Sexual dysfunction associated with antidepressant treatment is not uncommon.16
Although in many cases antidepressants can improve the sexual dysfunction associated with depression, the dysfunction consequent to the medications themselves are potentially important concerns for the patient.16
In the present study, approximately half the patients taking antidepressants experienced sexual dysfunction. Comparison of the prevalence of sexual dysfunction among the participants according to the different drugs they were taking revealed relevant differences, as follows: citalopram 60%, fluoxetine 46.2%, paroxetine 54.2%, venlafaxine 54.5%, and mirtazapine 18.2%. These findings replicate the results of previous studies, which have shown both a substantial number of patients suffering from sexual dysfunction and that SSRI users experience a higher incidence of sexual dysfunction than do mirtazapine users.17
The overall incidence and the type of sexual dysfunction appear to be differentially associated among the classes of antidepressants, and also, possibly, within the classes.4,18
Tricyclic antidepressants, SSRIs, and monoamine oxidase inhibitors are frequently associated with sexual dysfunction. Other antidepressants (e.g., bupropion, moclobemide, reboxetine, mirtazapine, and nefazodone) seem to be associated with lower incidence of sexual dysfunction than the older antidepressants.4
As a group, SSRIs, venlafaxine, and mirtazpine are among the most commonly prescribed medications for controlling the symptoms of depression, due to their reduced side effect profiles, which enhance patient compliance. Nevertheless, because of their different mechanisms of action on the receptors, these medication types have different impacts on sexual functioning. Of the newer antidepressants, SSRIs seem most likely to cause sexual dysfunction. SSRIs act specifically on the serotonin system, but they also affect other monoamines. For instance, paroxetine has D2-blocking properties, thereby affecting the dopaminergic mesolimbic reward system.19
This can increase the risk of hyperprolactinemia and sexual dysfunction.20,21
In addition, paroxetine inhibits nitric oxide synthase activity, which is required for erection.22,23
In the study by Montejo et al.,17
which compared all five SSRIs, paroxetine and citalopram were associated with the highest overall prevalences of sexual dysfunction. In the present study, citalopram (60%) and paroxetine (54.2%) tended to be associated with more frequent sexual dysfunction than fluoxetine was (46.2%), though the difference was not statistically significant.
From the standpoint of sexual dysfunction, patients seem to tolerate the dual action antidepressants relatively well. The SNRIs now comprise three medications: venlafaxine, milnacipran, and duloxetine. The use of venlafaxine produces some degree of delayed orgasm, but the frequency of this is considerably lower than for SSRI use.24
In the case of milnacipran, there have been no systematic surveys. However, studies in volunteers25
have not revealed any such effects. With regard to sexual dysfunction, the difference between venlafaxine and milnacipran may be due to the former's relative selectivity toward serotonin reuptake and the latter's toward noradrenaline reuptake. Venlafaxine at low doses only blocks serotonin reuptake, whereas at higher doses (generally described as >150 mg/d), it is also a potent norepinephrine reuptake inhibitor.26
At very high doses, venlafaxine blocks dopamine reuptake.26
Thus, theoretically, sexual side-effects should decrease as the venlafaxine dose increases. Because this study used relatively low doses of venlafaxine (115 mg), the sexual dysfunction frequency associated with venlafaxine was similar to that of the SSRIs.
Studies have shown that mirtazapine is associated with a low rate of sexual dysfunction. About 24.4% of mirtazapine-treated patients experience any type of sexual dysfunction.17
One of the noradrenergic and specific serotonergic antidepressants (NaSSAs), mirtazapine is a presynaptic alpha2-adrenergic receptor antagonist, facilitating the release of norepinephrine and serotonin. However, mirtazapine's 5HT2 blocking properties reduce the potential for sexual dysfunction, particularly anorgasmia. Mirtazapine is also a potent antagonist of postsynaptic 5-HT3 receptors, which may further promote orgasm. The present study, showing mirtazapine was associated with both lowest overall sexual dysfunction frequency and greatest ease of orgasm, is in line with mirtazapine's unique mechanisms of action.
This study has several limitations. First, the small sample size did not facilitate a comparison between the low-incidence adverse effects. Since response rate is generally low in surveys on sensitive topics,27,28
interpretation of the findings requires caution. Future studies need to use larger sample sizes. Second, the participants were free to take medications other than those analyzed in the study. Therefore, we cannot rule out the possibility that the incidence of side effects might have been influenced by other medications the participants were taking. Third, we did not make an initial assessment of participants' sexual dysfunction before treatment. Thus, it is difficult to distinguish antidepressant-induced sexual dysfunction from the participants' remaining symptoms of depression. However, since the participants' severity of depression was mild (mean BDI score was 11.9±9.0) and improved with treatment, their sexual dysfunction may more likely be the result of medication side effects. Fifthly, a comparison with a non-depressed control group may provide more information about the medications' side effects.
In conclusion, this study suggests that sexual dysfunction often occurs with antidepressants treatment and may occur at different rates in patients treated with different medications. Clinicians should be alert to the appearance of this undesirable side effect in order to adopt the best strategy for managing depression, thus avoiding a deterioration in the patient's quality of life and possible withdrawal from the treatment.