Bupropion is a new generation or atypical antidepressant. It is a dopamine-norepinephrine reuptake inhibitor and is used not only in major depressive disorders but also to treat episodes of depression in patients with bipolar disorder and to treat attention deficit hyperactivity disorder (ADHD).

In order to maximize the benefit of antidepressant therapy for each individual patient, not only must be taken into account the efficacy of the drug, but, at the same time, one must select those drugs causing the lesser side effects, and therefore a compromis between efficacy/tolerability must be reached. That is why understanding the individual differences in each patient regarding side effects is essential to personalize the treatment of depression.

In this item we study the genetic factors that affect the development of adverse effects during treatment with bupropion.

To detect which polymorphisms affected tolerability to bupropion, in 2012 Clark SL. et al. used data from the STAR*D study ("Sequenced Treatment Alternatives to Relieve Depression") carried out by Rush et al. in 2004, where the genotype of patients previously treated with another antidepressant such as citalopram was compared to those patients who did not response with the side effects that occurred when they were comedicated with another drug for the treatment of major depression states, such as for example bupropion. From this STAR*D study the data of 128 patients who had been previously treated with citalopram and who were treated together with citalopram+bupropion were used.

In this study carried out in 2012, genetic polymorphisms or SNPs were found that were associated to the manifestation of side effects during antidepressant treatment.

The rs2742417 or g.45731451 C>T, a genetic variant found in the SACM1L gene, was one of these polymorphisms. The presence of a variant allele (T allele) was related to a reduction in the side effects of sexual dysfunction. The SACML1 gene is related to hormonal secretion and certain neurotransmitters, so it is attributed a role in sexual dysfunction.

Another genetic polymorphism that was associated with a lower risk of sexual dysfunction in this study was rs17150687 or c.1046-44761 A>G that is found in the MAGI2 gene. Patients with a variant G allele suffered less sexual dysfunction than patients with AA genotype. The MAGI2 gene plays an important role in neurotransmission, which suggests that alterations in the cellular traffic of these transmitters may be associated with sexual dysfunction.

Although bupropion is a last generation antidepressant that causes fewer side effects related to sexual dysfunction than other antidepressants of previous generations, it can generate some disorder in sexual behavior, especially if combined with other antidepressants, such as the usual, since bupropion is usually prescribed as adjuvant along with other SSRIs (selective serotonin reuptake inhibitors) antidepressants.

Another genetic polymorphism in wich the presence of the variant allele diminished the development of certain side effects, decreased dizziness produced by the antidepressant treatment, it was rs6795349 or g.130794 A>G, located in the chromosomal region 3p26.3 at about 60 kilobases of the CHL1 gene. Polymorphisms in the CHL1 gene have previously been associated with the development of schizophrenia.

Another polymorphism associated with the development of fewer side effects is the rs10857636 or c.3098 + 81 C>T in the WDFY4 gene, where the presence of the variant allele T predisposes to suffer less adverse effects in general in the treatment with bupropion.

Due to the fact that there are still few clinical trials with a high number of patients that allow 100% assurance of the relationship of the genotype with the side effects produced by bupropion, this information must be taken with caution, although it provides good evidence to determine "a priori " if bupropion is going to work in a right way with the patient or not.

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