Journal Article Annotations
2023, 1st Quarter
Annotations by Samuel Kohrman, MD
From the combined six observational cohort studies, eight case series and 79 case reports, 119 of 182 (>80%) patients with catatonia reached a partial or full remission of catatonic symptoms following clozapine treatment. Of the 81 patients from cohort studies, 74% of patients reached partial and 10% reached full remission; 55 patients (68%) were diagnosed with schizophrenia while the remaining patients had unspecified diagnoses. From the case reports and case series, 81% of patients combined reached either partial remission (18%) or full remission (63%); 24 patients (24%) had clozapine withdrawal catatonia, 64 patients (63%) were diagnosed with a schizophrenia or related disorder. Concurrent treatment for catatonia included benzodiazepines (61%),antipsychotics (72%), and/or ECT (41%). In case reports and case series, clozapine took weeks to lead to resolution in partial responders (mean 41 days) and in complete responders (mean 54 days).
Strength and weaknesses:
This is the first systematic review to specifically investigate clozapine usage to treat catatonia. As a systematic review of observational studies, only an associative relationship can be drawn and findings should be interpreted with caution given the overall low and moderate quality of studies used. Cohort studies demonstrated more of a partial response finding than did the case reports and case series, which suggests in the latter likely confirmation and publication biases towards publishing positive outcomes. We cannot draw direct conclusions on the effect of clozapine on catatonia as more than half of patients received one or a combination of concurrent treatments (benzodiazepine, antipsychotic, and/or ECT) rather than clozapine alone. Additionally, there were no included head-to-head comparisons of clozapine to other treatments.
With a low to perhaps a cautiously low-to-medium level of evidence, it is reasonable to consider clozapine as part of the armamentarium of non-first line agents for treating catatonia. Given the overall challenges of treating catatonia, clozapine may be helpful in treating catatonia in cases of co-existing psychosis, in undifferentiated aetiology, or in clozapine withdrawal catatonia particularly if first line therapies of benzodiazepines and or ECT are ineffective, partially effective, or not fully feasible. Further studies are surely warranted.
Out of 335 studies included in this systematic review, 707 patients were included to determine the accuracy of EEGs in discerning between neuropathological processes and primary mental disorders as aetiologies for catatonia. Large studies showed that an abnormal EEG could predict medical causes of catatonia with sensitivity of 0.82 and specificity of 0.66, as compared to smaller studies with sensitivity of 0.76 and specificity of 0.67. Limbic encephalitis, epileptiform discharges, focal abnormalities and status epilepticus were highly specificfor medical causes, even though with varying sensitivity. Interestingly, features of encephalopathy were found in both medical and psychiatric proposed aetiologies of catatonia; a significant minority (23%) of patients with a presumed psychiatric cause for catatonia had an abnormal EEG, most often with signs of encephalopathy.
Strength and weaknesses:
This is the first systematic review and meta-analysis investigating the test accuracy of EEGs in determining aetiology of catatonia. All studies included were observational and the threshold for classifying an EEG as abnormal differed between studies. Selection bias and reporting bias may have played a role in findings; only patients whose clinical presentation justified use of an EEG were included in this study.
As recommendations vary about when to use EEGs in the workup of catatonia, this study can guide C-L psychiatrists to utilize EEGs as a component of the medical workup in cases of catatonia with diagnostic uncertainty, including when there is uncertainty regarding a possible neuropathologic cause. Given the broad aetiologies of catatonia, C–L psychiatrists encounter a large majority of cases in a general medical setting. Thus, for hospital-based C-L psychiatrists, the question of utilizing EEGs in the workup of diagnostically uncertain catatonia may be less of a question of clinical utility and more of a question of availability of resources and timing as it could delay treatment. Furthermore, the state of catatonia can be considered as a neuropathological process, whether its aetiology is a primary mental disorder, a medical process or a combination of the two.