Preliminary report published on antidepressants

Benefit of bupropion is / benefit of reboxetine not used: Manufacturer keeps trial data under lock and key

On June 10, 2009, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) presented the preliminary results of its benefit assessment of certain newer antidepressants. The project commissioned by the Federal Joint Committee (G-BA) is concerned with evaluating the benefits of the three active ingredients reboxetine, mirtazapine and bupropion XL in adult patients with depression. Interested persons and institutions can submit written comments on the preliminary report until 9 July.

Reboxetine: No evidence of benefit

The assessment was different for the three active substances. According to the institute's research, the active ingredient reboxetine (manufacturer: Pfizer) has been tested in at least 16 studies in around 4600 patients with depression. However, the institute only had data from around 1600 of these patients. If the unpublished data is not included, there is a high risk of misjudging the benefits and harms of the active substance. The IQWiG therefore comes to the preliminary conclusion that no evidence for the benefit of treatment with reboxetine can be derived from the currently available data. IQWIG takes more detailed account of this position.

Mirtazapine: Results are subject to change

Research into mirtazapine (Essex Pharma) revealed that the active ingredient was tested in at least 31 studies that could be potentially relevant to the report. However, only 27 studies were available to the institute in such a way that they could also be evaluated. Because here too there is a possibility that the results of the assessment will be postponed when the data is complete, the institute places all results under a reservation.

Mirtazapine has not been shown to be superior in numerous comparisons with other antidepressants. Only in comparison with placebo was there evidence that more patients experienced an improvement in depression in acute treatment when they were treated with mirtazapine. However, the prospects of complete healing in the mirtazapine group were no better than in the placebo group. It has also been shown that patients treated with mirtazapine discontinue therapy more often because of side effects (adverse events) than patients treated with placebo or with some other antidepressants.

Bupropion: evidence of benefits

Six studies were identified in the research on the active ingredient Bupropion XL, the study reports of which were made available in full to the institute by the manufacturer GlaxoSmithKline. In comparison to placebo in acute therapy and to prevent relapse into a so-called winter depression, there was evidence of a benefit for this active substance, but there was no evidence of damage here. Venlafaxin XR is the only drug used to treat depression that has been compared in studies with Bupropion XL. In acute therapy, Bupropion XL is inferior to Venlafaxin XR. Further details can be found in the short version of the preliminary report (see below).

Unpublished data have potential for deception

If not all available study data are available, this can lead to a highly distorted assessment. This potential for deception is of fundamental importance for all scientists who systematically evaluate drugs and other medical technologies. The experience of the institute shows that voluntary commitments cannot be relied on. The institute therefore considers it urgently necessary to legally oblige study sponsors, to register clinical studies before the start and to publish the results promptly.

Opinion procedure

Written comments on this preliminary report can be submitted until July 9, 2009. The IQWiG will review and appreciate the statements. If the institute believes there is a need for further questions, an oral discussion will take place. The preliminary report is then revised and forwarded to the G-BA as a final report.

The following summary gives an overview of the background, procedure and further results of the preliminary report PDF file

Source: Cologne [IQWIG]