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Psychiatric diagnoses are currently categorized on a syndromic basis. The syndrome of catatonia, however, remains in a diagnostic limbo, acknowledged predominantly as a subtype of schizophrenia. Yet, catatonia is present in about 10% of acutely ill psychiatry patients, only a minority of whom have schizophrenia. Among those with comorbid affective disorders, who comprise the largest subgroup of catatonic patients, the catatonic signs typically resolve dramatically and completely with benzodiazepine therapy. Those with schizophrenia respond less reliably, suggesting that the underlying processes causing the catatonia may be different in this group. The majority of patients with catatonia have concurrent psychosis. Failure to treat the catatonia before institution of antipsychotic medication may increase the risk of inducing neuroleptic malignant syndrome. At this point of time, the pathobiology of catatonia is unknown; the major reason for considering catatonia as a separate diagnostic entity would be to increase recognition of this eminently treatable neuropsychiatric syndrome.
One of the most dramatic of clinical phenomena is the response of catatonia to treatment with benzodiazepines (BZPs).1–4 Within 3 hours of receiving lorazepam 1–3 mg sublingually or intramuscularly, the vast majority of catatonic patients, who have been immobile, mute, withdrawn, and refusing to eat or drink, enjoy complete release from their “frozen” state. This situation is remarkably akin to the “awakenings,” described by those who first treated parkinsonian patients with levodopa.5 As Fink et al6 emphasize in their article, the availability of a safe, convenient, and highly efficacious treatment demands a rethinking of the “place” or status of catatonia in our current diagnostic system.
Because an estimated 9%–15% of patients admitted to a typical acute care psychiatric service meet diagnostic criteria for catatonia,2,7,8 it is of obvious interest to know whether all catatonic patients respond equally to BZPs. We have had the opportunity to address this issue in 180 episodes of catatonia in 148 individuals (78 men and 70 women; mean age = 44 y, range = 14–89 y) studied in our acute care service over the past 20 years. The diagnosis of catatonia was made according to previously published criteria2 that include 12 different clinical features, based upon the original description of this condition by Kahlbaum et al9. Similar to those described in Kahlbaum et al's monograph, our patients have had a predominantly retarded type of catatonia. Almost every patient displayed the combination of immobility, mutism, and withdrawal; negativism, posturing, grimacing, and rigidity were present in 55%–65%, whereas the more unusual features of waxy flexibility, stereotypy, echolalia, echopraxia, and episodic verbigeration were seen in less than 35% of cases.10 The distribution of concurrent or underlying diagnoses in these catatonic patients has been as follows: affective disorder (AD): 46%, schizophrenia: 20%, schizoaffective (SA) disorder: 6%, a range of medical/neurological illnesses: 16%,10 BZP withdrawal: 4%,11 and other psychiatric disorders: 8%. As we have followed almost all these patients in our clinic over the past 20 years, we are confident of these diagnoses. The range of clinical settings in which catatonia has developed would support the proposal of Fink et al6 that catatonia be divorced from its present association with schizophrenia.
In our series, we have found a differential response to BZP therapy among the various diagnostic subgroups. Response is defined as a complete resolution of all catatonic signs. The more unusual features, such as waxy flexibility, clear and patients begin to talk, eat, move about, and cooperate with an assessment. For the vast majority of patients, this occurs within 3 hours of the first dose of lorazepam or within 3 hours of a second dose. More than 80% of those with AD enjoyed a prompt and robust resolution of catatonic signs after introduction of the medication, as did 70% of the patients with SA disorder. By contrast, those with a diagnosis of schizophrenia did not fare nearly as well,2,10 a result consistent with an earlier report by Ungvari et al.12
We have considered a number of reasons why catatonic patients with a primary diagnosis of schizophrenia may not respond as reliably or robustly to BZPs.
If, then, the majority of patients with catatonia are psychotic, and if catatonia, in those with core psychotic illnesses such as schizophrenia, responds less well to BZPs, how should one approach treatment? This is a highly relevant issue given that catatonia might be a risk factor for the development of neuroleptic malignant syndrome (NMS), an observation reported by Weinberger and Kelly18 as early 1977. White and Robbins19 described 5 patients with excited catatonia—characterized more by frenzied activity than immobility—who went on to develop NMS after being treated with antipsychotic drugs (APDs), and Lee20 confirmed this finding, proposing that low serum iron might be a marker for those at risk of developing NMS when exposed to APDs. Most recently, Paparrigopoulos et al21 reviewed this issue in the context of reporting a catatonic patient who developed NMS after treatment with clozapine. At the present time, however, there is no information available regarding the proportion of catatonia case subjects who might go on to develop NMS when treated with APDs. Our extensive experience with both catatonia and NMS22,23 may shed some light on this issue. Of the 180 catatonic episodes we have studied, 82 patients received APDs, at some point, while catatonic. In 3 instances (3.6%), NMS developed. This rate is significantly higher than the currently estimated incidence of 0.07%–1.8% in all APD-treated patients.24 Looking at this from another perspective, we have assessed and treated 56 cases of NMS over the past 25 years and have carried out careful chart reviews to determine the psychomotor status of the patients at the time they received the APD that resulted in the NMS episode. In 15 instances (27%), retarded catatonia was specifically documented. Given the inevitable deficiencies in documentation and the underrecognition of catatonia as a clinical syndrome, it is likely that this is an underestimation of how frequently catatonia and NMS are temporally linked. Taken together, our finding that hypoferremia (an indicator of acute phase activation) is a consistent and reproducible finding in NMS25, in conjunction with Lee’s20 observation that exposure to APDs is much more likely to induce NMS in catatonic patients with low serum iron, and our own data indicating that NMS is a manifestation of the acute phase response,26 we would propose that the prior activation of acute phase proteins might be the key feature that predicts which catatonic patients are at risk of developing NMS on exposure to APDs.
While we support a reclassification of catatonia that would lead to improved recognition and treatment of the syndrome, we are less enthusiastic about the proposal by Fink et al6 to include NMS and serotonin syndrome as subtypes of catatonia. These toxidromes have distinctive autonomic and biochemical profiles and are typically associated with an encephalopathy as opposed to the clear consciousness of most patients with catatonia. Furthermore, the currently available evidence indicates that the critical interventions in both NMS and serotonin syndrome are withdrawal of the offending agents and timely supportive care. The main reason for rethinking the categorization of catatonia, in our opinion, is the availability of a safe and effective treatment in the form of BZP medication. While we agree with Ungvari et al15 in this issue that there is a lack of conceptual clarity regarding the term catatonia, there is a consistent and compelling literature supporting the therapeutic efficacy of BZPs in the treatment of the clinical syndrome characterized by immobility, mutism, and withdrawal.
To summarize, (1) retarded catatonia is common in the acutely ill psychiatric population; (2) although no double-blind placebo-controlled trials have been carried out, it has been consistently observed to be highly responsive to BZP treatment; (3) the presence of catatonia may increase the risk of NMS if patients are exposed initially to APDs while still catatonic; and (4) catatonia can occur in a very wide range of illnesses, both medical and psychiatric. At a practice level, we recommend the following approach.
While BZPs are extremely safe medications when used in the short term, several issues should be kept in mind during BZP treatment. They include (1) the risk of hypoventilation in obese patients or those with obstructive sleep apnea, (2) falls in elderly patients or those with balance problems after they start to move about following resolution of their catatonia, and (3) the potential, albeit small, for previously immobile patients to switch into a more excited form of catatonia. When the catatonic state is successfully treated and patients become more cooperative, physical and psychiatric examinations as well as additional investigations can be carried out if required. Expeditious treatment will typically obviate the need for interventions such as intravenous hydration and catheterization as patients begin to eat and drink almost immediately.