In short
Methohexital is a short-acting intravenous general anaesthetic belonging to the barbiturate class, also known as methohexitone and sold under the brand name Brevital. It is authorised as a medicine for inducing deep sedation and anaesthesia. One Phase 3 clinical trial with 174 participants is currently authorised to compare methohexital against propofol and etomidate in patients receiving electroconvulsive therapy (ECT) for severe unipolar depression.
Key points
- Methohexital is a short-acting barbiturate general anaesthetic given by intravenous injection.
- One Phase 3 trial with 174 participants is authorised to study methohexital in electroconvulsive therapy for severe unipolar depression.
- The trial compares methohexital with propofol and etomidate as anaesthetic agents during ECT.
- The main outcome is the time to first clinical response, measured by the number of ECT sessions needed for a 50% reduction in depression scores.
- Methohexital works by enhancing the inhibitory effects of GABA at the GABAA receptor in the brain.
- The trial is currently in Authorised status, meaning it has received regulatory approval to proceed.
What is methohexital?
Methohexital is a short-acting intravenous general anaesthetic that belongs to the barbiturate class of medications. It is also known as methohexitone and is sold under the brand name Brevital. Methohexital was first approved in Canada and the United States in 1960, and it is classified as a small molecule with the chemical formula C14H18N2O3. The product Brevital Sodium is available as a 500 mg powder for solution for injection in vials. Methohexital is an authorised medicine used to cause drowsiness and block pain signals during procedures.
How does methohexital work?
Methohexital works by binding to a specific site on the GABAA receptor in the brain, which is associated with a chloride ion channel. By binding to this site, methohexital increases the length of time the chloride ion channel remains open. This prolongs the inhibitory effect of GABA (gamma-aminobutyric acid), a neurotransmitter that reduces nerve activity in the brain. As a result, pain signals are blocked and the patient becomes drowsy and unconscious during a procedure.
Which conditions is methohexital used or studied for?
- General anaesthesia — Methohexital is authorised for use as an intravenous anaesthetic to induce deep sedation before and during surgical or diagnostic procedures.
- Severe unipolar depression treated with electroconvulsive therapy — Methohexital is being studied as one of three anaesthetic agents used during ECT sessions for patients with severe unipolar depression.
How is methohexital given?
Methohexital is injected into a vein by a healthcare professional in a hospital or clinic setting. The marketed product is a 500 mg powder that is prepared as a solution for injection before being given intravenously. In the authorised clinical trial, methohexital is administered as an intravenous bolus injection or intravenous infusion at a dose of 500 mg.
What do the clinical trials show?
One Phase 3 clinical trial is authorised to investigate methohexital in patients with severe unipolar depression who are treated with electroconvulsive therapy. The trial plans to enrol 174 participants and has the EU trial identifier 2025-524829-40-00. The study is interventional, meaning participants receive one of three anaesthetic agents during their ECT sessions: methohexital, propofol, or etomidate. Suxamethonium, a muscle relaxant, is also given intravenously as part of the anaesthetic regimen.
The main goal of the trial is to determine whether the choice of anaesthetic agent influences how quickly patients respond to ECT. The primary endpoint is the time to first clinical response, measured as the number of completed ECT sessions needed before a patient shows at least a 50% reduction from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard questionnaire used to assess the severity of depression.
The trial status is Authorised, which means the study has received regulatory approval and may proceed with participant recruitment and treatment. The trial record does not specify additional eligibility criteria such as age limits or exclusion conditions beyond the diagnosis of severe unipolar depression requiring ECT.
What side effects are known?
The supplementary sources provided do not include a detailed list of side effects for methohexital. The Cleveland Clinic drug information states that methohexital causes drowsiness before and during a procedure, which is its intended effect rather than a side effect. People with certain pre-existing conditions, such as heart disease, high or low blood pressure, liver disease, low red blood cell levels, lung or breathing disease including asthma or COPD, porphyria, or seizures, may need special consideration before receiving methohexital. No specific common or serious side effect frequencies are reported in the available sources.
Which drugs interact with methohexital?
Methohexital should not be taken together with certain medications, including elbasvir/grazoprevir, lenacapavir, lonafarnib, lurasidone, mavacamten, nirmatrelvir/ritonavir, ranolazine, and sodium oxybate. Methohexital may also interact with certain seizure medications such as phenytoin or phenobarbital. This list may not include all possible interactions.