Clinically measured, I've seen plenty of IRL evidence that high doses of ashwaganda change people's physiological measures such as cortisol, thyroid and androgen hormones, there's no reason for me to doubt the psychological effects.
How do androgen, cortisol and thyroid levels change?
It changes from person to person. I like to call ashwagandha a pseudo-adaptogen, because it is not perfectly adaptogenic, I'll explain. In a majority of people ashwagandha normalizes cortisol and thyroid markers, if they're high then it decreases them, if they're low then it increases them. However, for some people it will decrease cortisol and increase thyroid dose dependently, which can lead to hyperthyroidism. Ashwagandha doesn't directly increase sex hormones, but can indirectly effect them as it changes the cortisol and thyroid levels. Decreasing high levels of cortisol can increase sex hormones. Increasing low levels of cortisol can restore sex hormones too. Increasing hypothyroid to euthyroid can increase estrogen and testosterone, but if it increases further to hyperthyroidism then that can increase SHBG which decreases "free" sex hormones.
I don't know when to start with clomipramine. I'm at 5 weeks of fluvoxamine now, 150 mg.
My gdoc wants me to stay at 150 for about 4 weeks, but it hasn't kicked in really....
I could work my way up to 300 mg if my docter allows it, on the other hand, the RLS (restless legs) and the teeth grinding in the evening are getting more annoying.
I wonder why side effects are noticable, but no big noticable effects on the intrusive thought.
I looked into some meta-analyses and there is some contention about whether clomipramine is meaningfully better than fluvoxamine. Some say clomi's effect sizes are bigger, but side effects can be greater, too. Others say the effect sizes are not comparable because of methodological differences across studies, and that the response rates are about the same. They tend to agree drop-outs (probably from side effects) are more frequent for clomi.
I am thinking, there is no guarantee clomi will work if fluvoxamine isn't working, they are both known to 'work' for a longer time than other SSRIs, perhaps when one poops-out on enough SRI-based drugs, then no SRI will keep working. If that's the case, then you need to focus on the cause of the poop-out (for which the models, we all can admit, are highly theoretical at this point).
https://www.ncbi.nlm...pubmed/21508860
Sarcosine therapy for obsessive compulsive disorder: a prospective, open-label study.
BACKGROUND:
Several lines of evidence implicate glutamatergic neurotransmission in the pathophysiology of obsessive compulsive disorder (OCD). Sarcosine is an endogenous antagonist of glycine transporter-1. By blocking glycine uptake, sarcosine may increase the availability of synaptic glycine and enhance N-methyl-d-aspartate (NMDA) subtype glutamatergic neurotransmission. In this 10-week open-label trial, we examined the potential benefit of sarcosine treatment in OCD patients.
METHOD:
Twenty-six outpatients with OCD and baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) scores higher than 16 were enrolled. Drug-naive subjects (group 1, n = 8) and those who had discontinued serotonin reuptake inhibitors for at least 8 weeks at study entry (group 2, n = 6) received sarcosine monotherapy. The other subjects (group 3, n = 12) received sarcosine as adjunctive treatment. A flexible dosage schedule of sarcosine 500 to 2000 mg/d was applied. The primary outcome measures were Y-BOCS and Hamilton Anxiety Inventory, rated at weeks 0, 2, 4, 6, 8, and 10. Results were analyzed by repeated-measures analysis of variance.
RESULTS:
Data of 25 subjects were eligible for analysis. The mean ± SD Y-BOCS scores decreased from 27.6 ± 5.8 to 22.7 ± 8.7, indicating a mean decrease of 19.8% ± 21.7% (P = 0.0035). Eight (32%) subjects were regarded as responders with greater than 35% reduction of Y-BOCS scores. Five of the responders achieved the good response early by week 4. Although not statistically significant, drug-naive (group 1) subjects had more profound and sustained improvement and more responders than the subjects who had received treatment before (groups 2 and 3). Sarcosine was tolerated well; only one subject withdrew owing to transient headache.
CONCLUSION:
Sarcosine treatment can achieve a fast therapeutic effect in some OCD patients, particularly those who are treatment naive. The study supports the glycine transporter-1 as a novel target for developing new OCD treatment. Large-series placebo-controlled, double-blind studies are recommended.
Sarcosine and Agmatine are dirt cheap, and are very low risk when taken at clinically relevant dosages. I don't see why you shouldn't experiment with them before moving to clomipramine. According to animal models, 200-400 mg of Agmatine per day is all you need for anti-ocd/anti-depressant potentiation effects, and 500-1000 mg Sarcosine.
Edited by Adam Karlovsky, 10 November 2017 - 05:36 AM.