Low Dose SSRIs Increases Neurosteroid Synthesis Witohut Any Effect On Serotonin Reuptake

[rei]

Upregulation of neurosteroid biosynthesis as a pharmacological strategy to improve behavioral deficits in a putative mouse model of PTSD

Seems like many SSRIs at 10-50 times smaller dose than commonly prescribed act as selective brain steroidogenic stimulants (SBSSs). This leads to immediate notable increase in many neurosteroid levels, this paper focuses on allopregnanolone.

It is very clear that SSRIs are extremely problematic and with next to no benefit at commonly prescribed doses, but this study makes me wonder if doctors just prescribe it at ridiculous overdose, and used sanely at 0.2-1 mg /day they could be beneficial?

This effect seems to exist in many SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine) and in addition in SNRI venlafaxine and additionally in mirtazapine.

 

[RobertJM]

I used to to take Lexapro at a dose of 1.25mg per day and it kept my despressive symptoms at bay. It also had prosexual effects. I think the usual dose was at least 10mg for most folk.

However, there was nothing liberating about it. It really was all about keeping symptoms at bay. I knew it wasn't solving anything and just masking pre-existing problems that I knew I had.

It pooped out after about a year on this protocol. I started feeling quite unpleasant on it. I remember when I first started coming off've it. I heard a tune on the radio that I liked and it actually brought me to tears in my car . I had forgotten what it felt like to feel human again.

I tried the low dose approach with other SSRIs as well. But low dose Prozac wasn't pretty. That caused sexual dysfunction even in the lower doses. I was hoping it would be more dopaminergic (5ht2c antagonist).

Lexapro was the only one that seemed to work in lower doses. Not surprising, as it seemed to be one of the 'kinder' and more effficacious SSRIs based on studies and efficacy for depression/sexual function.

 

[rei]

Maybe halving your escitalopram to about 0.6mg would be closer to the desired dose so it stays at zero SSRI effect. What was your lowest sustained dose on the fluoxetine?

Anyhow, to me the most interesting of these is mirtazapine, as it is serotonin blocking.

 

[Kingpinguin]

I did experience the same. Taking 1/2 or 1/4 of the minimum so called ”active dose” gave me benefits with zero side effects basically. I did experience both increased mood and libido.

 

[Blossom]

Yes, and that is what I am doing with zoloft currently, until I can get some mirtazapine. I take about 6 mg (the doctor prescribed 25mg which is pretty much the lowest dose because they assume it's for serotonin reuptake inhibition/"anti-depressant"! lol) Anyways, it's been fine. In fact, the research shows that the purpose of low dose ssri is to avoid the sleepiness of progesterone supplementation.

There was some discussion about this last year. Here’s a good thread on the subject.
Allopregnanolone May Soon Be Approved As A Fast-acting Antidepressant