Sexual dysfunction caused by antidepressant medications

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 to either 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 and 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 disfunction and their causes and treatment.

Rivas-Vazquez et al. report on "Psychologists becoming aware of sexual dysfunction with antidepressants."

In 2000 Rivas-Vazquez and his team reported on the increase in interest among researchers on treatment-induced sexual dysfunction, chronicling the many recent discoveries concerning sexual side effects. Though they complained that existing literature dealt mainly with case studies, small-scale trials, and tests which 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 MAOI inhibitors and tricyclics), those which interfered with serotonin levels (SSRIs and venlafaxine) had far more severe sexual side effects than the atypical drugs (bupropion, nefazodone, and mirtazapine) which did not directly effect serotonin.

Rivas-Vazquez et al. record 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 effects. The suggest that trazadone has been known to infrequently cause priapism, and that fluoxetine, venlafaxine, and bupropin have all been known to occasionally cause increased libido. However, both venlafaxine and fluoxetine have also been known cause serious sexual dysfunction including decreased sexual desire, inability to function sexually, and decreased orgasmic reactions. Similar negative effects have been discovered in 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 which prompted their use. Depression itself can cause sexual dysfunctions, or create strains in personal relationships which may continue even past the resolution of the illness itself. So, for example, fluoxetine might usually decrease sexual desire physically, but provide such a release from depression that the individual has a higher sex drive than before they became depressed (albeit reduced from a natural baseline which 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.

It is generally understood that serotonin does affect sexual functioning by changing the levels of other neurotransmitters which directly control sexual functions at different stages of the sexual style. Dopamine, for example, enhances sexual pleasure and libido, is an intrinsic part of the orgasmic experience and has had some level 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 orgasm. Hence SSRIs may necessarily decrease dopamine levels and sexual functioning. Not all antidepressants are equally likely to cause sexual dysfunction, because not all antidepressants directly affect serotonin or dopamine levels.

Rivas-Vasquez et al. suggest that the most appropriate response to unwelcomed sexual side effects in treatment 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 this medication is also strongly recommended, as some patients may hesitate to mention sexual dysfunctions. Through using drugs which have very low incidences of sexual side effects, the degree to which these effects interfere with recovery and with relationships can be minimalized.

Michael Gitlin reports on "Psychotropic medications and their effects on sexual function: diagnosis, biology, and treatment approaches"

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 blames the emergence of this concern on "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 of this subject, Gitlin reviews numerous MEDLINE articles, coming to the conclusion that though clinicians need to be aware of and question their patients regarding sexual side effects, there does not appear to be a specific antidote to these problems clearly indicated by prior research.

Gitilin suggests that clinicians need to evaluate their patient's sexual functioning based on all possible causation for existing problems. Though dopamine is generally understood to increase sexual functioning which 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 boast an array of mild, effects. SSRIs, clomipramine and MAO inhibitors can cause severe side effects, while others like the tricyclics cause more mild effects.

There are a variety of possible, though not entirely proven, tactics which may be taken to reduce iatrogenic sexual disorders. These tactics include attempting to out-wait the symptoms and hope they go away, switching to a different drug, and lowering the dose to provide less effect. Additionally, a few antidotes have been proposed, including yohimbine and cyproheptadine, which may reverse problems with sexual side effects. Gitilin reasonably suggests that lowering the dose, attempting to outwait the effects, and using antidotes should all be attempted before abandoning a drug that works well for the patient's symptoms. Hopefully, in the future there will be more and better research on antidotes.

Nafziger et al. report on the "Incidence of sexual dysfunction in healthy volunteers on Fluvoxamine therapy"

Because of the problems, noted by prior researchers, regarding discriminating the differences between the symptoms of mental illness and the side effects of psychotropics used to cure those illnesses, Nafziger and his colleagues chose to conduct a study on the side effects of the antidepressant fluvoxamine on healthy volunteers. Prior research on fluvoxamine 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 up to 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. The present study closely monitors effects and questions patients regarding their experiences with fluvoxamine.

In this study, among healthy volunteers who took 150mg of fluvoxamine daily, 20% experienced sexual dysfunctions within two weeks, and 35% experienced sexual dysfunction within four weeks. This was much higher than previously assumed, and this rate was comparative to the experiences of patients on SSRIs, and (according to this article) that of tricyclic and heterocyclic antidepressants and MAOIs.

The fact that this study found much higher than expected rates of sexual side-effects from fluvoxamine than was expected highlights the importance of specifically asking individuals about their experiences in determining rates of sexual side effects, rather than depending on self-reporting. One might have expected that fluvoxamine, being an SSRI, would have many of the same side effects of other SSRIs, but the fact that otherwise had been suggested is importance to notice.

Michelson et al. report on "Female sexual dysfunction associated with antidepressant administration: A randomized, placebo-controlled study of pharmacological intervention"

One of the main frustrations among researchers in this field is the lack of double-blind and placebo-controlled studies. The importance of having such studies is highlighted by Michelson et al.'s controlled trial assessing the results of supplementing fluoxetine with buspirone or amantadine (or a placebo) for a period of time. Michelson found that though uncontrolled case studies had suggested that such supplements could help with female iatrogenic sexual dysfunction, in his own study it appeared that though buspirone and amantadine worked to improve most of the patient's conditions, a placebo worked equally well. As the article explains, "The mechanisms underlying this improvement are uncertain but probably relate to the intensive self-monitoring of sexual function and regular clinic visits as well as to nonspecific effects associated with medication administration."

Some evidence that buspirone and amantadine might help had been available prior to the study, and there is a chance that the functionality of a placebo does not entirely discredit their use. Michelson explains that buspirone could manipulate certain serotonin receptors in an attempt to ameliorate the overload of serotonin, and that amantadine was thought to increase dopamine activity. As such, either might theoretically help with SSRI-related sexual dysfunction. However, when the double-blind test was performed, it found that the success of treatment was roughly the same regardless of whether these pills were taken or a placebo was used. One significant difference was that those on admantadine had greater energy levels than they study-mates, which did not seem to directly affect sexual functioning. Michelson and his colleagues speculated that the reason for such marked improvement in all categories was the extensive journaling and attention paid to the sexual activity.

Ashton and Rosen report on "Bupropion as an antidote for serotonin reuptake inhibitor-induced sexual dysfunction"

Unlike the Michelson study, Ashton and Rosen's work on using bupropion to ameliorate the sexual dysfunctions associated with SSRIs was neither double-blind nor placebo-controlled, and so there must remain some degree on uncertainty regarding its implications for medical practice. Regardless of whether or not it is certain in its conclusions, the fact that a two-thirds majority showed positive improvements in sexual functioning when taking doses of bupropion does tend to indicate that this drug may be of some aid in reducing the negative affects of SSRIs on sexual experience.

Bupropion is itself anaminoketone antidepressant, which could theoretically be used in the place of SSRIs to treat depression. However, for patients who had successfully stabilized with another antidepressant (and might not so successfully transfer to a new drug), bupropion has already b been in use to help treat SRI-induced dysfunctions. Despite its common use, until Ashton and Rosen's work was released, there had been no studies released on the success rate of bupropion or the actual necessary dosage, which required individual doctors and patients to experiment rather blindly with it.

Ashton and Rosen found that 66% of their subjects had favorable experienced with bupropion. About 19% responded to taking 75mg shortly before sex, 26% responded to taking 150 mg shortly before sex, but a full 57% responded to taking 75 mg on a regular basis, which tends to indicate a gradual change in body chemistry. Of patients treated with paroxetine, 80% experienced positive results. Flouxetine, sertaline and venlafaxine had between 50-65% success rates, while fluvoxamine only yielded 33% success rates. That there was a significant difference in which treatments responded to bupropion might indicate that something beyond placebo affect was at work. However, further studies are in order.

Ashton & Bennet's Letter to Editor

Ashton and Bennet, whose work was neither placebo-controlled or very large in scale, chose to merely write a letter to the medical community regarding their observations of the results of using Sildenafil to treat iatrogenic male erectile dysfunction. They acknowledged that many of the former antidote options did not appear to be entirely dependable. Options they mentioned included stimulants and gingko biloba, in addition to other drugs such as cyproheptadine, yohimbine, amantadine, buspirone, and bupropion; they also mentioned the use of "drug holidays" which gave the body a short break from its treatment. The idea of merely waiting to see if the problem resolves itself (which has actually been proposed in several articles) had a very low chance of success, and only 5.8-9.8% of iatrogenic SSRI-induced sexual dysfunctions have been indicated to spontaneously resolve themselves. Instead, Ashton and Bennet suggested the use of Sildenafil, which is a phosphodiesterase type 5 inhibitor.

Sildenafil was released to treat male erectile dysfunction of physical, psychological, or mixed origin. Their few case studies appear to be the first to test sildenafil in the treatment of iatrogenic erectile dysfunction. In the first case, in which the gentleman was currently taking fluoxetine, bupropion had not succeeded in curing his sexual dysfunctions. sildenafil, on the other hand, was reported as working 80% to (in his words) "110%" when taken an hour before sex. In the second case study, in which the patient was using a mix of sertraline and methylphenidate, the sexual dysfunction in question had withstood attempts to treat it wit venlafaxine, bupropion, and nefazodone. In this case too, sildenafil taken one hour before sex normalized his system responses. Ashton and Bennet admit they cannot draw conclusive evidence from these studies, but suggest that they are grounds for further research.