Cheryl Taylor, RPN

1
New Treatment and Mental Health Issues

• Cheryl Taylor, RPN
• Positive Wellness North Island Services

2
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.

3
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.

4
HCV and Mental Health Issues

• Overall, depression during IFN-a treatment
  develops in 3070 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-a 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.

5
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.

6
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.

7
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.

8
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.

9
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
  its Management, Ntl. Centre of HIV Research,
  2006

10
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

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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

12
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

13
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.

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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.

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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.

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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

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WHY IS TIMING SO IMPORTANT?

• 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 dont 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)

• 1-4 wks 4-16 wks 16-48
  weeks

Standard therapy
Peginterferon and Ribavirin

Add one of two protease inhibitors
Te l a p r e v i r
or
B o c e p r i v i r
Neuro-vegetative Sx start immediately
NEUROPSYCHIATRIC SYMPTOMS Hypomania Mania Rare
Adverse Events Psychoses 3

• NEURO-VEGETATIVE/ SOMATIC SYMPTOMS
• Fatigue
• Decreased appetite
• Pain
• GI Issues

Mood/Cognitive Sx start Week 4, peak Week 8,
cont 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
Schaefer M. et al. Hepatitis C. Antiviral
Treatment and Mental Health A European Expert
Consensus Statement. Journal of Hepatology, 2012.
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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

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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 SSRIs
• 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.

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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.

22
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.

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Take Away

• 2/3 of your clients on tx may be experiencing
  undiagnosed depression implications for tx
  discontinuation and compliance.

24
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

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QUESTIONS?
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Contact

• Cheryl Taylor, RPN
• Mental Health and Addictions Services
• 941-C England Avenue
• Courtenay, BC
• Email cheryl.taylor_at_viha.ca
• Phone[phone]
• 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.p
  df
• 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