Trimbos instituut 2005 1

1
Psychiatric Co-Morbidity in Cancer Redefining
the Issues

• James C. Coyne, Ph.D.
• Abramson Cancer Center of the University of
  Pennsylvania
• jcoyne_at_mail.med.upenn.edu

2
Disclaimer

• While much of the background to my talk is
  derived from contract work with the National
  Cancer Institute or as a member of an Expert
  Consensus Panel convened by the Depression
  Bipolar Support Alliance, the opinions expressed
  are my own and do not necessarily reflect those
  of the NCI or DBSA.

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• Prevalence of Psychiatric Disorder Among Cancer
  Patients

4
Estimates of Psychiatric Morbidity Associated
With Cancer Have Been Overly Broad or Wildly
Inaccurate

• Massies 2004 review of papers published up to
  2002 cites a range of 0-38 for major depression
  and 0-58 for depression spectrum disorders.
• Half of all cancer patients have a psychiatric
  disorder, usually an adjustment disorder with
  depressed mood (Spiegel, 1996).

5
Psychiatric Morbidity Based on Research Interview

• Major Depressive Disorder 9 (5 - 16)
• Generalized Anxiety Disorder 6 (3 - 12)
• Post Traumatic Stress Disorder 4 (2 - 9)
• MDD, GAD, or PTSD 17 (11-25)

6
Best Estimates of Risk of Major Depression

• Rates of major depression and psychological
  distress among cancer patients is a common as or
  a little more common than what is found in a
  primary care waiting room population.
• Rates higher for pancreatic and head and neck
  cancer.
• Cancer is a risk factor, rather than a mandate,
  for depression (Raison and Miller, 2003).
• Much of the depression in cancer patients
  represents a recurrence in persons with past
  histories of of depression.

7
PTSD and Cancer as Trauma

• Of breast cancer patients who indicated their
  initial response to diagnosis involved intense
  fear, helplessness, or horror, only 11 developed
  PTSD.
• Rates of PTSD among breast cancer patients are
  similar to women from the general population.
• Most breast cancer patients with PTSD had prior
  trauma not related to breast cancer and a history
  of psychiatric disorder.

8

• Screening Cancer Patients for Distress and
  Depression Not a Panacea

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The next goal for psycho-oncology is to 'stamp
out distress. Jimmie Holland, 2001
10
Screening for Distress and Depression Among
Cancer Patients

• Widely recommended, but lack of evidence that
  results in improved clinical outcomes, some
  negative evidence (McLachlan et al, 2001).
• Resources screening consumes take away from what
  is available for already detected depression.
• Much distress is self-limiting and patients do
  not desire formal specialty mental health
  services.
• Inevitable high rates of false positives consumes
  resources and alienates staff.

11
Resistance to Intervention

• Only 40 of testicular cancer patients accepted
  psychological therapy. We make a plea for
  caution with regard to the blind faith that
  counseling will be gratefully received and will
  be effective despite a dearth of sound evidence
  (Moynihan et al., 1999).
• 53 of patients rejected a problem-solving
  intervention but 37 also rejected the control
  condition where there was simply monitoring of
  depression and usual care (Sharp et al. 2004).
• Only 42 of breast cancer patients who screened
  positive on a measure of distress were interested
  in counselling, a proportion no greater than for
  non-distressed breast cancer patients (Sollner et
  al, 2004).

12
The Futility of Aggressive Screening for Distress

• "Our results provide little support for the idea
  that...systematic screening of
• psychological distress during the first year
  after diagnosis, with extra psychosocial
• help offered only to high distress patients...
  results in better quality of life in the year
  after diagnosis among such patients.
• Maunsell, Brisson, Deschenes, Frasure-Smith,
  1996

13
Developing a Stratified Risk Profile

• Most cancer patients will not become clinically
  depressed.
• Those that do tend to have a history of
  depression.
• Cancer patients who become clinically depressed
  have a vulnerability and need for follow up that
  extends beyond the period of acute cancer care.
• Many patients who do not become depressed seek
  basic support and basic medical information,
  preferably from a cancer care, rather than a
  mental health specialist.

14

• Empirical Basis for Treatment of Depression Among
  Cancer Patients

15
Surprising Lack of Research Concerning Efficacy
of Antidepressants for Depressed Cancer Patients

• Available evidence strongly suggests that
  depression in the patient with cancer responds to
  TCAs, SSRIs, mirtazapine, and mianserin. (DBSA,
  2005).
• Yet, this assessment based on only 7 studies.
• Two were double blind, randomized placebo
  controlled trials supporting the efficacy of
  mianserin, a heterocyclic antidepressant that is
  not commonly prescribed.
• No other study was a double blind, randomized
  placebo controlled trial in which an
  antidepressant was shown to be superior to
  placebo.

16
Nezu, A., et al., Project Genesis Assessing the
efficacy of problem-solving therapy for
distressed adult cancer patients. J Consult Clin
Psych, 2003. 71 1036-1048.

• Patients were not selected on the basis of a
  diagnosis of major depression but had levels of
  depressive symptoms comparable to a depressed
  general medical population.
• Significant treatment x time interaction effect
  favoring problem solving therapy intervention
  over control condition.
• Involving a significant other in the problem
  solving therapy significantly increased its
  efficacy.

17
Making the Case for Treatment of Depression in
Cancer Patients

• Given paucity of evidence for efficacy of
  treatments of depression specifically with cancer
  patients, we are left depending on the broader
  literature concerning the efficacy of these
  treatments with other populations the treatments
  work in general medical populations and should
  work with cancer patients.
• Medical co-morbidity interferes with effective
  delivery of treatment.
• Challenge may lie not in the efficacy of
  treatment, but the effectiveness with which it is
  delivered to cancer patients.

18
Musselman DL, Lawson DH, Gumnick JF, et
al.(2001). Paroxetine for the prevention of
depression induced by high-dose interferon alfa 
NEJM 344 961-966

• Double-blind study of 40 patients with malignant
  melanoma who were eligible for high-dose
  interferon alfa therapy.
• During the first 12 weeks of interferon alfa
  therapy, symptoms consistent with a diagnosis of
  major depression developed in 2 of 18 patients in
  the paroxetine group and 9 of 20 patients in the
  placebo group
• Severe depression necessitated the
  discontinuation of interferon alfa before 12
  weeks in 1 of the 20 patients in the paroxetine
  group, as compared with 7 patients in the placebo
  group.

19

• The Problem of Overtreatment and Inappropriate
  Treatment with Antidepressants.

20
Rates of Antidepressant Prescription

• All breast cancer patients 33
• Major depression 75
• Past depression 53
• No current or past depression 29

21
Fisch MJ, Loehrer PJ, Kristeller J, et al
Fluoxetine versus placebo in advanced cancer
outpatients A double-blinded trial of the
Hoosier Oncology Group. J Clin Oncol
211937-1943, 2003.

• Effort made to recruit any cancer patient who had
  at least minimal depressive symptoms upon
  screening.
• Either placebo or SSRI mailed to patients, who
  were told to get follow up care from oncologists.
• Investigators claim an effect for SSRI, but
  limited to one follow up assessment at which 17
  patients assessed.

22

• Are Antidepressants Replacing Support and
  Compassion?

23

• Will Treating Depression Affect Progression and
  Extend Survival?

24
Can Psychotherapy Prolong the Lives of Cancer
Patients?

• Conclusion of Systematic Review No evidence of
  an effect.
• Original Spiegel study does not have an effect
  when one examines the proper measure of survival,
  median survival.
• Fawzy et al threw out data (not intent to treat),
  and even then effect lost if outcome of one
  patient changed.
• No randomized trial in which survival was an a
  priori primary outcome has yielded an effect.

25
Does Depression Affect Progression of Cancer?

• Mechanism by which depression might influence
  development of cancer is highly speculative and
  controversial.
• Limited range of cancers for which immune
  functioning is conceivably relevant research
  have consistently failed to find effects of
  psychosocial interventions on the immune
  functioning of cancer patients.
• Recent large scale observational studies failed
  to find that emotional well-being predicts
  survival in metastaticor early breast cancer
  patients or head and neck patients.
• skepticism whether causal role for depression can
  demonstrated when appropriate controls are
  introduced for known biological prognostic
  indicators, physical symptoms, and side effects
  of treatment.

26
Death is Not Everything (Lesperance
Frasure-Smith, 1999).

• Prevention of mortality has always been one of
  the most important factors in determining the
  allocation of funding for research and clinical
  activities.
• Although the prevention of death is a powerful
  tool to influence many of our medical
  colleaguesdeath is not everything.
• Staking the main claim for the importance of
  treatment of depression on survival distracts
  from more readily demonstrable effects on overall
  disease burden and quality of life.

27

• Depression Disease Management with Cancer Patients

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• we have learned that improving the care and
  outcomes of depressionrequires some or all of
  the following a systematic approach to the
  recognition and assessment of depression
  evidence-based decision support patient
  education and activation ongoing monitoring and
  feedback regarding patient adherence and
  outcomes integration of mental health
  specialists for patients who are not improving as
  expected and physician education (Brody, 2003).

29
Practical Barriers to Providing Quality Care for
Depression to Cancer Patients

• Competing Demands of Treating a Life-Threatening
  Condition.
• Lower Priority for Both Cancer Patients and
  Professionals.
• Lack of Training of Key Cancer Care
  Professionals.
• Much Cancer Care Occurs in Tertiary Care Settings
  to Which Patients Travel from a Distance.
• Fracturing of Care, Discontinuities Between
  Cancer Care and Primary Care.

30
Strong V, Sharpe M, Cull A, Maguire P, House A,
Ramirez A. Can oncology nurses treat depression?
A pilot project. J.Adv.Nurs. 200446542-8.

• Delivered a nurse-led intervention to cancer
  patients with a major depression, in which a
  cancer nurse was trained to deliver a
  problem-solving therapy and encourage the patient
  to consult with a primary care physician
  concerning antidepressants.
• Patients receiving the intervention showed
  significant reductions in depression compared to
  the control group.
• Noted a number of difficulties associated with
  patient rejection of participation in the program
  and primary care physicians rejecting the advice
  of the depression specialists

31
Dwight-Johnson M, Ell K, Lee PJ. Can
collaborative care address the needs of
low-income Latinas with comorbid depression and
cancer? Results from a randomized pilot study.
Psychosomatics 200546224-32

• 55 low-income Latina patients with breast or
  cervical cancer and comorbid depression were
  randomly assigned to receive collaborative care.
• Patients receiving collaborative care were more
  likely to show improvement in depressive
  symptoms.
• Despite health system, provider, and patient
  barriers to care, these initial results suggest
  that patients in public sector oncology clinics
  can benefit from onsite depression treatment.