Antidepressants: Sad Effect

31. March 2010

Depressions? It’s fast and easy to prescribe psychotropic drugs. The trend: Psychotropic poly-pharmaceuticals therapy. But in many cases the effectiveness of antidepressants isn’t a whole lot better than placebo.

Frequently the diagnosis depression is followed by antidepressant medication. Most cases are mild to moderate but pills don’t help here. This is the result of a meta-analysis made by Jay Fournier and his colleagues at the University of Pennsylvania in Philadelphia. They collected the results of six studies and compared the effectiveness of the serotonin-reuptake inhibitor Paroxetin and the tricyclic antidepressant Imipramin with placebo. Their conclusion: A substantial benefit is only verifiable with severe symptoms measured with the Hamilton Rating Scale of Depression (HDRS). Those patients reach HDRS scores of 25. Patients with a baseline HDRS below 23 showed hardly any difference between the antidepressant therapy and the placebo.

Why antidepressants don’t work

“The assumption of effectiveness of antidepressants is based on studies taking only patients with severe depressions into account” says Fournier. It shouldn’t surprise physicians and patients that this fact is not mentioned in any marketing activities of those products. US researchers at the Columbia University in New York are on the scent of the biological root of the absent response to SSRI. A large number of autoreceptors on serotonergic nerve cells of the raphe nuclei is responsible according to the researchers’ publication in the professional magazine Neuron. Too many serotonin receptors type 1A of the raphe nuclei cause a negative feedback. As a result less serotonin is produced.

The researchers created mice with higher and a lower autoreceptor levels on serotonergic cells of the raphe nuclei. Those mice received food in a bright environment which prompts fear. Antidepressants were supposed to work against that, but the drugs failed to have any effect on the animals with a surplus of autoreceptors. “The more antidepressants were given to increase te serotonin level, the less serotonin was produced by the nerve cells”, says the pharmacologist Rene Hen. A reduction of those autoreceptors for example by a blockage could improve the response rate to SSRI.

Many pills don’t necessarily mean better effectiveness

You welcome to doubt that such findings might influence tomorrow’s prescribing practice. The trend is clearly going towards psychotropic poly-pharmaceuticals therapy for mental disorders. More and more patients get therapies combining antidepressants and antipsychotics – data about prescription patterns of US psychiatrists reveals this. Especially if an antidepressant does not work, a second is added even though proof of effectiveness is missing.

Between 1996/97 and 2005/6, the ratio of visits at the physician’s office increased from 42.5 percent to 59.8 percent during which the doctor prescribed two or more drugs. Prescriptions of three or more drugs skyrocketed up from 16.6 to 33.2 percent. As an average, patient received – contrary to before – not one but two drugs which equals to an increase of 40 percent. Most frequently prescribed combinations were antidepressants and sedatives/hypnotics (23.1 percent), followed by combinations with antidepressants and antipsychotics (12.9 percent) and combinations with two antidepressants (12.6 percent).

Dynamic psychotherapy comparatively highly effective

Evidence of an addition benefit of a polytherapy with psychotropic substances is limited according to the authors of the report. More importantly, side effects during polytherapies increase and turn out to being more than a substantial gain of weight but also influence the metabolism sustainably.

If you don’t want to take any pills during a mild or moderate depressive disorder you might be better advised with other therapies. The psychodynamic therapy just recently proved to be – although not quite as comfortable – but long-term effective. Jonathan Shedler at the University of Colorado in Denver, School of Medicine has checked eight meta-analyses with 160 studies concerning the psychodynamic therapy and nine meta-analyses concerning other psychological therapy forms and the therapy with antidepressants in case of mental illness.

With an effect size of 0.97 in a large meta-analysis with over 1,400 patients, Shedler attests the psychodynamic therapy a very good effectiveness in cases of depression, anxiety-, panic disorders and stress-related physical symptoms. Eight months after finishing the therapy, the effect of the treatment had increased even more by another 50 percent. As a comparison: Effect sizes for the most frequently applied antidepressants for depressive disorders were only at 0.31.

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