On 10 June 2009, the Institute for Quality and Efficiency in Health Care (IQWiG) 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 assessing the benefit of three agents, reboxetine, mirtazapine and bupropion XL in adult patients with depression, according to the German drug approval status. Interested parties and institutions may submit written comments on the preliminary report up until 9 July.
Reboxetine: no proof of benefit
The assessment produced different results for the three agents. According to a literature search performed by the Institute, reboxetine (manufacturer: Pfizer) was tested in at least 16 trials on approximately 4600 patients with depression. However, the Institute only had access to data on approximately 1600 of these patients. If the unpublished data are not included, there is a high risk of incorrectly estimating the benefit and harm of this agent. IQWiG has therefore come to the preliminary conclusion that no proof of benefit from treatment with reboxetine can be deduced from the data currently available.
Mirtazapine: results must be viewed with reservation
In the search for trials on mirtazapine (Essex Pharma), it was found that this agent had been tested in at least 31 trials that could be potentially relevant to the report. However, the Institute only had access to 27 evaluable trials. As it is also possible in this case that the results of the assessment may change if all data became available, all results presented by the Institute must be viewed with reservation.
In numerous comparisons with other antidepressants, mirtazapine showed no proof of superiority. Only when compared to placebo was there proof that in acute treatment more patients experienced an improvement of depression when they were treated with mirtazapine. However, the prognosis for a full recovery was no better in the mirtazapine group than in the placebo group. In addition, it was shown that patients treated with mirtazapine discontinue treatment more often due to side effects (adverse events) than patients treated with placebo or with some of the other antidepressants.
Bupropion: proof of benefit
The search identified 6 trials on bupropion XL (up to 300 mg/d) and the Institute was given access to the complete clinical study reports by the manufacturer, GlaxoSmithKline. There was proof of benefit for this agent compared to placebo in acute therapy and in the prevention of relapse into seasonal affective disorder, while on the other hand the data provided no indications of harm. The only antidepressant that was compared with bupropion XL in trials was venlafaxine XR. Bupropion XL showed inferiority to venlafaxine XR in acute therapy. Further information can be found in the executive summary of the preliminary report (see below).
Unpublished data contain the potential for deception
If not all available study data are available, this can lead to a strongly biased assessment. This potential for deception is of fundamental importance to all researchers who systematically assess drugs and other medical technologies. The experience of the Institute shows that voluntary self-commitment cannot be relied upon. The Institute therefore considers it an urgent necessity to make it compulsory by law for study sponsors to register clinical trials before commencement and publish the results soon after study completion. IQWiG's position is described in a second press release.
Commenting procedure
Written comments on this preliminary report may be submitted up until 9 July. IQWiG will screen and evaluate the comments. If, in the opinion of the Institute, there is a need for further discussion of the comments, an oral debate will take place. The preliminary report will then be revised and sent as a final report to the contracting agency, the Federal Joint Committee.