Revisiting lorazepam challenge test: Clinical response with dose variations and utility for catatonia in a psychiatric emergency setting.

OBJECTIVE: Catatonia can be life-threatening unless timely identified and treated. Lorazepam's ubiquitous response has led to its universal acceptance as being the first-line management of catatonia and alludes to catatonia's neurobiological underpinnings. Lorazepam challenge test (LCT) is widely used to either confirm a catatonia diagnosis or determine lorazepam sensitivity. It has a proposed schedule for administering lorazepam. However, efficacy of recommended LCT doses lack systematic evidence, resulting in variable LCT doses used in clinical and research settings contributing to findings that are challenging to generalize or assist with developing standardized lorazepam treatment protocols for catatonia. Given the same, this study aimed to objectively compare the response between two groups receiving different LCT doses and factors influencing the same. METHODS: The 6-month study in a psychiatric emergency setting at a tertiary neuropsychiatric center in India evaluated 57 catatonia patients, before and after administration of single 2 mg (n = 37; LCT-2) or 4 mg (n = 20; LCT-4) lorazepam dose, applying Bush Francis Catatonia Rating Scale (BFCRS), Mini International Neuropsychiatric Interview (MINI 5.0) and obtaining sociodemographic, clinical data. RESULTS: No between-group differences (LCT-2 vs LCT-4) for sociodemographic, clinical profiles or BFCRS severity score changes to lorazepam on Mann-Whitney U test were noted. Applying Wilcoxon signed rank test comparing individual sign severity demonstrated response variability, with significant response noted to both doses (stupor, mutism, staring, posturing, withdrawal, ambitendency, automatic obedience) and others selectively to 2 mg (echolalia, rigidity, negativism, mitgehen). Notably, sign resolution (present/absent) only to 2 mg was significant for stupor, mutism, staring, posturing, echolalia, rigidity, negativism and mitgehen. CONCLUSION: This study suggests 2 mg lorazepam may be an optimal LCT dose, given significant response to most catatonic signs thereby ensuring accurate detection and preventing misinterpretation of response. It offers future studies direction for standardizing lorazepam dosing schedules for catatonia management and exploring neurobiological underpinnings for individual catatonic signs that may be potentially different, given these findings.

Complexities of cooccurrence of catatonia and autoimmune thyroiditis in bipolar disorder: A case series and selective review.

In recent years the neurobiological underpinnings of catatonia have been an emerging area of interest. Catatonia is frequently encountered in mood disorders, neurological disorders and systemic illnesses. Furthermore, the manifestation of catatonia in autoimmune disorders such as NMDA receptor antibody encephalitis and thyroiditis reinforces its neuropsychiatric nature. Irrespective of cause benzodiazepines and electroconvulsive therapy remain the standard treatments for catatonia, although a proportion fail to respond to the same. This report describes three women with pre-existing bipolar disorder presenting in catatonia. Interestingly in all three, while benzodiazepines and electroconvulsive therapy failed, a dramatic resolution of catatonia with corticosteroids was noted following the detection of Hashimoto's thyroiditis. Hashimoto's encephalopathy presenting as catatonia has been reported, but our patients' profile differed in having had an a priory diagnosis of bipolar disorder. Given that both catatonia and thyroid dysfunction are frequently encountered in bipolar disorder, Hashimoto's encephalopathy as a potential cause for this concurrent manifestation in bipolar disorder may be overlooked. Therefore, it is essential to suspect Hashimoto's encephalopathy when catatonia manifests in bipolar disorder. A timely evaluation would be prudent as they may fail to respond to standard treatments for catatonia but respond remarkably to corticosteroids, saving much time and angst. Recent evidence implicates immune system dysfunction, with neuroinflammation and peripheral immune dysregulation contributing to the pathophysiology of bipolar disorder as well as catatonia. Findings from this study reaffirm the role of immune system dysfunction common to the etiopathogenesis of all these disorders, highlighting the complex interplay between catatonia, thyroiditis and bipolar disorder.

Diagnosing catatonia and its dimensions: Cluster analysis and factor solution using the Bush Francis Catatonia Rating Scale (BFCRS).

Advances in research into catatonia in the preceding two decades has offered increasing clarity and an improved understanding of various aspects of this complex syndrome. Despite the above, there are several aspects that hinder a broader interpretation of these findings, the most common being a lack of consensus on the criteria required for diagnosing catatonia. Whilst being the most frequently used tool for diagnosis, the number of signs from Bush-Francis Catatonia Rating Scale (BFCRS) needed to diagnose catatonia remain unclear. This study aimed to determine the number of signs required to accurately diagnose catatonia using BFCRS and delineate its dimensions in an acute inpatient unit in the Indian setting. A random sample of 300 patients were evaluated for catatonia within 24 h of admission. Cluster Analysis followed by discriminant analysis and receiver operating curve analysis (ROC) provided cut-off values for diagnosing catatonia syndrome. Principle Component Analysis (PCA) with varimax rotation was used to identify factors in those with catatonia. Findings revealed that a cut off of two signs from both Bush-Francis Catatonia Screening Instrument or BFCSI (sensitivity of 100 %, specificity of 96.2 % as well as a positive predictive value [PPV] of 79.6 % and negative predictive value [NPV] 100 % with ROC AUC value of 0.98) and complete BFCRS (sensitivity of 100 % and specificity of 90.7 %, PPV of 80.7 and NPV of 100 % with ROC AUC for at least two items cut-off being 0.95) accurately detected catatonia. However, the prevalence of catatonia in the same population increased by 4% from 16.3% to 20.3% using the BFCRS rather than the BFCSI. The BFCRS generated a 3-factor model accounting for 65.48 % variance offering the best fit, indicating three discrete dimensions to catatonia, namely retarded, excited and what we named as "aberrant volitional". Interestingly, the aberrant volitional dimension comprises of signs that need to be elicited rather than passively observed and excluding one, none of them are part of the BFCSI. Findings of this study suggest that the BFCRS more accurately detects catatonia rather than the BFCSI. Additionally, three dimensions of catatonia more coherently explain the catatonic syndrome given that 55.7 % of the sample had signs from more than one factor concurrently. We propose that the BFCRS rather than BFCSI be routinely administered for evaluating all suspected cases of catatonia to ensure more accurate detection as well as identifying the aberrant volitional dimensional signs more consistently. The three-dimensional model also offers great opportunities to further unravel the pathophysiological basis of catatonic signs more systematically.