ISRN: effects and functioning of this type of antidepressant

Fourth-generation antidepressants, which act specifically on certain neurotransmitters To prevent adverse reactions as far as possible, they are being prescribed more and more frequency. However, they remain not as popular as the SSRIs, which dominate the field of drug therapy for depression.

In this article we will analyze the efficacy of selective norepinephrine reuptake inhibitors or SNRIs, which are part of this group of novel drugs. We will focus primarily on reboxetine, the only ISRN that has been studied in some depth, and on its comparison with other types of antidepressants.

• Related article: "Types of antidepressants: characteristics and effects"

Fourth generation antidepressants

In 1952, the first antidepressant drug in history was discovered: iproniazid, which had developed to treat tuberculosis but was found to be effective in improving the state of cheer up. Iproniazid belonged to the pharmacological class of inhibitors of the enzyme monoamine oxidase (MAOI), very powerful and dangerous for general health.

Later, tricyclic antidepressants such as imipramine appeared, clomipramine and nortriptyline. In this case, the origin was the research on the medical treatment of psychoses. These in turn were displaced by the selective serotonin reuptake inhibitors, better known by the abbreviation "SSRI".

In recent years, a series of medications for depression have appeared that have been attributed greater safety than SSRIs; We are talking about fourth generation antidepressants, which include selective inhibitors of norepinephrine reuptake (SNRI) and dual serotonin reuptake inhibitors and noradrenaline (SNRI).

Unlike tricyclics and MAOIs, fourth-generation antidepressants have a high selectivity index; this means that they exert their action specifically on one or more neurotransmitters, which theoretically should reduce the risk of side effects. In this sense, the new antidepressants resemble the SSRIs.

Selective norepinephrine reuptake inhibitors (SNRIs)

ISRNs are a class of psychotropic drugs with antidepressant effects that act specifically on one of the fundamental neurotransmitters of the nervous system: noradrenaline. This chemical compound is involved in a wide set of physiological and cognitive responses related to activation.

Thus, norepinephrine influences stress responses (both physiological and cognitive), mood, motivation, maintenance awareness and alertness, in blood circulation, in the management of attentional resources, in aggressive behavior, in sexual pleasure and in the orgasm.

As the name suggests, the ISRN exert their action through the inhibition of norepinephrine reuptake. This means that, when taking one of these drugs, the presynaptic neurons have a greater difficulty to absorb norepinephrine from the synaptic space, increasing the amount that is available for neurotransmission.

Selective norepinephrine reuptake inhibitors are also called simply by the abbreviation "IRN"; in this case the term "selective" is ignored. The best known of these drugs is reboxetine., which is marketed under the names "Irenor", "Norebox", "Prolift", "Edronax" and "Vestra", among others.

There are, however, other drugs that can be categorized within this pharmacological class. These include atomoxetine, talopram, talsupram, nisoxetine, viloxazine, amedaline, lortalamine, tandamine, daledaline, edivoxetine or esreboxetine.

The effectiveness of reboxetine

At present, and partly as a consequence of its recent appearance, research available around selective norepinephrine reuptake inhibitors is relatively limited. That is why the degree of efficacy of these types of drugs is not entirely clear, and we also find very contradictory findings.

The meta-analysis by the Eyding team (2010) evaluated the efficacy of reboxetine for the treatment of major depression, using 13 studies with more than 4 thousand patients as a starting point. These authors found no significant difference between placebo and reboxetine in the remission of symptoms and concluded that SSRIs are more effective than SNRIs.

By cons, the UK Government Medicines and Health Products Regulatory Agency (MHRA) analyzed 11 studies on the efficacy of reboxetine and found it to be effective in severe cases of depression. They also denied that it had a greater potential for causing side effects than placebo, as Eyding's team proposed.

Currently available data suggest that SNRIs may have a somewhat less severe side effect profile than SSRIs, the most widely used antidepressants; however, its power is probably lower. Both classes of drug seem more effective in severe cases than mild or moderate. In either case, more research is required.

Bibliographic references:

• Eyding, D., Lelgemann, M., Grouven, U., Härter, M., Kromp, M., Kaiser, T., Kerekes, M. F., Gerken, M. & Wieseler, B. (2010). Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ, 341: c4737

• The Medicines and Healthcare products Regulatory Agency (MHRA) (2011). MHRA UK Public Assessment Report: Reboxetine: a review of the benefits and risks.