Evenamide

What it is

Evenamide is an experimental medicine for people with schizophrenia whose symptoms persist despite antipsychotics. It is taken alongside their current antipsychotic, and it does not act on dopamine.¹

How it works

Evenamide blocks sodium channels, which nerve cells use to fire. It reduces abnormal, excessive release of glutamate, the brain’s main excitatory messenger, but leaves normal release alone.¹ In treatment-resistant schizophrenia, brain scans have found more glutamate in the front of the brain than in people who respond to antipsychotics; the reasoning behind glutamate medicines is explained in Beyond dopamine (opens in a new tab).²

How well it works

In the main trial so far, 291 people whose symptoms had not responded well enough to an antipsychotic took evenamide or a placebo for four weeks, at 45 hospitals in 11 countries in Europe, Asia and Latin America. Symptoms improved by 10.2 points on evenamide and 7.6 on placebo, on the 30-to-210-point PANSS scale: a small difference.¹

In an earlier study in India, Sri Lanka and Italy, 161 people with treatment-resistant schizophrenia took evenamide for up to a year, without a placebo group. After a year, 41 in 100 had improved by at least a fifth. Without a comparison, the study cannot show how much of this came from the medicine.³

Side effects

In the four-week trial, side effects were as common on evenamide as on placebo, about 25 in 100 people; the most frequent were headache, vomiting and cold symptoms.¹

Across all studies, four people taking evenamide have died, against one on placebo. The US Food and Drug Administration treats this as a possible sign that evenamide could disturb the heart’s rhythm, a known risk of some sodium-channel blockers, and evenamide slightly shortens one interval on the heart trace (ECG). Since April 2026, the FDA has stopped new enrolment at US sites of one phase 3 trial; no US patient had received evenamide. The company points out that, adjusted for time on treatment, deaths were not more frequent on evenamide.⁴

Trials in Europe

The phase 3 trial ENIGMA-TRS 1 has enrolled 618 people with treatment-resistant schizophrenia, including people on clozapine, at more than 80 hospitals in 19 countries in Europe, Asia, Latin America and Canada. They take one of two doses of evenamide or a placebo for a year, and the main result, at 12 weeks, is expected in early 2027.⁵ The EU countries include Bulgaria, Czechia, France, Poland and Spain.⁶

Alternatives

Clozapine (opens in a new tab) is the medicine approved for treatment-resistant schizophrenia. Other medicines tested against glutamate include sodium benzoate (opens in a new tab) and memantine (opens in a new tab).

What we don’t know yet

• Whether evenamide helps more than placebo over a year, in people who meet strict criteria for treatment resistance.
• Whether it affects the heart’s rhythm.