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John Read, Placebo

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  • 1. NZPsS Conference 2011
    • DOES IT MATTER IF ITS
    • MOSTLY A PLACEBO
    • EFFECT?
    • THE EFFICACY OF
    • ANTI-DEPRESSANTS
    • ANTI-PSYCHOTICS
    • AND ELECTROSHOCK THERAPY
    • Professor John Read
    • University of Auckland
    • [email_address]
  • 2. PLACEBO EFFECTS
    • Placebo = Latin for ‘I please’
    • Instillation of hope
    • Expectancy of recovery
    • Operate on clients AND clinicians
  • 3. Much Touted “Depression Risk Gene” May Not Add to Risk After All. New Look at Data Confirms Strong Association between Depression and Stressful Life Events http://www.nimh.nih.gov/science-news/2009
    • Merikangas, K. Journal of the American Medical Association June 17, 2009,
    • Re-analyzing data on 14,250 participants in 14 studies . ..
    • … . found a strong association between the number of stressful life events and risk of depression across the studies.
    • However, the presumed high-risk version of the serotonin transporter gene did not show a relationship to increased risk for major depression, alone or in interaction with stressful life events.
  • 4.  
  • 5. ‘ Initial Severity and Antidepressant Benefits’ Kirsch et al. (2008)
    • Meta-analysis of all available studies, including those previously kept secret by the drug companies:
    • Drug–placebo differences:
    • Virtually no difference at moderate levels of initial depression
    • Small difference for patients with very severe initial depression . . .
    • . . . reaching ‘clinical significance’ only for patients at the upper end of the very severely depressed category.
  • 6. Most Common Adverse effects of anti-depressants
    • Nausea 22%
    • Headache 21%  
    • Insomnia 19%
    • Nervousness 13%
    • Anxiety 12%  
    • Somnolence 12%  
    • Asthenia 11% 
    • Diarrhea 11%  
    • Anorexia 10%
  • 7. No evidence of genetic predisposition to schizophrenia (Hamilton, 2008, American Journal of Psychiatry)
    • ‘ The most comprehensive genetic association study of genes previously reported to contribute to the susceptibility to schizophrenia’ found that ‘none of the polymorphisms were associated with the schizophrenia phenotype at a reasonable threshold for statistical significance’
    • ‘ The distribution of test statistics suggests nothing outside of what would be expected by chance’
  • 8. Cochrane review of Risperidone (Rattehalli, Jayaram, & Smith, 2010).
    • “ Risperidone appears to have a marginal benefit in terms of clinical improvement compared with placebo in the first few weeks of treatment but the margin of improvement may not be clinically meaningful.
    • Global effects suggests that there is no clear difference between risperidone and placebo
    • Risperidone causes many adverse effects and, these effects are important and common.
    • People with schizophrenia or their advocates may want to lobby regulatory authorities to insist on better studies being available before wide release of a compound with the subsequent beguiling advertising.”
  • 9.  
  • 10. Antipsychotic Drugs
    • Adverse Effects
    • Traditional antipsychiotics:
    • Tardive Dyskinesia (20-50%)
    • irreversible in two-thirds
    • Neuroleptic Malignant Syndrome (often fatal) (1-2%)
    • New ‘atypical’ antipsychotics:
    • F.D.A. ‘no safer or more effective’
    • Agranulocytosis
    • Weight gain
    • Diabetes
    • Sexual dysfunction
    • Neurodegeneration
    • Mortality ?
  • 11. Influence of antipsychotics on mortality in schizophrenia: Systematic review Weinmann, S., Aderhold, V., Read, J. Schizophrenia Research (2009)
    • Only 12 studies met the inclusion criteria.
    • Three out of five studies examining antipsychotic dosage and higher mortality showed a significant association for one or more antipsychotics.
    • Two out of four found negative effects of antipsychotic polypharmacy on life-expectancy
    • A major confounding factor may be a higher risk factor load for somatic disorders in the most severely mentally ill.
    • Conclusion: There is some evidence that long-term exposure to antipsychotics increases mortality in schizophrenia.
    • More rigorously designed, prospective studies are urgently needed.
  • 12. Long-term Antipsychotic Treatment and Brain Volumes A Longitudinal Study of First-Episode Schizophrenia Ho,B et al. ARCH GEN PSYCHIATRY/VOL 68 (NO. 2), FEB 2011
    • Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of 3 predictors.
    • More antipsychotic treatment was associated with smaller gray matter volumes.
    • Progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment.
  • 13. The public prefer psychotherapy to anti-psychotic drugs in:
    • Australia
    • Austria
    • Canada
    • China
    • England
    • Germany
    • Hong Kong
    • India
    • Italy
    • Japan
    • Russia
    • South Africa
    • Slovakia
    • Switzerland
    • Turkey
    • Read J (2007) Australian Psychologist
  • 14. Why the public rejects anti-psychotic medication
    • Australia (Jorm et al., 2000)
    • ‘ have more risks than benefits’
    • ‘ lack efficacy because they do not deal with the roots of the problem’
    • ‘ are prescribed for the wrong reasons (e.g., to avoid talking about problems, as a straight jacket)’
  • 15.  
  • 16. The effectiveness of electroconvulsive therapy: A literature review JOHN READ and RICHARD BENTALL Epidemiologia e Psichiatria Sociale, 19, 4, 2010
    • Placebo controlled studies show minimal support for
    • effectiveness with either depression or
    • schizophrenia’ during the course of treatment (i.e.
    • only for some patients, on some measures,
    • sometimes perceived only by psychiatrists but not by
    • other raters), and no evidence , for either diagnostic
    • group, of any benefits beyond the treatment
    • period .
    • There are no placebo-controlled studies evaluating
    • the hypothesis that ECT prevents suicide , and no
    • robust evidence from other kinds of studies to
    • support the hypothesis.
    • Given the strong evidence of persistent and, for
    • some, permanent brain dysfunction , primarily
    • evidenced in the form of retrograde and
    • anterograde amnesia, and the evidence of a slight
    • but significant increased risk of death , the cost-
    • benefit analysis for ECT is so poor that its use
    • cannot be scientifically justified.
  • 17.
    • The role of psychologists?
    • Ethical principle of INFORMED CONSENT