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Women are the majority of patients who are prescribed antidepressants – two out of three patients who have been prescribed a drug for depression are female. But in many pre-clinical trials it is still mainly male participants who are tested, although there is clear evidence of sex-specific differences in disease and the response to medication. In order to bridge this gap neuroscientists around Julia Sacher & collegues have tested 64 healthy women, to see how their brain reacts to the combination of motor learning while taking a common antidepressant. Surprisingly, and in contrast to previous clinical trials, they found no improvement in motor learning among the participants.
Women are the majority of patients who are prescribed antidepressants – two out of three patients who have been prescribed a drug for depression are female. Some of these antidepressants are thought to help with motor recovery after stroke. While age-specific stroke rates are higher in men, women experience more frequent and more severe stroke events, and are less likely to recover. But in many pre-clinical trials it is still mainly male participants who are tested, although there is clear evidence of sex-specific differences in disease and the response to medication. In order to bridge this gap neuroscientists around Julia Sacher from the Max-Planck-Institute for Human Cognitive and Brain Sciences have tested 64 healthy women, to see how their brain reacts to the combination of motor learning while taking a common antidepressant. Surprisingly, and in contrast to previous clinical trials, they found no improvement in motor learning among the participants.
„We gave the healthy female participants a very common antidepressant, called escitalopram, and we tested how well they performed on a motor task in an MRI scanner. We expected that the drug would improve their performance on the task. What we actually found was that it didn’t.“, first author of the study, Eóin Molloy, explains the results. „So the motor performance of the women who took the drug and the women who took a placebo was very similar.“ But what the scientists found was, that in central motor regions of the brain there was a different response compared to the placebo. „There was less brain response in the regions that are involved in performing that type of task.“, continued Molloy. „We think that the lower response in the brain might mean that the brain is working less hard to perform the task. The drug might be improving the efficiency of the brain during similar performance of the task.“
Why did the scientists collect data that explain more than other findings have up to this point? Previous studies that had shown positive results on this topic were too small in terms of sample size. And current large clinical trials that found that the antidepressant had no effect in stroke patients were problematic in terms of methodology. For example, the participants did not have to do a standardized motor learning task in combination with the drug. But a main reason was to test women whose endogenous sex hormones are downregulated by the pill. „This is important because in many similar pre-clinical trials it is still mainly male participants who are tested, although there is clear evidence of sex-specific differences in both the response to this kind of medication in general and how this drug can affect performance of this motor learning task.“, study director Julia Sacher says. „Sex hormones have a significant effect, and in addition, the majority of patients who are prescribed these drugs are female.“
The women took the drug for seven days in a clinically relevant dose – similar to what would be prescribed if a patient went to the doctor for antidepressive treatment. The idea of going for a week continuously is a step beyond of what previous studies have done – and measuring the brain at the end is something quite unique. The scientists recommend that future studies in males, naturally cycling females, as well as healthy aged participants and stroke patients are needed for a successful translation from healthy models to patients.
Julia Sacher and her team think that there could be a relationship between hormonal fluctuation and how antidepressants affect the female brain including how patients recover from neuropsychiatric disease, such as depression or stroke, and are currently investigating this suspicion in follow-up studies.
Eóin Molloy
PhD student
molloy@cbs.mpg.de
Eóin N Molloy, Karsten Mueller, Nathalie Beinhölzl, Maria Blöchl, Fabian A Piecha, André Pampel, Christopher J Steele, Ulrike Scharrer, Gergana Zheleva, Ralf Regenthal, Bernhard Sehm, Vadim V Nikulin, Harald E Möller, Arno Villringer, Julia Sacher:
"Modulation of premotor cortex response to sequence motor learning during escitalopram intake"
Journal of Cerebral Blood Flow & Metabolism: https://journals.sagepub.com/doi/full/10.1177/0271678X20965161
The scientists gave the healthy female participants a very common antidepressant and tested how well ...
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