New Treatment and Mental
Health Issues
CHERYL TAYLOR, RPN
POSITIVE WELLNESS
NORTH ISLAND
SERVICES
HCV and Mental Health Issues
 A European Consensus Statement on HCV infection, antiviral
treatment and Mental Health was published in The Journal of
Hepatology, Dec. 2012. (43 recommendations)
 The paper summarizes current knowledge
of HCV and the brain; prevalence, course,
and neurobiology of IFN associated
psychiatric side effects; possible risk factors
for INF associated depression and suicide
attempts, psychiatric management of HCV
patients before, during and AFTER antiviral treatment;
prevention of IFN associated side effects and psychiatric
aspects of new antivirals.
HCV and Mental Health Issues
 Psychiatric co-morbidity is significantly more
prevalent in patients with chronic HCV infection
than in the general population.
 Emerging evidence suggests that mental health
problems may be associated with the infection itself,
possibly mediated by an effect on the CNS
 Mental health problems during antiviral treatment
may reduce treatment compliance and are risk
factors for treatment failure.
Schaefer et Al, Hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012.
HCV and Mental Health Issues
 Overall, depression during IFN-α treatment develops
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in 30–70% of the treated patients.
Fatigue represents probably the most prominent
neuropsychiatric side effect as it develops in up to
80% of the patients.
Sleep alterations, irritability, anxiety, and cognitive
disturbances may occur in up to 50% of the patients.
Mania, and psychosis represent more rare adverse
events of IFN-α treatment- up to 3% of pts.
Suicidal ideation up to 10%-attempts or completion
reports remain anecdotal
Schaefer et Al, Hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012.
New Medications and Mental Health Issues
 Currently available data show that both new
antivirals do not have specific neuropsychiatric side
effects.
 Telaprevir- the most common “psychiatric” adverse
events are fatigue and insomnia, depression was only
evaluated in one trial with an incidence of 20-22% in
all groups.
 Boceprevir- no additional psychiatric side effects
 Antipsychotic treatment- olanzepine is
recommended based on the low rate of interactions.
Schaefer et Al, Hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012.
New Medications and Mental Health Issues
 The treatment of psychiatric side effects may be
complicated by possible drug-drug interactions.
 Benzodiazepines such as midazolam, alprazolam
(Xanax) and triazolam(Halcion) should NOT be
combined with the new antivirals due to increased
blood levels and sedative effects.
 Escitalopram (Cipralex) showed a lowered blood
concentration of around 35% with Telaprevir.
Schaefer et Al, Hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012.
New Medications and Mental Health Issues
 Antipsychotic treatment- olanzepine is
recommended based on the low rate of interactions.
 Up to date information about possible drug-drug
interactions should be considered for in the
management of tx induced psychiatric side effects.
 Many possible drug-drug interactions with
hypnotics, antidepressants, antipsychotic,
methadone, and antiepeleptics and more specific
data are required.
Schaefer et Al, hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012.
New Medications and Mental Health Issues
 Timing is important ! Multiple overlay of symptoms
early on in treatment make it more difficult to
identifying psychiatric symptoms.
 Consensus conference suggests that :
a) 10-14% of patients discontinue therapy due to a
psychiatric adverse event such as fatigue, depression,
irritability or insomnia.
b) Only approximately one third of pts. who develop
depression on tx are correctly diagnosed.
Schaefer et Al, hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012.
Case Study
 Kate – 54 yrs. Stage II Fibrosis
 Hx of psoriasis and Psoriatic Arthritis
 On disability pension due to chronic pain
 Partner heavy drinker, hx of violence in home
 Client very private.
 BDI score 8 indicating no current depressive
symptoms. Intermittent trouble with anxiety, taking
clonazepan 0.5mg prn. Psychiatric Hx as teenager.
 No sleep disruption
 High level of “unrealistic optimism” about tx. 1
Hopwood et al. “Experiences of HCV Treatment and it’s Management”, Ntl. Centre of HIV Research, 2006
Case Study
 Safety plan made with Kate should she need to leave





her home during tx
Started attending clinic Tx support group
Started tx Nov 7/12
Hg fell quickly, VERY fatigued, loss of appetite
In first few weeks flare of her arthirits. Concerns re:
med interactions, rheumatologist consult, no med
changes made.
Week 3 sleep disruption. Imovane initiated wk 4
Case Study
 Week 8, rash and flare up of psoriasis, query Incivik
rash
 Week 1o BDI score 13, indication of mild depressive
symptoms, client reports being teary, anxious, and
overwhelmed- sent to GP who was reluctant to start
Celexa, started on suboptimal dose 10 mg, good
effect in one week
(f/u letter sent to GP with tx guidelines)
 Week 12 Kate presents with another rash. She thinks
it started shortly after starting Celexa-on view clinic
RN queries Ribavirin rash
Case Study
 Clinic Gastroenterologist d/c Celexa and initiates
Trazadone with urgent referral to skin specialist.
 5 days on Trazadone, depressive symptoms increase,
client not coping well, feeling “drugged in am”,
having panic attacks, using clonazepam daily,
Requested she discuss Celexa with specialist at next
day appointment . (Remains DETERMINED!)
 At appointment, specialist decided to biopsy, client
so overwhelmed she forgets to ask about Celexa
Case Study
 Contacted specialist re: Celexa . GP calls client to re-
initiate Celexa, as specialist did NOT think it was a
Celexa rash- continue to query Ribavirin rash????
 Client reinitiated Celexa, stopped Trazadone
 Week 12 PCR- 
 Continue to monitor and client continues to attend
Tx support group.
Timing of Side Effects
 Differentiating physical side effects and psychiatric
issues challenging complex due to timing of
presentation.
 Differential Time difference for
neurovegetative/somatic symptoms vs.
mood/cognitive symptoms.
 Neurovegetative and somatic symptoms i.e. fatigue,
decreased appetite, pain, GI disorders, develop early,
usually in first weeks of tx
Timing of Side Effects
Mood and cognitive symptoms including depression,
anhedonia, memory disturbances, and
concentration usually develop after Week 4, with
the greater intensity of depressive symptoms
between Weeks 8 - 16
Schaefer M. et al. Hepatitis C. Antiviral Treatment and Mental Health: A European Expert Consensus Statement. Journal of
Hepatology, 2012.
Timing of Side Effects
 Most neuropsychiatric side effects (hypomania,
mania, psychoses) appear between weeks 10 and 24
and may persist until tx completion, then resolve with
treatment cessation
 Cases of persistent, recurring or new developing
symptoms have been described
Schaefer et Al, Hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012
MOOD AND COGNITIVE SYMPTOMS
•Difficulty concentrating, remembering details, and making decisions
•Fatigue and decreased energy
•Persistent aches or pains, headaches, cramps, or GI problems that don’t ease w. Tx
cessation
•Overeating
or appetite
loss
1-4
wks
4-16
wks
16-48 weeks
•Insomnia, early-morning wakefulness, or excessive sleeping
Standardrestlessness
therapy:
•Irritability,
•Feelings
of guilt,and
worthlessness,
Peginterferon
Ribavirin and/or helplessness
•Feelings of hopelessness and/or pessimism
Addofone
of two
protease
inhibitors:
•Loss
interest
in activities
or hobbies
once pleasurable, including sex
•Persistent
or "empty" feelings
Te l a p sad,
r e vanxious,
ir
•Thoughts of suicide (up to 10% of patients)
or attempts
• Suicide
B o(case
c e preports,
r i v i r anecdotal)
WHY IS TIMING SO IMPORTANT?
NEUROPSYCHIATRIC SYMPTOMS
Neuro-vegetative
Sx start
immediately
NEURO-VEGETATIVE/
SOMATIC
SYMPTOMS
•Fatigue
Hypomania
•Decreased appetite
Mood/Cognitive
startEvents
Week 4, peak Week 8, con’t through Tx
Mania
RareSx
Adverse
•Pain
Psychoses
3% •GI Issues
Neuropsychiat ric symptoms
Schaefer M. et al. Hepatitis C. Antiviral Treatment and Mental Health: A European Expert Consensus Statement. Journal of Hepatology, 2012.
IMPLICATIONS FOR PRACTICE
Not assessing for risk factors puts patients at
RISK
Risk factors for depression on tx:
 Depression during previous IFN Tx
 Depressive symptoms pre-Tx
 Sleep disturbances pre-Tx
 Early vegetative symptoms (sleep disruption, loss
of appetite)
 Baseline stress and lack of social support
Schaefer et Al, Hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012
MANAGEMENT OF ACUTE
DEPRESSION AND PREVENTION
 Symptoms are highly responsive to serotonergic
antidepressants
 Agent selection needs to consider drug-drug
interaction and underlying hepatic toxicity
 First line antidepressant is Celexa (not above 40
mg)
 Second line antidepressants include Cipralex,
Paxil, Zoloft and Remeron and other SSRI’s
 Continue for 12 weeks after Tx cessation
 Early Tx of sleep disturbances
Schaefer et Al, Hep. C infections and antiviral treatment and mental health. J. of Hepatology, Dec 2012.
MANAGEMENT OF ACUTE
DEPRESSION AND PREVENTION
 Prophylactic Tx with antidepressants in clients
with previous Hx of IFN-based depression
 HCV clients with symptoms of depression at
baseline should receive antidepressants pretreatment-proper assessment is critical.
 Antidepressant therapy is so far NOT generally
recommended for all HCV clients during antiviral
therapy and should be based on a case by case
decision.
Schaefer M. et al. Hepatitis C. Antiviral Treatment and Mental Health: A European Expert Consensus Statement. Journal of
Hepatology, 2012.
CONSENSUS
STATEMENT
 A concomitant and continuous psychotherapeutic support
program has recently been shown to be able to reduce
acute psychiatric complications and the need for
pharmacological interventions during antiviral therapy.1
 Strategies to improve psychological adjustment to chronic
medical illness increase social support, social
stigmatization, promote lifestyle changes (alcohol use,
nutrition, exercise, work) and give information about
possible side effects of antiviral therapy all significantly
improve treatment adherance.2
 Lends support for standardized psychiatric pre-tx
assessment and pre-tx planning .
1,2,Schaefer M. et al. Hepatitis C. antiviral treatment and mental Health : A European expert Consensus Statement. Journal
of Hepatology 2012.
Take Away
2/3 of your clients on tx may be experiencing
undiagnosed depression – implications for tx
discontinuation and compliance.
Take Away
Mood Assessment Tools are the “bloodwork” of
psychiatry. Pre/during and post tx mood assessment
at structured intervals using validated tools + sleep
assessment are now considered best practice
QUESTIONS?
Contact
Cheryl Taylor, RPN
Mental Health and Addictions Services
941-C England Avenue
Courtenay, BC
Email: [email protected]
Phone:250-331-8524
Resources:
Hepatitis C infection, antiviral treatment and Mental Health : A European Expert
Consensus Statement-Schaefer M. et al. Journal of Hepatology, 2012.
PHQ-9 - http://www.deanbrown.ca/forms/MHA/PHQ9.pdf
“Experiences of Hepatitis C Treatment and its Management: What some patients
and health professionals say.” Hopwood, et Al, National Centre in HIV Social
Research Faculty of Arts and Social Sciences, University of New South Wales