DAAs found highly tolerable (and effective) in people with mental health conditions

Researchers at the University of Maryland and the U.S. National Institutes of Health (NIH) have found a relatively high rate of mental health conditions among some people who sought treatment for chronic hepatitis C virus (HCV) infection. Drugs that have been historically used to treat HCV—interferon and ribavirin—can significantly affect mental health in some people. As more new potent anti-HCV drugs (called direct acting antivirals, or DAAs) become available in Canada and other high-income countries, it will be important to formally assess their impact on mental health. To sum up the present study’s findings, the DAAs assessed did not cause depression, anxiety or any other mental health issues, unlike the older HCV drug interferon. What’s more, rates of depression fell after participants were cured.

Study details

As part of a sub-study of three important clinical trials, researchers reviewed data from a small sub-group of 45 participants (who were part of a larger group of participants in the three clinical trials). Below are the numbers of participants who were in the mental health sub-study:

  • Spare – sofosbuvir + ribavirin; 23 participants
  • Synergy-A – sofosbuvir + ledipasvir; 7 participants
  • Eradicate – sofosbuvir + ledipasvir; 15 participants

On average, most participants were in their mid-50s; 60% were men and 40% were women.

Participants were screened for mental health issues before, during and after the study.

Below is the overall distribution of mental health conditions at the start of the study (prior to starting DAAs). The proportion of people with a particular diagnosis was different in each study, so what appears below is the range between all three studies:

  • depression – between 53% and 61% of participants
  • anxiety – between 7% and 43% of participants
  • bipolar disorder – between 17% and 43% of participants
  • post-traumatic stress disorder – between 7% and 20% of participants

One participant had schizophrenia.

Effectiveness of DAAs

According to the research team, in all three clinical trials rates of cure did not differ significantly between people who had mental health conditions and people who did not. In Synergy-A, which had only one DAA (sofosbuvir), cure rates were between 61% and 68%. However, in the other two trials, which had two DAAs (sofosbuvir + ledipasvir), cure rates were between 97% and 100%.

Assessment of depression

Researchers found that, on average, the intensity of depression decreased while participants were in the study and taking DAAs. Once DAA therapy was completed, participants were less depressed than before they started this therapy. This should not be interpreted as DAAs having an antidepressant-like effect. Rather, it is likely that participants experienced improved mental (and physical) health because they were being treated with potent anti-HCV drugs, and as a result, in the majority of cases, they became cured. Chronic HCV infection causes inflammation. In some cases, elevated levels of proteins associated with inflammation could, in theory, increase the risk of depression in some people with HCV who may be susceptible to depression and/or anxiety. Another study reported later in this issue of TreatmentUpdate found improvements in physical and mental health among people who were cured with DAAs.

For comparison, researchers also examined previously collected data from participants who were treated with interferon. They found that rates of depression were greater while participants took interferon and even when they ceased taking interferon compared to participants who used DAAs.

Other assessments

Researchers also checked other measures that might have been impacted by mental health, including the following:

  • the ability to visit the study clinic as required
  • the concentration of DAAs in participants’ blood samples

Researchers found that the mental health status of patients did not affect these issues.

Key point

Bear in mind that the researchers’ analysis was a sub-study of three larger studies. Furthermore, the main purpose of the three larger clinical trials was to investigate the ability of DAAs to cure people. These two limitations mean that the sub-study’s analysis about DAAs and depression are not definitive. However, the findings from the mental health sub-study are still important and suggest that DAAs do not cause depression and may even indirectly decrease feelings of depression because they cure HCV, a chronic viral infection.

—Sean R. Hosein


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  2. Curry MP, Moczynski NP, Liu L, et al. The effect of sustained virologic response on cerebral metabolism and neurocognition in patients with chronic genotype 1 HCV infection. The International Liver Congress, 13-17 April 2017, Barcelona, Spain. Abstract SAT-215.
  3. Golabi P, Elshekh E, Karrar A, et al. The levels of monoamine neurotransmitters in HCV patients treated with ledipasvir/sofosbuvir. The International Liver Congress, 13-17 April 2017, Barcelona, Spain. Abstract SAT-201.