Side Effects of zuranolone: A Synthesis of Findings from 4 Studies

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Original Abstract of the Article

Main research findings

Zuranolone is recognized as a promising antidepressant agent. 1 investigated the efficacy and safety of zuranolone in treating major depressive disorder (MDD) through meta-analysis, suggesting its effectiveness.

Zuranolone is structurally similar to brexanolone, which was approved by the FDA in 2019 for the treatment of postpartum depression, and has greatly influenced further research into potential drugs like zuranolone, currently undergoing phase 3 of clinical trials. 3 provides a comprehensive literature review on the clinical aspects of the allopregnanolone agonists brexanolone and zuranolone. Although these drugs show improvement in depressive disorder symptoms, they also exhibit notable side effects, requiring further research for their future clinical use.

Meanwhile, 2 discusses the role of atypical antipsychotics in treating depression. While atypical antipsychotics can be effective in improving depressive symptoms, long-term use raises concerns about side effects such as weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia.

Reasons for side effects

Neuroactive steroids, such as zuranolone and brexanolone, act as positive allosteric modulators of GABAA receptors, enhancing the effects of the neurotransmitter GABA. 4 . GABAA receptors are widely distributed in the central nervous system and play a role in inhibiting neuronal activity. Neuroactive steroids are thought to improve anxiety and depressive symptoms by promoting GABAA receptor activation, thus inhibiting neuronal activity.

However, GABAA receptors are present in various brain regions, and neuroactive steroids can overactivate GABAA receptors, leading to side effects such as sedation, motor impairment, and respiratory depression. 4 .

Common side effects

Sedation

Neuroactive steroids, such as zuranolone and brexanolone, can cause sedation. 4 , 3 .

Motor impairment

Neuroactive steroids, such as zuranolone and brexanolone, can cause motor impairment. 4 , 3 .

Respiratory depression

Neuroactive steroids, such as zuranolone and brexanolone, can cause respiratory depression. 4 , 3 .

Other side effects

Neuroactive steroids, such as zuranolone and brexanolone, can cause side effects such as dizziness, lightheadedness, fatigue, nausea, and vomiting. 3 .

Atypical antipsychotics can cause side effects such as weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia. 2 .

Side effect management

Sedation

Sedation caused by neuroactive steroids, such as zuranolone and brexanolone, can be mitigated by adjusting the dosage. 4 , 3 .

Motor impairment

Motor impairment caused by neuroactive steroids, such as zuranolone and brexanolone, can be mitigated by adjusting the dosage. 4 , 3 .

Respiratory depression

Respiratory depression caused by neuroactive steroids, such as zuranolone and brexanolone, can be mitigated by adjusting the dosage. 4 , 3 .

Other side effects

Other side effects caused by neuroactive steroids, such as zuranolone and brexanolone, can be mitigated by adjusting the dosage. 3 .

Side effects caused by atypical antipsychotics can be managed by lifestyle modifications (diet, exercise), and medication. 2 .

Comparison of studies

Commonalities of studies

Several studies have shown that neuroactive steroids, such as zuranolone and brexanolone, can improve symptoms of depression but also have the potential to cause side effects such as sedation, motor impairment, and respiratory depression.

Differences between studies

2 focuses on the role of atypical antipsychotics, concluding that long-term use raises concerns about side effects such as weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia. In contrast, other studies focus on the efficacy and safety of neuroactive steroids.

Points to note regarding real-world application

While neuroactive steroids like zuranolone and brexanolone hold promise as treatments for depression, it's crucial to consider the potential for side effects like sedation. When using these medications, following your doctor's instructions and closely monitoring for side effects is essential.

Current limitations of research

Research on neuroactive steroids like zuranolone and brexanolone is still in its early stages. There are many unknowns regarding long-term safety and effectiveness. These drugs may not be effective for all depression patients, and the risk of side effects must be considered.

Future research directions

Further research is needed to evaluate the long-term safety and effectiveness of neuroactive steroids like zuranolone and brexanolone. It's also essential to investigate whether these drugs are effective for all depression patients or if they are more suitable for specific patient groups.

Conclusion

Neuroactive steroids like zuranolone and brexanolone show promise as treatments for depression, but the potential for side effects like sedation must be considered. When using these medications, following your doctor's instructions and closely monitoring for side effects is essential. Further research is expected to shed light on the safety and effectiveness of these drugs.

Literature analysis of 4 papers
Positive Content
3
Neutral Content
1
Negative Content
0
Article Type
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2.

Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape.

Author: JhaManish K, MathewSanjay J

Depression symptom improvement
Extrapyramidal symptoms
Metabolic dysfunction
Tardive dyskinesia
Weight gain

Treatment-resistant depression (TRD), affecting about one-third of adults with major depressive disorder, is associated with significant morbidity, mortality, and healthcare expenses. While atypical antipsychotics are approved for treating depression, they often provide limited remission and have concerning side effects, especially with long-term use.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Exploring Novel Therapeutic Approaches for Depressive Disorders: The Role of Allopregnanolone Agonists.

Author: BhattiNajeeha Ahmad, JobilalAnna, AsifKainat, Jaramillo VillegasMateo, PandeyPriyanka, TahirAyzal Noor, BallaNeeharika, Arellano CamargoMaryoreht Paola, AhmadSana, KatariaJanvi, AbdinZain U, AyyanMuhammad

Depression treatment
Side effects

Allopregnanolone, a progesterone metabolite, is reduced in patients with depressive disorders. This review focuses on brexanolone and zuranolone, allopregnanolone agonists, for treating these disorders. Brexanolone, FDA-approved for postpartum depression, has shown promise in reducing depressive symptoms but also has notable side effects. Zuranolone, currently in Phase 3 trials, may provide similar benefits. While these drugs offer potential, more research is needed for their widespread use.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABA<sub>A</sub> receptors.

Author: CerneRok, LippaArnold, PoeMichael M, SmithJodi L, JinXiaoming, PingXingjie, GolaniLalit K, CookJames M, WitkinJeffrey M

Anxiety treatment
Epilepsy treatment
Sleep disorders treatment
Dependence
Motor impairment
Respiratory depression
Sedation
Tolerance

This review examines the therapeutic potential of positive allosteric modulators of GABA<sub>A</sub> receptors (GABAkines) in treating neurological and psychiatric disorders. While traditional GABAkines like diazepam have safety concerns, newer compounds like neuroactive steroids and imidazodiazepines are being investigated for their potential to provide safer and more effective treatment options for conditions such as epilepsy, anxiety, and depression.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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