Many psychotropic drugs have been developed throughout history to treat different disorders and illnesses, both physical and mental. Among the different mental disorders, depression is one of the most common, which has led to the synthesis of multiple types of substance in order to combat its symptoms.

One of them is nefazodone, a little known antidepressant and used in this article.

Nefazodone: basic drug characteristics

Nefazodone is an antidepressant type of psychopharmaceutical, derived from phenylpiperazine and synthesized with the purpose of relieving and treating the symptoms of depression: low mood, lack of motivation, anhedonia, passivity and sleep problems, among others.

It is one of the so-called atypical antidepressants, as its mechanism of action does not coincide with that of other antidepressants. Specifically, it is part of the group of drugs known as weak serotonin, noradrenaline and dopamine reuptake inhibitors or SDRIs, as is mazindol. Other substances have similar functioning although they act through different mechanisms of action, such as ketamine, cocaine and ecstasy.

As with most antidepressants, it takes time to make the necessary brain changes to visualize a real effect, this time being about four weeks. This drug is an effective antidepressant, which also has the advantage of producing hardly any alterations at the sexual level, weight gain or alterations in appetite.

However, although it is an effective antidepressant, its prescription is not usual and in fact between 2003 and 2004 its commercialization was suspended in different countries (including Spain and the United States) because it was shown that it could pose a high risk to health as it is highly toxic at a hepatic level, even leading to death.

Mechanism of action

The main mechanism of action of nefazodone is its action on the receptors of the different monoamines: serotonin, dopamine and noradrenaline. In a similar way to non-selective MAOIs, it increases the action of the three main monoamines but at a weaker and more controlled level.

It mainly acts as an antagonist of the 5-HT2 serotonin receptors at a post-synaptic level while inhibiting reuptake of serotonin. This generates an increase in the brain’s serotonin levels. It also contributes to inhibiting the reuptake of noradrenaline and dopamine, although at a much lower level. Finally, it also has a slight effect on histamine and acetylcholine , but the latter are practically negligible.

Uses and applications of this medicine

Nefazodone is mainly known as an antidepressant, with major depression being its main indication. It is also used in premenstrual syndrome or other types of depression, such as that associated with the suffering of various pathologies. However, in addition to the activity on depressive disorders , this drug may be useful in the treatment of other psychopathologies and problems.

Among them we can observe that nefazodone is useful in the treatment of various anxiety problems and in post-traumatic stress disorder, as well as for insomnia problems, although it increases the latency of REM sleep.

Side effects of this antidepressant

Despite its great usefulness, the consumption of nefazodone can generate various side effects and in some cases can have its risks, there being different contraindications.

The most common side effects of nefazodon are dry mouth and drowsiness, along with nausea and dizziness. Confusion, vision problems and asthenia are also relatively common. More rarely, hypotension and bradycardia have been observed, which is especially dangerous for those subjects who already suffer from cardiac pathologies.

However, the most serious problem associated with this drug (and which in fact led to its discontinuation) is its high hepatotoxicity. In some cases, liver failure has been observed, which can even lead to death, or jaundice. For this reason, if prescribed (which is not very common), continuous control should be exercised over the patient’s state of hepatic health , with regular tests being carried out. It may also have renal effects, as the drug is eliminated mainly by this route.

Another aspect to take into account is the risk of suffering from a serotonergic syndrome, a problem derived from an excess of serotonin (often caused by an overdose or interactions with other drugs and medicines) that can cause anxiety, alterations in consciousness, hyperactivity, tremors, vomiting , tachycardia, lack of coordination, mydriasis, convulsions, respiratory problems or even death.

Contraindications

As far as contraindications are concerned, one of the main ones is in those people who already suffer from liver problems, as well as coronary disorders. Also is contraindicated in people who consume certain drugs and especially MAOIs, as it could generate serotonergic syndrome and even cause death.

It is not recommended to administer it together with ISRS , as they interact. Likewise, some retrovirals such as those used with HIV interact with this substance, and if nefazodone is used (to treat depressions associated with this disease), the doses and possible interaction must be regulated to a great extent.

Minors and pregnant women should not take this medicine. Also, people with epilepsy or a history of suicide attempts should not use this drug or use it with special caution. It is generally not recommended for bipolar disorders.

Bibliographic references:

  • Jufe, G. (2001). Practical Psychopharmacology. Buenos Aires, Editorial Polemos.
  • McConville, B.J.; Chaney, R.O.; Browne, K.L. et al. Newer antidepressants-beyond selective serotonin reuptake inhibitor antidepressants. Ped Clin North Am. 45:1157-71.
  • Tatsumi, M.; Groshan, K.; Blakely, R.D. & Richelson, E. (1997). “Pharmacological Profile of Antidepressants and Related Compounds at Human Monoamine Transporters. Eur J Pharmacol.340 (2-3): 249-258.