Post-SSRI Sexual Dysfunction

from Wikipedia, the free encyclopedia
Classification according to ICD-10
  Undesirable side effects ...
N48.4 Impotence of organic origin
F52.0 Lack or loss of sexual desire
  ... for therapeutic use of pharmaceuticals, drugs or biologically active substances
Y49.2 Other and unspecified antidepressants
ICD-10 online (WHO version 2019)

In post-SSRI sexual dysfunction ( PSSD ) (to be interpreted. Persistent sexual dysfunction after discontinuation of SSRI / SNRI ) is, to a treatment caused kind of sexual dysfunction . It is triggered by taking antidepressants that belong to the group of selective serotonin reuptake inhibitors or selective serotonin-noradrenaline reuptake inhibitors . PSSD is considered a scientifically unproven hypothesis.

The disorder can persist for months to years after discontinuing the SSRI; in some cases it remains permanent. Taking it for just a few days can lead to this syndrome . In the meantime, the possible persistence of SSRI-induced sexual dysfunction after discontinuation of treatment is recognized in the specialist information for the SSRI Fluoxetine, in DSM-5 and by the European Medicines Agency .
In some cases, PSSD may be a specific subtype of SSRI withdrawal syndrome .

Symptoms

One or more of the following sexual symptoms may occur with PSSD. They either start with withdrawal of the SSRI or persist after withdrawal. Symptoms may worsen after discontinuation.

A common PSSD symptom is genital deafness or decreased genital sensitivity.

frequency

In the majority of cases, PSSD does not occur, that is, the SSRI-induced sexual dysfunction goes away after discontinuation.
However, the frequency of PSSD is not clear. In science, epidemiological studies are required.

Initially underestimating the frequency of sexual side effects while taking it

It is known that SSRIs can cause numerous sexual dysfunctions while ingested. Early studies concluded that fewer than 10% of patients experienced such side effects . However, because these studies only considered unsolicited reports, they underestimated the frequency of sexual impairment. In more recent studies, doctors specifically asked about sexual problems that had occurred; some achieved an affected rate of up to 60%. A large study that differentiated between different SSRIs found an incidence of over 70% for the SSRIs citalopram and paroxetine , and 67.3% for the SNRI venlafaxine. If one compares studies that are based only on spontaneous reports with those that are based on a systematic survey, the result is a difference of up to 60% in terms of the frequency of sexual side effects found.
Consequently, SSRIs like dapoxetine are also used for the treatment of premature ejaculation. The effect of delayed ejaculation occurs in 70–80% of men and, according to a study on fluoxetine, is associated with an increase in the penile sensation threshold. The study authors concluded that this effect is likely to be responsible for the delayed ejaculation. Bahrick suspects reduced genital sensitivity or genital deafness as a characteristic side effect of SSRIs while they are being taken, although only a few studies have so far mentioned this side effect in addition to the study on the penile sensation threshold mentioned above. The studies mentioned by Bahrick come to the conclusion that SSRIs can actually cause this side effect during the treatment period; within the first few days. Bahrick cites as one possible reason for the infrequent recording that the primary tools for assessing psychiatric drug-induced sexual dysfunction, the CSFQ (The Changes in Sexual Functioning Questionnaire) and the ASEX (Arizona Sexual Experiences Scale), are genital changes Does not include sensitivity. Even when genital sensitivity was included, the symptom was not transparently reported.

Study data

The Dutch pharmacovigilance center LAREB writes the following:

"Emerging evidence (...) suggests that in some individuals, sexual dysfunction may persist indefinitely. Lareb received 19 reports of persistent sexual dysfunction after SSRI use. Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, these reports suggest that they may also be a consequence of SSRI treatment. The symptoms occurred soon after the start of the medication and some patients reported explicitly that relational problems or sexual function disorders were not present before the start of the SSRI. Some patients also reported that the depression remained in full remission, but the sexual function disorder persisted. "

“Recent evidence (...) suggests that the sexual dysfunction in some individuals may persist indefinitely. Lareb has received 19 reports of persistent sexual dysfunction following SSRI use. Although changes in sexual desire, sexual performance, and satisfaction are often manifestations of mental illness, the reports suggest that these could also be the result of treatment with SSRIs. Symptoms arose soon after starting the medication, and some patients pointed out that there were no relationship problems or sexual dysfunction prior to starting the SSRI. Some patients also stated that the depression remained in full remission but the sexual dysfunction persisted. "

PSSD is still considered a scientifically unproven hypothesis to this day. However, there is evidence that this phenomenon may exist but appears to be less common than the common sexual dysfunction associated with SSRI use. In any case, PSSD is less known and less researched. Apparently, in the majority of cases, sexual problems go away with discontinuation of the SSRI; however, some patients do not recover and continue to suffer from PSSD. In one study, patients affected by SSRI-induced sexual disorders were placed on amineptine , a dopamine-acting tricyclic antidepressant , and the use of the SSRI was stopped: 55% of them continued to have sexual problems six months later. In the control group, which only took amineptine, there were only 4% of sexual dysfunction: Current placebo-controlled double-blind studies, which analyzed the suitability of SSRIs for the treatment of premature ejaculation, found that the ejaculation-delaying effect of SSRIs was found in a high percentage of Experimental patients may persist for a long time after discontinuing the SSRI.

One thing should be noted in connection with studies: clinical studies rarely reveal permanent side effects. This could be due to the fact that such examinations are usually stopped during treatment, which carries the risk of biases. According to Eli Lilly and Company, there are no adequate and well-controlled studies investigating sexual dysfunction during treatment with the SSRI fluoxetine.

Case reports

Published cases

In addition to the 2012 Lareb report, which cites 19 cases, there are several case reports:
three PSSD cases were published in May 2006, a fourth shortly afterwards, a fifth in late 2007. In spring 2008, the Journal of Sexual Medicine reported three more Cases that it had selected from a Yahoo group with over 1300 (today 3800) people affected by PSSD. Among other things, one case has been reported in which the sexual dysfunction disappeared within a few days after the temporary discontinuation of citalopram ("Drug Holiday"), but persisted after the resumption of citalopram treatment and continued over the years deteriorated.
In 2013, Stinson examined the influence of PSSD on the quality of life of nine people in her dissertation. One finding was that the SSRI-induced emotional side effects, regardless of whether they were positive or negative, also appeared to have persisted after discontinuation in several PSSD sufferers.
In 2014, Hogan et al. a study of 91 cases from a side effects reporting website. A case of PSSD that has now lasted 18 years is mentioned, beginning with a brief intake of fluoxetine in the 1990s at the age of 18.
The Dutch neuropsychiatrist and sex researcher Marcel Waldinger reported in 2014 about a patient he diagnosed with PSSD and tried to treat with low-level laser therapy .
In 2015, a study based on an online survey was published in the Journal of Clinical Psychopharmacology , which found 183 possible PSSD cases according to defined criteria, including 23 highly probable. Of these 23 participants, 18 suffered from genital numbness, along with other symptoms.
In 2017, a Spanish journal reported on another case.
There are also some published cases of persistent genital arousal disorder (PGAD) and premature ejaculation after discontinuation of SSRIs. Persistent genital arousal disorder and premature ejaculation are fundamentally different from hypersexuality and should not be confused with it.

Monitoring and reporting

In order to record, monitor and control the development of PSSD in patients, psychiatrists could proceed as follows: They define measurable health parameters ( hormone levels , sexual function) with the help of a survey or a laboratory test ; this takes into account the patient's concerns about possible side effects. If PSSD occurs, it may be possible to establish a connection between the measured health parameters and PSSD.

Patients eligible for treatment with antidepressants are often unable to request tests of sexual function: on the one hand, because they are usually poorly informed about the side effects of antidepressants, on the other hand, because some suffer from depression . It is therefore required that patients be better informed about the possibility of permanent sexual disorders before prescribing SSRIs so that an informed decision can be made

Reports of side effects after drug discontinuation provide valuable guidance for new drug development and help patients make informed decisions. In Germany, the Federal Institute for Drugs and Medical Devices is responsible for reports of suspicions.

causes

The cause of PSSD is not exactly known at this point in time. Most doctors are unaware of the possibility of permanent effects or automatically blame them for psychological reasons. However, psychological relationships could not be found in several of the case reports mentioned above.
Regarding SSRI-associated sexual dysfunction, it is required that doctors be aware that delayed orgasm / delayed ejaculation is a symptom most commonly associated with SSRIs and usually not with depression. Likewise, decreased genital sensation, which may be the cause of delayed ejaculation, is associated in the literature with the use of SSRIs rather than the disorders or conditions for which they are prescribed.

The American Expert Committee on Reproductive Risks ( Center for the Evaluation of Risks to the Human Reproduction ) classifies the prototypical SSRI fluoxetine (Prozac) as a reproductive poison.

In the American specialist information on the SSRI fluoxetine, it has been stated since 2011 that symptoms of sexual dysfunction occasionally persist after discontinuing treatment with fluoxetine.

After an internal investigation, the pharmaceutical company Sanofi is said to have come to the conclusion that SSRIs could be associated with persistent sexual disorders after treatment discontinuation.

Animal studies

Experiments with rodents have shown that treatment with SSRIs for two or four weeks at a young age leads to permanent impairment of sexual behavior, which also persists in adulthood and is similar to several PSSD case reports. At the cerebral - molecular level there is a serious and permanent reduction in tryptophan hydroxylases in the dorsal raphe nucleus and a reduced level of serotonin transporters (SERT) in the cerebral cortex . It was also found that treating the dam with fluoxetine during pregnancy and breastfeeding also reduced the sex drive and fertility of her male offspring. It cannot be ruled out that later behavioral neurological consequences can also occur in humans, because no study examined children who were exposed to SSRIs in the womb beyond early childhood.

Long-term consequences

Some research suggests that all pharmaceutical drugs have epigenetic effects. For example, the chronic treatment of rats with fluoxetine for 14 days permanently dulls their 5-HT1A receptors , i.e. beyond the discontinuation of the SSRI. Such long-term adaptations of the 5-HT receptors as well as more complex global changes probably arise via changes in the gene expression. Some of these gene expression adaptations are the result of a changed DNA structure, caused by chromatin transformations: epigenetic modification of histones and gene silencing through DNA methylation due to the increased expression of the methyl-binding proteins MeCP2 and MBD1. Changes in gene expression and chromatin transformations are also part of the mechanism of action of electroconvulsive therapy.

Since changes in gene expression are complex and sometimes involve permanent modifications of the chromatin structure, it is sometimes assumed that the ingestion of SSRIs can cause a chronic change in gene expression in the brain, thereby impairing catecholaminergic neurotransmission and neuroendocrinological disorders such as decreased function of the Hypothalamus-pituitary-testicular axis, which manifests itself in a lower testosterone level, lower sperm count, and lower sperm quality with damaged DNA. However, in the absence of detailed neuropharmacological, pharmacogenomic, and toxicogenomic research, the definitive cause of PSSD remains uncertain for the time being.

Relation to the "chemical imbalance theory"

Some SSRI critics claim that TV and print advertising convey the wrong image, in particular by inadmissibly simplifying the effect of SSRIs and thus misleading the public. Much of the criticism has stemmed from doubt that SSRIs work by correcting chemical imbalances. Without tools for precise measurement and monitoring of the neurotransmitter levels before and during treatment, it is not possible to determine whether the correct neurotransmitter has actually been raised to the correct level, i.e. a chemical imbalance is corrected, or whether the level rises too high, for example. There is also the assumption that SSRIs cause chemical imbalances and abnormal brain conditions in the first place. One possible mechanism by which this can happen is the inhibition of dopaminergic neurotransmission, which results in the sexual disorders mentioned above.

Other drugs and psychotropic substances

Also, neuroleptics and other antidepressants (eg. As clomipramine ) can cause sexual dysfunction has been proven. Many affect the serotonergic system, just like SSRIs. This could also be the reason for sexual problems from taking antipsychotics. Today's neuroleptics mainly manipulate dopamine neurochemistry; this can also have an effect on a sexual level.

MDMA is also associated with persistent sexual dysfunction. It may lead to axonal damage. MDMA stimulates the release and inhibits the reuptake of serotonin. Ben-Sheetrit et al. point out that in MDMA the potency of the active ingredient is probably responsible for the neurogenic sexual impairment, while in PSSD an individual susceptibility is likely to play an important role, since SSRI treatment does not lead to PSSD in most patients.

The post-finasteride syndrome has similar symptoms as PSSD. The mechanism of post-finasteride syndrome is unknown.

therapy

Nothing is currently known about therapy for PSSD. As the cause is still unclear, this is not surprising. After all, studies from 2002 and 2009 theoretically examined possible treatments for sexual dysfunction during SSRI treatment. A placebo-controlled study on rats came to the conclusion that 5-HT1A antagonists could be advantageous. This may conflict with the use of flibanserin , a 5-HT1A agonist, to increase sexual satisfaction in women.

Individual evidence

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