Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?

[ihatelexapro444]

Check this out! -> https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC8370302/

I'm going to highlight some important and interesting statements from the research as summary:

"The “numbing” effect produced by SSRIs has similarities to the effect of rubbing lidocaine into the genital area"

"These genital effects do not occur on antidepressants that do not inhibit serotonin reuptake; other antidepressants and psychotropic drugs can cause erectile dysfunction but not the syndromes of numbness, pleasureless orgasm, loss of libido, or persistent arousal."

"Lidocaine, which also produces genital numbing, appears to do so through an action on late sodium currents,10 and serotonin reuptake inhibitors also have effects on late sodium currents."

"Two other syndromes have been described which appear closely related to PSSD. One is postfinasteride syndrome (PFS). First described in 2011, this occurs in young men taking finasteride to stall hair loss.7 It also happens with other 5-alpha reductase inhibitors—dutasteride and saw palmetto. Genital anesthesia, loss of libido, and sexual dysfunction are features of this syndrome. A postretinoid sexual dysfunction (PRSD) has also been described.8 This also includes genital anesthesia, sexual dysfunction, and loss of libido"

"Aiming at finding a treatment, PSSD sufferers have tried a wide range of agents active on various dopamine and serotonin receptors along with phosphodiesterase inhibitors and other drugs, but these have no therapeutic effect for PSSD, PFS, or PRSD. PFS sufferers have focused on evidence for androgen insensitivity."
(oddly amphetamine does temporarily relief PSSD, though never fully)

"It does appear that with time (several years) a degree of spontaneous recovery happens in some cases. In other cases, there are brief remissions (days), often triggered by stopping a brief course of another drug such as an antibiotic. There are grounds to think therefore that these enduring effects do not stem from permanent damage."

"multiples studies have found that SSRI treatment impacts planaria in numerous ways, including locomotion, light/dark preference (photophobic tendencies), DNA damage, and regenerative polarity.65,69–71"

"To assess the impact of transient fluoxetine treatment on bioelectric states, intact wild-type D. japonica were soaked in a 2 μM fluoxetine solution for 3 days, at which point the solution was washed out and the samples were placed in Poland Spring water for 1 week, Both the 1wk washout treated group and the 3d fluoxetine soak group were significantly depolarized relative to the controls, while there were no differences in relative polarization between the 1wk washout group and the fluoxetine soak group, This indicates that the depolarizing effect of fluoxetine is persistent far after the drug treatment has ended."

"Fluoxetine exposure results in long-term physiological changes in planaria. (A) Planarian flatworms were exposed to the drug Fluoxetine, washed extensively, and then kept for 1 week in plain water. They were then imaged using a fluorescent voltage reporter dye (see Materials and Methods section) and compared to controls (exposed to vehicle only) or animals after 3 days of continuous fluoxetine exposure. (B) Quantification of the fluorescence signal revealed that even after 7 days in plain water, a brief exposure to Fluoxetine depolarizes the animal as much as does 3 days of continuous exposure, revealing a persistent voltage memory induced by SSRI treatment. SSRI, selective serotonin reuptake inhibitor. ***indicates significance to p < 0.01."

"Bioelectric circuits can maintain long-term and stable changes of state after relatively brief alterations of Vmem, and we have previously suggested bioelectric state to be a target of SSRIs and other psychoactive drugs in the context of developmental defects. Such alterations can plausibly affect neural (and non-neural) responses such as could be important for human sexual function, either directly on somatic cells or through indirect effects acting through the microbiome, immune system, or brain."

"Bioelectric memory has not yet been demonstrated in human patient tissues, representing an important area for subsequent work, which could be addressed in vivo and in human organoid systems in vitro.106 Paralleling the development of ion channel modulator drug cocktails, guided by computational models of bioelectric circuits to induce desired pro-regenerative states, it's possible that the negative effects of SSRI exposure could someday be mitigated by rationally designed cocktails of already human-approved drugs acting as ionoceuticals."

It seems this has been posted once before, but I'd like to give it a revisit as it's some good information.
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