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CHERYL TAYLOR, RPN
POSITIVE WELLNESS NORTH ISLAND SERVICES
New Treatment and Mental Health Issues
HCV and Mental Health Issues
A European Consensus Statement on HCV infection, antiviraltreatment 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 factorsfor 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 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 effectsAntipsychotic 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 FibrosisHx of psoriasis and Psoriatic ArthritisOn disability pension due to chronic painPartner heavy drinker, hx of violence in homeClient 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 disruptionHigh 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 groupStarted tx Nov 7/12Hg fell quickly, VERY fatigued, loss of appetiteIn 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 TrazadoneWeek 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
Schaefer M. et al. Hepatitis C. Antiviral Treatment and Mental Health: A European Expert Consensus Statement. Journal of Hepatology, 2012.
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.
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
Timing of Side Effects
WHY IS TIMING SO IMPORTANT?
1-4 wks 4-16 wks 16-48 weeks
Schaefer M. et al. Hepatitis C. Antiviral Treatment and Mental Health: A European Expert Consensus Statement. Journal of Hepatology, 2012.
Standard therapy:Peginterferon and Ribavirin
Add one of two protease inhibitors: Te l a p r e v i r
B o c e p r i v i r
Neuro-vegetative Sx start immediately
Mood/Cognitive Sx start Week 4, peak Week 8, con’t through Tx
N e u r o p s y c h i a t r i c s y m p t o m s
or
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•Insomnia, early-morning wakefulness, or excessive sleeping•Irritability, restlessness•Feelings of guilt, worthlessness, and/or helplessness•Feelings of hopelessness and/or pessimism•Loss of interest in activities or hobbies once pleasurable, including sex •Persistent sad, anxious, or "empty" feelings•Thoughts of suicide (up to 10% of patients)• Suicide attempts (case reports, anecdotal) NEURO-VEGETATIVE/ SOMATIC
SYMPTOMS•Fatigue•Decreased appetite•Pain•GI Issues
NEUROPSYCHIATRIC SYMPTOMS
HypomaniaMania Rare Adverse EventsPsychoses 3%
Not assessing for risk factors puts patients at RISK
Risk factors for depression on tx:Depression during previous IFN TxDepressive symptoms pre-TxSleep disturbances pre-TxEarly 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
IMPLICATIONS FOR PRACTICE
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 cessationEarly Tx of sleep disturbancesSchaefer 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 pre-treatment-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, RPNMental Health and Addictions Services941-C England AvenueCourtenay, BCEmail: cheryl.taylor@viha.ca 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
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