COMT mutations and stimulants

I have ADHD that I’ve been treated for off and on throughout my life. Recently, I sought psychostimulant treatment as I was having trouble being interested in projects at work that were necessary and prolonged.

We started off with Adderall IR 10mg. In the past, I have tolerated Ritilan and Adderall just fine. So, it was a surprise to me when I started to experience symptoms that were not a problem in past treatments. These included:

We tried hopping around to nearly every other psychostimulant medication available: dextroamphetamine, methylphenidate, dexmethylphenidate, and extended release variations of some. They all produced the same results.

What was interesting about this problem was that the side effects would grow over days. When I started, the benefits were clearly worthwhile comparative to the nuisances. Once the side effects grew in severity, this intensifying effect also became evident within each day - they’d present in the afternoon and by the time the evening rolled around, I’d be in severe pain and crippling anxiety.

It wasn’t until tapering off, indending to restart at a lower dose after giving my brain a couple weeks to clear all the dopamine and norepinephrine out that I made a critical connection. I had a psychopharmacological genetic assay performed the year before after a problem with SSRIs. To my disdain, I found therein that I had a genetic mutation affecting COMT, the enzyme responsible for metabolizing those neurotransmitters that psychostimulants modulate the activity of.

I noticed that at a very low dose of 0.5mg BID of Adderall IR that the side effects were tolerable. So, I decided to try a slow titration. At first, I stayed on that dose for a week until the side effects were no longer present. Then, I increased the total daily dose by 0.5mg. They came back briefly, but no worse. Once they subsided again after three days, I increased by 1mg. Repeating this, I found that I could continue the milligram increase every 3 days.

I’m not yet at the typical starting dose of 10mg, but things look promising at this point. My hypothesis for what initially happened is that, due to the impaired metabolism of DA and NE, these neurotransmitters were building up with each passing day of treatment. My CNS became overstimulated, leading to most worrying for me, the severe anxiety and localized rhabdomyelosis in my thighs. Thus, starting at an unusually lower dose reduced post-synaptic neurotransmitter levels and slowly titrating up allowed my brain time to regulate receptors to compensate for their impaired breakdown.

To accomplish these low doses, I had to get creative. The IR formulation is composed into a tablet. I crushed this and filled the powder in a capsule. Using a milligram scale, I determined the weight and ratios of active consistuent to its total. I was then able to calculate and cap individual doses. While there’s some margin of error in using a consumer scale, the binders and fillers contributing to the total weight of the tablets added enough padding that it resulted in a mere +/- 0.25 - 0.5 mg fluctuation after scale calibration.

Hopefully this trend holds course. I’d prefer a psychostimulant over an alternate ADHD treatment such as Wellbutrin or Straterra, which I know don’t work as well, having tried them in the past. If it doesn’t pan out, though, I have other ideas. But that’s for another post.

Cautions against soy for folks on transfem HRT »