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ISRN: effects and functioning of this type of antidepressant drug

ISRN: effects and functioning of this type of antidepressant drug

January 25, 2022

The fourth-generation antidepressants, which act specifically on certain neurotransmitters to prevent adverse reactions as far as possible, are being prescribed more and more frequently. However, they are still not as popular as SSRIs, which dominate the field of drug therapy for depression.

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


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

The fourth generation antidepressants

In 1952, the first antidepressant drug in history was discovered: iproniazide, which had been developed to treat tuberculosis but proved effective in improving mood. Iproniazide belonged to the pharmacological class of monoamine oxidase inhibitors (MAOIs), very potent and dangerous for general health.

Subsequently, tricyclic antidepressants such as imipramine appeared , clomipramine and nortriptyline. In this case the origin was the investigation about 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 drugs for depression have appeared that have been attributed a greater safety than SSRIs; We are talking about fourth-generation antidepressants, which include selective norepinephrine reuptake inhibitors (SNRIs) and dual serotonin and norepinephrine reuptake inhibitors (SNRIs).

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

Selective noradrenaline reuptake inhibitors (ISRN)

The ISRN are a class of psychotropic drugs with antidepressant effects that act in a specific way in one of the fundamental neurotransmitters of the nervous system: noradrenaline. This chemical compound is involved in a broad set of physiological and cognitive responses related to activation.


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

As the name suggests, the ISRN they exert their action through the inhibition of the reuptake of norepinephrine . This means that, by consuming one of these drugs, presynaptic neurons have a greater difficulty in absorbing norepinephrine from the synaptic space, increasing the amount available for neurotransmission.

Selective noradrenaline 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 medications that can be categorized within this pharmacological class. Among these are atomoxetine, talopram, talsupram, nisoxetine, viloxazine, amedaline, lortalamine, tandamine, daledalin, edivoxetine or esreboxetine.

The effectiveness of reboxetine

Currently, and partly as a consequence of its recent appearance, the available research on selective noradrenaline reuptake inhibitors is relatively scarce. That is why the degree of effectiveness of this type of drugs is not entirely clear , and we also find very contradictory findings.

The meta-analysis of Eyding's team (2010) evaluated the efficacy of reboxetine for the treatment of major depression, using as starting point 13 studies with more than 4 thousand patients. These authors did not find significant differences between placebo and reboxetine in the remission of symptoms and concluded that SSRIs are more effective than ISRNs .

In contrast, the Regulatory Agency for Medicines and Health Products (MHRA) of the government of the United Kingdom analyzed 11 studies on the effectiveness of reboxetine and found that it was effective in severe cases of depression. They also denied that it had a greater potential to cause side effects than placebo, as proposed by Eyding's team.

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

Bibliographic references:

  • Eyding, D., Lelgemann, M., Grouven, U., Härter, M., Kromp, M., Kaiser, T., Kerekes, M., 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.

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