Is The $34,000 Postpartum Depression Drug Injection Safe and Effective?

It is estimated that each year over 400,000 women in the U.S. experience physical, emotional, and psychospiritual challenges, after having a baby, consistent with the clinical diagnostic criteria for postpartum depression (PPD). The FDA’s newest drug approval for the condition begs the question: can a patented drug really provide a solution to a problem whose origins are not solely physical? And if indeed it can, shouldn’t it at least be safe and effective and priced at a range that makes it accessible to those who are suffering?

On March 19th, 2019, the FDA gave market approval to an intravenously administered drug targeting women diagnosed with postpartum depression. The newly hyped drug is comprised of a proprietary form of a synthetic hormone (brexanalone) and will be sold under the brand name Zulresso by Sage Therapeutics, who sponsored all the drug's pre-approval clinical trials. It will cost $7,450 per vial, with a full course of treatment estimated to cost about $34,000. It is slated to hit the market this June.

Brexanalone is a synthetic analogue of a naturally occurring hormone called allopregnanolone which is synthesized in the human brain, and commonly measured in the urine. It is known to have anesthetic, hypnotic, and sedative properties, and levels of the hormone have been found to drop after pregnancy in the postpartum window coinciding with the onset of the "baby blues," as it was once known before the advent of the clinical term postpartum depression.

Allopregnanolone was first synthesized by scientists at the National Institute of Mental Health in the 1980’s, who modeled it after the metabolites of the steroid hormones progesterone and deoxycorticosterone, which among a number of known and unknown functions, bind to and act upon brain receptors for gamma-aminobutyric acid (GABA) -- considered to be an inhibitory, sedating neurotransmitter.

Ironically, two of the drug’s most common side effects are sedation and sleepiness. Sedation and sleepinesss are well known amplifying factors for those suffering with depression. Consider also that sedatives, as a drug category, are often described as depressives, as a common mechanism of their action is to depress the central nervous system.

One media report described the new drug's most common side effects as follows:

“Most commonly, patients experienced headaches, dizziness, and drowsiness. Yet the panel expressed concern about a particular side effect: Six of 140 women receiving brexanolone either were close to losing consciousness during the infusion or abruptly fell into a deep sleep.”

According to an FDA review of the drug's pre-approval trials, two of the study participants withdrew due to serious adverse events, including a Suicidal Ideation/Attempt, and a Syncope (Passing Out)/Altered State of Consciousness event. Additional adverse events, at least twice as likely to occur in the treatment group versus placebo group, included the following battery of complaints:

Sedation/somnolence,
Dizziness/lightheadness/presyncope/vertigo
Drymouth, thirst
Loss of consciousness, syncope (passing out)
Flushing, hot flush
Diarrhea
Oropharyangeal pain
Tachycardia
Dyspepsia, indigestion

These concerning side effects reflect the drug's high degree of toxicity, no doubt related to the unnatural route of administration (unlike intravenously admninistered drugs, those taken orally go to the liver before entering the bloodstream, an inbuilt safety mechanism).

Brexanalone has the same LD50 (the dose required to kill 50% of test animals) score as injected heroin; namely, a LD50 of 20 mg/kg versus 21.8 mg/kg for heroin, as determined by intravenous administration in the mouse model. This is why the drug will only be adminstered within a hospital setting. The drug also requires that breastfeeding be stopped for a 7 day window during the mother's treatment, as the chemical contaminates her breast milk.

Brexanalone was approved based on a very small improvement on the Hamilton Rating Scale for Depression (HAM-D) between placebo and treatment groups: a -2.5 placebo-substracted difference at 60 hours and 0.5 difference (ruled clinically insignificant) at 30 days. While the -2.5 difference was ruled "clinically significant" by those conducting the study and the FDA review board, the argument for the clinical relevance of a relatively small HAM-D score improvement is equivocal at best. If the Clinical Global Impressions (CGI) Scale was used instead, which is arguably of far greater relevance to positive changes observed and experienced in the real world, the drug may have not passed. Learn more about this subtle but profound difference by reading this article on the clinical (ir)relevance of drug-placebo differences.

When considering Brexanalone's purported benefits versus its known risks (nonwithstanding the financial burden, and interruption in the mother/infant’s breastfeeding and/or circadian cycles), is the drug really the “breakthrough drug” solution to postpartum depressioon that the FDA, Sage Therapeutics, and the mainstream media has declared it to be?

It's also important to consider that pharmaceutical drugs are not the only approaches that have been studied for PPM. There are evidence-based, natural treatments for postpartum depression such as saffron, which have been studied to be far safer, more effective, affordable and easily accessible.

For more information on this topic, watch women’s health expert and perinatal specialist Kelly Brogan, MD’s video. She discusses the psychospiritual and cultural context at the root of the postpartum depression issue and the attempt by pharmaceutical companies and conventional medicine to suppress women’s voices and the truth about the real causes and solutions for depression and related mental illness.

For more information on natural ways to address postpartum depression, go to the GreenMedInfo.com database on the topic: Postpartum Depression, and visit Dr. Kelly Brogan's website to read the following articles: