Catatonia vis-`a-vis delirium: The significance of recognizing catatonia in altered mental status Mark A. Oldham M.D., Hochang B. Lee M.D. PII: DOI: Reference:
S0163-8343(15)00148-6 doi: 10.1016/j.genhosppsych.2015.06.011 GHP 7033
To appear in:
General Hospital Psychiatry
Received date: Revised date: Accepted date:
31 January 2015 12 June 2015 12 June 2015
Please cite this article as: Oldham Mark A., Lee Hochang B., Catatonia vis-` a-vis delirium: The significance of recognizing catatonia in altered mental status, General Hospital Psychiatry (2015), doi: 10.1016/j.genhosppsych.2015.06.011
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ACCEPTED MANUSCRIPT Catatonia vis-à-vis delirium
Catatonia vis-à-vis delirium: The significance of recognizing catatonia in altered mental status Mark A. Oldham, M.D.,1* and Hochang B. Lee, M.D.2 1
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Assistant Professor of Psychiatry Yale School of Medicine 2
Associate Professor of Psychiatry Yale School of Medicine
Running head: Catatonia vis-à-vis delirium
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*Corresponding author 20 York St. Fitkin 615 New Haven, CT 06510 Office: 203-785-2618 Fax: 203-737-2221 [email protected]
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Key words: Catatonia, delirium, altered mental status, encephalopathy, diagnostic criteria, phenomenology
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Disclosures: We have no relevant financial conflicts of interest to disclose.
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Funding: None.
Acknowledgements: Dr. Oldham would like to thank Paul Desan, M.D., Ph.D., director of the Yale
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Psychosomatic Medicine Fellowship, for his abiding mentorship and ongoing professional development.
ACCEPTED MANUSCRIPT Catatonia vis-à-vis delirium
Abstract
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Background:
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Catatonia is seldom considered in evaluation of altered mental status (AMS) in medical settings. Furthermore, catatonia often meets delirium criteria due to incoherence, altered awareness, and behavioral
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change. Catatonia may co-occur with or be preferentially diagnosed as delirium.
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Methods:
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We conducted a systematic literature review of MEDLINE, EMBASE, and PsycINFO on the relationship between catatonia and delirium. We also juxtapose clinical features of these syndromes and outline a
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structured approach to catatonia evaluation and management in acute medical settings.
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Results:
These syndromes share tremendous overlap: the historical catatonia-related terms “delirious mania” and
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“delirious depression” bespeak of literal confusion differentiating them. Only recently has evidence on their relationship progressed beyond case series and reports. Neurological conditions account for the
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majority of medical catatonia cases.
Conclusions: New-onset catatonia warrants a medical workup, and catatonic features in AMS may guide clinicians to a neurological condition (e.g. encephalitis, seizures, or structural CNS disease). Lorazepam or electroconvulsive therapy (ECT) should be considered even in medical catatonia and neuroleptics used with caution. Moreover, ECT may prove life-saving in malignant catatonia. Further studies on the relationship between delirium and catatonia are warranted.
ACCEPTED MANUSCRIPT Catatonia vis-à-vis delirium
Introduction Catatonia among patients with altered mental status (AMS) receives relatively scant clinical or research
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attention and requires a high index of suspicion (see Table 1 for a differential for AMS). However,
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catatonic features are not uncommon in acute psychiatric and medical settings. Catatonia may be identified in one out of seven patients with psychosis and one out of five patients with a major mood
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episode [1]. In acute medical settings catatonia prevalence ranges from 1.6% [2, 3] to 6.3% [4, 5]. In fact, a recent study of sequential patients with delirium evaluated by a consult psychiatry service found a 12–
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37% incidence of catatonia depending on the symptom cut-off [6].
Because catatonia and delirium share many clinical features, catatonia may be misdiagnosed as delirium [7], managed as such [8] or even co-occur with delirium [9, 10]. Although delirium is often considered on
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the differential for catatonia [11, 12], the differential for delirium seldom includes catatonia [7]. This
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propensity for preferentially diagnosing catatonia as delirium is further encouraged by the high delirium prevalence in medical settings. Delirium occurs in one out of five medical inpatients [13], two out of five
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critical illness [15].
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intensive care unit (ICU) patients [14], and up to four out of five mechanically ventilated patients with
Recognizing catatonia has implications for underlying medical conditions and for timely clinical management. Medical catatonia warrants an expedient medical work-up, and alarmingly catatonia can progress to the potentially fatal syndrome of malignant catatonia for which effective treatment exists [16]. Lorazepam or electroconvulsive therapy (ECT) may prove liberating in medical catatonia [5, 12], and neuroleptics—particularly high-potency agents—should be used with caution [17]. Failing to recognize catatonia may prolong episodes of AMS thus lengthening hospital stay by compromising clinical decisions.
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Methods We conducted a systematic review of MEDLINE, EMBASE, and PsycINFO from 1980 through March
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2015 crossing the terms “delirium” and “catatoni*” to explore the state of the evidence on the relationship
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between delirium and catatonia. We chose 1980 because that year the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) introduced operationalized criteria for delirium. Search
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results were initially de-duplicated and limited to humans and manuscripts in English. Next, publications without abstracts were excluded as were book chapters and conference abstracts because these are not
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peer-reviewed. We retrieved full text articles of formal studies where both delirium and catatonic features
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are included as either inclusion criteria or study outcomes in order to understand systematic relationships between them. Catatonia reviews were also retrieved to identify other potentially-relevant studies.
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References of full-text articles retrieved were reviewed for additional studies.
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We follow this literature review by juxtaposing clinical features of delirium and catatonia, highlighting the potential value of identifying catatonic features in AMS. Finally, we describe a structured clinical
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approach to evaluating and managing catatonia, particularly as a cause of AMS in acute medical settings.
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Results of systematic review
See the Figure for a flow diagram of identified articles. Despite an abundance of case reports and series, only three studies met inclusion criteria [5, 6, 18], demonstrating the dearth of systematic investigation in this area. Among these studies, one describes catatonic features in delirium [6], another identifies delirium in catatonia [5], and a third describes catatonic features as a predictor of delirium after ECT [18]. In this third publication, however, delirium was identified without a validated instrument or formal diagnostic criteria. Additionally, proprofol, a known deliriogen, was successful in “treating” all cases of study-identified delirium. What these authors describe as delirium appears rather to be psychomotor agitation [18]. The other two studies are described below.
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In the first of these, Grover et al. studied a cohort of 205 patients with delirium per DSM-IV-TR and found several catatonic symptoms in greater than 5% of the sample: excitement (in 73% of sample),
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immobility/stupor (21%), mutism (16%), negativism (10%), combativeness (9%), staring (9%),
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withdrawal (9%), and impulsivity (8%) [6]. Other catatonic features, though, were uncommon: mannerisms, verbigeration, waxy flexibility, mitgehen, gegenhalten, ambitendency, and
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echopraxia/echolalia. In particular, it is curious that stereotypy and perseveration were identified in only one patient each. Carphology (synonymously, floccillation; stereotyped picking at linens) is a historical
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feature of delirium [19]. Perhaps, though, such observations that preceded operationalized criteria for
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delirium were documenting medical catatonia instead. Perseveration, on the other hand, is prevalent in delirium, occurring in more than 80% of cases [20].
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In the remaining study, older adults admitted to a general hospital were screened for catatonia using the
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Bush-Francis Catatonia Screening Instrument and subsequently rated using the Bush-Francis Catatonia Rating Scale (see Clinical evaluation and psychometrics below). Depending on the criteria used 6.3–
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8.9% of subjects were diagnosed with catatonia [5]. Among the ten who met research criteria for catatonia, three had concurrent delirium. Seven of these ten had baseline neurocognitive impairment, but
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it is unclear how this was differentiated from delirium. In fact, six of these patients were medically admitted for “cognitive impairment of unknown etiology,” which itself may have been delirium.
Taken together, these latter two studies suggest a considerable degree of overlap between delirium and catatonic features, but these data are preliminary and await confirmation. Further, such observational, cross-sectional studies are unable to answer questions of clinical management. In view of the limited systematic evidence on the relationship between delirium and catatonia, the remainder of this article provides a conceptual review of the relationship between catatonia and delirium followed by a structured approach to evaluating and managing patients with catatonic features in AMS.
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Juxtaposing catatonia and delirium Clinical presentation
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Although non-specific laboratory findings and biomarkers have been described in delirium and catatonia,
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each relies on clinical diagnosis. DSM-5 diagnosis of delirium requires five criteria whereas catatonia remains polythetic. That is, at least three of 12 criteria must be present for diagnosis. All deliria share the
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same core features, but catatonia presents with a variety of distinct, non-overlapping phenotypes, which makes recognition all the more difficult (American Psychiatric Association has granted to include DSM-5
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diagnostic criteria for delirium & catatonia here as tables: see Tables 2 and 3).
In 2013 the DSM-5 formally introduced delirium specifiers: hyperactive, hypoactive, or mixed level of activity [21]. By definition, delirium has a secondary cause, which can be a psychoactive substance,
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medical condition, or multifactorial. Catatonia is a clinical syndrome that may either be associated with a
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psychiatric illness or have a medical or substance-induced cause [21]. Contrary to historical lore, a minority of catatonia is associated with schizophrenia. Although the conditions associated with catatonia
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vary based on clinical setting, an estimated one in four patients with catatonia has medical catatonia (i.e.
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catatonia due to another medical condition per DSM-5) [1].
Differentiating catatonia from delirium The boundary between delirium and catatonia is often indistinct with catatonic features not uncommonly occurring in delirium [22]. Patients with catatonia exhibit altered communication and behavior, and catatonic features such as mutism, echolalia, negativism, or agitation can confound reliable delirium assessment. The inability to perform a reliable assessment of consciousness and attention in a patient with demonstrably altered mental status warrants a diagnosis of delirium in most clinical and research settings.
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DSM-5 refines the phenotype of catatonia substantially [23], but clinical overlap between delirium and catatonic features remains. This overlap suggests that they may co-exist as delirium with catatonic
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features or “catatonic delirium” [10]. In DSM-5, delirium is a universal exclusion for diagnosing any
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other psychiatric condition while delirium is present. This diagnostic preeminence of delirium ensures that underlying medical conditions are addressed and that primary psychiatric illness is not diagnosed
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erroneously because delirium can present with virtually any psychiatric symptom.
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In the case of medical catatonia, though, this delirium exclusion is without empirical rationale [10]. Patients with medical catatonia typically meet delirium criteria as well, which currently precludes the
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diagnosis of medical catatonia in most instances [24]. A diagnosis of “catatonia” may be easily misinterpreted by medical providers, particularly non-psychiatrists, as a de facto primary psychiatric
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condition, but identification of catatonic features in AMS as either a subtype of or co-morbidity with
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delirium diagnosis may guide the medical work up and have treatment implications as discussed below.
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Motor subtypes: Hyper- and hypokinetic states Both delirium and catatonia exhibit motoric variants. Unlike delirium, which was conceptualized as a
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purely hyperkinetic syndrome long before its hypokinetic variant was annexed, catatonia was originally described as a stuporous state. This historical distinction is likely a persisting reason why clinicians often have a fixed view of catatonia as a twilight state with bizarre posturing. Rather, catatonia has various phenotypes [8]. The clinical value of differentiating presentations based on motor activity remains unclear [25] aside from clinical vigilance related to motoric consequences (e.g. preventing pressure ulcers in patients who are immobile or treating hyperpyrexia in psychomotor agitation). Delirium presents with hyperactive, hypoactive, or mixed behavioral features. Similarly, excited and retarded/stuporous poles have been described in catatonia. Despite these contrasting pairs of terms, clinical heterogeneity and motoric fluctuations are often seen in both delirium [25] and catatonia [26].
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Historical nomenclature of catatonic subtypes is diverse. Catatonia is typically categorized based on level of behavioral and autonomic activity into stuporous, excited, and malignant catatonia [26].
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Stuporous/retarded catatonia, originally described by Kahlbaum, has alternatively been described
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eponymously as Kahlbaum syndrome or delirious melancholia/depression [27, 28]. Akinetic mutism, coma vigil, and benign stupor [29] may also describe stuporous catatonia, but these terms are non-specific
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and may refer to locked in syndrome, abulia due to anterior cingulate lesions, or minimally responsive states. Excited catatonia describes the hyperkinetic variant and has garnered the terms Bell’s mania [30],
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oneirophrenia, oneiroid/oneiric state or syndrome [31], catatonos raptus, delirium acutum [32], delirious
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mania per Kraepelin [33], and delirious catatonia [22]—the final three literally suggesting clinicians have had difficulty differentiating delirium from catatonia. The lack of an operationalized definition of delirium prior to DSM-III promulgated a vague notion of what delirium was, challenging the reliability
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and validity of historical delirium reports.
When autonomic instability and fever accompany either stuporous or excited catatonia, the patient is said
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to have malignant catatonia. Historical descriptions of malignant catatonia have included pernicious catatonia, deadly catatonia, and (Stauder’s) lethal catatonia [34, 35]. Neuroleptic malignant syndrome
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(NMS) and serotonin syndrome (SS) are often considered variants of malignant catatonia. Malignant catatonia may be life-threatening due to autonomic dysregulation, hyperpyrexia, rhabdomyolysis, or acute kidney injury. The terms deadly and lethal catatonia attest to the potential mortality associated with catatonia, but these terms are discouraged in view of the effective treatment widely available (see Clinical management below). In particular, the presence of autonomic findings in altered mental status presents a diagnostic dilemma: they may be “primary” as part of a broader catatonic syndrome or “secondary” to the underlying cause as in delirium tremens, encephalitis, or sepsis [36].
Clinical evaluation and psychometrics
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The most commonly used scale for catatonia, the Bush-Francis Catatonia Rating Scale (BFCRS) [37], allows for serial evaluation, but it does not provide a clinical cut-off for the diagnosis of catatonia. The
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first portion of the BFCRS is often used independently to screen for catatonia and called the Bush-Francis
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Catatonia Screening Instrument. As previously reviewed, several catatonia scales and screens have been published but met with limited use [38, 39] including the Rosebush criteria, Modified Rogers Scale,
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Northoff Catatonia Scale, Braunig Catatonia Rating Scale, Fink and Taylor criteria, KANNER scale, and
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the mnemonic WIRED ‘N MIRED.
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Over two dozen delirium scales have been published [40]. The Confusion Assessment Method (CAM) enjoys the most widespread use for delirium detection, and as described above the CAM would often yield a positive delirium diagnosis when being applied to patients with catatonia. Scale-specific
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psychometrics must be considered. For instance, some scales evaluate for confusion without specificity
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for delirium (e.g. Clinical Assessment of Confusion). Screening scales often do not provide an index of delirium severity (e.g. CAM) and should be used in conjunction with standardized neurocognitive screens
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to ensure adequate sensitivity. Others provide only severity measures and are not intended for diagnosis (e.g. Memorial Delirium Assessment Scale). Still others are useful for diagnosis and delirium severity,
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but these require a higher degree of training and time to use (e.g. Delirium Rating Scale-Revised-98). Additionally, the settings in which each scale has been validated should be considered.
Causes and medical work-up Delirium is always medically and/or substance-induced, but up to a quarter of patients with catatonia are due to medical condition or psychoactive substance [41], even when excluding cases of NMS and SS [2]. The range of medical conditions and medications that have can lead to catatonia is broad. Most classes of conditions that can cause delirium have been reported as a potential cause of catatonia as well. The acronym “I WATCH DEATH,” a mnemonic for recalling the delirium causes, may be applied to catatonia with only slight modification (see Table 4).
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A significant majority of medical catatonia appears to be due to neurological disease [42]. Historical
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reviews of medical catatonia have highlighted neurological causes [43], and three reviews of case reports
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and series attribute over two thirds of medical catatonia to a neurological cause [44-46]. An early systematic review of medical catatonia cases two decades ago found that roughly 70% were due to a
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neurological condition [44]. Specifically, 30% were associated with structural central nervous system (CNS) disease, 25% due to encephalitis or other CNS infection, and 10% attributed to a seizure disorder.
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Similarly, a retrospective Mayo Clinic chart review identified 95 in-house cases of catatonia per DSM-
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IV-TR criteria, of whom 20 had medical catatonia [45]. Among those 20 patients, 70% had neurological illness: encephalitis (n = 6), major neurocognitive disorder (4), seizure disorders (3), and CNS metastases (1). Additionally, a 2008 review of pediatric cases of medical catatonia identified 26 cases related to
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medical conditions and 12 related to medications or toxins [46]. Among the 26 medical catatonias, 10
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were related to neurological conditions, 6 genetic conditions (all known to affect brain development), and four viral encephalitides—that is, 77% with cerebral involvement. The fact that all three series of medical
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catatonia spanning two decades report a rate of ≥ 70% medical catatonias due to neurological illness is striking. In addition, anti-NMDA receptor encephalitis is an increasingly recognized cause of both
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catatonia and delirium [47]. In view of these prevalence data, one should maintain a high index of suspicion for neurological disease where medical catatonia is on the differential.
Electroencephalography (EEG) remains the most widely available physiologic measure of delirium and reveals diffuse background slowing, typically in the delta range [48]. Most catatonia tends to present with a normal EEG, but medical catatonia represents an exception to this rule. Over 80% of medical catatonia in one study exhibited abnormal EEG findings, the most common being diffuse slowing, lending further support for a catatonia–delirium spectrum or delirium with catatonic features [10, 11].
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Evaluation of catatonia in acute medical settings: Here we present a structured approach to evaluation and management where catatonic features are
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identified.
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1. Where possible, evaluate for comorbid delirium. The presence of delirium strongly suggests a medical cause of catatonic features, and according to the DSM-5 a diagnosis of delirium preempts
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other psychiatric diagnoses including catatonia due to another medical condition. 2. Obtain a clear history.
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a. Psychiatric history: A psychiatric history, in itself, does not exclude medical catatonia [45];
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however, new-onset catatonia in middle age and beyond should increase suspicion for a medical cause, particularly in those over 65 [5]. Catatonia in patients over age 40 has been associated with abnormal EEG recordings, which is a common clinical feature of medical
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catatonia [11]. Whether psychiatric illness associated with catatonia may contribute to a
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catatonic diathesis remains unexplored. Case series have found that psychiatric illness is common even in presumed medical catatonia [3, 11, 12], but conflicting reports exist [5, 49].
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In the retrospective Mayo Clinic review above, researchers found a 45% rate of psychiatric illness among the 20 cases of presumed medical catatonia [45].
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b. Natural history: Catatonia that persists over a week may be uncommon in mood disorders. After two weeks of persistent catatonia, the likelihood of psychotic illness or a medical condition increases markedly [50]. 3. Review medications. NMS and SS should be considered, particularly because non-psychiatric medications (e.g. prochlorperazine and linezolid, respectively) may cause these. Additional medication causes of catatonia include corticosteroids, disulfiram, ketamine, and phencyclidine as well as withdrawal from sedative-hypnotics [51]. 4. Rule out catatonia mimics. Several clinical conditions may present similarly to stuporous catatonia. These include selective mutism, aphasia with an expressive component, severe Parkinson disease and Parkinson-plus syndromes, malignant hyperthermia, locked-in syndrome,
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stiff-person syndrome, profound abulia, malingering, somatoform illness, or dissociative states [52, 53]. Perhaps, though, catatonia masquerades as some cases of inanition or failure to thrive in
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the elderly [5].
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5. Conduct a medical work up: Catatonia may herald unrecognized medical illness akin to delirium alerting clinicians to an otherwise asymptomatic urinary tract infection. When medical
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catatonia is suspected, a medical work up with an emphasis on neurological causes is warranted. Particular consideration should be given for EEG, brain imaging with a preference for magnetic
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resonance imaging (MRI), and lumbar puncture (LP).
Management of catatonia in acute medical settings
1. Treat the underlying cause: As with delirium, definitive treatment of medical catatonia is
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management of the underlying cause. Contributory medications should be avoided if medically
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feasible.
2. Conduct a lorazepam challenge: Treatment for catatonia classically involves oral (at times via
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nasogastric tube), intramuscular or intravenous lorazepam 2 mg in adults or 0.5–1 mg in children or the elderly. The only randomized pharmacologic trial for acute catatonia to date found
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intravenous amobarbital efficacious for 60% of patients with catatonic mutism [54]. Catatonic features should be monitored for improvement. Clinical response is defined as a 50% reduction in catatonic features as on the BFCRS. Lorazepam 2 mg can be scheduled thrice daily or increased in upward of 16 mg per day in divided doses over the following days pending clinical response [55]. Case series and expert experience suggests that up to 80–85% of patients will respond to lorazepam [56, 57] with response rates in psychosis-related catatonia [57] medical catatonia [45] and older adults [5] closer to 50%. One randomized, double-blind, placebo-controlled, crossover trial of lorazepam 6 mg/day for schizophrenia with chronic catatonic features found no improvement on BFCRS, suggesting that catatonia related to chronic psychosis may represent a distinct clinical entity [58]. An alternative to the lorazepam challenge is 10 mg zolpidem orally or
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via nasogastric tube [59], but response to zolpidem is likely to be brief. Such patients typically require ongoing management with lorazepam or other catatonia-specific treatment.
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3. Avoid high-potency neuroleptics. High-potency neuroleptics are not effective for catatonia.
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They can cause catatonic-like (i.e. extrapyramidal) side effects and may potentiate NMS [55]. Recent reports suggest that atypical antipsychotics may improve non-malignant catatonia [17, 55]
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but should be used with caution as an adjunct to a benzodiazepine or other catatonia-specific intervention. It is unclear whether high-potency neuroleptics for the management of catatonic
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excitement can be used safely as an adjunct to catatonia-specific treatment.
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4. Ensure appropriate supportive measures: Guidelines on the supportive management have been reviewed previously [60]. The first three apply to both excited and stuporous catatonia; the
a. Reverse hyperthermia.
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remaining five are exclusive to stuporous variants.
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b. Hydrate to prevent acute kidney injury. c. Maintain adequate nutrition.
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d. Monitor oxygenation closely. e. Provide prophylaxis for deep vein thrombosis or pulmonary embolism. Prevent pressure ulcers.
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f.
g. Prevent muscle contractures. h. Mitigate against aspiration pneumonia. 5. Consider an N-methyl-D-aspartate (NMDA) receptor antagonist or topiramate: Small case series support the use of the NMDA receptor antagonists amantadine or memantine or the anticonvulsant topiramate in catatonia unresponsive to lorazepam [61]. Despite the absence of formal guidelines, agents other than lorazepam may be considered within 1–3 days of a negative lorazepam trial [61]. 6. Initiate electroconvulsive therapy (ECT): Nearly 90% of catatonia respond to ECT including cases of malignant catatonia [62]. In cases of malignant catatonia (i.e. autonomic instability,
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hyperpyrexia, rhabdomyolysis, et al.), ECT should be considered as an emergent intervention. Where patients refuse to eat and are unable to provide self-care, ECT should be considered
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urgently. ECT should also be considered when only partial response is obtained from medication
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trials.
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Conclusions
Clinicians must maintain a high index of suspicion for catatonia, else it will be missed or preferentially
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diagnosed as another condition such as delirium. Expedient recognition of catatonia appears to have
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implications for medical work up and treatment. Medical catatonia is commonly associated with neurological illness including encephalitis, structural CNS disease, and seizure disorders.
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Further, catatonia implies certain treatment parameters. Contrary to traditional delirium management,
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lorazepam is the first-line agent for catatonia, and high-potency first-generation antipsychotics and monotherapy with second-generation antipsychotic are best avoided in patients with catatonic features. A
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fascinating conundrum arises when juxtaposing the management of catatonia and delirium: neuroleptics, often used to manage hyperactive delirium, may precipitate malignant catatonia whereas benzodiazepines,
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first-line for catatonia, may be deliriogenic. When lorazepam or other medication trials such as amantadine, memantine, or topiramate are ineffective or only partially effective for catatonia or where patients develop autonomic instability, ECT remains the gold-standard catatonia treatment with impressive efficacy even in the most critical cases. The remarkable degree of phenotypic overlap between delirium and catatonia should fuel further efforts to refine diagnostic criteria for these conditions, particularly where these syndromes co-occur. Historical and emerging reports warrant further investigation to elucidate the diagnostic and clinical management implications of catatonic features in cases of AMS.
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[21] Association AP. Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing, 2013. [22] Taylor MA and Fink M. Catatonia in psychiatric classification: a home of its own. The American journal of psychiatry 2003;160:1233-41. [23] Tandon R, Heckers S, Bustillo J, Barch DM, Gaebel W, Gur RE, et al. Catatonia in DSM-5. Schizophrenia research 2013;150:26-30. [24] Carroll BT. Catatonia on the consultation-liaison service. Psychosomatics 1992;33:310-5. [25] Stagno D, Gibson C and Breitbart W. The delirium subtypes: a review of prevalence, phenomenology, pathophysiology, and treatment response. Palliative & supportive care 2004;2:171-9. [26] Fink M and Taylor MA. Catatonia: subtype or syndrome in DSM? The American journal of psychiatry 2006;163:1875-6. [27] Bräunig P and Krüger S. In Caroff S, Mann S, Francis A and Fricchione G, editors Catatonia: From psychopathology to neurobiology. Washington, DC: American Psychiatric Publishing, 2004. p. 1-14. [28] Hoyer C, Kranaster L, Biedermann S, Lewien A, Aksay SS, Meyer-Lindenberg A, et al. The syndrome of delirious depression: conception and case description. Journal of clinical psychopharmacology 2014;34:286-8. [29] Hoch A. Benign Stupors. New York: Macmillan, 1921. [30] Bell L. On a form of disease resembling some advanced stages of mania and fever. American Journal of Insanity 1846;6:97-127. [31] Meduna L. Oneirophrenia. Urbana: University of Illinois Press, 1950. [32] Johnson J. Catatonia: the tension insanity. British Journal of Psychiatry 1993;162:733-8. [33] Bond TC. Recognition of acute delirious mania. Archives of general psychiatry 1980;37:553-4. [34] Stauder K. Die toedliche Katatonie. Arch Psychiatr Nervenkr 1934;102:614-634. [35] Tang CP, Leung CM, Ungvari GS and Leung WK. The syndrome of lethal catatonia. Singapore medical journal 1995;36:400-2. [36] Levin T and Martin R. Classification of catatonia. Am J Psychiatry 2004;161:1136; author reply 1136. [37] Bush G, Fink M, Petrides G, Dowling F and Francis A. Catatonia. I. Rating scale and standardized examination. Acta psychiatrica Scandinavica 1996;93:129-36. [38] Carroll BT, Kirkhart R, Ahuja N, Soovere I, Lauterbach EC, Dhossche D, et al. Katatonia: a new conceptual understanding of catatonia and a new rating scale. Psychiatry 2008;5:42-50. [39] Sienaert P, Rooseleer J and De Fruyt J. Measuring catatonia: a systematic review of rating scales. Journal of affective disorders 2011;135:1-9. [40] Adamis D, Sharma N, Whelan PJ and Macdonald AJ. Delirium scales: A review of current evidence. Aging & mental health 2010;14:543-55. [41] Carroll B and Goforth H. Medical catatonia. In Caroff S, Mann S, Francis A and Fricchione G, editors Catatonia: From psychopathology to neurobiology. Washington, DC: American Psychiatric Publishing, 2004. p. 121-127. [42] Ramirez-Bermudez J, Aguilar-Venegas LC, Calero-Moscoso C, Ramirez-Abascal M, Nente-Chavez F, Flores-Reynoso S, et al. [Neurology-psychiatry interface in central nervous system diseases]. Gaceta medica de Mexico 2010;146:108-11. [43] Taylor MA. Catatonia: A review of a behavioral neurologic syndrome. Neuropsychiatry, Neuropsychology, & Behavioral Neurology 1990;3:48-72. [44] Carroll BT, Anfinson TJ, Kennedy JC, Yendrek R, Boutros M and Bilon A. Catatonic disorder due to general medical conditions. The Journal of neuropsychiatry and clinical neurosciences 1994;6:122-33. [45] Smith JH, Smith VD, Philbrick KL and Kumar N. Catatonic disorder due to a general medical or psychiatric condition. The Journal of neuropsychiatry and clinical neurosciences 2012;24:198-207.
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[46] Lahutte B, Cornic F, Bonnot O, Consoli A, An-Gourfinkel I, Amoura Z, et al. Multidisciplinary approach of organic catatonia in children and adolescents may improve treatment decision making. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2008;32:1393-8. [47] Fink M. Rediscovering catatonia: the biography of a treatable syndrome. Acta psychiatrica Scandinavica Supplementum 2013:1-47. [48] Neufeld KJ and Thomas C. Delirium: definition, epidemiology, and diagnosis. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 2013;30:438-42. [49] Rizos DV, Peritogiannis V and Gkogkos C. Catatonia in the intensive care unit. General hospital psychiatry 2011;33:e1-2. [50] Huang TL, Ree SC, Huang YC, Liu HY and Yang YY. Catatonic features: differential diagnosis and treatments at an emergency unit. Psychiatry and clinical neurosciences 1999;53:63-6. [51] Duggal HS and Singh I. Drug-induced catatonia. Drugs of today 2005;41:599-607. [52] Fink M and Taylor M. Conditions that may be mistaken for catatonia. Catatonia: A clinician's guide to diagnosis and treatment. New York: Cambridge University Press, 2003. p. 105-113. [53] Muqit MM, Rakshi JS, Shakir RA and Larner AJ. Catatonia or abulia? A difficult differential diagnosis. Movement disorders : official journal of the Movement Disorder Society 2001;16:360-2. [54] McCall WV, Shelp FE and McDonald WM. Controlled investigation of the amobarbital interview for catatonic mutism. The American journal of psychiatry 1992;149:202-6. [55] Carroll B, Thomas C, Jayanti K, Hawkins J and Burbage C. Treating persistent catatonia when benzodiazepines fail. Current Psychiatry 2005;4:56-64. [56] Francis A. Catatonia: diagnosis, classification, and treatment. Current psychiatry reports 2010;12:180-5. [57] Rosebush PI and Mazurek MF. Catatonia: re-awakening to a forgotten disorder. Movement disorders : official journal of the Movement Disorder Society 1999;14:395-7. [58] Ungvari GS, Chiu HF, Chow LY, Lau BS and Tang WK. Lorazepam for chronic catatonia: a randomized, double-blind, placebo-controlled cross-over study. Psychopharmacology 1999;142:393-8. [59] Thomas P, Cottencin O, Rascle C, Vaiva G, Goudemand M and Bieder J. Catatonia in French psychiatry: Implications of the zolpidem challenge test. Psychiatric Annals 2007;37:45-54. [60] Clinebell K, Azzam PN, Gopalan P and Haskett R. Guidelines for preventing common medical complications of catatonia: case report and literature review. The Journal of clinical psychiatry 2014;75:644-51. [61] Carroll BT, Goforth HW, Thomas C, Ahuja N, McDaniel WW, Kraus MF, et al. Review of adjunctive glutamate antagonist therapy in the treatment of catatonic syndromes. The Journal of neuropsychiatry and clinical neurosciences 2007;19:406-12. [62] Hawkins JM, Archer KJ, Strakowski SM and Keck PE. Somatic treatment of catatonia. International journal of psychiatry in medicine 1995;25:345-69. [63] Wise M, Hilty D, Cerda G and Trzepacz P. Delirium (confusional states). In Wise M and Rundell J, editors Textbook of consultation-liaison psychiatry in the medically ill. Washington, DC: American Psychiatric Publishing, 2002. p. 257-272. [64] Geoffroy PA, Rolland B and Cottencin O. Catatonia and alcohol withdrawal: a complex and underestimated syndrome. Alcohol and alcoholism 2012;47:288-90. [65] Rosebush PI and Mazurek MF. Catatonia after benzodiazepine withdrawal. Journal of clinical psychopharmacology 1996;16:315-9. [66] Campbell R, Schaffer CB and Tupin J. Catatonia associated with glutethimide withdrawal. The Journal of clinical psychiatry 1983;44:32-3. [67] Kasture SB, Mandhane SN and Chopde CT. Baclofen-induced catatonia: modification by serotonergic agents. Neuropharmacology 1996;35:595-8.
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[68] Tarabar AF and Nelson LS. The gamma-hydroxybutyrate withdrawal syndrome. Toxicological reviews 2004;23:45-9. [69] Barnes MP, Saunders M, Walls TJ, Saunders I and Kirk CA. The syndrome of Karl Ludwig Kahlbaum. J Neurol Neurosurg Psychiatry 1986;49:991-6. [70] Quinn DK. "Burn catatonia": a case report and literature review. Journal of burn care & research : official publication of the American Burn Association 2014;35:e135-42. [71] Nzwalo H, Sa F, Cordeiro I, Ferreira F and Basilio C. Delayed hypoxic-ischemic leukoencephalopathy. BMJ case reports 2011;2011. [72] Teare JP, Hyams G and Pollock S. Acute encephalopathy due to coexistent nicotinic acid and thiamine deficiency. The British journal of clinical practice 1993;47:343-4. [73] Berry N, Sagar R and Tripathi BM. Catatonia and other psychiatric symptoms with vitamin B12 deficiency. Acta psychiatrica Scandinavica 2003;108:156-9. [74] Jauhar S, Blackett A, Srireddy P and McKenna PJ. Pernicious anaemia presenting as catatonia without signs of anaemia or macrocytosis. The British journal of psychiatry : the journal of mental science 2010;197:244-5. [75] Wong S, Hughes B, Pudek M and Li D. Malignant catatonia mimicking pheochromocytoma. Case reports in endocrinology 2013;2013:815821. [76] Bobo WV, Murphy MJ and Heckers SH. Recurring episodes of Bell's mania after cerebrovascular accident. Psychosomatics 2009;50:285-8. [77] Spiegel DR and Varnell C, Jr. A case of catatonia due to posterior reversible encephalopathy syndrome treated successfully with antihypertensives and adjunctive olanzapine. General hospital psychiatry 2011;33:302 e3-5.
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Figure: Flow diagram of articles reviewed 260 English publications limited to humans
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11 conference abstracts 14 book chapters
77 irrelevant* 87 case reports/series
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23 full-text articles retrieved 20 without systematic results
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*See text for description
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187 peer-reviewed publications
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Table 1: Differential diagnosis* for altered mental status Altered levels of consciousness** Agitation Lethargy Obtundation Minimally responsive state Coma Persistent vegetative state Delirium spectrum** Delirium Subsyndromal delirium Pseudo-delirium (as in Lewy body dementia) Sundowning in dementia Fixed or progressive neurocognitive disorders† Developmental (e.g. genetic or intrauterine event) Acquired (e.g. neurocognitive deficits due to cerebrovascular accident) Degenerative (e.g. neurocognitive disorder due to Alzheimer’s disease) Catatonia Intoxication (e.g. stimulants, ethanol) Seizure-related Non-convulsive status epilepticus Post-ictal (burst suppression) Syncopal episodes Primary psychiatric disorders Affective states (e.g. melancholic depression, manic episode) Psychosis (e.g. disorganized states) Somatic symptom and related disorders (e.g. conversion disorder) Dissociative states (e.g. flashbacks, fugue) *The differential here refers to phenomenological (or, in the case of seizures, semiological) presentation. Tremendous overlap may exist among the categories above. Imagine performing a mental status exam at 9PM on a patient with vascular neurocognitive disorder, slight expressive aphasia and sundowning behavior presenting from a skilled nursing facility after an alcohol withdrawal seizure. **Altered levels of consciousness are evaluated using scales such as the Glasgow Coma Scale or Richmond Agitation-Sedation Scale, which do not specify clarity of sensorium. Delirium is defined by DSM-5 and ICD10. Many states of altered awareness may involve confusion but do not meet delirium criteria. † Differentiating delirium from fixed or progressive neurocognitive disorders requires knowledge of the patient’s baseline.
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DSM-5 Catatonic Disorder Due to Another Medical Condition A. The clinical picture is dominated by three (or more) of the following symptoms 1. Stupor (i.e., no psychomotor activity; not actively relating to environment) 2. Catalepsy (i.e., passive induction of a posture held against gravity) 3. Waxy flexibility (i.e., slight, even resistance to positioning by the examiner) 4. Mutism (i.e., no, or very little, verbal response [exclude if known aphasia]) 5. Negativism (i.e., opposition or no response to instructions or external stimuli) 6. Posturing (i.e., spontaneous and active maintenance of a posture against gravity) 7. Mannerism (i.e., odd, circumstantial caricature of normal actions) 8. Stereotypy (i.e., repetitive, abnormally frequent, nongoal-directed movements) 9. Agitation, not influenced by external stimuli 10. Grimacing 11. Echolalia (i.e., mimicking another’s speech) 12. Echopraxia (i.e., mimicking another’s movements) B. There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiological consequence of another medical condition. C. The disturbance is not better explained by another mental disorder (e.g., a manic episode). D. The disturbance does not occur exclusively during the course of a delirium. E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
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DSM-5 Delirium A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment) The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception) The disturbance in Criteria A and C are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma. There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication, or withdrawal (i.e., due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies.
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Table 4: Mnemonic for delirium causes [63] adapted for catatonia* Category Notes Infection/inflammatory† Most commonly encephalitis or meningitis, either of which may be categorized as infectious, post-infectious, autoimmune, paraneoplastic or idiopathic [44, 45] Other infectious/inflammatory causes such as pneumonia and peritonitis have been reported [49] Withdrawal Sedative-hypnotics: alcohol [64], benzodiazepines [65], glutethimide [66], baclofen [67], and gamma-hydroxyburyrate [68] Dopamine agonists (clinically indistinguishable from NMS) Acute metabolic Diverse conditions reported (e.g. uremia, heart failure, liver failure, hyponatremia, acid/base disturbances, porphyria) [5, 50, 69] Trauma Polytrauma and traumatic brain injury [3, 49, 50] Burn trauma [70] Neurocognitive disorders [45] CNS disease† Space-occupying lesions, primary [3] or metastatic [45] Seizure-related [44, 45] Normal pressure hydrocephalus [69] Hypoxia Hypoxic-ischemic encephalopathy [71] Deficiency B1 (thiamine) or B3 (niacin) deficiency [72] B12 (cyanocobalamin) deficiency [73, 74] Endocrinopathy Hashimoto thyroiditis [45]‡ May mimic pheochromocytoma [75] Post-stroke recurrent episodes [76] Acute vascular† Toxins/medications Corticosteroids and disulfiram [41] Phencyclidine (PCP) and ketamine [51] Neuroleptics (particularly as neuroleptic malignant syndrome [NMS]) Serotonergic agents (as serotonin syndrome) Withdrawal from sedative-hypnotics and dopamine agonists (see “Withdrawal” above) In delirium, “H” stands for heavy metals. Low serum iron is often found in Hypertensive catatonia but is not thought to be causative. An alternate “H” for catatonia is encephalopathy hypertensive encephalopathy, often due to posterior reversible encephalopathy syndrome [77] *It remains unclear whether in each of these instances above the patient has a “pure” medical catatonia (minus delirium) or delirium with catatonic features. † These causes, namely encephalitis, CNS disease (i.e. structural disease and seizures), and cerebrovascular accidents, should be given particular consideration due to their prevalence in catatonia [44, 45]. ‡ Hashimoto encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis, may represent a cause of autoimmune encephalitis rather than an endocrinopathy per se.
S0163-8343(15)00148-6 doi: 10.1016/j.genhosppsych.2015.06.011 GHP 7033
To appear in:
General Hospital Psychiatry
Received date: Revised date: Accepted date:
31 January 2015 12 June 2015 12 June 2015
Please cite this article as: Oldham Mark A., Lee Hochang B., Catatonia vis-` a-vis delirium: The significance of recognizing catatonia in altered mental status, General Hospital Psychiatry (2015), doi: 10.1016/j.genhosppsych.2015.06.011
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ACCEPTED MANUSCRIPT Catatonia vis-à-vis delirium
Catatonia vis-à-vis delirium: The significance of recognizing catatonia in altered mental status Mark A. Oldham, M.D.,1* and Hochang B. Lee, M.D.2 1
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Assistant Professor of Psychiatry Yale School of Medicine 2
Associate Professor of Psychiatry Yale School of Medicine
Running head: Catatonia vis-à-vis delirium
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*Corresponding author 20 York St. Fitkin 615 New Haven, CT 06510 Office: 203-785-2618 Fax: 203-737-2221 [email protected]
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Key words: Catatonia, delirium, altered mental status, encephalopathy, diagnostic criteria, phenomenology
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Disclosures: We have no relevant financial conflicts of interest to disclose.
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Funding: None.
Acknowledgements: Dr. Oldham would like to thank Paul Desan, M.D., Ph.D., director of the Yale
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Psychosomatic Medicine Fellowship, for his abiding mentorship and ongoing professional development.
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Abstract
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Background:
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Catatonia is seldom considered in evaluation of altered mental status (AMS) in medical settings. Furthermore, catatonia often meets delirium criteria due to incoherence, altered awareness, and behavioral
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change. Catatonia may co-occur with or be preferentially diagnosed as delirium.
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Methods:
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We conducted a systematic literature review of MEDLINE, EMBASE, and PsycINFO on the relationship between catatonia and delirium. We also juxtapose clinical features of these syndromes and outline a
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structured approach to catatonia evaluation and management in acute medical settings.
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Results:
These syndromes share tremendous overlap: the historical catatonia-related terms “delirious mania” and
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“delirious depression” bespeak of literal confusion differentiating them. Only recently has evidence on their relationship progressed beyond case series and reports. Neurological conditions account for the
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majority of medical catatonia cases.
Conclusions: New-onset catatonia warrants a medical workup, and catatonic features in AMS may guide clinicians to a neurological condition (e.g. encephalitis, seizures, or structural CNS disease). Lorazepam or electroconvulsive therapy (ECT) should be considered even in medical catatonia and neuroleptics used with caution. Moreover, ECT may prove life-saving in malignant catatonia. Further studies on the relationship between delirium and catatonia are warranted.
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Introduction Catatonia among patients with altered mental status (AMS) receives relatively scant clinical or research
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attention and requires a high index of suspicion (see Table 1 for a differential for AMS). However,
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catatonic features are not uncommon in acute psychiatric and medical settings. Catatonia may be identified in one out of seven patients with psychosis and one out of five patients with a major mood
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episode [1]. In acute medical settings catatonia prevalence ranges from 1.6% [2, 3] to 6.3% [4, 5]. In fact, a recent study of sequential patients with delirium evaluated by a consult psychiatry service found a 12–
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37% incidence of catatonia depending on the symptom cut-off [6].
Because catatonia and delirium share many clinical features, catatonia may be misdiagnosed as delirium [7], managed as such [8] or even co-occur with delirium [9, 10]. Although delirium is often considered on
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the differential for catatonia [11, 12], the differential for delirium seldom includes catatonia [7]. This
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propensity for preferentially diagnosing catatonia as delirium is further encouraged by the high delirium prevalence in medical settings. Delirium occurs in one out of five medical inpatients [13], two out of five
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critical illness [15].
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intensive care unit (ICU) patients [14], and up to four out of five mechanically ventilated patients with
Recognizing catatonia has implications for underlying medical conditions and for timely clinical management. Medical catatonia warrants an expedient medical work-up, and alarmingly catatonia can progress to the potentially fatal syndrome of malignant catatonia for which effective treatment exists [16]. Lorazepam or electroconvulsive therapy (ECT) may prove liberating in medical catatonia [5, 12], and neuroleptics—particularly high-potency agents—should be used with caution [17]. Failing to recognize catatonia may prolong episodes of AMS thus lengthening hospital stay by compromising clinical decisions.
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Methods We conducted a systematic review of MEDLINE, EMBASE, and PsycINFO from 1980 through March
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2015 crossing the terms “delirium” and “catatoni*” to explore the state of the evidence on the relationship
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between delirium and catatonia. We chose 1980 because that year the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) introduced operationalized criteria for delirium. Search
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results were initially de-duplicated and limited to humans and manuscripts in English. Next, publications without abstracts were excluded as were book chapters and conference abstracts because these are not
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peer-reviewed. We retrieved full text articles of formal studies where both delirium and catatonic features
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are included as either inclusion criteria or study outcomes in order to understand systematic relationships between them. Catatonia reviews were also retrieved to identify other potentially-relevant studies.
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References of full-text articles retrieved were reviewed for additional studies.
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We follow this literature review by juxtaposing clinical features of delirium and catatonia, highlighting the potential value of identifying catatonic features in AMS. Finally, we describe a structured clinical
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approach to evaluating and managing catatonia, particularly as a cause of AMS in acute medical settings.
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Results of systematic review
See the Figure for a flow diagram of identified articles. Despite an abundance of case reports and series, only three studies met inclusion criteria [5, 6, 18], demonstrating the dearth of systematic investigation in this area. Among these studies, one describes catatonic features in delirium [6], another identifies delirium in catatonia [5], and a third describes catatonic features as a predictor of delirium after ECT [18]. In this third publication, however, delirium was identified without a validated instrument or formal diagnostic criteria. Additionally, proprofol, a known deliriogen, was successful in “treating” all cases of study-identified delirium. What these authors describe as delirium appears rather to be psychomotor agitation [18]. The other two studies are described below.
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In the first of these, Grover et al. studied a cohort of 205 patients with delirium per DSM-IV-TR and found several catatonic symptoms in greater than 5% of the sample: excitement (in 73% of sample),
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immobility/stupor (21%), mutism (16%), negativism (10%), combativeness (9%), staring (9%),
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withdrawal (9%), and impulsivity (8%) [6]. Other catatonic features, though, were uncommon: mannerisms, verbigeration, waxy flexibility, mitgehen, gegenhalten, ambitendency, and
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echopraxia/echolalia. In particular, it is curious that stereotypy and perseveration were identified in only one patient each. Carphology (synonymously, floccillation; stereotyped picking at linens) is a historical
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feature of delirium [19]. Perhaps, though, such observations that preceded operationalized criteria for
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delirium were documenting medical catatonia instead. Perseveration, on the other hand, is prevalent in delirium, occurring in more than 80% of cases [20].
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In the remaining study, older adults admitted to a general hospital were screened for catatonia using the
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Bush-Francis Catatonia Screening Instrument and subsequently rated using the Bush-Francis Catatonia Rating Scale (see Clinical evaluation and psychometrics below). Depending on the criteria used 6.3–
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8.9% of subjects were diagnosed with catatonia [5]. Among the ten who met research criteria for catatonia, three had concurrent delirium. Seven of these ten had baseline neurocognitive impairment, but
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it is unclear how this was differentiated from delirium. In fact, six of these patients were medically admitted for “cognitive impairment of unknown etiology,” which itself may have been delirium.
Taken together, these latter two studies suggest a considerable degree of overlap between delirium and catatonic features, but these data are preliminary and await confirmation. Further, such observational, cross-sectional studies are unable to answer questions of clinical management. In view of the limited systematic evidence on the relationship between delirium and catatonia, the remainder of this article provides a conceptual review of the relationship between catatonia and delirium followed by a structured approach to evaluating and managing patients with catatonic features in AMS.
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Juxtaposing catatonia and delirium Clinical presentation
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Although non-specific laboratory findings and biomarkers have been described in delirium and catatonia,
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each relies on clinical diagnosis. DSM-5 diagnosis of delirium requires five criteria whereas catatonia remains polythetic. That is, at least three of 12 criteria must be present for diagnosis. All deliria share the
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same core features, but catatonia presents with a variety of distinct, non-overlapping phenotypes, which makes recognition all the more difficult (American Psychiatric Association has granted to include DSM-5
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diagnostic criteria for delirium & catatonia here as tables: see Tables 2 and 3).
In 2013 the DSM-5 formally introduced delirium specifiers: hyperactive, hypoactive, or mixed level of activity [21]. By definition, delirium has a secondary cause, which can be a psychoactive substance,
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medical condition, or multifactorial. Catatonia is a clinical syndrome that may either be associated with a
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psychiatric illness or have a medical or substance-induced cause [21]. Contrary to historical lore, a minority of catatonia is associated with schizophrenia. Although the conditions associated with catatonia
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vary based on clinical setting, an estimated one in four patients with catatonia has medical catatonia (i.e.
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catatonia due to another medical condition per DSM-5) [1].
Differentiating catatonia from delirium The boundary between delirium and catatonia is often indistinct with catatonic features not uncommonly occurring in delirium [22]. Patients with catatonia exhibit altered communication and behavior, and catatonic features such as mutism, echolalia, negativism, or agitation can confound reliable delirium assessment. The inability to perform a reliable assessment of consciousness and attention in a patient with demonstrably altered mental status warrants a diagnosis of delirium in most clinical and research settings.
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DSM-5 refines the phenotype of catatonia substantially [23], but clinical overlap between delirium and catatonic features remains. This overlap suggests that they may co-exist as delirium with catatonic
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features or “catatonic delirium” [10]. In DSM-5, delirium is a universal exclusion for diagnosing any
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other psychiatric condition while delirium is present. This diagnostic preeminence of delirium ensures that underlying medical conditions are addressed and that primary psychiatric illness is not diagnosed
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erroneously because delirium can present with virtually any psychiatric symptom.
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In the case of medical catatonia, though, this delirium exclusion is without empirical rationale [10]. Patients with medical catatonia typically meet delirium criteria as well, which currently precludes the
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diagnosis of medical catatonia in most instances [24]. A diagnosis of “catatonia” may be easily misinterpreted by medical providers, particularly non-psychiatrists, as a de facto primary psychiatric
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condition, but identification of catatonic features in AMS as either a subtype of or co-morbidity with
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delirium diagnosis may guide the medical work up and have treatment implications as discussed below.
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Motor subtypes: Hyper- and hypokinetic states Both delirium and catatonia exhibit motoric variants. Unlike delirium, which was conceptualized as a
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purely hyperkinetic syndrome long before its hypokinetic variant was annexed, catatonia was originally described as a stuporous state. This historical distinction is likely a persisting reason why clinicians often have a fixed view of catatonia as a twilight state with bizarre posturing. Rather, catatonia has various phenotypes [8]. The clinical value of differentiating presentations based on motor activity remains unclear [25] aside from clinical vigilance related to motoric consequences (e.g. preventing pressure ulcers in patients who are immobile or treating hyperpyrexia in psychomotor agitation). Delirium presents with hyperactive, hypoactive, or mixed behavioral features. Similarly, excited and retarded/stuporous poles have been described in catatonia. Despite these contrasting pairs of terms, clinical heterogeneity and motoric fluctuations are often seen in both delirium [25] and catatonia [26].
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Historical nomenclature of catatonic subtypes is diverse. Catatonia is typically categorized based on level of behavioral and autonomic activity into stuporous, excited, and malignant catatonia [26].
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Stuporous/retarded catatonia, originally described by Kahlbaum, has alternatively been described
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eponymously as Kahlbaum syndrome or delirious melancholia/depression [27, 28]. Akinetic mutism, coma vigil, and benign stupor [29] may also describe stuporous catatonia, but these terms are non-specific
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and may refer to locked in syndrome, abulia due to anterior cingulate lesions, or minimally responsive states. Excited catatonia describes the hyperkinetic variant and has garnered the terms Bell’s mania [30],
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oneirophrenia, oneiroid/oneiric state or syndrome [31], catatonos raptus, delirium acutum [32], delirious
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mania per Kraepelin [33], and delirious catatonia [22]—the final three literally suggesting clinicians have had difficulty differentiating delirium from catatonia. The lack of an operationalized definition of delirium prior to DSM-III promulgated a vague notion of what delirium was, challenging the reliability
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and validity of historical delirium reports.
When autonomic instability and fever accompany either stuporous or excited catatonia, the patient is said
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to have malignant catatonia. Historical descriptions of malignant catatonia have included pernicious catatonia, deadly catatonia, and (Stauder’s) lethal catatonia [34, 35]. Neuroleptic malignant syndrome
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(NMS) and serotonin syndrome (SS) are often considered variants of malignant catatonia. Malignant catatonia may be life-threatening due to autonomic dysregulation, hyperpyrexia, rhabdomyolysis, or acute kidney injury. The terms deadly and lethal catatonia attest to the potential mortality associated with catatonia, but these terms are discouraged in view of the effective treatment widely available (see Clinical management below). In particular, the presence of autonomic findings in altered mental status presents a diagnostic dilemma: they may be “primary” as part of a broader catatonic syndrome or “secondary” to the underlying cause as in delirium tremens, encephalitis, or sepsis [36].
Clinical evaluation and psychometrics
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The most commonly used scale for catatonia, the Bush-Francis Catatonia Rating Scale (BFCRS) [37], allows for serial evaluation, but it does not provide a clinical cut-off for the diagnosis of catatonia. The
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first portion of the BFCRS is often used independently to screen for catatonia and called the Bush-Francis
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Catatonia Screening Instrument. As previously reviewed, several catatonia scales and screens have been published but met with limited use [38, 39] including the Rosebush criteria, Modified Rogers Scale,
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Northoff Catatonia Scale, Braunig Catatonia Rating Scale, Fink and Taylor criteria, KANNER scale, and
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the mnemonic WIRED ‘N MIRED.
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Over two dozen delirium scales have been published [40]. The Confusion Assessment Method (CAM) enjoys the most widespread use for delirium detection, and as described above the CAM would often yield a positive delirium diagnosis when being applied to patients with catatonia. Scale-specific
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psychometrics must be considered. For instance, some scales evaluate for confusion without specificity
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for delirium (e.g. Clinical Assessment of Confusion). Screening scales often do not provide an index of delirium severity (e.g. CAM) and should be used in conjunction with standardized neurocognitive screens
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to ensure adequate sensitivity. Others provide only severity measures and are not intended for diagnosis (e.g. Memorial Delirium Assessment Scale). Still others are useful for diagnosis and delirium severity,
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but these require a higher degree of training and time to use (e.g. Delirium Rating Scale-Revised-98). Additionally, the settings in which each scale has been validated should be considered.
Causes and medical work-up Delirium is always medically and/or substance-induced, but up to a quarter of patients with catatonia are due to medical condition or psychoactive substance [41], even when excluding cases of NMS and SS [2]. The range of medical conditions and medications that have can lead to catatonia is broad. Most classes of conditions that can cause delirium have been reported as a potential cause of catatonia as well. The acronym “I WATCH DEATH,” a mnemonic for recalling the delirium causes, may be applied to catatonia with only slight modification (see Table 4).
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A significant majority of medical catatonia appears to be due to neurological disease [42]. Historical
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reviews of medical catatonia have highlighted neurological causes [43], and three reviews of case reports
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and series attribute over two thirds of medical catatonia to a neurological cause [44-46]. An early systematic review of medical catatonia cases two decades ago found that roughly 70% were due to a
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neurological condition [44]. Specifically, 30% were associated with structural central nervous system (CNS) disease, 25% due to encephalitis or other CNS infection, and 10% attributed to a seizure disorder.
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Similarly, a retrospective Mayo Clinic chart review identified 95 in-house cases of catatonia per DSM-
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IV-TR criteria, of whom 20 had medical catatonia [45]. Among those 20 patients, 70% had neurological illness: encephalitis (n = 6), major neurocognitive disorder (4), seizure disorders (3), and CNS metastases (1). Additionally, a 2008 review of pediatric cases of medical catatonia identified 26 cases related to
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medical conditions and 12 related to medications or toxins [46]. Among the 26 medical catatonias, 10
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were related to neurological conditions, 6 genetic conditions (all known to affect brain development), and four viral encephalitides—that is, 77% with cerebral involvement. The fact that all three series of medical
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catatonia spanning two decades report a rate of ≥ 70% medical catatonias due to neurological illness is striking. In addition, anti-NMDA receptor encephalitis is an increasingly recognized cause of both
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catatonia and delirium [47]. In view of these prevalence data, one should maintain a high index of suspicion for neurological disease where medical catatonia is on the differential.
Electroencephalography (EEG) remains the most widely available physiologic measure of delirium and reveals diffuse background slowing, typically in the delta range [48]. Most catatonia tends to present with a normal EEG, but medical catatonia represents an exception to this rule. Over 80% of medical catatonia in one study exhibited abnormal EEG findings, the most common being diffuse slowing, lending further support for a catatonia–delirium spectrum or delirium with catatonic features [10, 11].
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Evaluation of catatonia in acute medical settings: Here we present a structured approach to evaluation and management where catatonic features are
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identified.
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1. Where possible, evaluate for comorbid delirium. The presence of delirium strongly suggests a medical cause of catatonic features, and according to the DSM-5 a diagnosis of delirium preempts
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other psychiatric diagnoses including catatonia due to another medical condition. 2. Obtain a clear history.
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a. Psychiatric history: A psychiatric history, in itself, does not exclude medical catatonia [45];
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however, new-onset catatonia in middle age and beyond should increase suspicion for a medical cause, particularly in those over 65 [5]. Catatonia in patients over age 40 has been associated with abnormal EEG recordings, which is a common clinical feature of medical
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catatonia [11]. Whether psychiatric illness associated with catatonia may contribute to a
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catatonic diathesis remains unexplored. Case series have found that psychiatric illness is common even in presumed medical catatonia [3, 11, 12], but conflicting reports exist [5, 49].
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In the retrospective Mayo Clinic review above, researchers found a 45% rate of psychiatric illness among the 20 cases of presumed medical catatonia [45].
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b. Natural history: Catatonia that persists over a week may be uncommon in mood disorders. After two weeks of persistent catatonia, the likelihood of psychotic illness or a medical condition increases markedly [50]. 3. Review medications. NMS and SS should be considered, particularly because non-psychiatric medications (e.g. prochlorperazine and linezolid, respectively) may cause these. Additional medication causes of catatonia include corticosteroids, disulfiram, ketamine, and phencyclidine as well as withdrawal from sedative-hypnotics [51]. 4. Rule out catatonia mimics. Several clinical conditions may present similarly to stuporous catatonia. These include selective mutism, aphasia with an expressive component, severe Parkinson disease and Parkinson-plus syndromes, malignant hyperthermia, locked-in syndrome,
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stiff-person syndrome, profound abulia, malingering, somatoform illness, or dissociative states [52, 53]. Perhaps, though, catatonia masquerades as some cases of inanition or failure to thrive in
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the elderly [5].
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5. Conduct a medical work up: Catatonia may herald unrecognized medical illness akin to delirium alerting clinicians to an otherwise asymptomatic urinary tract infection. When medical
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catatonia is suspected, a medical work up with an emphasis on neurological causes is warranted. Particular consideration should be given for EEG, brain imaging with a preference for magnetic
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resonance imaging (MRI), and lumbar puncture (LP).
Management of catatonia in acute medical settings
1. Treat the underlying cause: As with delirium, definitive treatment of medical catatonia is
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management of the underlying cause. Contributory medications should be avoided if medically
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feasible.
2. Conduct a lorazepam challenge: Treatment for catatonia classically involves oral (at times via
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nasogastric tube), intramuscular or intravenous lorazepam 2 mg in adults or 0.5–1 mg in children or the elderly. The only randomized pharmacologic trial for acute catatonia to date found
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intravenous amobarbital efficacious for 60% of patients with catatonic mutism [54]. Catatonic features should be monitored for improvement. Clinical response is defined as a 50% reduction in catatonic features as on the BFCRS. Lorazepam 2 mg can be scheduled thrice daily or increased in upward of 16 mg per day in divided doses over the following days pending clinical response [55]. Case series and expert experience suggests that up to 80–85% of patients will respond to lorazepam [56, 57] with response rates in psychosis-related catatonia [57] medical catatonia [45] and older adults [5] closer to 50%. One randomized, double-blind, placebo-controlled, crossover trial of lorazepam 6 mg/day for schizophrenia with chronic catatonic features found no improvement on BFCRS, suggesting that catatonia related to chronic psychosis may represent a distinct clinical entity [58]. An alternative to the lorazepam challenge is 10 mg zolpidem orally or
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via nasogastric tube [59], but response to zolpidem is likely to be brief. Such patients typically require ongoing management with lorazepam or other catatonia-specific treatment.
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3. Avoid high-potency neuroleptics. High-potency neuroleptics are not effective for catatonia.
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They can cause catatonic-like (i.e. extrapyramidal) side effects and may potentiate NMS [55]. Recent reports suggest that atypical antipsychotics may improve non-malignant catatonia [17, 55]
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but should be used with caution as an adjunct to a benzodiazepine or other catatonia-specific intervention. It is unclear whether high-potency neuroleptics for the management of catatonic
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excitement can be used safely as an adjunct to catatonia-specific treatment.
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4. Ensure appropriate supportive measures: Guidelines on the supportive management have been reviewed previously [60]. The first three apply to both excited and stuporous catatonia; the
a. Reverse hyperthermia.
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remaining five are exclusive to stuporous variants.
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b. Hydrate to prevent acute kidney injury. c. Maintain adequate nutrition.
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d. Monitor oxygenation closely. e. Provide prophylaxis for deep vein thrombosis or pulmonary embolism. Prevent pressure ulcers.
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f.
g. Prevent muscle contractures. h. Mitigate against aspiration pneumonia. 5. Consider an N-methyl-D-aspartate (NMDA) receptor antagonist or topiramate: Small case series support the use of the NMDA receptor antagonists amantadine or memantine or the anticonvulsant topiramate in catatonia unresponsive to lorazepam [61]. Despite the absence of formal guidelines, agents other than lorazepam may be considered within 1–3 days of a negative lorazepam trial [61]. 6. Initiate electroconvulsive therapy (ECT): Nearly 90% of catatonia respond to ECT including cases of malignant catatonia [62]. In cases of malignant catatonia (i.e. autonomic instability,
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hyperpyrexia, rhabdomyolysis, et al.), ECT should be considered as an emergent intervention. Where patients refuse to eat and are unable to provide self-care, ECT should be considered
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urgently. ECT should also be considered when only partial response is obtained from medication
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trials.
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Conclusions
Clinicians must maintain a high index of suspicion for catatonia, else it will be missed or preferentially
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diagnosed as another condition such as delirium. Expedient recognition of catatonia appears to have
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implications for medical work up and treatment. Medical catatonia is commonly associated with neurological illness including encephalitis, structural CNS disease, and seizure disorders.
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Further, catatonia implies certain treatment parameters. Contrary to traditional delirium management,
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lorazepam is the first-line agent for catatonia, and high-potency first-generation antipsychotics and monotherapy with second-generation antipsychotic are best avoided in patients with catatonic features. A
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fascinating conundrum arises when juxtaposing the management of catatonia and delirium: neuroleptics, often used to manage hyperactive delirium, may precipitate malignant catatonia whereas benzodiazepines,
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first-line for catatonia, may be deliriogenic. When lorazepam or other medication trials such as amantadine, memantine, or topiramate are ineffective or only partially effective for catatonia or where patients develop autonomic instability, ECT remains the gold-standard catatonia treatment with impressive efficacy even in the most critical cases. The remarkable degree of phenotypic overlap between delirium and catatonia should fuel further efforts to refine diagnostic criteria for these conditions, particularly where these syndromes co-occur. Historical and emerging reports warrant further investigation to elucidate the diagnostic and clinical management implications of catatonic features in cases of AMS.
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[46] Lahutte B, Cornic F, Bonnot O, Consoli A, An-Gourfinkel I, Amoura Z, et al. Multidisciplinary approach of organic catatonia in children and adolescents may improve treatment decision making. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2008;32:1393-8. [47] Fink M. Rediscovering catatonia: the biography of a treatable syndrome. Acta psychiatrica Scandinavica Supplementum 2013:1-47. [48] Neufeld KJ and Thomas C. Delirium: definition, epidemiology, and diagnosis. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 2013;30:438-42. [49] Rizos DV, Peritogiannis V and Gkogkos C. Catatonia in the intensive care unit. General hospital psychiatry 2011;33:e1-2. [50] Huang TL, Ree SC, Huang YC, Liu HY and Yang YY. Catatonic features: differential diagnosis and treatments at an emergency unit. Psychiatry and clinical neurosciences 1999;53:63-6. [51] Duggal HS and Singh I. Drug-induced catatonia. Drugs of today 2005;41:599-607. [52] Fink M and Taylor M. Conditions that may be mistaken for catatonia. Catatonia: A clinician's guide to diagnosis and treatment. New York: Cambridge University Press, 2003. p. 105-113. [53] Muqit MM, Rakshi JS, Shakir RA and Larner AJ. Catatonia or abulia? A difficult differential diagnosis. Movement disorders : official journal of the Movement Disorder Society 2001;16:360-2. [54] McCall WV, Shelp FE and McDonald WM. Controlled investigation of the amobarbital interview for catatonic mutism. The American journal of psychiatry 1992;149:202-6. [55] Carroll B, Thomas C, Jayanti K, Hawkins J and Burbage C. Treating persistent catatonia when benzodiazepines fail. Current Psychiatry 2005;4:56-64. [56] Francis A. Catatonia: diagnosis, classification, and treatment. Current psychiatry reports 2010;12:180-5. [57] Rosebush PI and Mazurek MF. Catatonia: re-awakening to a forgotten disorder. Movement disorders : official journal of the Movement Disorder Society 1999;14:395-7. [58] Ungvari GS, Chiu HF, Chow LY, Lau BS and Tang WK. Lorazepam for chronic catatonia: a randomized, double-blind, placebo-controlled cross-over study. Psychopharmacology 1999;142:393-8. [59] Thomas P, Cottencin O, Rascle C, Vaiva G, Goudemand M and Bieder J. Catatonia in French psychiatry: Implications of the zolpidem challenge test. Psychiatric Annals 2007;37:45-54. [60] Clinebell K, Azzam PN, Gopalan P and Haskett R. Guidelines for preventing common medical complications of catatonia: case report and literature review. The Journal of clinical psychiatry 2014;75:644-51. [61] Carroll BT, Goforth HW, Thomas C, Ahuja N, McDaniel WW, Kraus MF, et al. Review of adjunctive glutamate antagonist therapy in the treatment of catatonic syndromes. The Journal of neuropsychiatry and clinical neurosciences 2007;19:406-12. [62] Hawkins JM, Archer KJ, Strakowski SM and Keck PE. Somatic treatment of catatonia. International journal of psychiatry in medicine 1995;25:345-69. [63] Wise M, Hilty D, Cerda G and Trzepacz P. Delirium (confusional states). In Wise M and Rundell J, editors Textbook of consultation-liaison psychiatry in the medically ill. Washington, DC: American Psychiatric Publishing, 2002. p. 257-272. [64] Geoffroy PA, Rolland B and Cottencin O. Catatonia and alcohol withdrawal: a complex and underestimated syndrome. Alcohol and alcoholism 2012;47:288-90. [65] Rosebush PI and Mazurek MF. Catatonia after benzodiazepine withdrawal. Journal of clinical psychopharmacology 1996;16:315-9. [66] Campbell R, Schaffer CB and Tupin J. Catatonia associated with glutethimide withdrawal. The Journal of clinical psychiatry 1983;44:32-3. [67] Kasture SB, Mandhane SN and Chopde CT. Baclofen-induced catatonia: modification by serotonergic agents. Neuropharmacology 1996;35:595-8.
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[68] Tarabar AF and Nelson LS. The gamma-hydroxybutyrate withdrawal syndrome. Toxicological reviews 2004;23:45-9. [69] Barnes MP, Saunders M, Walls TJ, Saunders I and Kirk CA. The syndrome of Karl Ludwig Kahlbaum. J Neurol Neurosurg Psychiatry 1986;49:991-6. [70] Quinn DK. "Burn catatonia": a case report and literature review. Journal of burn care & research : official publication of the American Burn Association 2014;35:e135-42. [71] Nzwalo H, Sa F, Cordeiro I, Ferreira F and Basilio C. Delayed hypoxic-ischemic leukoencephalopathy. BMJ case reports 2011;2011. [72] Teare JP, Hyams G and Pollock S. Acute encephalopathy due to coexistent nicotinic acid and thiamine deficiency. The British journal of clinical practice 1993;47:343-4. [73] Berry N, Sagar R and Tripathi BM. Catatonia and other psychiatric symptoms with vitamin B12 deficiency. Acta psychiatrica Scandinavica 2003;108:156-9. [74] Jauhar S, Blackett A, Srireddy P and McKenna PJ. Pernicious anaemia presenting as catatonia without signs of anaemia or macrocytosis. The British journal of psychiatry : the journal of mental science 2010;197:244-5. [75] Wong S, Hughes B, Pudek M and Li D. Malignant catatonia mimicking pheochromocytoma. Case reports in endocrinology 2013;2013:815821. [76] Bobo WV, Murphy MJ and Heckers SH. Recurring episodes of Bell's mania after cerebrovascular accident. Psychosomatics 2009;50:285-8. [77] Spiegel DR and Varnell C, Jr. A case of catatonia due to posterior reversible encephalopathy syndrome treated successfully with antihypertensives and adjunctive olanzapine. General hospital psychiatry 2011;33:302 e3-5.
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Figure: Flow diagram of articles reviewed 260 English publications limited to humans
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48 without abstract
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212 articles with abstract
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11 conference abstracts 14 book chapters
77 irrelevant* 87 case reports/series
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23 full-text articles retrieved 20 without systematic results
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3 systematic studies
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*See text for description
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187 peer-reviewed publications
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Table 1: Differential diagnosis* for altered mental status Altered levels of consciousness** Agitation Lethargy Obtundation Minimally responsive state Coma Persistent vegetative state Delirium spectrum** Delirium Subsyndromal delirium Pseudo-delirium (as in Lewy body dementia) Sundowning in dementia Fixed or progressive neurocognitive disorders† Developmental (e.g. genetic or intrauterine event) Acquired (e.g. neurocognitive deficits due to cerebrovascular accident) Degenerative (e.g. neurocognitive disorder due to Alzheimer’s disease) Catatonia Intoxication (e.g. stimulants, ethanol) Seizure-related Non-convulsive status epilepticus Post-ictal (burst suppression) Syncopal episodes Primary psychiatric disorders Affective states (e.g. melancholic depression, manic episode) Psychosis (e.g. disorganized states) Somatic symptom and related disorders (e.g. conversion disorder) Dissociative states (e.g. flashbacks, fugue) *The differential here refers to phenomenological (or, in the case of seizures, semiological) presentation. Tremendous overlap may exist among the categories above. Imagine performing a mental status exam at 9PM on a patient with vascular neurocognitive disorder, slight expressive aphasia and sundowning behavior presenting from a skilled nursing facility after an alcohol withdrawal seizure. **Altered levels of consciousness are evaluated using scales such as the Glasgow Coma Scale or Richmond Agitation-Sedation Scale, which do not specify clarity of sensorium. Delirium is defined by DSM-5 and ICD10. Many states of altered awareness may involve confusion but do not meet delirium criteria. † Differentiating delirium from fixed or progressive neurocognitive disorders requires knowledge of the patient’s baseline.
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DSM-5 Catatonic Disorder Due to Another Medical Condition A. The clinical picture is dominated by three (or more) of the following symptoms 1. Stupor (i.e., no psychomotor activity; not actively relating to environment) 2. Catalepsy (i.e., passive induction of a posture held against gravity) 3. Waxy flexibility (i.e., slight, even resistance to positioning by the examiner) 4. Mutism (i.e., no, or very little, verbal response [exclude if known aphasia]) 5. Negativism (i.e., opposition or no response to instructions or external stimuli) 6. Posturing (i.e., spontaneous and active maintenance of a posture against gravity) 7. Mannerism (i.e., odd, circumstantial caricature of normal actions) 8. Stereotypy (i.e., repetitive, abnormally frequent, nongoal-directed movements) 9. Agitation, not influenced by external stimuli 10. Grimacing 11. Echolalia (i.e., mimicking another’s speech) 12. Echopraxia (i.e., mimicking another’s movements) B. There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiological consequence of another medical condition. C. The disturbance is not better explained by another mental disorder (e.g., a manic episode). D. The disturbance does not occur exclusively during the course of a delirium. E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
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Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright ©2013). American Psychiatric Association. All Rights Reserved.
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DSM-5 Delirium A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment) The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception) The disturbance in Criteria A and C are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma. There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication, or withdrawal (i.e., due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies.
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Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright ©2013). American Psychiatric Association. All Rights Reserved.
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Table 4: Mnemonic for delirium causes [63] adapted for catatonia* Category Notes Infection/inflammatory† Most commonly encephalitis or meningitis, either of which may be categorized as infectious, post-infectious, autoimmune, paraneoplastic or idiopathic [44, 45] Other infectious/inflammatory causes such as pneumonia and peritonitis have been reported [49] Withdrawal Sedative-hypnotics: alcohol [64], benzodiazepines [65], glutethimide [66], baclofen [67], and gamma-hydroxyburyrate [68] Dopamine agonists (clinically indistinguishable from NMS) Acute metabolic Diverse conditions reported (e.g. uremia, heart failure, liver failure, hyponatremia, acid/base disturbances, porphyria) [5, 50, 69] Trauma Polytrauma and traumatic brain injury [3, 49, 50] Burn trauma [70] Neurocognitive disorders [45] CNS disease† Space-occupying lesions, primary [3] or metastatic [45] Seizure-related [44, 45] Normal pressure hydrocephalus [69] Hypoxia Hypoxic-ischemic encephalopathy [71] Deficiency B1 (thiamine) or B3 (niacin) deficiency [72] B12 (cyanocobalamin) deficiency [73, 74] Endocrinopathy Hashimoto thyroiditis [45]‡ May mimic pheochromocytoma [75] Post-stroke recurrent episodes [76] Acute vascular† Toxins/medications Corticosteroids and disulfiram [41] Phencyclidine (PCP) and ketamine [51] Neuroleptics (particularly as neuroleptic malignant syndrome [NMS]) Serotonergic agents (as serotonin syndrome) Withdrawal from sedative-hypnotics and dopamine agonists (see “Withdrawal” above) In delirium, “H” stands for heavy metals. Low serum iron is often found in Hypertensive catatonia but is not thought to be causative. An alternate “H” for catatonia is encephalopathy hypertensive encephalopathy, often due to posterior reversible encephalopathy syndrome [77] *It remains unclear whether in each of these instances above the patient has a “pure” medical catatonia (minus delirium) or delirium with catatonic features. † These causes, namely encephalitis, CNS disease (i.e. structural disease and seizures), and cerebrovascular accidents, should be given particular consideration due to their prevalence in catatonia [44, 45]. ‡ Hashimoto encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis, may represent a cause of autoimmune encephalitis rather than an endocrinopathy per se.
