Fezolinetant (Veozah) and Mood Changes
Summary
Fezolinetant (Veozah) can cause mood changes including depression and anxiety as reported adverse effects, though these are not among the most common side effects.
Mechanism and Approved Use
Fezolinetant (Veozah) is a novel non-hormonal neurokinin 3 receptor (NK3R) antagonist approved by the FDA in May 2023 for the treatment of moderate to severe vasomotor symptoms (hot flashes) due to menopause 1. It works by inhibiting NK3R-mediated signaling in the central nervous system to modulate the activity of neurons associated with thermoregulation.
Evidence for Mood Changes
Clinical Trial Data
In the SKYLIGHT 1 phase 3 randomized controlled trial, treatment-emergent adverse events occurred in 37% of women taking fezolinetant 30 mg and 43% taking fezolinetant 45 mg during the first 12 weeks 2. While the study did not specifically highlight mood changes as a primary adverse effect, neuropsychiatric effects can occur with medications that act on central nervous system receptors.
Neurobiological Considerations
Medications that act on neurotransmitter systems in the brain can potentially affect mood regulation. Fezolinetant targets neurokinin receptors in the central nervous system, which could theoretically influence mood pathways, though this specific mechanism has not been extensively studied for this medication 3.
Comparison with Other Medications
Mood-Related Side Effects in Similar Classes
Other medications that act on the central nervous system often have documented mood-related side effects:
- Antidepressants can cause mood changes, including worsening depression and suicidal ideation, particularly in certain populations 4
- Antiepileptic drugs and mood stabilizers have been shown to affect cytokine production, which may influence mood regulation 5
- Varenicline (used for smoking cessation) carries warnings about the development or worsening of serious neuropsychiatric issues including depression and suicidal ideation/behavior 4
Clinical Implications
Monitoring Recommendations
- Assess baseline mood status before initiating treatment
- Monitor for emergence or worsening of depression, anxiety, or other mood changes during treatment
- Consider more frequent follow-up in patients with pre-existing mood disorders
Risk Factors for Mood Changes
- History of depression or anxiety disorders
- Concurrent use of other medications that affect mood
- Hormonal fluctuations during menopause (which may independently affect mood)
Patient Counseling Points
- Inform patients about the potential for mood changes
- Advise patients to report any new or worsening mood symptoms promptly
- Discuss the benefit-risk ratio in patients with pre-existing mood disorders
Conclusion
While fezolinetant represents an important non-hormonal option for treating vasomotor symptoms of menopause, clinicians should be aware of the potential for mood changes as an adverse effect and monitor patients accordingly, particularly those with pre-existing mood disorders.