Institute for Response-Genetics (e.V.)Chairman: Prof. Dr. Hans H. StassenPsychiatric Hospital (KPPP), University of Zurich |
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Placebo-Drug DifferencesPlacebo-drug differences are generally modest for all classes of pychotropic drugs, although their onset of action is immediate [e.g., Angst and Stassen 2001; Agid et al 2003]. Differences between active compounds and placebo evolve from the very beginning of treatment, achieving over 65% of the maximal difference within the first two weeks, while differences among active compounds remain marginal throughout a typical drug trial of six weeks. There is no distinct increase in the number of patients benefitting from treatment after 3-4 weeks as postulated by the "delayed onset-of-action hypothesis". For the "average patient", response rates under active compounds are in the range of 55% while those under placebo lie around 30%. The "Average Patient"However, the "average patient" is rarely encountered in the treatment of psychiatric disorders and single case analyses reveal that there is a lot of between-patient variation. For example, the efficacy of antidepressants in the treatment of MDD depends essentially on the severity of depression at baseline, with drug-placebo differences hardly ever reaching significance in mild MDD cases. For this reason, clinical drug trials typically require a minimum baseline score of at least 15 points on the 17-item HAM-D scale at entry into study (after washout), whereas the Figure suggests a minimum baseline score >18 as inclusion criterion. ⇒ For mild depression the patients' benefits from antidepressant drug treatment are marginal and rarely outweigh the burden of the drugs' side effects. Alternative Treatments in Mild DepressionSeeing a doctor should always be the patient's first step in dealing with depression, but there are some ways patients can deal with depression on a daily basis. Though it may seem impossible, exercise is one of the best ways to deal with mild depression. In fact, several studies have reported more depressive symptoms in physically inactive individuals. Regular exercise has also been shown to protect against relapse to previous levels of depression and a 16-week exercise intervention found exercise to be as effective as antidepressants in treating older patients with depression. References
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Bhake R, Kluckner V, Stassen HH, Russell GM, Leendertz J, Stevens K, Linthorst ACE, Lightman S:
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[get the article]
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Greil W, Zhang X, Stassen HH, Grohmann R, Bridler R, Hasler G, Toto S, Bleich S, Kasper S:
Cutaneous adverse drug reactions to psychotropic drugs and their risk factors - a case-control study.
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[get the article]
Greil W, de Bardeci M, Seifert J, Bernegger X, Cattapan K, Stassen HH, Wagner AL, Sieberer M,
Grohmann R, Toto S: Treatment of depression: Are psychotropic drugs appropriately dosed in women
and in the elderly? Dosages of psychotropic drugs by sex and age in routine clinical practice.
Hum Psychopharmacol. 2022; 37(1): e2809
[get the article]
Greil W, de Bardeci M, Müller-Oerlinghausen B, Nievergelt N, Stassen HH, Hasler G, Erfurth A,
Cattapan K, Rüther E, Seifert J, Toto S, Bleich S, Schoretsanitis G. Controversies regarding
lithium-associated weight gain: case-control study of real-world drug safety data.
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[get the article]
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Kemp DE, Ganocy SJ, Brecher M, Carlson BX, Edwards S, Eudicone JM, Evoniuk G, Jansen W, Leon AC,
Minkwitz M, Pikalov A, Stassen HH, Szegedi A, Tohen M, Van Willigenburg AP, Calabrese JR:
Clinical value of early partial symptomatic improvement in the prediction of response and
remission during short-term treatment trials in 3369 subjects with bipolar I or II depression.
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the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to
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among patients with schizophrenia. J Clin Psychiatry. 2007; 68(3): 352-360
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underlying behavioral mechanisms. Neuropsychopharmacology. 2007; 32(2): 263-272
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practice versus empirical evidence. Eur Neuropsychopharmacol. 2010; 20 (Suppl. 3): 378-379
Mohr C, Braun S, Bridler R, Chmetz F, Delfino JP, Kluckner VJ, Lott P, Schrag Y, Seifritz E, Stassen HH:
Insufficient Coping Behavior under Chronic Stress and Vulnerability to Psychiatric Disorders.
Psychopathology 2014; 47: 235-243
Moragrega I, Bridler R, Mohr C, Possenti M, Rochat D, Sanchez Parramon J, Stassen HH:
Monitoring Mental Health and the Effects of Therapeutic Interventions through Self-Assessment
Voice Analyses. Res Psychother. 2021, 24(3): 250-262
[get the article]
Motivala SJ, Sarfatti A, Olmos L, Irwin MR. Inflammatory markers and sleep disturbance
in major depression. Psychosom Med. 2005; 67(2): 187-194
Papakostas GI, Perlis RH, Scalia MJ, Petersen TJ, Fava M. A meta-analysis of early
sustained response rates between antidepressants and placebo for the treatment of
major depressive disorder. J Clin Psychopharmacol 2006; 26(1): 56-60
Pollak TA, Lennox B, Müller S, Benros ME, Prüss H, Tebartz van Elst L, Klein H, Steiner J,
Frodl T, Bogerts B, Tian L, Groc L, Hasan A, Baune BT, Endres D, Haroon E, Yolken R,
Benedetti F, Halaris A, Meyer J, Stassen HH, Leboyer M, Fuchs D, Otto M, Brown DA, Vincent A,
Najjar S, Bechter K: An international consensus on an approach to the diagnosis and
management of psychosis of suspected autoimmune origin: the concept of autoimmune psychosis.
Lancet Psychiatry 2020; 7(1): 93-108
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and the metabolic syndrome. Biol Psychiatry. 2007; 62(11): 1251-1257
Stassen HH, Angst J, Hell D, Scharfetter C, Szegedi A. Is there a common resilience
mechanism underlying antidepressant drug response? Evidence from 2848 patients. J
Clin Psychiatry. 2007; 68(8): 1195-1205
Stassen HH, Anghelescu IG, Braun S, Hoffmann K, Rujescu D, Scharfetter C, Szegedi A, Tadic A:
Vulnerability to major psychiatric disorders, response to treatment and medical comorbidity —
shared genetic factors? Eur Neuropsychopharmacol. 2009; 19 (Suppl. 3): 262
Stassen HH, Anghelescu IG, Angst J, Böker H, Lötscher K, Rujescu D, Szegedi A, Scharfetter C:
Predicting Response to Psychopharmacological Treatment. Survey of Recent Results.
Pharmacopsychiatry 2011; 44: 263-272
Stassen HH, Delfino JP, Kluckner VJ, Lott P, Mohr C: Vulnerabilität und psychische Erkrankung.
Swiss Archives of Neurology and Psychiatry 2014; 165(5): 152-157
Stassen HH: Heterogeneity of schizophrenic disorders and link to chronically elevated IgM values.
Neurology, psychiatry and brain research 2018; 29: 23-24
Stassen HH, Bachmann S, Bridler R, Cattapan K, Herzig D, Schneeberger A, Seifritz E. Inflammatory
Processes linked to Major Depression and Schizophrenic Disorders and the Effects of Polypharmacy
in Psychiatry: Evidence from a longitudinal Study of 279 Patients under Therapy. Eur Arch
Psychiatry Clin Neurosci. 2021; 271(3): 507-520
[get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Herzig D, Schneeberger A, Seifritz E:
Detailing the Effects of Polypharmacy in Psychiatry: Longitudinal Study of 320 Patients
Hospitalized for Depression or Schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2022;
272(4): 603-619
[get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Seifritz E. Polypharmacy in Psychiatry and
Weight Gain: Longitudinal Study of 832 Patients Hospitalized for Depression or Schizophrenia,
along with Data of 3,180 Students from Europe, the U.S., South America, and China.
Eur Arch Psychiatry Clin Neurosci. 2024; https://doi.org/10.1007/s00406-024-01767-2
(Epub ahead of print)
[get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Hartmann AM, Rujescu D, Seifritz E, Weisbrod M,
Scharfetter C: Genetic Determinants of Antidepressant and Antipsychotic Drug Response:
A molecular-genetic study of 902 patients over 6 weeks. Psychiatry Res. 2024 [submitted for publication]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Hartmann AM, Rujescu D, Seifritz E, Weisbrod M,
Scharfetter C. Analysis of genetic diversity in patients with major psychiatric disorders
versus healthy controls: A molecular-genetic study of 1698 subjects genotyped for 100 candidate
genes (549 SNPs). Psychiatry Res. 2024; 333: 115720. doi: 10.1016/j.psychres.2024.115720
[get the article]
Szegedi A, Jansen WT, Van Willigenburg AP, Van der Meulen E, Stassen HH, Thase ME: Early
improvement as a predictor of treatment outcome in patients with major depressive disorder:
Why the first 2 weeks really matter —evidence from 6562 patients. J Clin Psychiatry 2009;
70(3): 344-353
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trials using the cure model and the Cramer-von Mises test. Stat Med 2000; 19(16): 2169-2184
Thase ME. Comparing the methods used to compare antidepressants. Psychopharmacol Bull 2002; 36
Suppl 1: 1-17
Zhang M, Bridler R, Mohr C, Moragrega I, Sun N, Xu Z, Yang Z, Possenti M, Stassen HH:
Early Detection of the Risk of Developing Psychiatric Disorders: A Study of 461 Chinese University
Students under Chronic Stress. Psychopathology 2019; 52(6): 367-377
[get the article]
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Response to treatment under imipramine (circles, n=506), moclobemide (triangles, n=580) and placebo (squares, n=191) as a function of HAM-D17 baseline score after placebo washout. The 4-week response rates are plotted along the y-axis for baseline scores of HAM-D17 ≤ 15; 15 < HAM-D17 ≤ 18; and 18 < HAM-D17 ≤ 21. The data suggest that placebo-drug differences reach 30% for HAM-D17 baseline scores >27.
Please note: placebo-drug differences rarely ever reach statistical statistical significance
in mild cases (HAM-D17 ≤ 20).
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