ADHD Drugs May Alleviate Menopausal Brain Fog

— Small review has limitations, but findings warrant larger trials, expert says

Attention deficit-hyperactivity disorder (ADHD) medications may improve subjective experiences with menopausal brain fog, but more research is needed, a scoping review suggested.

Data from three crossover, randomized controlled trials suggested that both the stimulant lisdexamfetamine (Vyvanse) and the non-stimulant atomoxetine (Strattera) significantly improved executive function among women without prior ADHD, reported Pallavi Khanna, MD, of the University of Tennessee Health Science Center College of Medicine in Memphis, and colleagues a poster presentation at the Menopause Societyopens in a new tab or window annual meeting.

On the Brown ADD Scales (BADDS; lower scores mean less executive dysfunction), scores for women who took lisdexamfetamine fell significantly from 35.7 to 21.2, compared with dropping to 29.8 for those on placebo (P<0.001). Scores for those on atomoxetine also fell, from a baseline of 38.6, to 25.5 compared with 30.1 for those on placebo (P=0.009), they found.

However, neither drug significantly improved executive function on objective tests, the researchers reported.

"Both drugs improved how women rated their executive function, but not their scores on objective cognitive tests," Khanna told MedPage Today, adding that brain fog "is one of the most common complaints in my menopause clinic, and it often looks a lot like ADHD."

There are no FDA-approved treatments for menopausal brain fog and cognitive benefits for menopausal hormone therapy have been inconsistentopens in a new tab or window -- but Khanna urged clinicians to "take brain fog seriously." That's in part why she and her team decided to explore whether ADHD medications could help with menopause-related brain fog and if women with more ADHD symptoms were more likely to be affected by menopause symptoms.

As estradiol depletes during the menopause transition, dopamine and norepinephrine also decline. ADHD has these same deficits, hence the rationale for using ADHD medications to treat menopausal brain fog, she explained.

For this scoping review, Khanna and colleagues searched Embase, PubMed, Scopus, PsychINFO, and Central databases for menopause terms combined with executive function, ADHD, and ADHD medications.

Ultimately, five studies were included in analysis: three crossover randomized controlled trials involving 60 patients total, measuring BADDS plus objective cognitive tests; and two cross-sectional studies of 6,048 patients from Iceland and the U.K., measuring the Adult ADHD Self-Report Scale (ASRS) and validated menopause scales.

Further analyses of the two large cross-sectional studies showed that among women with previous ADHD diagnoses, those with more ADHD symptoms also had worse menopause symptoms.

In the Icelandic study, women with ADHD had higher menopause symptom scores than their counterparts without diagnoses (18.0 vs 13.0, P<0.01). Also, more of these women reported severe menopause symptoms compared to those without ADHD (54.2% vs 30.1%). The same was true when focusing on more severe ADHD (72.8% vs 28.9%), suggesting a potential correlation between ADHD symptom severity and more intense menopausal symptoms.

Meanwhile, in the U.K. study, ADHD diagnosis had no effect, but those with higher ASRS scores had worse menopause symptoms, the authors noted.

"Symptom severity, not a formal ADHD diagnosis, predicted menopausal burden," Khanna said. "Many women were never diagnosed, so relying on a chart diagnosis misses the women most at risk."

JoAnn E. Manson, MD, MPH, DrPH, of Harvard Medical School in Boston and past president of the Menopause Society, told MedPage Today that while this study is purely hypothesis-generating and needs to be replicated, the findings are "exciting and warrant testing in larger randomized trials," including comparisons to menopausal hormone therapy.

"There may be overlap in vulnerability to ADHD and to menopausal cognitive symptoms such as brain fog," said Manson, who was not involved in the study. "Moreover, the study found that ADHD medications may improve these symptoms and subjective executive function, possibly by raising dopamine and reducing glutamate in working memory regions of the brain."

The study was limited because all of the randomized controlled trials included in the analysis came from one research group at a single institution and excluded women diagnosed with ADHD. Also, there were no studies of methylphenidate (Ritalin) or comparisons with hormone therapy. Khanna said that larger, independent trials are needed.