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DOI: 10.1055/s-2005-922235
© Georg Thieme Verlag Stuttgart · New York
Antidepressiva: Lebensgefährliche Plazebos? - Arznei-Telegramm: fahrlässiges Journal
Antidepressants: Life threatening Placebos?Publikationsverlauf
Publikationsdatum:
22. November 2005 (online)
![](https://www.thieme-connect.de/media/psychoneuro/200510/lookinside/thumbnails/10.1055-s-2005-922235-1.jpg)
Zusammenfassung
Das Arznei-Telegramm suggeriert, Antidepressiva seien nicht in klinisch relevantem Maße wirksam und wegen der Möglichkeit der Induktion suizidaler Phänomene lebensgefährlich. Beides ist falsch. Die in Meta-Analysen von Akutstudien scheinbar geringe Effektstärke ist als Hauptgrund auf den variablen Plazebo-Effekt zurückzuführen. Absetzstudien bilden am ehesten die „wahre” Effektstärke (23 %) ab. Selbst wenn die Effektstärke nur bei 10 % läge, wäre das aus systemischer Perspektive hoch relevant. Derzeit gibt es keine Evidenz, dass Antidepressiva das Suizidrisiko erhöhen. Nicht auszuschließen ist, dass Antidepressiva zu Therapiebeginn das Risiko von suizidalen Gedanken und Suizidversuchen erhöhen, möglicherweise eher SSRI als andere. Deshalb muß den Patienten zu Therapiebeginn besondere Aufmerksamkeit gewidmet werden. Das gilt insbesondere für Kinder und Jugendliche, für die bisher ein eindeutiger Wirksamkeitsnachweis nicht erbracht wurde, wahrscheinlich wegen des hier besonders hohen Plazebo-Effektes. Insbesondere weil es sich um seltene Ereignisse zu Therapiebeginn handelt, können doppelblinde Langzeitstudien nichts zur weiteren Klärung beitragen, zumal sie ethisch unvertretbar wären. Vielmehr muss der Pharmakovigilanz erhöhte Aufmerksamkeit gewidmet werden.
Summary
The periodical „Arznei-Telegramm” has published a suggestive paper entitled „Antidepressants: Life-threatening Placebos?”. This suggests that the efficacy of antidepressants is clinically irrelevant and - because of the possibility of the induction of suicidal phenomena life-threatening. Both is wrong. The apparent effect size demonstrated in meta-analyses of acute trials is flawed essentially by the variable placebo effect. Discontinuation trials probably yield the best estimate of the „true” effect size (23 %). Even if the effect size were only 10 % this would be highly relevant from the systemic perspective. Actually, there is no evidence for antidepressants increasing the risk of suicide. The possibility can, however, not be excluded that in the initial phase of treatment antidepressants increase the risk of suicidal ideation and suicide attempts, possibly more so SSRIs than other antidepressants. Therefore, patients must be subject to specific awareness in this inital phase. This applies especially for children and adolescents in view of the - due to the particularly high placebo effect - lacking definite proof of efficacy in this age group. Double-blind long-term trials cannot be expected to contribute to further clarification because the suicidal phenomena are rare events typically in the initial phase of treatment. Moreover, such trials would be ethically unacceptable. Instead, pharmacovigilance should focus on these phenomena.
Literatur:
- 1 Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: A meta-analysis of efficacy and tolerability. J Affective Disord. 2000; 58 19-36
- 2 Anderson IM, Haddad P. Clinical trials of antidepressant medications are producing meaningless results - Against. Br J Psychiatry. 2003; 183 102-104
- 3 Baldessarini RJ, Tondo L, Hennen J. Lithium treatment and suicide risk in major affective disorders: update and new findings. J Clin Psychiatry. 2003; 64 44-52
- 4 Brown WA. Are Antidepressants as Ineffective as They Look?. Prevention & Treatment, journals.apa.org/prevention/volume5/pre0050026c.html . 2002; Volume 5, Article 25
- 5 Cipriani A, Barbui C, Geddes JR. Suicide, depression, and antidepressants. BMJ. 2005; 330 373-374
- 6 Entsuah R, Huang H, Willard L. Venlafaxine and SSRIs: pooled remission analysis (Mega-analysis of 31 studies of > 7000 patients). Poster bei: World Congress of Psychiatry (WCP), Yokohama, Japan 2002
- 7 Fergusson D, Doucette S, Cranley K Glass, Shapiro S, Healy D, Hebert P, Hutton B. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ. 2005; 330 396-402
- 8 Fritze J. The Adrenergic-Cholinergic Imbalance Hypothesis of Depression: A Review and a Perspective. Rev Neurosci. 1993; 4 63-93
- 9 Fritze J, Lanczik M, Sofic E, Struck M, Riederer P. Cholinergic neurotransission seems not to be involved in the category depression but possibly in personality. J Psychiatry Neurosci. 1995; 20 39-48
- 10 Fritze J, Möller H-J. Design of clinical trials of antidepressants: should a placebo arm be included?. CNS Drugs. 2001; 15 755-764
- 11 Fritze J. Nicht-selektive Monoamin-Rückaufnahme-Inhibitoren: Neurochemie, Wirkmechanismus. In: Riederer P, Laux G, Pöldinger W (eds.). Neuro-Psychopharmaka, Vol 3: Antidepressiva, Phasenprophylaktika und Stimmungsstabilisierer. Heidelberg, Springer 2002: 120-138
- 12 Fritze J, Schneider B, Weber B. Venlafaxin ist kein SSRI, sondern ein SNRI, und das ist relevant. Psychoneuro. 2003; 29 240-244
- 13 Fritze J. Psychopharmaka-Verordnungen: Ergebnisse und Kommentare zum Arzneiverordnungsreport 2004. Psychoneuro. 2005; 31 46-52
- 14 Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, Goodwin GM. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. 2003; 361 653-661
- 15 Greenberg RP. Reflections On The Emperor's New Drugs. Prevention & Treatment, journals.apa.org/prevention/volume5/pre0050027c.html . 2002; Volume 5, Article 27
- 16 Gunnell D, Saperia J, Ashby D. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review. BMJ. 2005; 330 385-389
- 17 Guo B, Scott A, Bowker S. Suicide Prevention Strategies. Evidence from Systematic Reviews. Alberta Heritage Foundation for Medical Research, HTA 28: Health Technology Assessment 2003
- 18 Hansen L. A critical review of akathisia, and its possible association with suicidal behaviour. Hum Psychopharmacol. 2001; 16 495-505
- 19 Hintikka J, Pesonen T, Saarinen P, Tanskanen A, Lehtonen J, Viinamaki H. Suicidal ideation in the Finnish general population. A 12-month follow-up study. Soc Psychiatry Psychiatr Epidemiol. 2001; 36 590-594
- 20 Jureidini JN, Doecke C, Mansfield R, Haby M. et al. . Efficacy and safety of antidepressants for children and adolescents. BMJ. 2004; 328 879-883
- 21 Khan A, Leventhal RM, Khan SR, Brown WA. Severity of depression and response to antidepressants and placebo: An analysis of the Food and Drug Administration database. J C Psychopharmacology. 2002; 22 40-45
- 22 Kirsch I, Moore TJ, Scoboria A, Nicholls SS. The Emperor's New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration. Prevention & Treatment, journals.apa.org/prevention/volume5/pre0050023a.html . 2002; Volume 5, Article 23
- 23 Kirsch I, Sapirstein G. Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication. Prevention & Treatment, journals.apa.org/prevention/volume1/pre0010002a.html . 1998; Volume 1, Article 0002a
- 24 Klein DF. Listening to Meta-Analysis but Hearing Bias. Prevention & Treatment, journals.apa.org/prevention/volume1/pre0010006c.html . 1998; Volume 1, Article 0006c
- 25 Maier W, Möller H-J. Metaanalyses - highest level of empirical evidence?. Eur Arch Psychiatry Clin Neurosci (in press)
- 26 Martinez C, Rietbrock S, Wise L, Ashby D, Chick J, Moseley J, Evans S, Gunnell D. Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study. BMJ. 2005; 330 389-395
- 27 Möller HJ. Antidepressants - do they decrease or increase suicidality?. Pharmacopsychiatry. 1992; 25 249-253
- 28 Moncrieff J, Wessely S, Hardy R. Meta-analysis of trials comparing antidepressants with active placebos. Br J Psychiatry. 1998; 172 227-231
- 29 Moncrieff J, Wessely S, Hardy R. Active placebos versus antidepressants for depression. The Cochrane Database of Systematic Reviews 2004
- 30 Oeljeschläger B, Müller-Oerlinghausen B. Wege zur Optimierung der individuellen antidepressiven Therapie. Deutsches Ärzteblatt. 2004; 101 A1337-A1340
- 31 Quitkin FM, Rabkin JG, Gerald J, Davis JM, Klein DF. Validity of clinical trials of antidepressants. Am J Psychiatry. 2000; 157 327-337
- 32 Smith D, Dempster C, Glanville J, Freemantle N, Anderson I. Efficacy and tolerability of venlafaxine with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. British Journal of Psychiatry. 2002; 180 396-494
- 33 Storosum JG, Elferink AJA, van Zwieten BJ, van den Brink W, Gersons BPR, van Strik R, Broekmans AW. Short-term efficacy of tricyclic antidepressants revisited: a meta-analytic study. European Neuropsychopharmacology. 2001; 11 173-180
- 34 Thase M, Entsuah A, Rudolph R. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry. 2001; 178 234-241
- 35 Thase ME. Antidepressant Effects: The Suit May Be Small, but the Fabric is Real. Prevention & Treatment, journals.apa.org/prevention/volume5/pre0050023c.html . 2002; Volume 5, Article 32
- 36 Tondo L, Hennen J, Baldessarini RJ. Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand. 2001; 104 163-172
- 37 Vitiello B, Swedo S. Antidepressant medications in children. N Engl J Med. 2004; 350 1489-91
- 38 Walsh BT, Seidman SN, Sysko R, Gould M. Placebo response in studies of major depression: Variable, substantial, and growing. J Am Med Ass. 2002; 287 1840-1847
Korrespondenzadresse:
Prof. Dr. med. Jürgen Fritze
Gesundheitspolitischer Sprecher
Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde (DGPPN)
Asternweg 65
50259 Pulheim