Antidepressants: benefit of SNRI is

Venlafaxine and duloxetine relieve symptoms better than a placebo

On behalf of the Federal Joint Committee (G-BA), the Institute for Quality and Efficiency in Health Care (IQWiG) examined whether patients with depression benefit from drugs from the active substance class of selective serotonin and norepinephrine reuptake inhibitors (SNRI). So far, two of these active ingredients have been approved as antidepressants in Germany: venlafaxine and duloxetine. On August 18, 2009, the institute presented its final report. According to this, the benefit of both active ingredients compared to a dummy drug (placebo) has been proven: the patients respond better to the therapy and suffer less from the symptoms of their depression. There is also evidence that both substances not only relieve symptoms, but also protect against relapse.

Interplay of biological and psychosocial factors

There are different assumptions as to when and how depression arise. The possible causes and influencing factors are manifold. It is undisputed that the so-called frame of depression from a complex interaction of biological and psychosocial factors arises. There is evidence that an altered or reduced transmission of certain neurotransmitters in the central nervous system plays a role. This is where most drug therapies. In the relatively new class of SNRI should equal influenced two of these messenger substances (neurotransmitters): They inhibit the reuptake of serotonin and norepinephrine.

Manufacturers provide unpublished data

The scientists found a total of 80 clinical studies that they could include in the assessment. 16 compared duloxetine (manufacturer: Lilly) with a dummy drug or another antidepressant, 62 compared venlafaxine

(Manufacturer: Wyeth) put to the test in the same way, two studies compared the two active ingredients directly with one another. The manufacturers of the two preparations examined (Lilly and Wyeth) provided extensive, previously unpublished data.

In these studies, the effect of the medication is mostly measured using scales on which patients and / or medical staff document the change in symptoms. The outcomes of the IQWiG benefit assessment were changes in symptoms caused by depression and accompanying symptoms such as anxiety, pain or sleep disorders, mortality, suicidal tendencies, quality of life, dealing with everyday situations (social functional level) and adverse drug effects.

Patients respond better to both substances than to placebo

The scientists come to the conclusion that in acute therapy, patients respond better to both active ingredients than to a dummy drug. The symptoms are alleviated more and some even go away to the point where they no longer meet the criteria for a diagnosis of "depression". When it comes to preventing relapse, there is at least one indication that those affected benefit more from duloxetine and venlafaxine than from a dummy drug. In contrast to duloxetine, there is also evidence with venlafaxine that the drug is more effective than placebo against recurrence of symptoms of depression (relapse prevention). In a direct comparison between venlafaxine and duloxetine, no drug proves to be superior to the other in terms of alleviating the symptoms caused by depression.

If one considers the health-related quality of life, an advantage over placebo has been proven for duloxetine, but not for venlafaxine. However, if the substances are compared directly with one another, no relevant difference is found. Compared to a dummy drug, both active ingredients also improve the patient's ability to cope with everyday life (social function level).

Venlafaxine has limited additional benefit compared to other antidepressants

In comparison with another substance class of antidepressants, the selective serotonin reuptake inhibitors (SSRI), venlafaxine has an advantage: it alleviates depressive symptoms better than the comparison drugs. However, this does not apply to duloxetine.

Differences visible in side effects

The investigation of the adverse drug effects showed: In a direct comparison, venlafaxine is superior to duloxetine, since fewer patients stopped the therapy because of side effects. However, both substances fare worse here than SSRIs.

Little impact on accompanying symptoms of depression

With regard to the accompanying symptoms of depression, such as anxiety, pain or sleep disorders, the included studies showed only one relevant difference: in the venlafaxine group, patients suffered less from anxiety than in the placebo group. For the other accompanying symptoms investigated, however, no relevant effect could be determined for either of the two substances. This applies to the comparison with a dummy drug as well as for the comparison with other antidepressants.

About the report creation process

IQWiG published the preliminary results, the so-called preliminary report, at the beginning of December 2008 and put them up for discussion. After the end of the commenting procedure, the preliminary report was revised and sent to the client as a final report at the end of June 2009. Documentation of the written comments and minutes of the oral discussion are published in a separate document at the same time as the final report. The report was drawn up together with external experts.

This preliminary report is part of an order package on antidepressants: In a separate report, IQWiG is also examining the active ingredients bupropion, mirtazapine and reboxetine.

Source: Cologne [IQWiG]