JMIR Publications

ABSTRACT

Background:

Catatonia is a severe psychomotor syndrome predominantly associated with depressive-, bipolar- and psychotic disorders. Untreated, catatonia has a 10% mortality rate and can lead to complications such as renal failure, rhabdomyolysis, pneumonia, embolism and contractures. High doses of the benzodiazepine lorazepam, a gamma-aminobutyric acid (GABA)-A receptor modulator, is the primary pharmacological treatment, enhancing GABA’s inhibitory effect, potentially reducing symptoms of catatonia. However, lorazepam is ineffective in about 25% of cases, leaving electroconvulsive therapy (ECT) as the only well investigated alternative. Although often effective, ECT may have severe side effects and is not easily accepted among patients and caregivers. There is thus an urgent need for novel therapies for catatonia. Observational evidence suggests that sodium oxybate, a GABA precursor and GABA-B receptor agonist, could have efficacy for catatonia, but this has never been thoroughly investigated.

Objective:

The objective of this study is to provide robust evidence on the efficacy and safety of sodium oxybate for treating catatonia unresponsive to lorazepam, while also capturing the natural course and determinants of catatonia through its observational cohort.

Methods:

The Laborit trial consist of a cohort study and an embedded single-blind randomized controlled trial (RCT). Patients with catatonia admitted to a psychiatric ward can join the study’s cohort, where their clinical characteristics are recorded. Standard care, including lorazepam up to 24 mg/day, will be administered. On day four, the Bush Francis Catatonia Rating Scale (BFCRS) will be used to measure symptom response. Patients showing 50% or less improvement on the BFCRS, compared to the score at start, will be eligible for the trial. Forty-two patients will be randomly assigned to either the sodium oxybate group, after a two day lorazepam reduction period, or the continuation of lorazepam. The primary endpoint is response, as measured by a decrease in BFCRS score, and will be evaluated after four days of treatment. Responders (defined by at least a 50% reduction in BFCRS scores from start of the allocated treatment), will continue treatment for an additional 10 days, with a secondary endpoint at 14 days.

Results:

This study was funded by the Dutch Brain Foundation (Hersenstichting) in December 2020. The study protocol was approved by Institutional Ethics board Amsterdam UMC on 22-05-2023. Preparations for first inclusion are ongoing.

Conclusions:

If positive, the results of this RCT can pave the way for international catatonia researchers and clinicians to introduce a new pharmacological treatment option for catatonia. Implementation could potentially benefit patients that suffer from this severe syndrome and present health care professionals with an additional treatment option. Clinical Trial: This trial is registered at ISRCTN with reference number 45554, on May 31th, 2024