2002 and 2005.
The researchers noted that not only are veterans about three times more likely than the general population to have chronic hepatitis C (5.4% vs 1.8% in one analysis), they also commonly have comorbid psychiatric diagnoses. In this study, 54 patients (66%) had been diagnosed with a psychiatric or substance use disorder more than one year prior to starting interferon, eight (10%) were diagnosed in the year before starting interferon, and the remaining 20 subjects (24%) had no reported psychiatric or substance use diagnoses.

The most common psychiatric and substance use conditions were:

	major depression in 35 patients (56%)
	post-traumatic stress disorder in 25 patients (40%)
	anxiety disorders in eight patients (13%)
	"alcohol abuse" in 24 patients (39%)
	"dependence on alcohol" in 23 patients (37%)
	cocaine use in six patients (10%)
	opiate use in four patients (6%)
	use of other illicit drugs in 12 patients (19%)

Of the 20 patients with no reported history of psychiatric conditions, six started psychotropic medications during interferon therapy, as did six out of 22 patients who had a psychiatric history but had not used such medications before starting interferon.

Results

Half or more patients completed therapy, ranging from 50% among those with a psychiatric diagnosis within the past year to 62% among those with an earlier diagnosis.

Among patients who completed interferon therapy, sustained virological response (SVR) rates were similar regardless of prior or current psychiatric history (38%-45%).

Although 39% of patients overall discontinued treatment early, only one stopped due to psychiatric reasons.

Conclusion

The researchers concluded that "these findings suggest that with routine mental health screening and coordinated care involving mental health, chemical dependency, and medical professionals, patients with comorbid psychiatric diagnoses can successfully complete interferon therapy and achieve response rates comparable to those [of] patients without psychiatric disorders."

Depression During Hepatitis C Treatment

The second study, by A. Knott and colleagues, looked at the safety and efficacy of pegylated interferon-based therapy in chronic hepatitis C patients with active depressive illness.

The researchers conducted a review of the medical records of 91 hepatitis C patients at four urban VA Medical Centers who had positive screenings for depressive symptoms. Most were men (96%), Caucasians (87%), and had genotype 1 HCV (64%); about half had advanced fibrosis or cirrhosis (stage F3-F4). Patients were treated with pegylated interferon plus weight-based ribavirin.

Beck Depression Inventory Scoring 0-13: absent or minimal depression 14-19: mild depression 20-28: moderate depression 29-63: severe depression

The average Beck Depression Inventory (BDI) score was 18, and 33% of patients had scores of 20 or greater. Overall, the most frequent psychiatric and related diagnoses were:

current diagnosis of depression in 68 patients (75%)

anxiety disorders in 43 patients (47%)

other psychiatric diagnoses in 15 patients (16%)

"alcohol use disorder" in 20 patients (22%)

other substance use disorders (marijuana, cocaine, methamphetamine) in 15 patients (16%)

use of recreational drugs in the past year by 24 patients (26%)

Most patients (71%) were on antidepressants prior to starting therapy for hepatitis C, and 10% started antidepressants during treatment.

Results

Overall, 24 patients (26%) stopped interferon-based treatment early.

Only 1 patient (1%) discontinued due to psychiatric and 3 patients (3%) due to substance use-related non-compliance with therapy.

11 patients (12%) were unable to tolerate side effects, 2 (2%) experienced adverse events, 1 (1%) stopped for medical reasons, and 4 (4%) discontinued due to multiple reasons.

Having a baseline BDI >= 20 (odds ratio = 4.09, 95% CI 1.34-12.49) and using drugs during the prior 12 months (OR = 3.99, 95% CI 1.14-13.99) were associated with early discontinuation of hepatitis C treatment.

Patients with more advanced liver disease (biopsy stage >= 2) were less likely to stop treatment (OR = .25, 95% CI .07-.88).

Of 72 evaluable patients, 27 (37%) achieved SVR and 17 (25%) were non-responders after 24 weeks.

Conclusion

The authors concluded that hepatitis C patients with depressive symptoms who start antiviral treatment with BDI scores >= 20 and/or recent history of recreational drug use are at higher risk for early termination of hepatitis C therapy, and that "these patients warrant closer medical and psychiatric follow up prior to and during antiviral treatment."

However, patients with stable depressive disorders and baseline BDI score below 20 may be effectively treated with interferon-based therapy. The authors also noted that few patients stopped treatment due to psychiatric or substance-use related non-compliance, indicating that this concern is not a valid reason for automatically withholding therapy from this population.

Post-Traumatic Stress Disorder

An estimated one-third of veterans with chronic hepatitis C have a diagnosis of post-traumatic stress disorder (PTSD), and these patients are sometimes excluded from anti-HCV treatment, despite lack of evidence concerning the effects of interferon on PTSD.

In the third study, E. Dieperink and colleagues aimed to characterize PTSD symptoms among patients being treated for hepatitis C. This prospective study included five hepatitis C patients with PTSD who were treated with pegylated interferon plus ribavirin (all but one with genotype 1 HCV, four with stage F3 fibrosis), and a control group of 11 patients with HCV and PTSD who did not receive treatment (most did not have advanced fibrosis).

At baseline and at weeks 4, 8, 12, and 24, participants were screened using two measures of PTSD (the Mississippi Scale for Combat-Related PTSD and the PTSD Checklist-Military Version), a measure of hostility/irritability (the Buss-Durkee questionnaire), and the BDI. At baseline, the mean PTSD scores were 113.8 and 59.4, respectively, and the mean BDI score was 21.5.

Results

Total PTSD scores using both measures increased over time, but there was no significant difference between the increases in the pegylated interferon arm and the untreated group.

Subjects who received pegylated interferon showed a significant increase in irritability score compared with untreated subjects (P = 0.0009).

No significant differences were observed in other factors measured by the Buss-Durkee scale, including suspicion, assault, indirect hostility, irritability, or verbal hostility.

Depression scores increased significantly over time in subjects treated with pegylated interferon, and were significantly higher than those observed in the untreated arm (P = 0.0002).

All patients completed a full course of pegylated interferon plus ribavirin.

2 out of 5 patients (40%) achieved SVR, while 3 were non-responders.

Conclusion

The authors concluded that, "Depressive symptoms, but not PTSD or hostility, worsen during antiviral therapy in patients with PTSD." They added that "PTSD by itself does not appear to be a contraindication to HCV antiviral treatment when administered with psychiatric collaboration."

Taken together, these three studies add to the evidence that patients with various types of psychiatric and substance use conditions can adhere to therapy for hepatitis C, and a considerable proportion can achieve lasting virological response, especially if they receive careful monitoring and adjunct therapy with antidepressants or other appropriate psychiatric medications.

6/16/06

References

J Nelligan, JM Loftis, M Fireman, and others. Interferon-? therapy for patients with comorbid hepatitis C and psychiatric diagnoses. Abstract T1830. Digestive Disease Week 2006 (DDW 2006). May 20-25, 2006. Los Angeles, CA.

A Knott, E Dieperink, M Wingert, and others. Antiviral outcomes of patients with chronic hepatitis C and depression treated with pegylated interferon alfa-based therapy: a multicenter experience. Abstract T1812. DDW 2006. May 20-25, 2006. Los Angeles, CA.

E Dieperink, J Leskela, M Dieperink, and others. The effect of pegylated interferon and ribavirin on posttraumatic stress disorder symptoms in veterans. Abstract T1832. DDW 2006. May 20-25, 2006. Los Angeles, CA.