Antidepressiva: Lebensgefährliche Plazebos? - Arznei-Telegramm: fahrlässiges Journal

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.

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