N-acetylcysteine (NAC) is a form of a natural amino acid called cysteine and has gained attention for its potential beneficial role in physical and mental health. It acts as a precursor for a substance called glutathione which is an important antioxidant in our body. Generally, antioxidants help protect our cells from damage caused by harmful molecules called free radicals.
A team of scientists around first-author Dr. Rajabi recently published “the first study assessing the role of NAC for the treatment of PMDD based on its antioxidant effect” (p. 95). The authors explain that their rationale for doing so is two previous studies that “have raised the theory of the role of oxidative metabolism in the symptoms of PMDD and therefore the value of using antioxidant agents whether for the prevention or the treatment, though the evidence is not appropriate enough and controversial” (p. 95).
Dr. Rajabi and colleagues’ study can be summarized as follows:
A total of 119 naturally-cycling individuals with PMDD were randomly assigned to three groups of treatment:
(1) fluoxetine (an SSRI (antidepressant) used for PMDD treatment),
(2) NAC,
or (3) placebo.
Interestingly, the medication/placebo “were administered daily for two weeks within the initiation of menstruation” (p.94), which is the follicular phase of the menstrual cycle.
The authors report that when they compared self-reported symptoms in all three groups, they found “remarkable inferiority of placebo to the other two groups while no statistical difference was found between NAC with fluoxetine” (p. 94).
While this finding hints at a beneficial role of NAC for PMDD symptoms, several methodological limitations of the study must be considered, including:
It is unclear whether the PMDD diagnosis of the participants was prospectively confirmed by the approved method using the DRSP - daily symptom tracking.
In addition, PMDD symptoms were assessed starting seven days before the onset of menses (i.e., premenstrual week) until “at most four days following the bleeding” (p. 96). This, unfortunately, does not cover the postmenstrual window during which symptoms have to become minimal or absent for DSM-5 PMDD diagnosis.
This leaves us with significant gaps in knowledge in the outcome of this study.
More empirical work must be done to fully understand NAC’s potential role in PMDD treatment. You can read more about evidence-based treatments for PMDD here.
Dr. Katja Maria Schmalenberger - IAPMD Clinical Advisory Board Member / Clinical and Cognitive Psychologist at the University of Illinois Chicago.
Added July 2023