Psychological Medicine

Original Articles

The generalizability of antidepressant efficacy trials to routine psychiatric out-patient practice

R. van der Lema1 c1, N. J. A. van der Weea1a2, T. van Veena1 and F. G. Zitmana1

a1 Leiden University Medical Center/Rivierduinen, Department of Psychiatry, Leiden, The Netherlands

a2 Leiden Institute for Brain and Cognition, Leiden, The Netherlands


Background Generalizability of antidepressant efficacy trials (AETs) to daily practice is questioned because of their very stringent patient selection. This study aims to determine eligibility for AETs of out-patients suffering from major depression in a routine out-patient setting and investigates influence of eligibility on treatment outcome.

Method Data collection (n=1653) was performed through routine outcome monitoring by independent trained research nurses. The Mini-International Neuropsychiatric Interview Plus and the Dimensional Assessment of Personality Pathology, short Dutch version were used for diagnostic assessment and personality pathology screening. The Montgomery–Asberg Depression Rating Scale (MADRS) was used for assessment of baseline severity and treatment outcome. Eligibility was assessed by stepwise application of commonly used exclusion criteria. Influence of eligibility on treatment outcome was investigated in a subsample of the 1653 patients who had at least one follow-up assessment (n=626). Eligible and non-eligible patients were compared on proportion of response (50% reduction) and remission on MADRS (MADRS≤10).

Results Altogether, 17–25% of the patients were eligible for AETs. The most common reasons for exclusion would be ‘not meeting minimum baseline severity’ and ‘presence of co-morbid Axis I disorder’. Eligible and non-eligible patients did not differ in treatment outcome. Only ‘meeting the minimum baseline severity’ is associated with remission.

Conclusions The majority of ‘real life’ out-patients are not eligible for AETs. However, the influence of eligibility on treatment outcome seems to be small. This suggests that stringent patient selection by eligibility criteria is not the major reason for lack of generalizability of AETs. Exclusion of less severely depressed patients from the analyses resulted in better treatment outcome. Milder depression is highly prevalent in daily practice and more research into treatment effectiveness in milder depression is warranted.

(Received January 05 2010)

(Revised September 29 2010)

(Accepted September 29 2010)

(Online publication November 16 2010)


c1 Address for correspondence: Drs. R. van der Lem, LUMC, Department of Psychiatry, Albinusdreef 2, PO box 9600, 2300 RC Leiden, The Netherlands. (Email: