The reason behind asking this is because imipramine was shown to have no appreciable effect on 3a-HSD activity in a study of SSRI effects on neurosteroid levels, but does have a potent effect of inhibiting serotonin reuptake.
Our results indicate that the SSRIs fluoxetine, sertraline, and paroxetine decrease the K m of the conversion of 5α-dihydroprogesterone to allopregnanolone by human 3α-HSD type III 10- to 30-fold. Only sertraline inhibited the reverse oxidative reaction. SSRIs also affected conversions of androgens to 3α- and 3α, 17β-reduced or -oxidized androgens mediated by 3α-HSD type IIBrain. Another antidepressant, imipramine, was without any effect on allopregnanolone or androstanediol production
While it is associated with a high rate of sexual dysfunction during use, there appears to be no mention of anyone developing a condition similar to PFS/PSSD after its use.
Have you ever wondered why TCAs, that have been on the market way longer than SSRIs, are rarely associated with PSSD? and post-TCA sexual dysfunction is easier to fix than post-SSRI sexual dysfunction? here’s why:
“Postsynaptic 5-HT1A receptor sensitivity in the hippocampus, measured by the effect of 8-OH-DPAT to increase cAMP levels in the dialysate, was increased after chronic clomipramine.”
“he lack of an effect of clomipramine on the response to 8-OH- DPAT contrasts with results obtained after long-term administration of SSRI drugs (Li et al. 1993Li et al. , 1994Li et al. , 1996Li et al. , 1997) where subsensitivity of hormonal responses was obtained. Therefore, the 5-HT uptake blocking action of a drug per se does not appear to be sufficient to induce subsensitivity of post-synaptic 5-HT 1A receptors in the hypothalamus, and indeed the finding of an increased cAMP response to 8-OH-DPAT in the hippocampus after chronic clomipramine indicates that subsensitivity of postsynaptic 5-HT 1A receptors was not obtained in this tissue either”
Clomipramine binds extremely strongly to SERT (0.14–0.28), but despite this, it doesn’t cause postsynaptic 5HT1A receptors to downregulate/desensitize, but in fact it upregulates them. Whereas, SSRIs even weak binding ones to SERT can downregulate postsynaptic 5HT1A receptors. This means that SSRIs can also potently disrupt steroidogenesis and sex receptors sensitivity whereas TCAs do less of that.
Considering trying Clomipramine myself, was the first thing my psychiatrist recommend but I went for a low dose of aripiprazole instead, which made me restless and agitated, now i’m on buproprion which is worse, anxiety and depression increased drastically, so getting off that asap, my last option is clomiprmine I suppose.
Another PAS patient emailed me earlier this week about the study linked in the opening post and asked whether the effect on increasing androstanediol at the expense of decreasing DHT was a candidate etiology for PSSD. I think so, it makes sense, but can’t say with any certainty. It was discussed on this site many years ago as a possible link between PFS and PSSD long before I was able to make any clear sense of the science discussed here.
The SSRIs in the study linked in the first post lowered DHT similarly to 5-ar inhibitors, only by a different means (3a-HSD induction), while imipramine did not have such an effect.
So, I figured if this effect on DHT was the culprit, then imipramine shouldn’t cause PSSD. It also “may” be a safer alternative to SSRIs for people with this post-drug syndrome who are desperately in need of an antidepressant. A consideration if one is insistent upon taking an antidepressant and bupropion doesn’t work well for them.
@Knifli, Thanks for providing the info that it doesn’t appear to have been reported as a drug causing anyone to suffer PSSD! Surprising that someone from the PSSD forum caught onto this recently too.
There has also been some discussion emerge on this forum recently that serotonin itself can exert an anti-androgenic effect via 5-HT receptors, and not necessarily by decreasing DHT:
Since, androgens are a major prostatic stimulatory factor, we asked if the 5-HT inhibitory effect was related to the AR stimulatory pathway. By western blot analysis we showed that testosterone supplementation induced AR up-regulation, but 5-HT treatment significantly decreased AR expression either with or without testosterone supplementation (Fig. 2a and b) suggesting that the inhibitory function of 5-HT could be related to inhibition of the AR pathway. Similarly, both the selective 5-Htr1a agonist 8-OH-DPAT, (Fig. 2a and c) and the selective 5-Htr1b agonist, anpirtoline, (Fig. 2a and d) induced a significant AR down-regulation, more evident in anpirtoline treated VPs. Taken together these results indicate that in vitro 5-HT inhibits rat prostate growth through 5-Htr1a and 5-Htr1b , by down-regulating AR.
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This includes excessive synaptic serotonin acting on steroidogenic cells:
Had to question whether that was something from a scientific journal or literotica.com for a moment.
Impramine seemed to be cited as a drug that causes negative sexual side effects for humans in everything I read about it. Disappointing. Couldn’t find one case of someone mentioning post-drug symptoms though.
