Catatonic Disorder due to another medical condition (CD-AMC) is the most common form of catatonia in the medically ill population. • The clinical presentation of
Treatments: Lorazepam
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Catatonia in Medically Ill Patients An Evidence -Based Medicine ( EBM) Monograph for Psychosomatic Medicine Practice Published jointly by The Guidelines and Evidence -Based Medicine Subc ommittee of the Academy of Psychosomatic Medicine (APM) and The Europea n Association of Psychosomatic Medicine (EAPM) Author s/Workgroup : Lex Denysenko Oliver Freudenreich Kem uel Philbrick Thomas Penders Paula Zimbrean Shamim Nejad Lydia Chwastiak Anna Dickerman Shehzad Niazi Jewel Shim Wolfgang Soellner Audrey Walker Invi ted External Reviewers : Brendan Carroll Andrew Francis Ver. 4 .17.2015
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 2 CATATONIA IN THE MEDICALLY ILL — EBM SUMMARY KEY POINTS Catatonia in medically ill patients is rare but often unrecognized. Catatonia occurs with varying degrees of sever ity, with malignant catatonia on the severe side of the spectrum. In the pediatric population, catatonia is exceedingly unrecognized and undertreated. Pediatric catatonia is often associated with general medical illness, as well as autistic spectrum and developmental disorders. Catatonic Disorder due to another medical condition (CD -AMC) is the most common form of catatonia in the medically ill population . The clinical presentation of CD -AMC is similar to catatonia in patients with psychiatric illness es. Intravenous lorazepam is th e preferred initial treatment for catatonia . Amantadine or memantine may be helpful augmentation agents . Electroconvulsive therapy (ECT) often produces remission when pharmacologic treatment options have failed. Dopamine antagon ists can be used if the patient with catatonia has shown a favorable response to certain agents in the past, with careful monitoring for progression to malignant catatonia . INTRODUCTION : Objective and method s: This monograph summarizes current knowle dge related to the diagnosis, epidemiology, etiology, and management of catatonia in the medically ill population . Specifically, this monograph primarily discusses catatonia due to another medical condition (CD -AMC) , previously known as catatonia due to a general medical condition (CDGMC) under DSM -IV-TR terminology . This monograph also discusses catatonia occurring in the setting of another mental disorder when encountered by a consultation psychiatry service in a general hospital setting . Malignant catato nia, otherwise known as the Neuroleptic Malignant Syndrome (NMS) is also discussed. A more thorough review of the pathophysiology of catatonia, and catat onia occurring in the setting of another mental disorder (such as bipo lar disorder, major depression, neurodevelopmental disorder, or schizophrenia ) is beyond the focus of this monograph . Readers are encouraged to consult the recommended readings for more detailed information on this topic (Appendix A ).
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 3 Definition and Diagnostic Criteria: Catatonia is a neuropsychiatric syndrome with motor, vocal, affective, and behavioral peculiarities , including alterations in external (environmental) and internal (proprioceptive) awareness . Features may include mutism or impoverished /quiet speech, reduced interaction w ith the environment (stupor), negativis m, increased motor tone/rigidity , posturing and grimacing , gegenhalten, mitgehen/mitmachen, automatic obedience, ambitendency, echola lia, stereotypy, verbi geratio n, echopraxia, extreme anxiety /fear , and impulsive/ biza rre behavior . In malignant cases (see fiMalignant Catatoniafl below) , autonomic instability , severe muscle rigidity, and hyperthermia occur which can lead to rhabdomyolysis, coma, and death. Catatonia most o ften occurs in patients with major depression or b ipolar disorder. However, it is also seen in schizophrenia, or as a result of a medical condition. 1 When one includes NMS, then CD -AMC is the most common form of catatonia in the medically ill. 2 The Diagnostic and Statistical Manual of Mental D isorders, fifth edition (DSM -5) recognizes that catatonia can occur in the context of another mental disorder or as a disorder du e to another medical condition . Additionally, patients not meeting full criteria can be coded as Unspecified Catatonia . The fifth edition improves upon the fourth, in that it now provides brief definitions for 12 symptoms delineated by the criteria . However, symptom duration and severity remains undefined. The lexicon of some catatonic phenomena, such as waxy flexibility and catalepsy, are problematic in that they have been poorly defined, and are often incorrectly used by trainees and experienced clinicians alike, and even differ between published rating scales. 3 More work is needed to standardize the definitions of certain catatonic phen omena . A glossary of definitions for selected fiproblematicfl catatonic phenomena is included in Appendix B. Catatonic signs and symp toms in patients with CD -AMC appear to be indistinguishable to those seen in psychiatric patients with catatonia . This was t he conclusion of o ne retrosp ective chart review of 47 cases, which revealed a slightly higher prevalence of negativism in patients with CD -AMC. 4 The same study also identified a higher frequency of echophe nomena in CD -AMC patients, but i n general found a s imilar distribution of catatonic signs regardless of the etiology of the catatonic disorder. Differential Diagnosis : The differential diagnosis of catatonia includes other hypokinetic and hyperkinetic states with rigidity , such as Parkinson™s disease, advanced dementia, malignant hyperthermia, serotonin syndrome, stiff -person syndrome, locked -in
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 4 syndrome, and non-convulsive status epilepticus . Catatonia can also be mistaken for conversion disorder, selective mutism, oppositional defiant disorder, disso ciative disorder, volitional uncooperativeness, maladaptive coping with medical illness, or behavior that is the product of ego defense mechanisms including denial, regression, acting -out, and reaction -formation . Catatonia is not synonymous with akinetic mutism. 5 This latter neurologic syndrome generally differs from catatonia in pathophysiology and treatment, but is often loosely applied by clinicians to refer to any condition in which a patient is not moving and not talking. A key difference, however, i s that akinetic mutism lacks the behavioral and affective alterations observed in catatonia. Most cases of akinetic mutism have an identifiable neurologic lesion. However, since all cases of akinetic mutism involve stupor, immobility, and mutism, the disor der fulfills DSM -5 criteria for CD -AMC. This is complicated by the fact that some medical conditions (e.g. prion disease) and medications (e.g. tacrolimus) have been implicated in the development of both akinetic mutism and catatonia. 6,7,8,9,10 In general, akinetic mutism should not be diagnosed as catatonia unless additional catatonic features are present, and catatonia should be ruled out in cases of akinetic mutism. Catatonia and Delirium: The DSM -5 notes that catatonic disorder due to another medical condition cannot occur exclusively during the course of a delirium . This is diagnostically problematic, as many patients with catatonic features in the context of another medical condition may also meet criteria for delirium, and assessment of alterations in consciousness in a mute and catatonic patient is challenging . The possibility of delirium and catatonia co -occurring has bee n hypothesized by Francis et al ., and previously described in a series of 3 clinical cases and a cohort of 13 cases identified by a review of the literature. 11 More recently, Grover et al. assessed 205 patients referred to the consultation psychiatry service wit h delirium for the prevalence of catatonic findings .12 The study found 30.2 % patients with delirium met criteria for cataton ia by scoring positive on 2 of the first 14 items of the Bush -Francis Catatonia Rating Scale (BFCRS) . 12.7% met criteria for catatonia using the proposed DSM -5 criteria . Excitement, immobility/stupor, and mutism were the three most commonly ranked items on the BFCRS, with a frequency of 72.7, 21.4, and 15.6 percent, respectively. There does not appear to be any evidence in the literature that validates the exclusion of catatonia as a diagnosis in patients with delirium . Furthermore, in NMS, delirium is rec ognized as a diagnostic feature . It may now be possible by DSM -5 criteria to code catatonia associated with anothe r mental disorder, and indicate delirium as the name of the associated mental disorder . Alternatively, cases of catatonia coexisting with deli rium may be coded as Unspecified C atatonia.
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 5 Malignant Catatonia : Malignant catatonia is characterized by severe catatonia with muscle rigidity, hyperthermia , autonomic nervous system instability, delirium, and agitation , which can then proceed to coma and death. 13 It has also been called lethal catatonia. Unfortunately , the DSM -5 does not provide criteria for malignant catatonia. This monograph supports the conceptualization of Philbrick and Rummans that catatonia exists on a continuum , with simple cata tonia on one end of the spectrum, and malignant catatonia being the more severe form of the disorder on the other end of the spectrum .14 When malignant catatonia occurs in the setting of exposure to dopamine antagonists, it has been called Neuroleptic Mali gnant Syndrome (NMS). Both disorders share many signs and symptoms. 15 However, the term is misleading, because NMS also can occur after abrupt discontinuation of dopamine agonists, and after exposure to agents that are not considered dopamine antagonists. 16 Up to 20% of cases of NMS may be indistinguishable from malignant catatonia. 17 The DSM -5 recognizes that malignant catatonia may be indistinguishable from NMS. For the purposes of this monograph, malignant catatonia and NMS are viewed as the same condition. Delirious mania is a term applied to a neuropsychiatric syndrome characterized by acute onset of delirium, mania, psychosis, and catatonia. It has also been known as Bell™s mania, manic delirium, and excited catatonia, yet none of these terms are recogni zed by the DSM -5.18 Patients may rapidly progress to malignant catatonia within hours or days . The authors of a recent review describe a proposed work -up and treatment for delirious mania that is essentially identical to that of catatonia. 19 They suggest a workup for organic causes, but add that delirious mania cannot be due to another medical condition. There does not appear to be any reason to characterize delirious mania as anything other than a form of malignant catatonia with manic features , nor does it appear prudent to limit delirious mania as a condition of purely psychiatric etiology . Paroxysmal Sympathetic H yperactivity (PSH) is a syndrome known to neurology and intensive care medicine that occurs in the setting of severe brain injury . It has also been known as autonomic dysfunction syndrome , sympathetic storm, or paroxysmal autonomic instability with dystonia. Due to a confusion of eponyms, diagnostic criteria, nomenclature, and definitions, a recent international panel issued a consensus statement that the syndrome is a diagnosis of exclusion, and that t he core features of PSH include: transient and paroxysmal increases in sympathetic activity (tachycardia, tachypnea, hypertension, hyperthermia, sweating) and rigidity with extensor posturing. 20 Pati ents usually display intermittent agitation , dystonia, catatonic posturing, opisthotonus, and may transition to malignant catatonia/NMS. 21 Indeed, PSH shares many clinical features and similar proposed pharmacologic treatment to malignant catatonia/NMS .22 Cases of catatonia in setting of brain injury have been discussed in the literature since at least 1959.23 It is unclear how PSH could be conceptually different from a brain injury induce d form of malignant catatonia , and further research is needed.
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 6 Excited Delirium Syndrome (ExDS) is a syndrome known to law enforcement, prehospital care, emergency medicine and forensic medicine , wherein the pathophysiology is not understood. The majority of cases of ExDS occur in the setting of intoxication with a sympathomi metic agent , historically cocaine, but also methamphetamine, phencyclidine (PCP), l ysergic acid diethylamide (LSD), and more recently synthetic cathinones (fibath saltsfl) .24 ,25 ExDS cases have also been described in patients with psychiatric disease. Accordin g to the 2011 ExDS Task Force consensus, t he features of ExDS include : acute onset, fulminating delirium and psychosis with extreme aggression (frenzy/rage) , hyperkinetic agitation , attraction to bright lights/loud sounds/reflective surfaces, spontaneous d isrobing, keening ( unintelligible animal -like noises), extreme pain tolerance, excessive strength, hyperthermia, diaphoresis, and tachypnea .26 Patients may progress to sudden r espiratory and cardiac arrest. The DSM -5 does not recognize ExDS as a d isorder. However, the 2011 ExDS Task Force likens ExDS with delirious mania . ExDS could be best viewed as a form of malignant catatonia usually due to intoxication with a sympathomimetic agent . In conclusion, m alignant catatonia ha s gone by many different names. A lack of open communication between medical disciplines has further compounded the problem, with different fields ascribing their own name or multiple na mes to the same syndrome. While further research is needed to better characterize malignant catatonia in its various forms, the medical community should also work on a unified model for better conceptualization of this syndrome.
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 8 The findings are similar to a literature review by Lahutte et al ., which found 38 reported cases of pediatric catatonia associated with medical conditions. 32 The most common medical conditions included: lupus encephalitis (4), viral encephalitis (4), typhus (4), epilepsy (3), and 3,4 -methylenedioxy -N-methamphetamine (MDMA) intoxication (3). Co-occurrence with Autism Spectrum Disorder : Catatonia and catatonic -like features are also often found in pa tients with autism spectrum disorders (ASDs), which has led to hypotheses that catatonic and autistic features may be related. 33 Catatonic phenomena in patents with ASDs are typically observed at a later age than when the autistic symptoms were first observed . Case reports of catatonia in ASD patients have often reported antecedent stressful life events as precipitants for the development of catatonia. One six -year retrospective study by Wing and Shah, of 506 ch ildren and adults referred to an ASD specialty center found 30 patients (6%) with essential features of catatonia (which they defined as: increased slowness affecting motoric and verbal responses, difficulty initiating and completing actions, increased reliance o n prompting by others, and increased passivity or apparent lack of motivation). 34 All 30 patients were 15 years old or older, representing 17% of all patients seen within this age range . The majority of patients first developed catatonic features between th e ages of 10 -19 years. A prospective study of 120 ASD patients reported 13 patients ( 12%) were clinically diagnosed with comorbid catatonia, all diagnosed at or after adolescence, although the study was unclear regarding methods used to make this diagnosi s.35 Slowness initiating movements appeared to be the most common finding, similar to the Wing and Shah study. Further studies to determine prevalence, mechanisms, and optimal management of catatonia in ASD patients are needed . Mazzone et al . recently prop osed an algorithm for management and treatment of catatonia in ASD patients, not unlike to the proposed standard algorithm proposed in this monograph in Appendix D. 36 Assessment and Rating Scales: There is no evidence to suggest that catatonia in childr en should be assessed or rated differently than in adults . The Bush Francis Catatonia Rating Scale (BFCRS) is the gold standard for screening and rating catatonia in adults, although it has not been validated in the pediatric population . The Kanner scale was developed to better capture catatonic fe atures in patients with ASD and pe rvasive developmental disorders, however, it has not been validated.
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 9 Treatment of Pediatric Catatonia : Catatonia in children and adolescents is treated identically to catatoni a in adults . However, among cases of catatonia due to a general medical condition, while benzodiazepines are often recommended, in practice they are rarely prescribed, which may indicate a need for greater awareness of the condition . One case series of 6 6 children ages 9 -19 with catatonia found benzodiazepines to be effective in 65% of patients, but only 51 out of the 66 ever underwent a benzodiazepine challenge. 37 The previously mentioned review by Lahutte et al . revealed that benzodiazepines and electroc onvulsive therapy were respectively used in only 39% and 32% of reported cases. 32
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 10 ADULT CATATONIA: Occurrence and Etiology : The occurrence of adult catatonia in the general medical setting is difficult to characterize , in part due to the lack of a s tandardized approach to identification and diagnosis . Among all patients encountered by a consultation -liaison psychiatry service , the inc idence of catatonia ranges from 1.6 -5.5%, based on 2 retrospective and 3 prospective studies : Zarr and Nowak (1990) retrospectively found 11 cases of catatonia out of 349 consult requests throughout the general medical hospital, a frequency of 3% (although the criteria for catatonia diagnosis were not specified) .38 They also reported an occurrence of 9.1% among patients o n a burn unit, but this was only 2 out of 22 consultations to the burn unit. Carroll et al. (1994) prospectively screened for catatonia in all patients referred to the consultation service of a large general medical hospital and cancer center over a 6 mon th period . They found 5 cases of catatonia out of 297 consult requests, a frequency of 1.6% (DSM -IV criteria ).39 One patient had AIDS , 3 had bipolar affective disorder, 1 had schizophrenia, and 1 had mental retardation . 4 patients had delirium as well as ca tatonia. Cottencin et al. (2007) retrospectively found 12 cases of catatonia out of 656 consult requests, a frequency of 1.82% (using Carroll 1992 criteria) .40 Of these cases, 5 had no other psychiatric diagnosis, 1 had schizophrenia, 5 had major depressi ve disorder, and 1 had bereavement. Jaimes -Albornoz and Serra -Mestres (2013) prospectively screened for catatonia in all patients referred to the consultation service of a large general medical hospital over a 4 month period .41 They found 13 cases of catat onia out of 236 consult requests, a frequency of 5.5% (DSM -IV criteria) . Denysenko et al. (2014) prospectively screened for catatonia in all patients referred to the consultation service of a small community hospital over a 12 month period .42 They found 13 cases of catatonia out of 661 consult requests, a frequency of 1.97% (DSM -5 criteria) . In the Jaimes -Albornoz study, when cases were stratified based on age, the frequency of catatonia was higher in patients over the age of 65 . Catatonia was found in 7 (6.3%) out of 112 patients older than 65 years using DSM -IV criteria (an additional 3 patients were included by using Fink/Taylor Criteria, for a total frequency of 8.9% ). In comparison, catatonia was found in 3 (2.4%) out of 124 patients younger than 65 ye ars (using DSM -IV and Fink/Taylor Criteria) . Among the patients over the age of 65 years , 4 patients had catatonia due to a medical condition, including thalamic infarct (1),
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Catatonia in Medically Ill Patients, an APM & EAPM Monograph, 4.17. 2015 11 hyponatremia (2), and Parkinson™s disease dementia with agitated behavior and exp osure to antipsychotics (1) . 2 developed catatonia following extubation in the setting of resolving critical medical illness . They also had a pre -hospitalization history of depression in treatment with serotonergic antidepressants and antipsychotics . Among the 10 cases in patients older than 65 years , 4 had a history of depression, 2 had a history of alcohol dependence , 4 had dementia , 3 had delirium. Smit h et al. (2012) performed a 20 -year retrospective cohort analysis of all adult patients at a tertiary care medical center , meeting D SM-IV-TR criteria for CD-AMC, catatonic schizophrenia, or mood disorder with catatonic features .43 They found 236 patients, but only 95 met all study inclusion cr iteria . Of the 95 patients: 33.7% had major depressive disorder, 22.1% has bipolar affective disorder, 21% had CD-AMC, 11.6% had schizophrenia, and 11.6% had schizoaffective disorder . Excluded from the study were 18 patents with NMS, 13 with delirium , and 68 for whom catatonia was suspected but could not be clinically confirmed . Thus if patients with NMS were included as neurolep tic-induced catatonia, then CD -AMC would be the most prevalent disorder, representing more than a third of all catatonic medically ill patients. In conclusion, catatonia in a general medical ho spital is not exceedingly rare, an d is likely to be underestimated and under recognized . The prevalence of C D-AMC compared to psychiatric catatonia is difficult to determine, as many pat ients who meet criteria for CD -AMC also have a concurrent psychiatric disorder . The prevalence of catatonia in the geriatric medical population may be higher than in the general medical population . Cases of catatonia that come to the attention of a consultation psychiatry service appear to occur with similar frequency in bot h large, tertiary care medical centers as well as small , community hospitals . Additional research is needed to better determine the prevalence of adult catatonia in the medically ill.
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