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Post SSRI Sexual Dysfunction (PSSD) is a type of sexual dysfunction caused directly by the previous use of SSRI antidepressants. While apparently uncommon, it can last for months, years, or sometimes indefinitely after the discontinuation of SSRIs.

Symptoms

One or more of the following symptoms persist or begin after the discontinuation of SSRIs.

Frequency

It is well known that the selective serotonin reuptake inhibitors (SSRIs) can cause some types of sexual dysfunction. Initial studies found that such side effects occur in less than 10% of patients, but those studies relied on unprompted reporting, so the frequency of such problems was underestimated. In more recent studies, doctors have specifically asked about sexual difficulties, and found that they are present at between 83% (Hu et al. 2004) and 98% of patients (Clayton et al. 2006).

However, while sexual dysfunction is obviously very common while taking SSRIs, the problem of persistent dysfunction after discontinuation does not appear to be as frequent, or at least not as well-known or researched. Onset of sexual problems often occurs during and after extended SSRI use but there have been reports of fairly rapid onset as well. It appears as though the majority of people regain their sexual function after stopping SSRIs, but a growing number of people report Post SSRI Sexual Dysfunction (PSSD).

Case Reports

The first three cases of PSSD were published in May 2006 (Csoka and Shipko, 2006), and a fourth case was published soon after (Bolton et al., 2006). While PSSD usually refers to downregulation of sexuality, SSRI withdrawal can also cause long-term premature ejaculation (Adson and Kotlyar, 2003) and persistent sexual arousal syndrome (PSAS) (Goldmeier and Leiblum 2006), (Goldmeier et al. 2006). These symptoms are quite different from, and should not be confused with, hypersexuality.

Cause

It is currently not known what causes PSSD. Unaware of the possibility of this long-lasting effect, most doctors automatically attribute it to psychological causes. However, a growing number of physicians whose patients suffer from this condition have come to believe that it is indeed caused by the prior use of antidepressants. It has been shown that both clinical depression itself, and antidepressants, cause large-scale changes in gene expression (Palotas et al., 2004), (Kalman et al., 2005), (Yamada et al., 2005), (Boehm et al., 2006). Some of these gene expression changes are a result of altered DNA structure caused by chromatin remodeling (Hyman, 2006), (Newton and Duman, 2006), specifically epigenetic modification of histones (Tsankova et al., 2006) and gene silencing by DNA methylation due to increased expression of the methyl binding proteins MeCP2 and MBD1 (Cassel et al., 2006). Altered gene expression and chromatin remodeling are also involved in the mechanism of action of electroconvulsive therapy (ECT) (Altar et al., 2004), (Tsankova et al., 2004).

Because described gene expression changes are complex, and can involve persistent modifications of chromatin structure, it has been suggested that SSRI use can result in persistently altered cerebral gene expression leading to compromised catecholaminergic neurotransmission and neuroendocrine disturbances (Csoka and Shipko, 2006). However, without detailed neuropsychopharmacological, pharmacogenomic and toxicogenomic (Szyf, 2004) research, the definitive cause remains unknown.

Some critics of SSRIs claim that the widely-disseminated television and print advertising of SSRIs promotes an inaccurate message, oversimplifying what these medications actually do and misinforming the public (Lacasse & Leo, 2005). Much of the criticism stems from questions about the validity of claims that SSRIs work by 'correcting' chemical imbalances. Without tools to accurately measure neurotransmitter levels and to allow for continuous monitoring during treatment, it is impossible to know if one is correctly targeting a deficient neurotransmitter (i.e. correcting an imbalance), reaching a desirable level, or even introducing too much of a particular neurotransmitter. Thus it has been aruged that SSRIs can actually cause chemical imbalances and abnormal brain states (Moncrieff and Cohen, 2006). One possible mechanism is by inhibition of dopaminergic neurotransmission (Damsa et al., 2004), resulting in described persistent sexual dysfunction.

Experimental evidence

Experiments with rodents have shown that chronic treatement with SSRIs at a young age results in profound reductions in both the rate-limiting serotonin synthetic enzyme, tryptophan hydroxylase, in dorsal raphe and in serotonin transporter (SERT) expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram (Celexa) produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on SERT. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences (Maciag et al. 2006) and (de Jong et al. 2006). Long-term alterations in gene expression may result from disturbances in 5-HT neurotransmission in the brain of the animals (Hansen and Mikkelsen, 1998).

Chronic treatment with fluoxetine (Prozac) has been shown to cause persistent desensitization of 5HT1A receptors even after removal of the SSRI (Raap et al. 1999). Long-term adaptive changes in 5-HT receptors are likely to be mediated through alterations of gene expression (Faure et al., 2006).

References

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