Tolerance to antidepressants - an empirically obtained solution

If in need, people dramatically benefit from antidepressants.

Even more dramatic therefore is that for a small group of these people medicine tolerance comes about: demise of the positive effect due to adaptation of the nervous system. It is scarcely admitted in medical literature. Remedies have tried but without consistent&lasting succes.

I belong to the particular group. I suffer from autism. Antidepressants break my typically autistic inertia and reduce my need of sleep dramatically (less than 6 hours instead of about 14 on average). Also, a state is achieved in which I am not only able to function and take care of myself, but even apt to enjoy what I am doing, work concentrated and well - and thereby... enjoy life.

Tolerance first appeared after the fourth month using paroxetine. Second, fluvoxamine was tried, with moderate succes, again ending in tolerance. A row of other compounds was to follow, of which some had effect initially, while others showed no noticable activity apart from side-effects. Also, at every new succes-try tolerance seemed to appear quicker.

By lack of alternatives and wishing to avoid unnessecary tolerance-breed, I started combining tryptisol and clomipramine. This worked well for about 6 months, but then again, tolerance set in.

Then the first little speck of hope arose. Contrary to the experience with other compounds, tolerance for clomipramine turned out to be wearing out: after minimally six weeks of abstinence ("drug holiday"), the effect of the medicine turned out to re-appear on new try. This is the first reason why clomipramine should be considered unique.

Having taken notice of the tenacity of my quest, my chemist advised me to try mirtazapine. This would turn out a discovery, be it for very different reasons than he might have anticipated. The essence turned out to be this: mirtazapine blocks the 5ht2 and 5ht3-receptors. Thereby, the over-all reaction of the nervous-system is altered.

With only mirtazapine, there was no effect at all. Frustrated, I added clomipramine. Then some effect was there. Interestingly it was different from what I was used to for it was gradual in onset. Also, the effect turned out dimmed (I found later on, of course, that both effects were due to the receptor-blocking). So very soon I was adding the maximum dose of clomipramine. And then even the little effect began to fade away.

Frustrated, again I added: 20 mg paroxetine. Be it now with virtually immediate and overwhelming effect! This would turn out to be due to the fact hat the CYP2D6-liver-enzyme responsible for breaking down the clomipramine, gets over-adressed by the paroxetine having higher affinity, thereby roughly doubling the clomipramine-bloodrate. According to the books, the result of this is poisonous. Yet not so in my case (at least not up till now)!

Experimenting with higher (that is: higher than what is officially allowed: 250 mg) doses of clomipramine without paroxetine were then to show that the paroxetine somehow eliminates the (here) one (manifested) side-effect of high doses of clomipramine, i.e. tremor.

After usually roughly three months of taking the drug-cocktail, the light rather suddenly goes out again. Then I typically stop taking the pills immediately, resulting in days of inertia on which I "sleep" almost constantly, be it nastily lightly. Then precisely 11 weeks follow in which I can function well to very-well without the pills (abstinence-effect turning out elongated by the mirtazapine)! After that, the cycle repeats. And such for about 6 years now.

This result is offered for those who also suffer tolerance. If you wish to be advised on how to try this, please contact me and I will offer you whatever I can (except the pills themselves, for that, unfortunately is yet quite another matter if there is no doctor willing to have compassion with you).