Zolpidem for the Management of Catatonia: A Systematic Review

Catatonia is a psychomotor syndrome associated with neurotransmitter disturbances, common in both psychiatric and medical settings. Hypoactivity of the GABA_A receptor is one of the predominant theories behind the pathophysiology of catatonia, affecting both motor functioning and emotional regulation. Benzodiazepines such as lorazepam are considered the first-line treatment for catatonia. However, up to 27% of catatonia cases fail to respond to benzodiazepines alone. Zolpidem, which can be used as a challenge, monotherapy, or augmentation agent, serves as a promising pharmacological agent for catatonia due to its unique pharmacodynamic and pharmacokinetic profile.

We sought to systematically examine the evidence behind zolpidem's use among adult patients to understand its clinical utility in the management of catatonia against prevailing treatments such as lorazepam and electroconvulsive therapy.

We conducted a systematic review using search terms related to zolpidem and catatonia in PubMed, EMBASE, and Web of Science. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 29 studies, including case studies and case series that met inclusion criteria.

We reviewed 35 cases in which zolpidem was used for catatonia management (age: mean = 51.5 ± 21.0 standard deviation years; 68.6% female; Bush Francis Catatonia Rating Scale: mean = 22.2 ± 9.0 standard deviation). Proportions of positive responses for zolpidem on catatonia varied by treatment approach: 91% as a challenge agent (n = 10), 100% as a first-line monotherapy agent (n = 3), 57% as a first-line combination therapy agent (n = 4), 70% as a second-line monotherapy agent (n = 7), and 100% as a second-line augmentation agent (n = 4). In total, 28 out of the 35 reported cases of catatonia (80%) responded positively to zolpidem.

An 80% positive response rate for zolpidem in lysing catatonia is encouraging but may be an overestimate due to reporting bias of case-level data. Results may be explained by zolpidem's selectivity for the α₁ subunit of the GABA_A receptor. Thus, zolpidem may be an underutilized catatonia treatment and prove useful in situations when benzodiazepines fail or when electroconvulsive therapy access is limited. Given that current literature on the use of zolpidem for catatonia is limited to case reports, more robust research in this area is warranted.