ADHD – Medication across the menstrual cycle, is cyclic dosing a way to go?

Many ADHD-women report that they react differently on their medication depending on their current hormonal status. Some have, in collaboration with their doctor or nurse, have tried out a more individualized dosing strategy for their ADHD-medications. They describe how cyclic dosing of their meds give them better functioning and less side effects. But what does cyclic dosing mean and what could it look like in real life? This is the topic of this week’s blog post from Letterlife.

Hormones in play

Beginning in puberty and ending in menopause, we as girls and women, live our entire reproductive lives in dramatic and constant hormonal fluctuation. Given that our brains are packed with hormone receptors it should come as no surprise that dramatic changes in sex hormones will affect not only how we feel, and function, but also our ADHD-symptoms and the effect of medications. For example, research shows that females respond differently to alcohol, nicotine, and cocaine in different phases of the menstrual cycle1. More specifically, it seems like women may experience less effect of stimulants in the luteal phase (the 2 weeks after ovulation when estrogen levels fall back, and progesterone levels increase).

Even though there are yet little to no studies exploring how different doses of stimulant ADHD-medication may affect girls and women with ADHD in different periods of the menstrual cycle or in different periods of their reproductive lives, a consequence of the interaction between dopamine and estrogen could be both over- or undermedication of naturally cycling females when using a dose regimen tailored for males. It seems like estrogen levels, modulate dopamine activity in the brain, and thereby may influence both the efficacy and the tolerability of ADHD-medications in females. This basic theoretical framework for why cyclic dosing may be an interesting field to explore in females is nothing new really. Cyclic dosing of antidepressants (SSRIs) for PMS/PMDS-problems in women have been used for many years already. There are even international consensus reports published on this2. But since there is no such consensus on how female hormones affect ADHD-symptoms there are not much evidence to rely on when guiding girls and women regarding their ADHD-medications and doses. 

Mias story

Mia 38, describe her personalized medication strategy like this: 

“I started tracking my menstrual cycle after I had my last child 4 years ago. I also reinitiated my ADHD-meds that I had discontinued during the pregnancy, and it very soon became painfully obvious to me that both my mood and functional level fluctuated dramatically across my cycle. The first one and a half week following my period were pretty smooth. Then a couple of days before ovulation my thoughts started racing and I was increasingly irritated and restless. My husband said I was like “myself on steroids” during these days, talking really fast, getting annoyed with everyone that were so “slow and stupid”. I was acting really hypomanic! Then after a week and half it was like I entered yet another phase where I was almost lethargic and depressed. I had no energy even for the smallest things at home and my mind was constantly kidnaped by catastrophic thoughts and feelings of being a total failure.”

She continues:

“So, I showed this pattern of an emotional and functional roller-coaster to my doctor and together we agreed on the hypothesis that the hormones and meds probably interacted in a way that may explain at least some of the drama. That’s why we decided to try the experiment of tailoring my doses with respect to my cycle. We set one baseline dose for the first 10 days, lowered the dose temporarily 4 days before ovulation, went back to the baseline dose for 7 days and then increased it for the last 6 to 7 days before menstruation. It may sound complicated and messy but for me it totally changed the playfield. I function on a much more stable level across the cycle and a save so much energy by not having to deal with the mess I usually ended up in due to poor ADHD-symptom control because of too low a dose some days and the side effects from too high a dose other day”.

In summary

The concept of cyclic dosing for ADHD medication aims to tailor dosage to hormonal variations, optimizing treatment outcomes for females with ADHD. This shouldn’t have to be described as an isolated “experiment” but be the core of precision health. Precision medicine should include women as well! It’s important however to acknowledge that research is limited or even non existing, and that there are many women, both with and without ADHD who are largely unaffected by hormonal fluctuations. Therefore, any adjustments to medication should be made in consultation with a healthcare professional who can monitor treatment effectiveness.

We have to remember that we are pioneers in this field. Our Letterlife research group have several epidemiological and qualitative studies as well as clinical trials in the pipeline. Together we hope that we will by collecting real-life data, will give girls and women the power to predict periods of resilience or, to plan to mitigate negative consequences and to adjust their pharmacological treatment according to their individual hormonal profile. Our common and clear goal? To improve quality of life, physical, mental, and sexual health across the female lifespan.

References:

1Handy AB, Greenfield SF, Yonkers KA, Payne LA. Psychiatric Symptoms Across the Menstrual Cycle in Adult Women: A Comprehensive Review. Harv Rev Psychiatry. 2022 Mar-Apr 01;30(2):100-117. doi: 10.1097/HRP.0000000000000329. PMID: 35267252; PMCID: PMC8906247.

2Nevatte T, O’Brien PM, Bäckström T, Brown C, Dennerstein L, Endicott J, Epperson CN, Eriksson E, Freeman EW, Halbreich U, Ismail K, Panay N, Pearlstein T, Rapkin A, Reid R, Rubinow D, Schmidt P, Steiner M, Studd J, Sundström-Poromaa I, Yonkers K; Consensus Group of the International Society for Premenstrual Disorders. ISPMD consensus on the management of premenstrual disorders. Arch Womens Ment Health. 2013 Aug;16(4):279-91. doi: 10.1007/s00737-013-0346-y. Epub 2013 Apr 27. PMID: 23624686; PMCID: PMC3955202.

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