Dr. Ahmed Zuranolone Vs Brexanolone is a general comparison of the two novel therapies recently approved by the FDA for managing postpartum depression.
Both Zuranolone and Brexanolone (Zulresso) belong to a different class of drugs called tonic GABA-A receptor modulators.
Benzodiazepines act on the GABA receptors, however, their effect is “phasic” compared to the effect of Zuranolone and Brexanolone which have a sustained tonic effect on the GABA-A receptors.
Here is the general comparison between benzodiazepines and Brexanolone/ Zuranolone:
Comparisons | Benzodiazepines | Zuranolone and Brexanolone |
| Class | Phasic GABA receptor modulators | Tonic GABA-A receptor modulators, a neurosteroid (allopregnanolone-analog that mimics the naturally occurring progesterone) |
| Duration of treatment | Prolonged and daily treatment is required. | Treatment is short. Continuous IV infusion over 60 hours for Brexanolone and daily oral treatment for 14 days for Zuranolone |
| Short term Side effects |
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| Use | Primarily used for the treatment of anxiety, insomnia, and panic attacks | Indicated only for the treatment of postpartum depression |
| Brands and Generics | Multiple brands and formulations are available | Only Generic medications are available |
| Cost | Very Cheap | Very costly |
Zuranolone Vs Brexanolone: General Comparison:
Zuranolone and Brexanolone are both from the same class of medicines. Both are only indicated for managing moderate to severe symptoms of postpartum depression.
In addition, both these drugs have a rapid onset of action and are only used for a brief period of time, unlike benzodiazepines and SSRIs.
However, compared to Brexanolone, Zuranolone is a newer formulation and available as oral capsules which are best administered once daily after 14 days with an evening meal.
On the other hand, Brexanolone is administered as an intravenous infusion for about 60 consecutive hours.
Here is a table summarizing the key differences between Zuranolone and Brexanolone:
| Pharmacokinetic Parameter | Brexanolone | Zuranolone |
| Route of Administration | Intravenous infusion | Oral Capsules |
| Half-life | 9 hours | 19.7 – 24.6 hours |
| Time to Peak Concentration | Achieved by the end of the infusion | 5 – 6 hours after ingestion |
| Metabolism | Non CYP-based pathways | CYP3A4 pathway |
| Excretion | 47% feces, 42% urine | 41% in feces and 45% in urine |
| Protein Binding | 99% | 99.5% |
Zuranolone has the advantage of oral administration. It is available as oral capsules, under the brand name, ZURZUVAE. It is administered as a once-daily dose with the evening meal. Taking it with a fatty meal enhances its absorption.
On the other hand, Brexanolone is available as an intravenous injection under the brand name, Zulresso. It is given as an intravenous infusion over 60 hours under supervision.
Zulresso (Brexanolone) is a single 60-hours infusion while Zuranolone (Zurzuvae) is given once daily for 14 days.
Unlike SSRIs which start working after 14 days, both these medications become effective rapidly as soon as 3 days after treatment initiation.
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Zuranolone Vs Brexanolone: Comparing efficacy in postpartum depression:
Zuranolone and Brexanolone have not been compared in a head-to-head comparison trial.
The FDA prescribing information highlights the efficacies of these drugs based on the following information extracted from clinical trials.
Three clinical trials were conducted in women with postpartum depression. All three trials resulted in a significant difference in the HAMD score after the end of the infusion and at 30 days.
Here is a table summarizing the results of the 3 clinical trials:
| Brexanolone (Zulresso) Studies in PPD | HAMD score (Difference Vs Placebo) | P value (<0.05 is a significant change) |
| ZULRESSO target dosage 90 mcg/kg/hour (n=41) | -3.7 (-6.9, -0.5) | P=0.0252 |
| ZULRESSO target dosage 60 mcg/kg/hour (n=38) | -5.5 (-8.8, -2.2) | P=0.0013 |
| ZULRESSO target dosage 90 mcg/kg/hour (n=51) | -2.5 (-4.5, -0.5) | P=0.0160 |
Likewise, Zuranolone (ZURZUVAE) was also studied in 2 clinical trials. Improvement in the HAMD-17 score was assessed after 14 days in comparison to placebo medicine.
Here is a table summarizing the results of the 2 clinical trials which were conducted on women with postpartum depression:
| Zuranolone (ZURZUVAE) Studies in PPD | HAMD score (Difference Vs Placebo) |
| 50 mg of ZURZUVAE | -4.0 (-6.3, -1.7) |
| 50 mg of Zuranolone | -4.2 (-6.9, -1.5) |
It is obvious from the FDA data that both Zulresso and Zurzuvae significantly improve depression scores in women with postpartum depression as measured by the HAMD score.
The only difference between the two drugs was that the efficacy of Zulresso (Brexanolone) was assessed after the end of the infusion (60 hours) while that of Zurzuvae (Zuranolone) was assessed after 14 days.
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Comparing the Side Effects of Zuranolone Vs Brexanolone:
Zuranolone and Brexanolone act on the GABA receptors and hence somnolence, drowsiness, and altered mentation are among the most common side effects of both these drugs.
Women are advised not to drive or participate in activities that may lead to significant harm or injury to themselves or others such as operating heavy machinery, driving a car or public transport, or swimming, etc.
Both these drugs are also to be avoided in pregnancy as they may be harmful to the fetus.
Here is a table summarizing the most common side effects of Zuranolone and Brexanolone with a frequency exceeding 2% or more:
Side effects | Brexanolone (Zulresso) | Zuranolone (Zurzuvae) |
| Somnolence | 13 – 21% | 19 – 36% |
| Dizziness and Vertigo | 12 – 13% | 8 – 13% |
| Loss of consciousness | 3 – 5% | Reported only in overdose |
| Hot flashes or flushing | 2 – 5% | Not reported |
| Diarrhea | 2 – 3% | 5 – 5% |
| Dry mouth | 3 – 11% | 4% |
| Oral pain | 2 – 3% | Not reported |
| Dyspepsia | 2% | Not reported |
| Tachycardia | 3% | Not reported |
| Fatigue | 7% | 5% |
| Sinus congestion | Not reported | 3% |
| Toothache | Not reported | 3% |
| Nasopharyngitis | Not reported | 9% |
| UTI | Not reported | 5% |
| Memory impairment | Not reported | 3% |
| Abdominal pain | Not reported | 3% |
| Anxiety | Not reported | 2% |
| Rash | Not reported | 2% |
| Hypoesthesia | Not reported | 2% |
| Muscle twitching | Not reported | 2% |
| Myalgia | Not reported | 2% |
In conclusion:
Brexanolone Vs Zuranolone is a rough comparison of the two novel neurosteroids. Both these drugs are only indicated for treating women with postpartum depression.
These drugs are given only for a short duration. Brexanolone is administered as an intravenous infusion over 60 hours as a single infusion while Zuranolone (Zurzuvae) is an oral capsule administered once daily with the evening meal for 14 days.
Because these drugs have a rapid onset of action and are given for a very short duration, unlike SSRIs, these drugs may be best for women with PPD (postpartum depression).
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