Post-SSRI Sexual Dysfunction (PSSD) and PFS : Exploring the Overlaps and Potential Treatments

post SSRI sexual dysfunction or pssd is a condition that has stumped many in the medical community some may even call it controversial but for many patients it has been nothing short of devastating pssd is a debilitating condition that severely affects quality of life we still don't know enough about it various theories have been proposed to explain the pathophysiology of this condition however there remains a lot to be discovered the diagnosis of pssd is usually made by ruling out all other causes medical and psychological causes treatment continues to remain challenging with no specific treatments identified for this condition today we'll be tackling this critical topic and understanding more about this condition through insights derived from PFS which is post finero syndrome stay with me until the end of the video where we look at the overlaps in pathophysiologies between PFS and pssd and then move towards the potential treatment Avenues available so let's get started welcome to Psychiatry simplified I'm Dr seil regga consultant psychiatrist if you'd like to explore the world of Neuroscience Psychiatry and mental health then this is a channel for you don't forget to hit the Subscribe button to stay in touch with all our future Rel reles before we go deeper into these conditions don't forget to check out this video here where I've covered pssd in more detail so let's start off with post feride syndrome or PFS what are the medications that are involved in PFS we have medications such as feride also known as Propecia or prar and utest also known as Avodart now these are primarily used to treat benign prostatic hypoplasia and androgenetic alopecia hair loss so how do these medications act they act primarily by inhibiting the 5 Alpha reductase enzyme what this enzyme does is it's responsible for the conversion of testosterone into dihydrotestosterone or DHT DHT is a more potent Androgen feride selectively inhibits type two of this enzyme whilst dutasteride inhibits both type 1 and type two despite their efficacy in treating BPH or benign prostatic hypoplasia and androgenetic alpascia they come with sexual side effects these include decreased libido erectile dysfunction and ejaculation disorders now just like post SSRI sexual dysfunction which can persist even after the medication stopped with feride and dutasteride the same thing can happen even after cessation of feride and dester these sexual side effects can persist leading to the condition known as PFS now evidence suggests that dester and feride can affect both the Central and the peripheral nervous system and the sexual side effects that are associated include decreased or loss of liido erectile dysfunction testicular atrophy and orgasmic disorders these symptoms can sometimes be Associated or accompanied by psychological changes such as depression anxiety and cognitive disturbances now as we go through this I'd like you to think about these specific sexual side effects and psychological side effects and Link them to what happens in post SSRI sexual dysfunction so if we look at sexual dysfunction in a bit more detail we find that some Studies have shown that patients frequently report low libido erectile dysfunction decreased arousal and these adverse effects did not result olve in most individuals even after 9 to 16 months of stopping the medication physical symptoms include gynecomastia reported in almost 70% of cases diminished seamen volume in force testicular atrophy and genital numbness or paresthesia the cognitive side effects include mental cloudiness or brain fog difficulty in concentration and general memory issues the study by ganza etal 2015 showed that 75% of patients reported brain fog and cognitive disturbances the same study showed elevated anxiety in 74% of cases depression irritability and suicidal ideation in 63% of cases so clearly these psychological complaints were deemed as severe and persistent patients also complained of muscle spasms chronic fatigue join pain musle muscle aches and symptoms such as dizziness the range of symptoms tells us that these medications affect both the brain and the periphery and it's not completely surprising because it involves hormones and we know that hormonal receptors are present and distributed all over the body and brain so let's explore the mechanisms behind PFS and here I'm going to cover five main postulated mechanisms first the neural active steroid levels we know that feride and dester reduces dihydrotestosterone and increases testosterone and andrastin Dion and it does this through the inhibition of the five Alpha reductase enzyme PFS patients also showed lower Alo pregnanolone now Alo pregnanolone is a neuroactive steroid and this particular neurosteroid plays a prominent role in both sexual fun function but also regulation of mood in fact neurosteroids such as zuranolone and brexanolone have been approved for the treatment of postpartum depression and are showing promise in a range of mood disorders so one postulated mechanism of PFS is linked to the changes in neuroactive steroid level two Androgen receptor upregulation now feride and dester increases the upregulation of Androgen receptors and they may some genetic polymorphisms that may be linked to the risk which means that in some individuals there may be a genetic predisposition towards the development of PFS number three gene expression changes in PFS patients there are 1,446 genes that are overexpressed and 2318 genes are underexpressed in penile skin this of course raises the question is the genital numbness and anesthesia that individuals experience linked to these gene expression changes for epigenetic modifications PFS patients seem to show increased DNA methylation in a specific Gene promoter in the CSF affecting gene expression and PFS symptoms and number five the gut brain axis now this is really interesting because feride affects the gut microb biome reducing its diversity in PFS patients this change may be linked to both the depressive symptomatology while the gut brain axis has been shown to be important for sexual function this is the first time this is being raised in relation to PFS so to summarize we can see that post feride syndrome can result in persistent sexual dysfunction even after the medication ceased and again the pathophysiology is not clear cut there are some postulated mechanisms as we saw linked to gut brain AIS the changes in neurosteroid levels and genetic polymorphisms as well with that in mind let's now move towards pssd or post SSRI sexual dysfunction and explore that with the insights that we've learned about PFS pssd like PFS is a condition where sexual dysfunction persists even after cessation of The Selective serotonin reuptake Inhibitors now I've covered the mechanisms of ssris in more detail in the video here so do check that out to learn more about these medications I've also covered pssd as I mentioned before here but it may be worth looking at this video here about ssris and emotional blunting because there is a strong correlation between emotional blunting and sexual dysfunction there are a range of treatment options a available to treat sexual dysfunction induced by ssris what we're talking about in this video is post SSRI sexual dysfunction where by definition the sexual side effects persist and it's a condition defined after a number of other psychological and medical causes are ruled out treated and despite all of that the sexual side effects persist that is what we're going to dig deeper into so what are the sexual side effects that persist after discontinuation of the drug first decreased libido and sex dve a significant number of patients report a sustained decrease in sexual desire even after stopping the medication two weak or nonp pleasurable orgasms many patients experience weak orgasms or a lack of pleasure during orgasm which can severely of course affect the quality of life third genital anesthesia very similar to what we saw in PFS this symptom is characterized by a loss of sensation in the genital area making sexual activity less enjoyable or even distressing four erectile dysfunction persistent erectile dysfunction has also been reported number five a lack of connection between the brain and the genitals some Studies have described it where patients describe a disconnect between their sexual thoughts and physical arousal indicating a deeper neurobiological issue now let's explore the postulated mechanisms once again this video isn't all exhaustive because I've covered many of these aspects in this video here so don't forget to check that one out the aim of this video is to look at the overlaps between the two and to see what potential treatments may be on the horizon for these two conditions so coming back to the mechanisms of pssd first the postulated mechanism of serotonergic inhibition of dopamine release we know that dopamine plays a crucial role in libido reward and sexual function it is crucial for sexual motivation and behavior ssris reduce dopamine in the ventral strim also known as nucleus accumbent the reward center and it is this mechanism that contributes to both emotional blunting and sexual dysfunction two neurotoxicity and genetic predisposition just like with FS there may be a genetic vulnerability towards developing pssd for example polymorphisms and genes related to the glutamatergic system have been linked to decreased libido and difficulties in achieving erections and orgasms in patients treated with Citalopram this is from the study by peus eel 2009 additionally serotonin neurotoxicity has also been postulated similar to what happens with MDMA X stasy number three endocrine abnormalities endocrine changes such as low serum levels of gonadotropins and testosterone along with elevated levels of prolactin have been observed in depressed patients treated with ssris now we know that ssris can reduce dopamine and dopamine has an inverse relationship with prolactin so this may act potentially to increase prolactin levels these abnormalities are often often worse in patients specifically reporting sexual problems indicating a potential hormonal imbalance contributing to pssd so clinically it becomes really relevant to carry out a detailed hormonal evaluation including measuring not only serum testosterone but serum prolactin and we often find that this serum prolactin can be reversed when dopamin agents are considered in the treatment of depression four epigenetic mechanisms epigenetic modifications such as DNA methylation have been observed with chronic SSRI exposure this differential methylation in individuals may Point towards some individuals having a greater propensity again to develop pssd number five changes in neuroactive steroid levels just like we saw in PFS we know that ssris affect levels of neurosteroids in fact this is one of the postulated mechanisms that provides benefits in the treatment of depression and anxiety as well it is possible that these changes in neurosteroid levels in certain individuals results in side effects particularly the pssd unfortunately what we don't know is which of these individuals are at risk based on specific biomarkers number six the gut brain axis just like feride and dester ssris also influence the gut microbiome which we know influences the gut brain axis influencing mood sexual behavior anxiety and other psychological aspects we know that alterations in gut microbiome have been seen with SSRI treatment and these changes can affect gut steroid production and contribute to an inflammatory environment potentially linking gut health to pssd so what we can see here is that pssd just like PFS also involves a combination of neurosteroid changes epigenetic changes genetic polymorphisms and changes in the gut brain axis let's now look at what are the shared mechanisms for both PFS and pssd and the basis for this is based on this latest update from this paper here and the reason why we want to to look at these commonalities is because they can potentially help us understand what are the potential treatments that can address both of these conditions CU clearly from a pathophysiological point of view there seems to be an overlap so the first overlapping mechanism is sex steroids and neurotransmitters so let's start off with dopamine dopamine plays a crucial role in sexual behavior sexual motivation erection ejaculation and and the reward system the dopamin neurons in the brain are regulated by sex steroids such as testosterone and its more poent form dihydrotestosterone we know that in PFS and pssd alterations in sex steroid levels can disrupt dopamine Pathways leading to sexual dysfunction for example we know that testosterone influences dopamine release in the medial preoptic area through nitric oxide synthes and we know that Nitric ox side is the main non- neurotransmitter mediator of penile erection the second overlapping mechanism is the serotonergic impact on dopamine now serotonin generally has an inhibitory impact on sexual function in the dorsal rafine nucleus where serotonergic neurons are situated we know that serotonin's influence on sexual behavior is modulated by sex steroids so estrogens here Act directly via estrogen receptors while androgens like testosterone and dihydrotestosterone act indirectly the inhibitory action of Serotonin on dopamine is likely an important factor in sexual dysfunction number three the noradrenaline adrenaline balance or the nor epinephrine epinephrine balance Studies have shown that feride and SSRI specifically peroxin can inhibit the enzyme pnmt which converts noradrenaline to Adrenaline so what happens here is that there is an excess of noradrenaline we know that noradrenaline can impact on male sexual function as norepinephrine induces the flaccid state of the penis whilst epinephrine or adrenaline levels correlate with erection this is really interesting because we can see that in the context of anxiety as well there is El nor adrenaline and this can often be associated with sexual dysfunction or performance anxiety resulting in difficulty achieving an erection number four the gut brain axis both PFS and pssd involve alterations in the gut microbiome resulting in gut disbiosis so changes in the gut microbiome affect the gut brain axis which in turn can influence sexual behavior for example in the context of depression or anxiety sexual function is affected so gut brain axis may act as a mediator contributing to sexual dysfunction and mood abnormalities so the big question is what can we do about it whilst of course a lot more researchers needed knowing these pathophysiologies actually provides a potential path for the development of treatments to address these devastating conditions so let's explore some of these possibilities first neuroactive steroid therapy we know that aloon is a neuroactive steroid that influences both mood and sexual function and we know that zuranolone and brexanolone have been improved for the treatment of postpartum depression which is essentially a mood disorder so interestingly one potential treatment option is the use of neuroactive steroids like alo pregnanolone alo p as it's called at times you see Alo P has anti-in inflammatory properties and the way it acts is through the Gaba a receptors it is a positive allosteric modulator positive aleric modulation enhances the effect of Gaba on these receptors so it's almost like Gaba on steroids you see the advantage here is that it reduces anxiety reduces arousal but interestingly we saw that the nor adrenic potentiation is linked to penile acidity so therefore by modulating or reducing anxiety arousal levels and reducing nor adrenic potentiation one may improve sexual function so that's a really promising Avenue furthermore we know that alop treatment can counteract gut inflammation induced by feride withdrawal suggesting its potential use in PFS and pssd again noradrenalin May feature here because we know that assess noradrenaline increases gut inflammation as well number two modulation of the gut microbiome targeting the gut microbiome through probiotics or microbiom derived bioproducts could help restore healthy gut flora and alleviate symptoms essentially the strategy here is to improve gut health to reduce gut inflammation which we saw feeds into sexual function and mood the Third Avenue is is dopamine agonists since dopamine plays a crucial role in sexual behavior dopamine agonists might be explored as a potential treatment option these medications could help normalize dopamine function and improve sexual motivation and performance we already know that dopamin potentiators are used in the treatment of SSRI induced sexual dysfunction for example bupropion bupropion is known to reverse SSRI IND dued sexual dysfunction of course here as as a reminder we're talking about the persistent sexual dysfunction after an SSRI is stopped which tends to be different in individuals similarly we have agents such as agomelatine and vortioxetine which again have dopaminergic potentiation properties number four epigenetic modulators given the role of epigenetic changes that we talked about medications that modify these epigenetic markers may be beneficial for example medic that inhibit DNA methylation May reverse the epigenetic modifications that are associated with PFS and pssd number five hormone replacement therapy HRT to correct imbalances we know is something that we use in per menopausal depression for example we know that HRT can improve sexual function therefore this approach could help address some of these hormonal dysfunctions that we've just explored in p SSD as well so amongst the treatments that I've just talked about none of these are conclusively established as treatments for PFS or pssd there is a lot that we don't know about this condition however we can see certain connections being made and certain possibilities certain agents that can be implemented in clinical practice after a risk benefit analysis with your doctor for example we know that dopamine agonists such as buproprion are available one always has to consider risk benefit analysis at an individual level as to whether this is suitable so to summarize we can see that PFS and pssd are complex and multifaceted conditions we can see that understanding their respective pathophysiologies and their overlaps opens the door to potential treatments some that are testable in clinical practice from neuroactive steroid therapy to modulation of the gut microbiome these seem to be really promising avenues for future research and treatment development so I hope that you found this video useful if you like the video please leave us a like don't forget to subscribe to our channel to stay in touch with all the future releases and of course don't forget to leave your comments below I learn a lot from all of you I'd like to thank you all for supporting this channel it means a lot to us I look forward to seeing you in another video soon until then stay curious bye-bye

Channel: Psychiatry Simplified - Dr Sanil Rege

Views: 1,756

Keywords: PSSD, Post-SSRI Sexual Dysfunction, PFS, Post-Finasteride Syndrome, mental health, Dr. Sanil Rege, neuroscience, sexual dysfunction, gut-brain axis, neurosteroids, SSRIs, finasteride, Propecia, Proscar, dutasteride, Avodart, dopamine, serotonin, androgen receptors, gene expression changes, neuroactive steroids, hormonal imbalances, cognitive disturbances, libido, erectile dysfunction, genital anesthesia, hormonal evaluation, epigenetic modifications, probiotics

Id: CZATt5AoQjw

Length: 23min 37sec (1417 seconds)

Published: Wed Jul 03 2024