Blood Concentration in Lorazepam and Treatment in Adult Catatonia (PHARMAPREDICAT)

Catatonia is a severe form of psychomotor disturbance with a heterogenous presentation. It affects approximately 10% of acute psychiatric inpatients. According to the fifth edition of DSM-5 the diagnosis of catatonia can be made when three or more symptoms from the twelve following are present : catalepsy, waxy flexibility, stupor, agitation, mutism, negativism, posturing, mannerisms, stereotypies, grimacing, echolalia, echopraxia. It can occur in various psychiatric diseases, including mood disorders or schizophrenia, but also in various non-psychiatric disorders [metabolic disturbances, viral infections (including HIV), typhoid fever, heat stroke, and autoimmune disease].

Benzodiazepines, especially LORAZEPAM, are the most common initial treatment, with a remission rate of approximately 70-80 %, regardless of the cause or the clinical manifestations. This first line treatment is titrated gradually according to the therapeutic response over a few days up to 20-25 mg per day. Electroconvulsive therapy (ECT) is initiated on patients with catatonia who do not respond to benzodiazepines.

Interestingly, pharmacogenetic variants can alter the metabolism of lorazepam (e.g., the UGT2B15 * 2 allele slows it down).

The main objective of this study is to assess the link between clinical response to lorazepam, residual plasma concentrations of lorazepam after 72 hours of fixed dosage, and the existence of genetic polymorphisms modifying the metabolism of lorazepam. Our hypothesis is that non-responding patients have lowered blood concentrations of lorazepam associated to a genetic profile of rapid metabolism. Evaluating the predictive factors of the response to treatment would allow early and precise identification of non-responder patients in order to adapt their first-line treatment.

Study Overview

• Status: Recruiting
• Conditions: Catatonia

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Ali AMAD, MD; Phone Number: +33 03 20 44 44 60; Email: ali.amad@chru-lille.fr

Study Locations

• France
  • Lille, France, 59037
    • Recruiting
    • Hôpital Fontan, CHU lille
    • Principal Investigator: Ali Amad, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

102 patients with catatonia. 70 responder patients, 32 non responder

Description

Inclusion Criteria:

• catatonia according DSM-5

Exclusion Criteria:

• Subject is less than 18 years of age
• Subject is pregnant at the time of the study
• Subject/legal guardian unwilling to participate in the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of lorazepam measured after 72 hours of treatment with lorazepam at fixed dose	Compare the residual plasma concentration of lorazepam after 72 hours of taking fixed-dose lorazepam between responder and non-responder patients defined by the persistence of this diagnosis despite a daily dosage of 24 mg of lorazepam for 72 hours	at 72 hours of treatment with lorazepam

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Ali AMAD, MD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Catatonia
• Other Study ID Numbers: 2018_17; 2019-A01208-49 (Other Identifier: ID-RCB number, ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No