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

j.read@auckland.ac.nz

PLACEBO EFFECTS

Placebo = Latin for ‘I please’

• Instillation of hope

• Expectancy of recovery

Operate on clients AND clinicians

Much Touted “Depression Risk Gene” May Not Add to Risk After

All.New Look at Data Confirms Strong Association between Depression

and Stressful Life Eventshttp://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.

‘Initial Severity and AntidepressantBenefits’

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.

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%

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’

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.”

Antipsychotic Drugs• Adverse Effects

Traditional antipsychiotics:Tardive Dyskinesia (20-50%)

irreversible in two-thirdsNeuroleptic Malignant Syndrome (often fatal) (1-2%)

New ‘atypical’ antipsychotics:F.D.A. ‘no safer or more effective’

AgranulocytosisWeight gainDiabetesSexual dysfunctionNeurodegeneration

Mortality ?

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.

Long-term Antipsychotic Treatmentand 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.

The public prefer psychotherapy to anti-psychotic drugs in:

Australia Austria CanadaChina

England Germany

Hong KongIndiaItaly

JapanRussia

South Africa Slovakia

SwitzerlandTurkey

Read J (2007) Australian Psychologist

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)’

The effectiveness of electroconvulsive therapy:

A literature reviewJOHN 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 andanterograde 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.

• The role of psychologists?

• Ethical principle of INFORMED CONSENT