Dr. Ahmed
Postpartum depression treatment is focused to alleviate the symptoms with minimal interventions and focused therapies without exposing the baby to medications.
Postpartum depression is very common and under-reported because of several reasons including stigma and privacy. It is estimated to affect 1 in 7 women.
Compared to “baby blues” which is a transient change in emotions as a result of stress and expectations, postpartum depression is a more severe condition that may persist beyond the first 4 to 6 weeks following the birth of the child.
In addition, postpartum depression is associated with neglect and impairment in daily life activities including loss of interest and care for the child.
Here is a table of comparison between BabyBlues and Postpartum depression:
Factor | Baby Blues | Postpartum Depression |
| Onset | Within a few days after childbirth | Anytime within the first year after childbirth |
| Duration | Lasts for a few days to a couple of weeks | Persists for weeks or months |
| Intensity | Mild emotional symptoms | More intense and severe symptoms |
| Emotional Symptoms | Mood swings, tearfulness, irritability | Persistent sadness, hopelessness, anhedonia |
| Physical Symptoms | Fatigue, sleep disturbances | Appetite changes, physical discomfort |
| Cognitive Symptoms | Mild difficulty concentrating | Severe concentration and memory problems |
| Thoughts of Harm | Absent or fleeting | This may include thoughts of self-harm or harm |
| Functioning Impact | Minimal disruption in daily life | Significant interference with daily functioning |
| Need for Treatment | Usually self-resolving | Requires professional intervention |
| Treatment Options | Supportive care, self-care practices | Therapy, medication, or a combination |
| Risk Factors | Limited impact of risk factors | History of depression, lack of support, etc. |
| Support and Education | Important but not as intensive | Vital for diagnosis, treatment, and recovery |
| Medical Attention | Often not required | Essential for diagnosis and management |
| Impact on Mother-Baby Bonding | Mild, temporary impact | Potential for significant impact |
Conventional Postpartum Depression Treatment:
The treatment of postpartum depression is individualized. Support from family and friends is essential. For women with moderate to severe postpartum depression, the first line of treatment is with SSRIs (selective serotonin reuptake inhibitors).
Most studies suggest the use of Sertraline in postpartum depression. However, in patients who have a poor response to SSRIs, SNRIs such as Venlafaxine and Duloxetine or Mirtazapine (Remeron) may be used.
TMS or transcranial magnetic stimulation is a non-invasive and safe alternative for women who are worried about the exposure of medications in their babies.
Women who improve with SSRIs or SNRIs should continue their medications for 6 t o12 months.
If the patient does not respond to 4 different treatment regimens, ECT (electroconvulsive therapy) is recommended.
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Breaking Ground with Novel Therapies for Postpartum Depression: Brexanolone and Zuranolone
Brexanolone and Zuranolone are the two FDA-approved medications specifically approved for the treatment of postpartum depression.
Both these drugs target GABA-A receptors, modulating their activity. Brexanolone and Zuranolone are closely related to the female hormone progesterone, which is at its peak, during the 3rd trimester.
While benzodiazepines also modulate the GABA receptors, they do in a phasic form. Brexanolone and Zuranolone have a tonic or sustained effect on these receptors.
Brexanolone for the treatment of postpartum depression:
Brexanolone is an FDA-approved medication for treating postpartum depression. It is available under the brand name, Zulresso.
Zulresso (Brexanolone) is only available as an intravenous infusion, administered over 60 hours (2.5 days). Its efficacy was documented in two placebo-controlled trials [Ref].
The primary outcome was the mean change in depressive scores after the end of the infusion. The secondary end-point was the change in depression score as measured by HAM-D score at 4 weeks.
The results of the studies are tabulated here [Ref]:
| Zulresso Vs Placebo | Mean Baseline Score | Mean Δ from Baseline | Difference | P value |
| 90 mcg/kg/hour (n=41) | 28.4 | -17.7 | -3.7 | P=0.0252 |
| Placebo (n=43) | 28.6 | -14.0 | ||
| 60 mcg/kg/hour (n=38) | 29.0 | -19.5 | -5.5 (-8.8, -2.2) | P=0.0013 |
| Placebo (n=43) | 28.6 (2.5) | -14.0 | ||
| 90 mcg/kg/hour (n=51) | 22.6 (1.6) | -14.6 | -2.5 (-4.5, -0.5) | P=0.0160 |
| Placebo (n=53) | 22.7 (1.6) | -12.1 |
As can be seen in the table above, a significant improvement in the depression score was noted at the end of 60 hours of infusion.
The rapid onset of action and improvement in depression symptoms marked a new approach in the treatment of postpartum depression.
However, the only problem with Zulresso is the intravenous formulation and the prolonged infusion of 60 hours.
In addition, it is not indicated in women who are at risk of losing consciousness, or those with suicidal thoughts and is only available via the REMS program [Ref]
Zuranolone for postpartum depression treatment:
Zuranolone (Zurzuvaetm) is a drug indicated for the treatment of postpartum depression. It has not been given an official approval letter because the “controlled substance” labeling is still being verified.
Zuranolone (Zurzuvaetm) is available in 20, 25, and 30 mg capsules which can be administered once daily, preferably in the evening for 14 days.
It is taken with a high-fat meal. The efficacy of treating women with postpartum depression beyond 14 days is not recommended [Ref].
The efficacy of Zuranolone (Zurzuvaetm) in the treatment of postpartum depression was studied in two clinical trials.
These studies included women with postpartum depression diagnosed on the DSM-V criteria who had symptoms for at least 4 weeks.
The primary outcome was a change in the HAMD-17 score after treatment on Day 15. Here is a summary of the results [Ref]:
| Treatment Group | N | Mean Baseline Score | LS Mean Change from Baseline | Mean Difference |
| ZURZUVAE 50 mg | 98 | 28.6 | -15.6 | -4.0 |
| Placebo | 97 | 28.8 | -11.6 | |
| Zuranolone 40 mg | 76 | 28.4 | -17.8 | -4.2 |
| Placebo | 74 | 28.8 | -13.6 |
Zuranolone has also been studied in individuals with major depressive disorder. It rapidly improves the symptoms of depression within 3 days and has a sustained effect [Ref].
The effect of Zuranolone in relieving depressive symptoms in women with postpartum depression was also observed to be very rapid. A significant percentage of women with postpartum depression had symptom relief within 3 days of starting the treatment [Ref].
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In Conclusion:
Two breakthrough medical treatments for postpartum depression which may replace or may be used as an add-on to SSRIs or SNRIs for rapid improvement in the symptoms of depression have been approved by the FDA.
These include Brexanolone and Zuranolone. These drugs belong to a novel class of medicines which considered to work on the GABA-A receptors more like the active metabolites of progesterone.
Brexanolone is available as an intravenous infusion while Zuranolone is available as oral capsules which are to be taken once daily with the evening meal (preferably with a high-fat meal).
These breakthrough drugs act rapidly and improve the symptoms of postpartum depression within 3 days of treatment initiation.
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