Recently licensed
direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV)
infection do not pose a significant risk of psychiatric side-effects but have several
important interactions with drugs used to treat mental health problems, an article
published in BMC Gastroenterology
shows.
A review of data
from clinical trials indicated that the anti-HCV protease inhibitors telaprevir
(Incivek or Incivo) and boceprevir (Victrelis) did not add to the psychiatric adverse-event profile of existing
HCV therapy. However, the investigators identified several significant interactions
between the protease inhibitors and a number of antidepressants,
benzodiazepines, anticonvulsants and antipsychotics.
“DAAs do not
appear to confer additional neuropsychiatric risks to patients undergoing HCV
triple therapy,” write the authors. “The potential for clinically significant
and complex interactions between DAAs and psychotropic drug classes is high.”
Telaprevir and
boceprevir were recently approved for the treatment of HCV infection in
combination with pegylated interferon and ribavirin after clinical trials
showed they increased the proportion of people achieving a sustained
virological response (SVR). However, pegylated interferon remains a mainstay of HCV
therapy and is associated with significant neuropsychiatric side-effects,
especially depression. This can lead to treatment discontinuation, poor
adherence and serious psychiatric outcomes.
A team of Canadian investigators
therefore wished to see if the new DAAs caused additional psychiatric
complications.
The investigators
also noted that both telaprevir and boceprevir are metabolised via the cytochrome
P450 enzyme, a pathway used by approximately 50 to 60% of prescription medications. They
therefore wished to identify possible interactions between the new DAAs and
commonly used psychotropic medications.
Data concerning
potential side-effects and interactions were obtained from published studies,
conference abstracts and the drugs’ manufacturers.
There were limited
data concerning the neuropsychiatric side-effects of DAAs. However, results
from the registration trials showed that there were no significant differences
in rates of neuropsychiatric adverse events between people treated with DAAs
plus standard therapy and people taking pegylated interferon/ribavirin
alone.
However, the
authors note “rates of neuropsychiatric sequalae from DAAs may be an
underestimated” due to the exclusion of people with significant psychiatric
illnesses from clinical trials.
Nevertheless, they
believe that preliminary data “suggests that DAAs confer a minimal risk of
additional neuropsychiatric side effects.”
Potential
interactions were identified with drugs in all the major classes of
psychotropic medications.