Trial Shows Results for Depression Drug with Therapy

(Ulrike Mai, Pixabay. https://pixabay.com/photos/woman-desperate-sad-tears-cry-1006100/)

22 Dec. 2021. Findings from a clinical trial show an experimental drug helps people in therapy for major depression reduce their symptoms compared to a placebo. Results of the study testing the treatment candidate esmethadone, made by Relmada Therapeutics Inc. in Coral Gables, Florida, appear in today’s issue of American Journal of Psychiatry (paid subscription required).

Esmethadone, code-named REL-1017, is Relmada Therapeutics’ lead product, developed as a supplemental treatment for individuals with major depression when combined with psychotherapy. Depression is a widespread condition, which when it becomes persistent or severe, is called major depression, and can interfere with normal family and work life, and lead to disability. National Institute of Mental Health estimates in 2019, 19.4 million adults in the U.S., or 7.8 percent of the adult population, suffered a major depressive episode in the previous 12 months.

Relmada designs esmethadone as an N-methyl-D-aspartate, or NMDA, receptor antagonist. NMDA receptors are proteins that help keep synapses flexible, which affect memory, learning, and development of the central nervous system. Synapses are the signaling components of neurons, or nerve cells. The company says esmethadone does not cause opioid-style dependencies or toxicities in patients.

Mild to moderate and temporary adverse effects

The mid-stage clinical trial tested esmethadone among 62 adults at 10 sites in the U.S. with major depressive disorder that had not responded to previous treatments. Participants were randomly assigned to receive doses of 75 or 100 milligrams of esmethadone mixed with fruit juice on day one of the trial, followed by 25 or 50 milligrams of the drug respectively each day for the next six days. A comparison group of participants received only fruit juice on each of the seven days. All participants continued to take their regular anti-depression drugs during the trial, as well as esmethadone or fruit-juice placebo.

The study team looked primarily for adverse effects from esmethadone treatments for 21 days after the start of treatments. Researchers also tracked participants’ scores on a number of standard rating scales for depression during the seven days when esmethadone or a placebo were given and for seven days after treatments ended. Science & Enterprise reported on initial results from the trial released by Relmada in Oct. 2019 showing reduced symptoms among drug recipients compared to placebo recipients.

The new safety findings show adverse effects from the treatments are mild to moderate and temporary, with no evidence of psychosis, sensory distortions, opioid effects, or withdrawal symptoms. Scores on on the Montgomery-Asberg Depression Rating Scale, which the company says is the main efficacy measure, improve by the 4th day of taking esmethadone at both dose levels, with the differences sustained through days 7 and 14, one week following the end of treatment, compared to placebo recipients.

Maurizio Fava, chair of the psychiatry department at Massachusetts General Hospital in Boston and lead investigator of the trial, says in a Relmada Therapeutics statement, “We look forward to seeing esmethadone potentially helping millions of depressed patients with inadequate response to antidepressants if these efficacy and safety results are replicated in the ongoing phase 3 trials.” The company is now recruiting participants in four phase 3 or late-stage trials of esmethadone.

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