Antidepressants and Sexual Dysfunction: SSRIs and Treatment

Introduction: Antidepressants and Iatrogenic Sexual Disorders

Pharmaceutical drugs have become the first line of defense against depression, anxiety, and other psychological problems for a majority of patients. As they have become generally safer and more socially widespread, certain side effects have begun to attract a great deal more attention than they had previously. Currently, the attention of many researchers is being drawn to the issue of iatrogenic sexual disorders caused by antidepressants and other psychotropic drugs. It appears that many such medicines may cause mild to severe sexual dysfunction as a class side effect. This appears to be especially true of selective serotonin reuptake inhibitors (SSRIs). A number of other drugs have been suggested either to replace SSRIs as the drug of choice for young, sexually active patients, or to help ameliorate the side effects of traditional psychotropics.

There are many barriers to research in this area, including the lack of prior clinical studies, a lack of comprehensive knowledge about the biology of depression and the biology of sexual desire and functioning, and patient hesitance to volunteer information about sexual functioning. However, some steps have been made in remedying these effects. Six recent articles dealing with this topic shed some light on the issue of sexual dysfunction, its causes, and its treatment.

Rivas-Vazquez et al. reported on the increase in interest among researchers regarding treatment-induced sexual dysfunction, chronicling the many recent discoveries concerning sexual side effects. Though they noted that existing literature dealt mainly with case studies, small-scale trials, and tests that were not randomized and placebo-controlled, a rough understanding of the trends did emerge. They found that among the newer generation of antidepressants — which had replaced prior, less safe drugs such as MAO inhibitors and tricyclics — those that interfered with serotonin levels (SSRIs and venlafaxine) had far more severe sexual side effects than the atypical drugs (bupropion, nefazodone, and mirtazapine) that did not directly affect serotonin.

Rivas-Vazquez et al. also recorded a variety of sexual dysfunctions that may occur as side effects of psychotropics, ranging from unpleasantly increased erectile ability (such as priapism) and unusually high arousal levels to impotence and delayed or even painful orgasm. The article compiles a list of drugs and their effects. The authors suggest that trazodone has been known to infrequently cause priapism, and that fluoxetine, venlafaxine, and bupropion have all been known to occasionally cause increased libido. However, both venlafaxine and fluoxetine have also been known to cause serious sexual dysfunction, including decreased sexual desire, inability to function sexually, and decreased orgasmic response. Similar negative effects have been discovered with the use of paroxetine, sertraline, and fluvoxamine.

Part of the difficulty in determining exactly what effects drugs are having may be due to the comorbidity of their symptoms with the original psychiatric problems that prompted their use. Depression itself can cause sexual dysfunction or create strains in personal relationships that may persist even past the resolution of the illness. So, for example, fluoxetine might typically decrease sexual desire physically, yet provide such relief from depression that an individual has a higher sex drive than before becoming depressed — albeit reduced from a natural baseline that they may never have fully experienced, or may have forgotten. Additionally, the functioning of serotonin and its role in sexual arousal may not be fully understood.

Neurobiological Mechanisms: Serotonin, Dopamine, and Sexual Functioning

It is generally understood that serotonin affects sexual functioning by altering the levels of other neurotransmitters that directly control sexual functions at different stages of the sexual response cycle. Dopamine, for example, enhances sexual pleasure and libido, is an intrinsic part of the orgasmic experience, and has had some degree of the emotional bonding inherent in sex attributed to it. Increased serotonin levels can inhibit dopamine, among other neurotransmitters, which could reduce arousal, libido, and the capacity for orgasm. Hence, SSRIs may necessarily decrease dopamine levels and impair sexual functioning.

Not all antidepressants are equally likely to cause sexual dysfunction, because not all antidepressants directly affect serotonin or dopamine levels. Rivas-Vazquez et al. suggest that the most appropriate response to unwanted sexual side effects is to consider using atypical antidepressants as the first choice for treating targeted groups of sexually active patients. Careful monitoring of all patients' sexual functioning while on medication is also strongly recommended, as some patients may hesitate to mention sexual dysfunctions. By using drugs with very low incidences of sexual side effects, the degree to which these effects interfere with recovery and with relationships can be minimized.

Survey of Drug Classes and Their Sexual Side Effects

Like others before him, Gitlin suggests that the sexual side effects of psychotropic drugs are becoming an increasing concern to the clinical and therapeutic community. He attributes the emergence of this concern to "gaps in our understanding" regarding both the chemical biology of sexual functioning and the way in which this is affected by Axis I disorders without the intervention of medicine. In pursuit of further knowledge, Gitlin reviewed numerous MEDLINE articles and concluded that, though clinicians need to be aware of and to question their patients about sexual side effects, there does not appear to be a specific antidote to these problems clearly indicated by prior research.

Gitlin suggests that clinicians need to evaluate their patients' sexual functioning based on all possible causes for existing problems. Though dopamine is generally understood to increase sexual functioning while serotonin decreases it, and norepinephrine has mixed effects, there appear to be negative sexual side effects associated with all psychotropic classes. Neuroleptics can cause priapism. Anxiolytics and mood stabilizers produce an array of mild effects. SSRIs, clomipramine, and MAO inhibitors can cause severe side effects, while tricyclics cause more moderate effects.

Because of the problems noted by prior researchers regarding discriminating between the symptoms of mental illness and the side effects of the psychotropics used to treat those illnesses, Nafziger and his colleagues chose to conduct a study on the side effects of the antidepressant fluvoxamine on healthy volunteers. Prior research had suggested that only 1% to 8% of patients using this drug would experience sexual dysfunction. Considering that other SSRIs had reported sexual side effect rates as high as 75%, these very low numbers might encourage many people to switch to fluvoxamine. Nafziger points out that this prior research had, however, depended on self-reporting of sexual dysfunction, which might discourage embarrassed individuals from mentioning their problems.

In the Nafziger study, among healthy volunteers who took 150 mg of fluvoxamine daily, 20% experienced sexual dysfunction within two weeks and 35% experienced sexual dysfunction within four weeks. This was much higher than previously assumed, and the rate was comparable to that experienced by patients on other SSRIs, as well as to that of tricyclic, heterocyclic antidepressants, and MAOIs. The findings highlight the importance of specifically questioning individuals about their experiences rather than depending on self-reporting alone.

Conclusion and Research Recommendations

It appears that all authors agree that sexual dysfunction arising from the use of SSRIs and other antidepressants is a very serious matter, and one that has not been appropriately addressed. It is somewhat ironic that although every article mentions the glaring absence of placebo-controlled studies, only one of the original studies reviewed actually used a placebo. In that single study, evidence suggested that the antidotes being tested were no more effective than closely monitoring patient behavior and providing psychological support — which a placebo itself effectively delivers.

This is the most significant weakness shared by all of these articles: they all work from a position of incomplete knowledge. Each article is framed by an admission of ignorance suggesting that the author — and science itself — does not fully understand what role serotonin plays in sexual chemistry and functioning, nor what actual effects antidepressants such as SSRIs have on the psychology and sexuality of the patient beyond their intended purpose. That sexuality remains poorly understood by science — that it is, in effect, a black box — lends credibility to the suggestion offered by authors such as Rivas-Vazquez that clinicians will do best to avoid adding more chemical treatment to the regimen, and instead to try a different drug, scale the dosage carefully, apply close monitoring, and otherwise address the symptoms directly.

Of the solutions suggested, none seem truly satisfactory. Switching to non-SSRI medications may provide some degree of relief, though insufficient research exists to determine how much safer or less adverse these alternatives really are. Taking a "drug holiday" may or may not resolve the problem. Using other drugs to balance out the effects of SSRIs seems to work well for many patients, but possibly only through a placebo effect that might be more safely achieved without the use of expensive and potentially adverse additional medications.

In conclusion, these articles tell us only a little more than common sense might suggest: if antidepressants have negative effects, one may need to try something else, and failing that, one should monitor effects as carefully as possible in hopes of better understanding them. The main point on which all the articles agree is one the reader can wholeheartedly embrace: more rigorous research is absolutely necessary on the occurrence and treatment of iatrogenic sexual disorders, and this research should be conducted in a scientifically controlled manner — with double-blind safeguards, large and randomized trial pools, and the use of placebos.