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Active Placebos Versus Antidepressants For Depression.

J. Moncrieff, S. Wessely, R. Hardy
Published 2004 · Medicine

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BACKGROUND Although there is a consensus that antidepressants are effective in depression, placebo effects are also thought to be substantial. Side effects of antidepressants may reveal the identity of medication to participants or investigators and thus may bias the results of conventional trials using inert placebos. Using an 'active' placebo which mimics some of the side effects of antidepressants may help to counteract this potential bias. OBJECTIVES To investigate the efficacy of antidepressants when compared with 'active' placebos. SEARCH STRATEGY The Cochrane Collaboration Depression, Anxiety and Neurosis review groups's search strategy was used to search MEDLINE (1966-2000), PsychLIT (1980-2000) and EMBASE (1974-2000) and this was last done in July 2000. Reference lists from relevant articles and textbooks were searched and 12 specialist journals were handsearched up to 1996. SELECTION CRITERIA Randomised and quasi randomised controlled trials comparing antidepressants with active placebos in people with depression. DATA COLLECTION AND ANALYSIS Since many different outcome measures were used a standard measure of effect was calculated for each trial. A subgroup analysis of inpatient and outpatient trials was conducted. Two reviewers independently assessed whether each trial met inclusion criteria. MAIN RESULTS Nine studies involving 751 participants were included. Two of them produced effect sizes which showed a consistent and statistically significant difference in favour of the active drug. Combining all studies produced a pooled estimate of effect of 0.39 standard deviations (confidence interval, 0.24 to 0.54) in favour of the antidepressant measured by improvement in mood. There was high heterogeneity due to one strongly positive trial. Sensitivity analysis omitting this trial reduced the pooled effect to 0.17 (0.00 to 0.34). The pooled effect for inpatient and outpatient trials was highly sensitive to decisions about which combination of data was included but inpatient trials produced the lowest effects. REVIEWER'S CONCLUSIONS The more conservative estimates from the present analysis found that differences between antidepressants and active placebos were small. This suggests that unblinding effects may inflate the efficacy of antidepressants in trials using inert placebos. Further research into unblinding is warranted.
This paper references
10.1136/BMJ.1.1840.881
The Midwives' Registration Bill
L. Drage (1896)
10.1136/BMJ.1.2200.482
CASE OF DILATATION OF THE PYLORUS FOR SIMPLE STRICTURE
H. Symonds (1903)
10.1001/ARCHNEURPSYC.1957.02330330069013
Why patients leave psychotherapy.
J. Frank (1957)
Imipramine in office management of depressive reactions. (A double blind clinical study).
Daneman Ea (1961)
published data only) Friedman, 1966 ( published data only) Friedman, 1975 ( published data only) Hollister
Daneman (1961)
10.1176/AJP.119.6.573
The effect of MP-809 in depressive states: a multi-blind study.
H. Azima (1962)
10.1016/0022-3956(62)90013-4
Dimensions of manifest depression
J. Overall (1962)
10.1176/AJP.119.5.465
The effects of G-33040 in depressive states: a multi-blind study.
H. Azima (1962)
10.1002/J.1552-4604.1963.TB00073.X
EVALUATION OF DESIPRAMINE IN DEPRESSIVE STATES.
L. Hollister (1963)
women imipramine 150mg atropine 0.6mg Total Distress Score, Morale Loss Scale, doctors and patients
B Weintraub (1963)
published data only) Murphy, 1984 ( published data only) Uhlenhuth, 1963 ( published data only) Weintraub
Hussain (1963)
wome n i ipramine 150mg atropine 0.6mg Total Distress Score, Morale Loss Sc ale, doctors and patients
B Weintraub (1963)
10.1097/00005053-196410000-00009
CONTROLLED COMPARISON OF AMITRIPTYLINE, IMIPRAMINE AND PLACEBO IN HOSPITALIZED DEPRESSED PATIENTS
L. Hollister (1964)
10.1016/0022-3956(64)90006-8
THE INFLUENCE OF MEDICATION (IMIPRAMINE) AND DOCTOR IN RELIEVING DEPRESSED PSYCHONEUROTIC OUTPATIENTS.
E. Uhlenhuth (1964)
10.1001/JAMA.1964.03070180046007
THERAPEUTIC EFFICACY OF ANTIDEPRESSANT DRUGS. A REVIEW.
J. Cole (1964)
10.1097/00005053-196508000-00012
RESEARCH EVALUATING ANTIDEPRESSANT MEDICATIONS ON HOSPITALIZED MENTAL PATIENTS: A SURVEY OF PUBLISHED REPORTS DURING A FIVE‐YEAR PERIOD
H. Wechsler (1965)
CLINICAL PHARMACOLOGY OF IMIPRAMINE AND RELATED ANTIDEPRESSANT COMPOUNDS.
G. L. Klerman (1965)
10.1001/ARCHPSYC.1965.01730060070010
Efficacy of tranquilizing and antidepressant drugs.
J. Davis (1965)
10.1136/bmj.1.5439.881
Clinical Trial of the Treatment of Depressive Illness
M. Thiéry (1965)
10.1016/0022-3956(66)90012-4
Imipramine (Tofranil vs. placebo in hospitalized psychotic depressives. (a comparison of patients' self-ratings, psychiatrists' ratings and psychological test scores).
A. S. Friedman (1966)
10.1001/ARCHPSYC.1969.01740150059009
Physician bias and the double-blind.
D. Engelhardt (1969)
10.1136/bmj.2.5707.482-a
Drugs in Depressive Illness
Z. Hussain (1970)
10.1001/ARCHPSYC.1974.01760110083010
The efficacy of antidepressant drugs. A review of research (1958-1972).
J. Morris (1974)
10.1001/ARCHPSYC.1975.01760230085007
Interaction of drug therapy with marital therapy in depressive patients.
A. S. Friedman (1975)
10.1192/BJP.127.6.599
A statistical review of controlled trials of imipramine and placebo in the treatment of depressive illnesses.
S. Rogers (1975)
10.1055/S-2007-1019597
The anticholinergic biperiden in depressive disorders.
S. Kasper (1981)
10.1192/BJP.140.1.64
Side effects and placebo amplification.
R. Thomson (1982)
10.3109/00048678309159997
A Treatment Outline for Depressive Disorders
W. Hall (1983)
10.1001/ARCHPSYC.1983.01790080069009
Reliability of depression and associated clinical symptoms.
D. Cicchetti (1983)
10.1037/0022-006X.51.6.856
A meta-analysis of psychotherapy and drug therapy in the treatment of unipolar depression with adults.
S. M. Steinbrueck (1983)
10.1001/ARCHPSYC.1984.01790120037006
Cognitive therapy and pharmacotherapy. Singly and together in the treatment of depression.
G. Murphy (1984)
10.1097/00004714-198406000-00029
Cognitive therapy and pharmacotherapy
G. Murphy (1984)
10.1002/j.1552-4604.1986.tb02936.x
Treatment of Depression in Chronic Cocaine and Phencyclidine Abuse With Desipramine
A. Giannini (1986)
10.1212/WNL.37.4.589
Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood
M. Max (1987)
10.1016/0304-3959(91)90157-S
Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial
M. Max (1991)
10.1007/978-1-4612-2878-3_24
Perception of Whether Drug or Placebo Has Been Administered Is a Determinant of Drinking Reduction
T. Toneatto (1992)
10.1176/AJP.149.12.1730
Side effects and the "blindability" of clinical drug trials.
K. White (1992)
10.1176/JNP.4.3.331
Balancing risks and benefits: another approach to optimizing diagnostic tests.
D. Mossman (1992)
10.1037//0022-006X.60.5.664
A meta-analysis of antidepressant outcome under "blinder" conditions.
R. P. Greenberg (1992)
10.1007/978-1-4612-2878-3
Novel Pharmacological Interventions for Alcoholism
C. Naranjo (1992)
10.1192/S0007125000292350
Debits and credits in the management of depression.
J. Henry (1993)
10.1097/00005053-199410000-00003
A Meta‐Analysis of Fluoxetine Outcome in the Treatment of Depression
R. P. Greenberg (1994)
10.1016/0197-2456(94)90041-8
Suspended judgment. Seeing through the double-masked design: a commentary.
R. P. Greenberg (1994)
10.1016/0165-1781(95)02700-7
No antidepressant effect of biperiden compared with placebo in depression: A double-blind 6-week clinical trial
J.Christian Gillin (1995)
10.1001/JAMA.273.5.408
Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.
K. Schulz (1995)
10.1136/bmj.312.7033.742
Blinding and exclusions after allocation in randomised controlled trials: survey of published parallel group trials in obstetrics and gynaecology
K. Schulz (1996)
10.1136/bmj.313.7061.861
Cross sectional database analysis of antidepressant prescribing in general practice in the United Kingdom, 1993–5
J. Donoghue (1996)
10.1016/0197-2456(95)00134-4
Assessing the quality of reports of randomized clinical trials: is blinding necessary?
A. Jadad (1996)
10.1192/BJP.172.3.227
Meta-analysis of trials comparing antidepressants with active placebos.
J. Moncrieff (1998)
10.1002/MPR.108
Development of a quality assessment instrument for trials of treatments for depression and neurosis
J. Moncrieff (2001)
10.1159/000080392
Reasons for Quitting Serotonin Reuptake Inhibitor Therapy: Paradoxical Psychological Side Effects and Patient Satisfaction
Madelon Y. Bolling (2004)
10.1007/BF00428915
Self-evaluations of antidepressants
D. McNair (2004)
10.1007/BF01173502
Comparative efficacy of cognitive therapy and pharmacotherapy in the treatment of depressed outpatients
A. Rush (2005)
1963 ( published data only) * indicates the major publication for the study Cover sheet
Wilson



This paper is referenced by
10.1001/jamapsychiatry.2021.1419
Ten Practical Recommendations for Improving Blinding Integrity and Reporting in Psychotherapy Trials.
D. Mataix-Cols (2021)
10.1002/14651858.CD013495.pub2
Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults.
Ellen Van Leeuwen (2021)
10.1080/17512433.2021.1933434
Blinding and expectancy confounds in psychedelic randomized controlled trials
S. Muthukumaraswamy (2021)
10.1186/s13643-021-01789-0
Tricyclic antidepressants versus ‘active placebo’, placebo or no intervention for adults with major depressive disorder: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis
C. K. Jørgensen (2021)
10.1001/jamainternmed.2020.8670
Placebo-the Unknown Variable in a Controlled Trial.
M. Demasi (2021)
10.1016/j.neubiorev.2021.02.015
Neurofeedback training in major depressive disorder: A systematic review of clinical efficacy, study quality and reporting practices
L. Trambaiolli (2021)
10.1038/s41598-021-81446-7
Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing
L. Kaertner (2021)
10.1007/978-3-030-59181-6
Medically Unexplained Symptoms: A Brain-Centered Approach
R. Baloh (2021)
S003329171900285Xjra 2622..2633
S. Siafis (2020)
10.1016/j.evopsy.2020.07.003
L’évaluation et l’efficacité des psychothérapies psychanalytiques et de la psychanalyse
T. Rabeyron (2020)
10.1007/s00115-020-00940-x
Die Rolle von Placebo- und Nocebomechanismen bei depressiven Erkrankungen und ihrer Therapie
W. Rief (2020)
10.1136/bmjebm-2019-111328
Methylphenidate for ADHD rejected from the WHO Essential Medicines List due to uncertainties in benefit-harm profile
O. J. Storebø (2020)
10.1080/17461391.2020.1727021
Understanding placebo and nocebo effects in the context of sport: A psychological perspective
J. Raglin (2020)
10.1080/17522439.2020.1760338
“I remember…so, let’s not forget”: remembering our past lest we repeat it
James K. Mosher (2020)
10.1080/17512433.2020.1772054
Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments
Kyle T Greenway (2020)
10.3233/JRS-191023
Presentation of benefits and harms of antidepressants on websites: A cross-sectional study
M. Demasi (2020)
10.1002/14651858.CD006932.pub4
Pharmacological treatment of depression in people with a primary brain tumour.
Zachary C R Beevers (2020)
10.1371/journal.pmed.1003294
TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls
J. Howick (2020)
10.1186/s12888-020-02839-y
Comparative efficacy of placebos in short-term antidepressant trials for major depression: a secondary meta-analysis of placebo-controlled trials
L. Holper (2020)
Imaging serotonin and dopamine transporters in social anxiety disorder Characterization, treatment and expectancy effects
Olof Hjorth (2020)
Troubles dépressifs traités par thérapie cognitivo-comportementale effectuée par des infirmiers spécialisés en corrélation avec le retour au travail
Delphine Berger (2019)
10.1002/14651858.mr000055
Active placebo versus standard placebo control interventions in pharmacological randomised trials
D. L. T. Laursen (2019)
10.1136/bmjopen-2018-024886
Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis
K. Munkholm (2019)
10.1017/S003329171900285X
Antipsychotic drugs v. barbiturates or benzodiazepines used as active placebos for schizophrenia: a systematic review and meta-analysis
S. Siafis (2019)
On the Effects of Serotonin Reuptake Inhibitors in Major Depression
F. Hieronymus (2019)
10.1146/annurev-psych-010418-102907
Psychobiological Mechanisms of Placebo and Nocebo Effects: Pathways to Improve Treatments and Reduce Side Effects.
K. Petrie (2019)
10.1016/j.comppsych.2019.152124
Inpatient treatment decreases depression but antidepressants may not contribute. A prospective quasi-experimental study.
Reinhard Mass (2019)
10.3389/fpsyt.2019.00143
Re-evaluation of Significance and the Implications of Placebo Effect in Antidepressant Therapy
M. Ćurković (2019)
10.3233/JRS-195063
Benefits and harms of antipsychotic drugs in drug-naïve patients with psychosis: A systematic review
P. Danborg (2019)
10.1007/s40263-019-00654-y
Subjective Versus Objective Outcomes of Antipsychotics for the Treatment of Neuropsychiatric Symptoms Associated with Dementia
E. Vredeveld (2019)
10.1016/j.psyneuen.2018.08.008
The placebo and its effects: A psychoneuroendocrinological perspective
J. Gaab (2019)
Benefits and harms of antipsychotic drugs in drug-naı̈ve patients with psychosis: A systematic review
P. B. Danborga (2019)
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