A new antidepressant drug has been approved in the U.S. – the first-ever to specifically target postpartum depression

The U.S. Food and Drug Administration (FDA) has approved a new drug to treat postpartum depression. Called Zulresso, the drug contains the active ingredient brexanolone.

Postpartum depression is a type of mood disorder linked to childbirth, which can affect both sexes, although it is more common among women. The symptoms appear one week to one month after delivery and include sadness, low moods, lack of interest and pleasure, anxiety, irritability, and changes in sleeping and eating patterns. Postpartum depression occurs in approximately 10% of women after childbirth and affects the parents, the newborn baby and its development, and the entire family.

No therapy specifically targeting postpartum depression is currently available, and the patients receive the same medications as those administered in other types of depression. These drugs usually target the serotonin pathway in the brain. Serotonin is a neurotransmitter that affects emotions and is important in preventing depression; anti-depressants typically inhibit serotonin re-uptake in brain cells, thus increasing its local concentration – resulting in a better mood.

But these treatments are not always successful. In contrast to existing drugs, Zulresso targets the GABA pathway, which also affects the mood. GABA is a neurotransmitter that controls the HPA axis (the Hypothalamus–Pituitary gland–Adrenal gland axis). The HPA axis is responsible for the stress response and when activated, it causes a secretion of stress hormones, such as cortisol. Researchers found that the HPA axis is disrupted in postpartum depression and that it is tightly regulated by the GABA pathway.

An expensive treatment

This led the researchers to develop a molecule that activates the GABA pathway, which regulates the HPA axis. Contrary to existing antidepressants, Zulresso is administered in a single intravenous dose, rather than pills. It starts working faster than the current drugs – patients experience an improvement within hours and the effect lasts for about a month; in contrast to the existing medications, which can take several weeks before they lead to an improvement. Given over a period of two days, the treatment is considered to be complicated, as it requires hospitalization under supervision. It is also very expensive: $34,000 for a single treatment.

Side effects observed during the study include headaches, dizziness, and fatigue. In several patients, a more severely adverse side effect was observed – loss of consciousness during the infusion. Because of this, the FDA has instructed that the treatment be administered only under medical supervision.

Sage Therapeutics, which developed Zulresso, is currently studying another version of the drug in pill form (temporarily dubbed “217”). The company is also investigating the efficacy of the drug in other depression disorders, such as clinical depression, bipolar disorder, and insomnia.

A significant improvement

The treatment’s efficacy was evaluated in two clinical studies, one with 138 patients suffering from moderate postpartum depression, and another with 108 patients suffering from severe postpartum depression. In both studies, some of the participants received the treatment in one of two possible doses, while others (the control group) received a placebo – i.e., a “mock” treatment.

The researchers evaluated improvements in the depression using a questionnaire measuring the level of depression, ranking it on a scale known as the Hamilton Depression Rating Scale. In both clinical studies, the researchers found a significant improvement in the treatment group following the infusion. The improvement lasted throughout the 30 days of the study.

While no new drugs for depression were approved in recent decades, two new drugs – Esketamine and Zulresso, both innovative in their mechanism of action and method of administration – have been approved just in the past few weeks. Furthermore, Zulresso is the first drug specifically targeting postpartum depression.

Nonetheless, additional research on the drug’s mechanism of action and rare and long-term side effects is still required. Likewise, more information regarding the medication’s long-term efficacy and recurring treatment is needed.

The complete FDA report indicates that the placebo treatment (the “mock” treatment, lacking the active ingredient) also had a very significant effect. This phenomenon is very common in this kind of treatments, yet the researchers found a statistically significant difference between the placebo effect and the effect of Zulresso in both doses administered to patients.