Dextromethadone Effective in Treatment of Major Depressive Disorder


New data show significant therapeutic effects of dextraomethadone treatment in MDD patients below the median percentage of life-years from diagnosis.

Marco Pappagallo, MD

Marco Pappagallo, MD

While the duration of depression can not predict patient response to standard antidepressant treatments (SATs), new research finds early improvements after start of treatment are associated with better patient outcomes.

The findings were presented at the American Psychiatric Association Virtual Meeting.

The team, led by Marco Pappagallo, MD of the Albert Einstein College of Medicine, investigated the effectiveness of NMDAR channel blocker REL-1017 (dextromethadone) in treatment.

More severe first episodes of depression may prompt the prognosis of major depressive disorder (MDD).

The team noted dextromethadone showed rapid and sustained therapeutic effects in MDD patients.

Data show both 25 and 50 mg doses of REL-1017 had a significant effect in the reduction of Montgomery-Asberg Depression Rating Scale (MADRS) scores in patients below the median percentage of life-years from the start of MDD.


Investigators used data from a randomized Phase 2a study of REL-1017, where it was used as an adjunctive treatment in MDD patients who failed 1 – 3 adequate SATs.

The team then defined the duration of MDD as the difference between age at baseline and the start data of MDD in years.

The percentage of life-years since the start of MDD was calculated through by duration of MDD (years) divided by age at baseline recorded in the database, then multiplied by 100.

Patients were divided into subgroups below and above the median value of the percentage of life-years since the first diagnosis of MDD.

The MADRS change from baseline compared dextromethadone versus placebo by a t test for unpaired data.


Investigators included 62 randomized patients, with a 23% median percentage of life-years from the start data of MDD.

Patients below the median percentage life-years had a significant higher response to dextromethadone compared to placebo in 25mg and 50mg doses.

In treatment of MDD patients below the mean percentage, the 25mg dextromethadone versus placebo MADRS scores improved at day 7 (P = .0277) and day 14 (P = .0217).

Treatment with 50mg dextromethadone also showed significant improvement of MADRS scores with day 7 (p = .0075) and day 14 (p = .0483).

However, patients above the median percentage (23%) of life-years had no statistically significant response to dextromethadone in comparison to placebo.


Investigators conclude that the 25 and 50 mg doses of dextromethadone had a significant effect versus placebo in reducing MADRS scores below the median percentage of life-years from the onset of MDD.

The patients above the median percentage did not experience a significant statistical improvement from dextromethadone.

The team proposed future trials may hold more answers on the therapeutic effects of REL-1017 when administered during onset of MDD.

“The differential therapeutic effects of REL-1017 when administered earlier compared to later in the course of MDD may signal potential disease modifying effects related to neural plasticity,” investigators wrote. “If these preliminary findings are confirmed in a planned Phase 3 trial, REL-1017 could become first line treatment for patients with recent onset of MDD.”

The study, “Effect of Percentage of Life-Years From the Start of Major Depressive Disorder on the Therapeutic Response to REL-1017,” was presented virtually at APA.

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