A new drug for postpartum depression has taken a big step forward! What is so new about it?

After the new drug is launched, it can be expected that more pregnant women will be screened and treated for postpartum depression, thereby identifying more patients who need treatment. The manufacturer is likely to apply for a wider range of indications in the future.

Written by Li Changqing (Doctor of Medicine, practicing physician in the United States)

On August 4, the U.S. Food and Drug Administration (FDA) approved a new drug for postpartum depression, called Zuranolone, trade name Zurzuvae. This is an oral drug.

Prior to this, there were already many anti-postpartum depression drugs on the market, such as the commonly used sertraline, fluoxetine, venlafaxine, etc. This new drug was approved by the FDA, no doubt because it has new advantages, so what is "new" about it? Compared with other anti-postpartum depression drugs, what are its advantages?

Postpartum depression is a common mental disorder during pregnancy and childbirth. It is currently believed that it is mainly related to the drastic changes in estrogen and progesterone in the body after childbirth, but why some women are more sensitive to this is still unknown. In addition, physiological changes during pregnancy, social pressure, genetic factors, and health problems of the baby can also cause or aggravate postpartum depression. It is reported that one in every five to ten women may be affected by postpartum depression.

This mental disorder will have varying degrees of impact on the mother, the baby, and the entire family, as there are reports of women committing suicide due to postpartum depression. In June this year, a woman in Massachusetts, USA, committed suicide nine days after giving birth to twins, which aroused public concern about the mental health of mothers. There are also similar reports in China, such as a female doctoral student who jumped off a building and committed suicide five months after giving birth in May 2020.

Like any mental illness, early detection and intervention of postpartum depression are very important for recovery. Early treatment can not only reduce serious consequences including suicide, but also help prevent postpartum depression from turning into long-term chronic depression. There is no doubt that helping mothers achieve mental health is also of great benefit to the growth and development of their babies.

Most of the existing anti-postpartum depression drugs work by affecting the neurotransmitters related to depression in the body. For example, sertraline and fluoxetine are serotonin reuptake inhibitors, and venlafaxine is a serotonin-norepinephrine reuptake inhibitor. Studies have found that the mood changes of patients with depression are mainly related to neurotransmitters such as serotonin, and patients show insufficient or short-lasting serotonin secretion. These drugs can act on the protruding parts of neurons, allowing serotonin to act longer.

In general, the drugs available on the market take a long time to take effect, and many of them take one to two weeks or even longer to take effect. The corresponding medication time (treatment course) is also relatively long, and most patients need to take it continuously for several months. In addition, because serotonin receptors are widely distributed and also act on the digestive, cardiovascular, and reproductive systems, some patients will experience gastrointestinal symptoms after taking the medicine, such as nausea and diarrhea; followed by cardiac symptoms such as palpitations; and sexual dysfunction, etc.

Such shortcomings can easily affect the compliance of patients with postpartum depression. Some patients refuse to take medication because they consider that they need to take medication for a long time and may not see any effect in the short term.

Unlike several anti-postpartum depression drugs already on the market, the pharmacological components of Zuranolone are neurosteroid modifiers that can help regulate GABA-A receptors and increase the effects of inhibitory neurotransmission. Commonly used sedatives such as diazepam also produce sedative and anti-anxiety effects by affecting GABA-A receptors. However, diazepam drugs are not usually used as antidepressants because they do not act on the serotonin pathway and have a risk of dependence. However, why can Zuranolone, which also acts on GABA-A receptors and is not related to the serotonin pathway, be an antidepressant? It is still unknown.

Because the site of action is related to sedation, one of the common side effects of this drug is drowsiness. It needs to be taken before bedtime, and you cannot drive or perform dangerous operations for 9 hours after taking it. The company that developed this drug previously developed a similar intravenous preparation, but that preparation required continuous intravenous infusion for 60 hours in the hospital and cost as much as $34,000, which is obviously not suitable for most pregnant women. Changing to tablets once a day brings great convenience to patients, which is also an important reason why the new drug was approved by the FDA.

The more important reason why this new drug for postpartum depression was approved is probably that it has a significant advantage: it takes effect quickly and has a short treatment course.

The FDA approved the new drug mainly based on two randomized controlled trials. Participants were randomly assigned to take the drug and placebo for 14 days. The evaluation method was a depression scale called HAMD-17, which has 17 questions about depression symptoms. There will be a score according to the severity, including guilt, suicidal thoughts, sleep disorders, energy, interest, etc. The subjects were evaluated before taking the medicine, on the first day after taking the medicine, and four weeks later.

Clinical trials have shown that patients can experience significant symptom improvement on the third day of medication, and the improvement can last at least four weeks after stopping the medication. The rapid onset of action and the fact that medication does not require year-round medication make it more adaptable to postpartum depression, a specific period of depression.

After this new drug is launched, with the help of news dissemination, it can be expected that more mothers will be willing to accept screening and treatment for postpartum depression, and more obstetricians and family doctors will consciously screen for postpartum depression, thereby discovering more patients who need treatment. However, we can speculate that the manufacturer's goal will not be limited to postpartum depression, and it is likely to use this as an opportunity to gradually apply for a wider range of indications.

Depression is generally considered a chronic mental illness, but in fact, the diagnosis of depression does not require a chronic process. A diagnosis can be made if the symptoms meet the depression score for more than two weeks. The conditions of different depression patients vary greatly. Many patients show sporadic symptoms, such as intermittent depression symptoms, or intermittent severe depression symptoms on the basis of mild depression, including but not limited to suicidal thoughts.

Most commonly used antidepressants need to be taken for at least several months or even years, which is obviously not "friendly" to patients with intermittent depression. Drugs like Zuranolone that can be used in the short term and whose efficacy can last for several weeks seem to be more suitable as alternative products for treating such patients with depression.

The sales price of Zuranolone is still unknown. According to convention, various medical insurance programs will gradually include it in the medical insurance coverage after FDA approval. Of course, the drug must be used under the guidance of doctors and pharmacists.

Some doctors also warned that the drug may not be suitable for all patients with postpartum depression: for patients with mild to moderate depression, behavioral and psychological treatments are safer and more lasting; for patients with recurrent depression and those with a history of severe depressive symptoms (such as suicidal tendencies), some experts do not recommend the use of this new drug, fearing that the effects of short-term use may not be maintained in the long term.

In any case, the success of this new drug for postpartum depression does not entirely lie in its medication principle, but also in its formulation and the grasp of clinical indications.

Reference Links

https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

https://www.psychiatrist.com/news/mom-of-twins-postpartum-suicide-highlights-urgent-need-for-reproductive-psychiatry/

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

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