As depression is one of the most prevalent mental disorders worldwide and one of the major causes of disability, its treatment is an issue that the scientific community has taken into account for many years. The suffering it causes requires sometimes immediate attention, as it is one of the disorders with the highest risk of suicide and which causes the most pain to both the individual and his or her environment. The treatment of depression is carried out from different areas, one of them being psychopharmacology. One of the drugs used in the treatment of depression is trazodone , which we will discuss in this article.

Trazodone: what kind of substance is it?

Trazodone is a psychoactive drug classified among the antidepressants , substances that generate a neurochemical change at a cerebral level causing the alteration of the levels of certain neurotransmitters, specifically serotonin. Within antidepressants, it is part of and in fact is the main representative of the group of serotonin-2A antagonists and reuptake inhibitors or SARIs, a type of atypical antidepressant. This drug was designed in Italy in 1966 under the assumption that depression could be based on the existence of low thresholds regarding the perception of pain and suffering, being the product of the lack of integration of aversive experiences.

Trazodone has been shown to be an effective and efficient drug in the treatment of depression, reducing passivity and lack of activity as well as the discomfort and suffering associated with this condition and facilitating an increase in mood. However, in addition it also has an anxiolytic and tranquilizing action .

This substance is considered a second generation antidepressant, together with specific serotonin reuptake inhibitors (SSRIs), with which it shares part of its mechanism of action, and different dual antidepressants. In fact, sometimes trazodone is considered to be dual as it has two different effects, although they focus on the same neurotransmission system, compared to the rest, and in addition to an antidepressant effect it also has tranquilizing effects.

How does it work? Mechanism of action of the medicine

As indicated above, trazodone is classified as SARI, having a somewhat special mechanism of action among the other antidepressants. Trazodone acts at the serotonergic system level (like most antidepressants) in two specific ways.

First, this substance produces a blockage of the brain’s reuptake of serotonin, so that this neurotransmitter remains in the synaptic space for a longer time . This means that it has an agonist effect on the synthesis and maintenance of serotonin in the brain, increasing its levels (which are diminished during depression and this is something that correlates with the decrease in mood). This mechanism of action is that used by SSRIs, which is why these and trazodone are related and sometimes the latter is included among the former.

However, trazodone has a second effect that differentiates it from other drugs, and that in fact seems to be contrary to the previous mechanism of action. This is because it also acts as an antagonist of the serotonin 5-HT2A receptors, preventing or hindering the activation of these receptors. This second aspect is what makes trazodone have a slightly different profile and effects than other antidepressants.

With regard to its interaction with other neurotransmitter systems, does not present great anticholinergic effects , something that has made this drug a better option than tricyclics (although doses must be regulated as well) in patients with cerebrovascular and cardiac pathologies and dementias. However, it must be taken into account that it can generate arrhythmias. It also has a minor effect on the adrenergic system (blocking some receptors) and histaminergic system, something that can lead to side effects.

Main indications

The main indication for trazodone is obviously, as an antidepressant, major depression. Its efficacy is also high in those depressions that appear together with anxious symptoms. Its clinical utility has also been observed in other disorders in which there are anxiety components or that are based on it, such as generalized anxiety disorder, Obsessive-Compulsive Disorder or bulimia.

In addition, it has also been found to be useful in the treatment of substance addiction, being a good alternative for patients with benzodiazepine withdrawal syndrome, and in the treatment of alcoholism (including the presence of delirium tremens). Another of its indications is insomnia , which effectively reduces by increasing sleep time without greatly affecting the deep sleep phase.

Although most antidepressants can usually have as a side effect the presence of erectile dysfunction or ejaculation problems, this effect does not usually occur in trazodone, which in fact seems to generate an increase in libido and which is even used as a treatment indicated in erectile dysfunction .

Finally, trazodone has been applied (largely because of its relaxing properties) in some cases of schizophrenia, motor problems such as Gilles de la Tourette syndrome, the presence of manic episodes in bipolar disorder and behavioural disorders in Alzheimer’s disease, although more study is needed on the latter.

On a medical level, it has also been used as a sedative in patients infected with HIV and diabetic neuropathies, as well as in other pain disorders such as fibromyalgia. It has a very slight muscle relaxant effect.

Side effects and contraindications

Trazodone is a very useful drug that has been used in many pathologies and disorders, both mental and medical. However, it can have undesirable consequences in the form of side effects and is even contraindicated in some situations and pathologies.

In terms of secondary symptoms, sedation and fatigue, the presence of headaches, nausea and vomiting, gastric alterations (diarrhoea or constipation), alterations in appetite, sweating, tremors (which can lead to convulsions in some cases), buzzing, numbness and vision problems are common. In some cases it can also generate chest and muscle pain, alterations in consciousness, breathing problems and arrhythmias. Like other antidepressants, trazodone can also contribute to the genesis of suicidal ideation in the first moments of consumption.

Despite the fact that, unlike other antidepressants, it does not seem to generate but in fact contributes to improving cases of erectile dysfunction or ejaculatory problems, the use of trazodone has been observed and associated with the emergence of priapism, erections that do not disappear by themselves and that generate pain in those who suffer from them (and may even require urgent and even surgical treatment).

Although it is sometimes used in dementias and has a lower risk of generating heart problems than tricyclics, it requires a high degree of caution in its use and a dosage carefully prescribed by the physician, since it can generate arrhythmias. It is contraindicated in patients who have just suffered a heart attack , as well as those with liver or kidney disease.

Caution should be exercised in subjects with bipolarity, since if the medication is not regulated, the consumption of trazodone may cause a shift from a depressive phase to a manic phase. It is also contraindicated in people who have suffered from priapism or have Peyronie’s disease. Finally, it must be taken into account that trazodone can be excreted in breast milk and transmitted through the placenta, which means that pregnant and nursing women are not allowed to use it.

Bibliographic references

  • Alcántara-López, M.G.; Gutiérrez-García, A.G.; Hernández-Lozano, M. & Contreras, C.M. (2009). Trazodone, an atypical antidepressant with anxiolytic and sedative properties. Arch. Neurocien (Mex), 14 (4): 249-257.