SSRIs are notorious for causing sexual dysfunction in some users, which unfortunately for some can persist long after discontinuation.
Interestingly, many ex-SSRI users share almost the same symptoms we ex-Finasteride users do (loss of libido, ED, genital numbness, shrinkage, loss of spontaneous/nocturnal/morning erections, apathy, fatigue, blunted orgasm, memory & cognition problems etc).
Thus, this should be of interest to all of us, as IT MENTIONS FINASTERIDE. Consider bringing this with you to your doctor the next time he claims it’s all in your head.
While the conclusions of this document discuss epigenetic changes to neurochemistry, likely involving dopamine receptors, the upside is that some recovery seems possible thanks to Dopamine agonists or reuptake inhibitors. In addition – for ex-Fin users, after discontinuing Finasteride many found their Testosterone levels dropped – but some have had success with boosting T… in addition to getting the androgen/estrogen ratio under control, for starters.
Note: I am not saying this is THE DE FACTO CAUSE of our problems, only that many of their symptoms seem to parallel our own, and thus there may be some commonality of the mechanisms at work.
At the same time, keep in mind that this is not a double blind, placebo controlled study by any means… in fact it isn’t even a study, but more of a subjective case analysis as it involved 3 members of the Yahoo SSRI Side Effects group and is a synthesis of other [limited] research out there on the subject:
Nonetheless, perhaps in the future we may be able to participate in such a document or research article, or full-on study. I suggest everyone read through the FULL TEXT of this document.
[Size=4]Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors[/size]
The Journal of Sexual Medicine
Volume 5 Issue 1 Page 227-233, January 2008
FULL TEXT ONLINE: blackwell-synergy.com/doi/fu … 07.00630.x
PDF: blackwell-synergy.com/doi/pd … 07.00630.x
Abstract:
Introduction.
Sexual dysfunctions such as low libido, anorgasmia, genital anesthesia, and erectile dysfunction are very common in patients taking selective serotonin reuptake inhibitors (SSRIs). It has been assumed that these side effects always resolve after discontinuing treatment, but recently, four cases were presented in which sexual function did not return to baseline. Here, we describe three more cases.
Case #1: A 29-year-old with apparently permanent erectile dysfunction after taking fluoxetine 20 mg once daily for a 4-month period in 1996.
Case #2: A 44-year-old male with persistent loss of libido, genital anesthesia, ejaculatory anhedonia, and erectile dysfunction after taking 20-mg once daily citalopram for 18 months.
Case #3: A 28-year-old male with persistent loss of libido, genital anesthesia, and ejaculatory anhedonia since taking several different SSRIs over a 2-year period from 2003–2005.
Results.
No psychological issues related to sexuality were found in any of the three cases, and all common causes of sexual dysfunction such as decreased testosterone, increased prolactin or diabetes were ruled out. Erectile capacity is temporarily restored for Case #1 with injectable alprostadil, and for Case #2 with oral sildenafil, but their other symptoms remain. Case #3 has had some reversal of symptoms with extended-release methylphenidate, although it is not yet known if these prosexual effects will persist when the drug is discontinued.
Conclusion.
SSRIs can cause long-term effects on all aspects of the sexual response cycle that may persist after they are discontinued. Mechanistic hypotheses including persistent endocrine and epigenetic gene expression alterations were briefly discussed.
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“… Recently, it was found that dopamine agonists (pramipexole, ropinirole, cabergoline) or reuptake inhibitors (bupropion) can improve his symptoms somewhat, but only temporarily for a few weeks, before their effects wear off. Extended-release methylphenidate (Concerta; Alza Corp, Mountainview, CA, USA) 54 mg once daily, appears to have even greater efficacy at reversing his symptoms than the dopamine agonists or bupropion, but again, the prosexual effects are only temporary and go away when the drug is discontinued.”
“… It is currently not known what causes the sexual side effects of SSRIs to sometimes persist after discontinuation.”
“… Most doctors are unaware of the possibility of long-lasting effects or attribute them to psychological causes”
“… Various complex hormonal, central, and peripheral nervous system, and neurochemical changes occur during SSRI usage that could account for their sexual side effects. Changes include increased serotonin, decreased dopamine, blockade of cholinergic and alpha-1 adrenergic receptors, inhibition of nitric oxide synthase, elevation of prolactin levels [9,10], decreased oxytocin [11], and decreased testosterone levels [12].”
“…SSRIs change levels of neurotransmitters other than serotonin, likely through indirect mechanisms. A strong case can be made that many of the side effect of SSRIs, both sexual and otherwise, are dopamine dependent [13]. Data suggest that SSRIs can inhibit dopaminergic neurotransmission, not only by their effects on dopamine secretion or recapture, or on dopaminergic receptors, but also indirectly through serotonergic mediation [14]. Complex changes of dopaminergic neurotransmission (mostly antidopaminergic effects) have been described with SSRIs [10]. The partial reversal of symptoms with dopamine agonists or reuptake inhibitors in Case #3 strengthens the case for a role of downregulation of dopaminergic neurotransmission as a cause of persistent SSRI sexual side effects.”
“… More recently, it was shown that SSRIs can induce more complex changes in neurotransmission by forcing dopamine transporters to take up serotonin into dopamine terminals and subsequently corelease dopamine and serotonin signals [15]. It is unknown what long-term neuropsychophamacologic effects these types of synaptic alterations would have on human sexual behavior.”
“… Besides central nervous system (CNS) alterations, it is also possible that peripheral changes are caused by SSRIs. For example, 95% of the serotonin receptors in the body are outside the brain, many in the peripheral nerves [16], and only 1–2% of serotonin is located in the CNS [17]. Thus, it has been postulated that SSRIs, in part, cause sexual problems because of the inhibition of the serotonin receptors in the peripheral nerves [16,17].”
“… While any or all of these changes may be responsible for SSRI sexual side effects, no studies have been performed to validate that these changes are normalized after discontinuation of therapy. It is therefore possible that sometimes, these parameters remain persistently altered. However, at least two of these biomarkers––serum testosterone and prolactin––were normal in the cases reported here.”
“… Second, although rare, many publications point to a role of SSRIs in the occurrence of extrapyrimidal effects such as bradykinesia, rigidity, akathisia, and acute dystonia [18]. These effects can sometimes be persistent even after drug discontinuance [19], an example of other longer-lasting side effects caused by SSRIs. Perhaps, persistent sexual side effects are caused by a similar mechanism to extrapyramidal effects, namely, adverse but unclearly defined neurological alterations in areas of the nervous system responsible for sexual arousal and functioning.”
"… Third, the possibility of structural changes to brain regions involved in sexual response should also be considered. For example, it has been shown that the treatment of adolescent patients with obsessive–compulsive disorder with paroxetine causes significant reductions in the left amygdala volume [20], a part of the brain shown to be strongly involved in response to visually erotic stimuli [21]. Such structural changes may take a very long time to reverse, if at all, in some patients."
“… Finally, it is becoming increasingly clear that epigenetic changes are involved in human phenotypic expression and disease [22,23]. Antidepressants can cause quite complex changes in gene expression [24], and it is possible that some of these changes are not normalized simply by withdrawing the drugs [25]. It is not unprecedented for medications to cause persistent sexual side effects mediated by such epigenetic gene expression changes. Specifically, it has been hypothesized that persistent female sexual dysfunction caused by the oral contraceptive is caused by long-term or permanent epigenetic upregulation of steroid hormone-binding globulin expression [26].”
Also, experiments with rodents have shown that chronic treatment with SSRIs at a young age results in permanently decreased sexual behavior that persists into adulthood and is similar to the cases described here [27,28]. At the cerebral molecular level, there are profound and permanent reductions in both the rate-limiting serotonin synthetic enzyme, tryptophan hydroxylase, and the serotonin transporter, but it is not yet known if the neurochemical situation in rodents is recapitulated in humans.
"… An extensive search of the literature has not revealed other examples of iatrogenic sexual dysfunction that persist after the causative drug is discontinued, but the authors are aware of many unpublished cases. It is hypothesized that this phenomenon may apply generally to medications that can cause sexual dysfunction, such as antipsychotics (neuroleptics), beta-blockers, histamine-2 receptor blockers, [Size=4]finasteride (Propecia, Proscar; Merck, Whitehouse Station, NJ, USA[/size]), anti-androgens such as leuprorelin (Lupron; TAP Pharmaceuticals, Deerfield, IL, USA), tamsulosin (Flomax; Boehringer Ingelheim, Ingelheim, Germany), etc. Although the exact biochemical mechanism may differ between different classes of drug, the persistent sexual dysfunction is postulated to be caused by epigenetic changes in the expression of genes involved in the sexual response cycle. However, apart from the aforementioned contraceptive study [25] and rodent studies [27,28], no experiments have yet been performed to test this theory."
“…It is important that patients are informed about the high probability of sexual side effects while on SSRI medications. It is worth noting that none of the three patients received adequate informed consent with regards to the known risks of sexual side effects, so as to be able to consider those risks in their decision to take the medications. Patients should also be told that there are indications that in an unknown number of cases, the side effects may not resolve with cessation of the medication, and could be potentially irreversible.”
“… While the Internet source of the cases means we lack the same level of control over verifying the cases’ histories in the way that extended in-person interaction would provide, the Internet group membership currently provides the best available source of information about a condition of potential public health importance. Given the lack of awareness of the condition among clinicians, and the lack of follow-up data in the research literature, the problem seems unlikely to be identified either by current research paradigms or by voluntary Medwatch reports. While the patients’ accounts of their sexual functioning described here appear reliable, a limitation of these case reports is dependence on patients’ retrospective accounts. Until there are more data, it is impossible to know the true level of the risk of persistent SSRI-induced sexual dysfunction.”
“… Further study needs to be made concerning prolonged sexual dysfunction from SSRIs, which we tentatively term “post SSRI sexual dysfunction.” Epidemiologic, retrospective, and prospective investigations are necessary to address the frequency, severity, and quality of this problem, before its biologic and neurochemical etiology can be fully addressed.”
