Barbara J. van Zwieten

Short-term efficacy of tricyclic antidepressants revisited: A meta-analytic study

The original data from the placebo-arms and the tricyclic-arms of all parallel randomized controlled three-arm studies, which had been conducted in the period 1979-1991 for a drug under development in order to obtain marketing authorization for the indication major depression, were included in a meta-analysis. Thirty-two placebo-controlled studies including 4314 patients were analyzed. The intention to treat analysis resulted in 46% responders (at least 50% improvement on the Hamilton Depression Rating Scale) in the tricyclic antidepressant group and 31% in the placebo-group (CI(95%-difference) 11.5-17.1%). The number needed to treat for responders was 7 (CI(95%) 5-8). In 10 out of 32 studies, a statistically significant difference in favor of tricyclic antidepressant compared to placebo was found for responders. The responder rate in the placebo-group varied from 6 to 52%. We conclude that tricyclic antidepressants are efficacious in the short-term treatment of major depression. However, the magnitude of the effect is rather modest. Because 69% of the placebo-controlled studies with a tricyclic antidepressant did not show a statistically significant difference in favor of tricyclic antidepressant and the placebo rate varied considerably from study to study, equivalence studies with tricyclic antidepressant as comparator without a placebo-control are not sufficient for demonstrating efficacy. Therefore in major depression, placebo-controlled studies are still necessary to demonstrate efficacy.

Antidepressants use in children and adolescents and the risk of suicide

OBJECTIVE Antidepressants use in paediatric patients has been linked with risk of suicidal behaviours. The aim of this paper, therefore, is to examine whether all antidepressants are associated with such risk. METHOD All 22 paediatric short-term placebo-controlled trials of SSRIs and NSRIs that were submitted to European registration authorities by pharmaceutical companies were identified and examined for events related to suicidality, which were defined as suicide, suicide attempts or suicidal thoughts. Random effect meta-analysis was used to combine the information from all trials. RESULTS No completed suicides were reported. However, for each compound there was at least one study with an increased risk for events related to suicidality in the active compound group. The overall OR for these events in the depression studies was 1.67 (95% CI: 1.05-2.65) and for anxiety 1.33 (95% CI: 0.33-5.35). CONCLUSIONS Caution is called for in the use of all SSRIs and NSRIs in the paediatric population. Furthermore, in the absence of contradictory information, caution in the use of other antidepressants in this population should be exercised as well (e.g. tricyclic antidepressants).

Erratum to “Short-term efficacy of tricyclic antidepressants revisited: a meta-analytic study”

Kirsch, I., Sapirstein, G., 1998. Listening to prozac but hearing placebo: a clinically useful measures of the consequences of treatment. N. Engl. J. meta-analysis of antidepressant medication. Prev. Treat. (http. / / jourMed. 318, 1728–1733. nals.apa.org /prevention /volume1/pre001002a.html). Montgomery, S.A., 1995. Clinical relevance of response and improveKlein, D.F., Gittelman, R., Quitkin, F., Rifkin, A., 1980. In: 2nd Edition. ment in psychopharmacology. A statement from the European College Diagnosis and Drug Treatment of Psychiatric Disorders: Adults and of Neuropsychopharmacology, from an ECNP workshop, Jerusalem, Children. Williams and Wilkins, Baltimore. October 1995. Eur. Neuropsychopharmacol. 5, 511–533. Kuhn, R., 1958. The treatment of depressive states with G-22355 Rothman, K.J., Michels, K.B., 1994. The continuing unethical use of (imipramine hydrochloride). Am. J. Psychiatry 115, 459–464. placebo controls. N. Engl. J. Med. 331, 394–398. Laupacis, A., Sackett, D.L., Roberts, R.S., 1988. An assessment of