Fluvoxamine Plays an Integral Role in the Alteration of Sexual Behavioral Pattern more in Females than Males.

Sir,

The last decade has witnessed a dramatic increase in the number of psychotropic medications available to clinicians treating psychiatric disorders. The introduction of selective serotonin reuptake inhibitors (SSRIs)—fluoxetine, paroxetine, fluvoxamine, and sertraline—has substantially facilitated the treatment of depression. The role of the serotonergic system in influencing sexuality is well known. However, one of the most prominent adverse effects of these medications is sexual dysfunction. The World Health Organization (WHO) defines sexual dysfunction as “the various ways in which an individual is unable to participate in a sexual relationship as he or she would wish”. Most antidepressant drugs have adverse effects on sexual function, but accurate identification of the incidence of treatment-emergent dysfunction has proved troublesome, as disturbances of the sexual response can only be detected in a reliable fashion when systematic enquiries are made before and during the course of treatment.

Fluvoxamine-induced effect on sexuality was noted in a questionnaire-based scale, the Arizona Sexual Experiences Scale (ASEX).[1] The main reason for selecting ASEX is its reliability and validity for medical patients. The ASEX is a brief five-item scale designed to assess the core elements of sexual functioning: Drive, arousal, penile erection/vaginal lubrication, ability to reach orgasm, and satisfaction with orgasm. Each item is rated with a six-point Likert system, with lower scores reflecting enhanced sexual function and higher scores reflecting impaired sexual function. A total ASEX score of 19 or greater, any one item with an individual score of either 5 or 6, or three or more items with individual scores of 4 have all been found to be highly correlated with clinician-diagnosed sexual dysfunction. The overall study was carried out in accordance with the Helsinki declaration, and the study was approved by a properly constituted institutional ethics committee.

Two hundred consecutive adult patients comprising 100 in each sex were selected on the day of their diagnosis as cases of major depressive disorder and then followed up for the next four visits Which were at an interval of one month between them. Male and female patient groups were compared separately in time series analysis by Friedman's analysis of variance (ANOVA) test. Then, pairwise within-group comparison between pretreatment and different post-treatment weeks were done by the Wilcoxon matched pair signed rank test. A probability level less than 0.05 was considered statistically significant. Comparison of before and after administration of fluvoxamine in time series analysis upto four weeks of treatment showed a significant (P<0.05) increase in sexual dysfunction at weekly intervals in comparison to pretreatment value to reach the maximum at fourth week in females unlike males.

But in the study by Michelson,[2] during the course of treatment with fluoxetine, approximately 40% of the men and 50% of the women reported improvement in sexual function, whereas worsening of sexual function was reported by only 13.4% of the women and 17.6% of the men when compared to baseline sexual functioning. Thus, the extent of sexual dysfunction is greater in this study with fluvoxamine alone. This finding is in agreement with that of the study conducted by Zajecka et al.,[3] where males treated with SSRIs showed a statistically significant increase in the desire and frequency to initiate sexual activity and an increased overall degree of sexual satisfaction at the end of eight weeks of treatment compared to baseline measures. One possible mechanism is the inhibition of dopaminergic neurotransmission,[45] resulting in described persistent sexual dysfunction. Changes in gene expression are complex and can involve persistent modifications of chromatin structure. It has been suggested that the use of SSRIs can result in persistently altered cerebral gene expression leading to compromised catecholaminergic neurotransmission and neuroendocrine disturbances[6] such as reduced hypothalamic-pituitary-testis axis (HPTA) function, leading to decreased testosterone levels, reduced sperm counts, and reduced semen quality with damaged sperm DNA. Future studies of sexual dysfunction in depressed subjects should continue to clarify the aspects of sexual functioning that are affected by pharmacological treatments, including differential pharmacologic effects and the effect of depression on sexual functioning.