I
I
NDEXINTRODUCTION... 1
THE CATATONIC SYNDROME ... 4
1. Catatonia is common but frequently unrecognized ... 5
2. Catatonia is an identifiable syndrome ... 6
3. Catatonia can be delineated from other syndromes ... 12
4. Catatonia is more often associated with mood disorders ... 16
5. Catatonia has a typical course ... 17
6. Catatonia is the result of diverse etiologies... 18
7. Catatonia by other names ... 20
8. Catatonia has a specific neurobiological correlate ... 23
9. Catatonia has a specific diagnostic test ... 26
10. Catatonia responds to specific treatments and is worsened by others ... 27
11. Fink and Taylor’s criteria of Catatonia ... 29
12. Catatonic syndrome in DSM-5... 31
ELECTROCONVULSIVE THERAPY FOR CATATONIA ... 33
1. A history ... 33
2. Indications and efficacy ... 34
3. Administration and technique ... 36
4. Mode of ECT action in catatonia ... 39
5. Safety... 41
6. Cardiac effects of ECT ... 42
7. Consent to ECT ... 43
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9. Emergence of catatonia during ECT ... 45
10. Treatment failure ... 45
11. Clinical factors associated with response to ECT ... 46
12. Combined treatment: ECT plus benzodiazepines ... 47
13. ECT in maintenance treatment protocol ... 49
AIMS OF THE STUDY ... 51
MATERIALS AND METHODS ... 52
1. Sample ... 52
2. Consent to ECT ... 52
3. Definition of resistance to pharmacological treatment in catatonic patients ... 53
4.Definition of autonomic abnormalities and laboratory alterations ... 54
5.Patients evaluation ... 55
6.ECT Procedure ... 59
7.Statistical analyses ... 60
RESULTS ... 62
1.ECT response ... 63
2.Demographic and clinical features ... 63
3. ECT course and pharmacological treatments-associated features ... 64
4. Somatic comorbidity and complications, autonomic disturbances and laboratory alterations ... 66
5. Symptomatological evaluation ... 67
DISCUSSION ... 69
TABLES ... 82
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NTRODUCTIONCatatonia has long been a feature of human behavior. Galen “mentioneth a story
of a school-fellow of his, who…fell into a Catalepsis or Congelation; he lay…like a log all along, not to be bent, stiffe, and stretched out, and seemed to behold us with his eyes, but spake not a word. And he said, that he heard us what we said at the time, although not evidently and plainly, and told us some things that he remembered, and said, all that stood by him were seen of him, and could remember…but could not then speak, or move one part of his body…” (Robert Bayfield, 1663)(1).
Karl Kahlbaum, director of a private psychiatric hospital in Görlitz (Germany), in 1874 formally introduced catatonia as a syndrome characterized by motor dysregulation, with changes in thought, mood and vigilance. In his hallmark monograph, Die Katatonie, oder das Spannung-Irresein (Catatonia, the tension
insanity)(2) he provided a description of the disorder that is still valid today: “Catatonia is a brain disease with a cyclic, alternating course, in which the mental symptoms are, consecutively, melancholy, mania, stupor, confusion, and eventually dementia. One or more of these symptoms may be absent from the complete series of psychic ‘symptom complexes’. In addition to the mental symptoms…may be described as a state in which the patient remains entirely motionless, without speaking, and with a rigid, masklike facies; the eyes focused at a distance; he seems devoid of any will to move or react to any stimuli; there may be fully developed ‘waxen’ flexibility, as in cataleptic states… The general impression conveyed by such patients is one of profound mental anguish, or an immobility induced by several mental shock…”. The Author gives a clear
prominence to the motor and behavioral symptoms in the description of catatonia, while recognizing the affective and cognitive manifestations associated: melancholia, mania, confusion may in fact occur at different times of the disease. In the original description,
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the course of catatonia has a typical cyclic pattern with a stage of gradual onset, followed by a period of state, where the inhibited form usually precedes the excited one. Finally, a remission stage occurs, which clearly distinguish catatonia from schizophrenia; however, the outcome in dementia is possible.
Kahlbaum’s clustering of the signs of catatonia into a single disease entity is
considered his major contribution to psychiatry. The patients he described today would meet the diagnostic criteria for mood disorders, schizophrenia, delirium; at least seven of them presented a general medical condition (peritonitis, tuberculosis, dementia
paralitica). The range of his patients’ illnesses serves well our present image of
catatonia as a syndrome, which can manifest itself in the context of diverse psychiatric and somatic disorders (3). In the final chapter, then, Kahlbaum, finding no beneficial treatment, suggests supportive and non-punitive hospital treatments and ends his discussion anticipating the role of electricity: “it seems we have methods of very great
therapeutic importance in faradic and galvanic electricity, although for the time being the indication have not yet been worked out”(4).
Kahlbaum’s work attracted the attention of Emil Kraepelin. Although Kraepelin
admits the presence of catatonic symptoms in manic-depressive insanity, he marks catatonia as a principal sign of dementia praecox (5). The association of Catatonia with dementia praecox was suggested to Kraepelin by its poor prognosis and frequent evolution toward a chronic deteriorative course (6). A prolific writer of psychiatric textbooks, Kraepelin was the most prominent German psychiatrist up to World War I: his positions were essential for the development of subsequent diagnostic systems until nowadays. His demotion of catatonia from an individual syndrome to that of a subtype, a marker - in present classifications as a “specifier” – has hidden its recognition as an independent syndrome for more than a century (4).
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In the first Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association (APA), published in 1952, catatonia is designated simply as “schizophrenic reactions, catatonic type” (7). From the second edition of 1968, catatonia has been
ranked among the subtypes of schizophrenia (8). The DSM-IV-TR continues to recognize catatonia as a subtype of schizophrenia, but adds “catatonia due to a general medical condition” and a “catatonia specifier” for episodes of major depression or mania in the context of bipolar disorder (without specific numerical code)(9).
In DSM-5, catatonia is still included in the chapter of schizophrenia spectrum and other psychotic disorders. The manual does not treat catatonia as an independent class but recognizes “catatonia associated with another mental disorder” (catatonia “specifier”), “catatonic disorder due to a general medical condition” and “unspecified catatonia”. The catatonic subtype of schizophrenia has been deleted. According to the
Manual catatonia is considered only a specifier for schizophrenia, as for bipolar and major depressive disorders and for other additional disorders (schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, substance-induced psychotic disorder, neurodevelopmental disorders and others)(10-12).
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T
HEC
ATATONICS
YNDROMESince the last decades of past century, the nosological debate about catatonia focuses on the possibility to return to the original Kahlbaum’s concept of catatonia. Fink
and colleagues argue that it has been inappropriately subsumed under dementia praecox and, subsequently, schizophrenia. They ask for a divorce of catatonia from schizophrenia and the recognition of catatonia as an independent diagnostic class (10).
Taylor and Fink (13) observed that catatonia could be easily distinguished from other behavioral syndromes by a recognizable cluster of symptoms. It is sufficiently common to warrant classification as an independent syndrome. Catatonia has a typical course, responds to specific treatments and is worsened by others. It is associated with many pathophysiologic processes and more often with mood disorders.
A separate diagnostic category for catatonia may help in better recognition and appropriate treatment of catatonia, avoiding possible life threatening medical complications (electrolyte imbalance, pressure ulcers, rhabdomyolysis and acute renal failure, thromboembolism, acute urinary retention, systemic infections, aspiration pneumonia, flexion contractures and postural nerve palsies)(14). Then, it will encourage research to improve our understanding of the neurobiological mechanism of catatonia (15, 16).
Fink and Taylor organized the data about catatonia from the extensive literature along the five criteria suggested by Blashfield to justify the inclusion of a syndrome in a diagnostic system (17). Catatonia meets these criteria: 1) Adequate literature: there are at least 50 peer-reviewed journal articles discussing the syndrome; 2) Specific diagnostic criteria: the presence of well- defined and recognized syndrome criteria; 3) Acceptable inter-clinician agreement: there are at least two independent empiric studies demonstrating inter-clinician agreement equal or greater than 0.7; 4) The criteria form a
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syndrome: patients who meet one criterion for the disorder have at least a 0.50 probability of meeting another one; 5) Differentiation from other categories: signs and symptoms seen in catatonic patients are distinguishable from any other disorder with which it is likely to be confused (13).
1. Catatonia is common but frequently unrecognized
In six prevalence studies conducted after 1976, catatonia occurs in 6-38% hospitalized adult psychiatric patients (18-22). Thus, recent assessments that use standardized rating instruments in diverse academic medical centers find 6-15% of adult in-patients to meet criteria for catatonia (3). In the USA a total of approximately 90,000 in-patients exhibits signs of catatonia annually (13).
Catatonia is actually under-recognized and under-researched: in a Dutch study, clinicians could identify catatonia in only 2% of 139 psychiatric in-patients, while the research team was able to identify it in 18% (23).
In 1981 the neurologist B.Mahendra (24) asked “Where have all the catatonics gone?” noting a decline in incidence and suggesting it was a result from the increased use of psychotropic drugs, preventing the more dire forms of schizophrenia. However, we have to consider that, in the 20th century, the Freudian era shifted psychiatric interest from asylum people with severe mental illness to ambulatory patients complaining of anxiety, obsessions, phobias and so on. The role of medical examination was degraded and the recognition of catatonia languished (22). Other reasons for the under-recognition of catatonia are complex, but may include the historical decision to classify catatonia as a type of schizophrenia, the segregation of severely ill patients in long-term facilities and the perceived lack of anti-catatonic treatments. Finally, changing socio-cultural circumstances have suppressed more obvious symptoms of catatonia and the symptoms
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profile has shifted towards more subtle forms that require more clinical acumen to detect (25).
Catatonia is more common than usually considered even because forms of catatonia can also be observed in children and adolescents. About 18% of patients attending a child psychiatric unit presents two or more signs of catatonia (3). In a review of 30 case reports on catatonic manifestations in children and adolescents, Dhossche and Bouman revealed that one-third of subjects were affected by a neurological or general medical disease, six patients presented with a mood disorder, three with schizophrenia and eleven with a diagnosis of atypical psychosis (26, 27). A more recent investigation on 506 patients with autism or mental retardation reported the presence of catatonic features in 6% of the whole sample and in 17% of subjects older than 15 years. Signs of Obsessive-Compulsive Disorder (OCD) and of catatonia are prominent in adolescents with autism. Among these patients, it is difficult to separate the OCD, catatonia, and autism. The same difficulty may occur in patients with mental retardation who develop repetitive head-banging and self-mutilation (28).
The researchers advocating a separate diagnostic category for catatonia argue that it will help in better recognition of catatonia as well as encourage research to improve our understanding of the neurobiological and genetic mechanism of catatonia. Finally, if not recognized and treated catatonia can result in several somatic complications, and even death (16).
2. Catatonia is an identifiable syndrome
Catatonia is a motor dysregulation syndrome with patients unable to move normally despite full physical capacity. Movements cannot be initiated or stopped and become repetitive, posture is frozen or oddly positioned, and actions become contrary to
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intent. More than forty different signs and symptoms of catatonia have been recognized (Table I).
Table I. Definition of catatonic symptoms (adapted from Dhossche and Wachtel, 2008 (25))
Symptom Definition
Excitement Extreme hyperactivity, constant motor unrest that is apparently non purposeful
Immobility/stupor Extreme hypoactivity, immobility. Minimally responsive to stimuli Mutism Verbally unresponsive or minimally responsive
Staring Fixed gaze, little or no visual scanning of environment, decreased blinking
Posturing/catalepsy Maintains posture(s), including mundane (e.g., sitting or standing for hours without reacting)
Grimacing Maintenance of odd facial expressions Echopraxia/echolalia Mimicking of examiner’s movements/speech
Stereotypy Repetitive, nongoal-directed motor activity (e.g., finger play, repeatedly touching, patting, or rubbing self)
Mannerisms Odd, purposeful movements (hopping or walking tiptoe, saluting passers-by, exaggerated caricatures of mundane movements) Verbigeration Repetition of phrases or sentences
Rigidity Maintenance of a rigid position despite efforts to be moved Negativism Apparently motiveless resistance to instructions or to
attempts to move/examine the patient. Contrary behavior, does the opposite of the instruction
Waxy flexibility During reposturing, patients offers initial resistance before allowing himself to be repositioned (similar to that of bending a warm candle) Withdrawal Refusal to eat, drink, and/or make eye contact
Impulsivity Patient suddenly engages in inappropriate behavior (e.g., runs down the hallway, starts screaming, or takes off clothes) without provocation. Afterward, cannot explain
Automatic obedience Exaggerated cooperation with examiner’s request, or repeated movements that are requested once
Passive obedience (mitgehen) Raising arm in response to light pressure of finger, despite instructions to the contrary
Gegenhalten/counterpull Resistance to passive movement that is proportional to strength of the stimulus; response seems automatic rather than willful Ambitendency The patient seems stuck in indecisive, hesitant motor movements Grasp reflex Strike open palm of patient with two extended fingers of examiner’s
hand. Automatic closure of patient’s hand
Perseveration Repeatedly returns to the same topic or persists with same movements Combativeness Usually in an undirected manner, without explanation
Autonomic abnormality Abnormality of temperature (fever), blood pressure, pulse rate, respiratory rate, inappropriate sweating
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The pattern of symptoms and signs defines the catatonia syndrome but is not specific as to the cause. The main symptoms are mutism (failure to speak), negativism (motor and other behavioral resistance to following simple requests or commands), posturing and rigidity (abnormal body positions), persistent staring, repetitive movements (often self-injurious), automatic obedience (exaggerated cooperation with examiner’s request), and lack of response to pain. Stupor is a hallmark. Some features
of catatonia are also seen in the motor dysregulation states of parkinsonism, compulsions, tics, and seizures (22).
In developing a rating scale, Bush found mutism, withdrawal, posturing, negativism and stupor to be the most common signs in acutely ill patients (29). A 2007 study found immobility in 100% of the sample, extreme negativism or mutism in 96%, peculiarities of voluntary movement in 68% (30). In the ten principal prospective studies from sites around the world, catatonia syndrome was identified in a mean percentage of 9.8% of adult admissions. These patients had multiple signs of catatonia (commonly >5): 68% were mute and 62% were negativistic or withdrawn (31). The most recent study is a chart review of in-patients at the National Institute of Mental Health and Neurosciences: 77 patients were diagnosed of having catatonia. Mutism was the most common sign (97.7%), followed by withdrawal (93.2%), stupor (79.5%), staring (75%) and posturing (72.7%). Least common were combativeness (0%), verbigeration, echophenomena, perseveration (2.3%) and waxy flexibility (9.1%)(32).
The most common error in the evaluation of catatonia is of omission, because of the mistaken belief that all catatonic patients are stuporous and posturing. In fact, most patients with catatonia speaks and move about; stupor can alternate with excitement. Associated mood, speech and thought disturbances may be so intense that full attention to the motor signs is lost (33).
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In systematic studies of adult in-patient populations, using catatonia rating scales, between 8-14% of the samples exhibit two or more signs of catatonia for at least 24 hours (3).
However, the number of features required for the diagnosis is not experimentally established. DSM-IV-TR required the presence of two (only one for catatonia due to a general medical condition) of five set of symptoms (Table II)(9). In DSM-5 catatonia is defined on the basis of 3 or more out of 12 symptoms (Table III)(11).
Table II. Diagnostic criteria for catatonia in DSM-IV-TR (adapted from DSM-IV-TR, 2000 (9))
At least one (catatonia secondary to a medical disorder) / two (catatonic subtype of schizophrenia / specifier of mood disorder) of the following:
1. Motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor
2. Excessive motor activity (that is apparently purposeless and not influenced by external stimuli)
3. Extreme negativism (an apparently motiveless resistance to all instructions or maintenance of rigid posture against attempts to be moved)
4. Peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing
5. Echolalia or echopraxia
Table III. Diagnostic criteria for catatonia in DSM-5 (adapted from DSM-5, 2013 (12))
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 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, non-goal-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).
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Besides, there is a lack of consensus about the duration of the signs necessary to make the diagnosis. In some patients, the signs are unstable or transient, while in others they are present for days, weeks, or months. DSM-5 does not specify symptom duration. Fink’s work group proposes to identify catatonia when features are present for an hour
or longer or are reproducible on two or more occasions (Table IV)(3).
Table IV. Recommended diagnostic criteria for catatonia (adapted from Fink and Taylor, 2003 (3))
A. Immobility, mutism, or stupor of at least one hour duration, associated with at least one of the following: catalepsy, automatic obedience, posturing, observed or elicited on two or more occasions B. In the absence of immobility, mutism or stupor, at least two of the following, which can be observed or elicited on two or more occasions: stereotypy, echophenomena, catalepsy, automatic obedience, posturing, negativism, ambitendency
For descriptive purpose, we distinguish three forms of catatonia.
A retarded catatonia (Kahlbaum syndrome) is the most common syndrome. It begins with a prodromal stage of melancholia, then the patients exhibit mutism, negativism, posturing, repetitive actions and rigidity. Failure to respond to painful stimuli is a feature. Stupor may occur, as the most severe form of inhibition. Such patients require parental feeding and extended nursing care during these life-threating states. If properly treated this form has a benign outcome.
An acute excited state with prominent catatonic features have been described as excited catatonia (Bell’s mania): it is characterized by restless movements, talkativeness, disorganized speech, agitation, frenzy. Disorientation, confusion and confabulation may be recognized as coexisting delirium. Catatonic features are always prominent. These states are commonly seen in patients with manic-depressive illnesses and in acute toxic states. Distinguishing catatonic excitement from manic excitement is quite hard. Catatonic excitement is sudden in onset, at times purposeless, and of short
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duration. Manic excitement, in contrast, is said to occur within a manic mood state, often has a purpose and may last for days or weeks. However, it is often difficult to distinguish them. Without a systematic comparison study that has yet to be done, it is most parsimonious to consider these states the same condition (22).
A form of malignant catatonia (MC) has been described by Stauder in 1934 (34), as the sudden onset of intense excitement, delirium, high fever, marked rigidity and catalepsy in patients previously in good general medical health. Patients are autonomically unstable, with diaphoresis, tachycardia, tachypnea, and hypertension of life-threatening dimensions. Behavior fluctuates dramatically. Speech is disorganized and thoughts delusional. The patients refuse food and liquids. Self-harm is possible. There are laboratory alterations as increased levels of serum myoglobin and creatine phosphokinase (CPK), elevated liver enzymes, low serum iron and potassium, leukocytosis. Prior to the use of somatic treatments, the patients affected by MC could either recover spontaneously or grow increasingly severe and die from physiologic collapse, cardiac arrest, or infection. The Author originally termed the syndrome
todliche katatonie (fatal catatonia). ECT is described as the life-saving measure in
numerous reports. Memory and other cognitive difficulties, persistent motor features, and cerebellar degeneration have been anecdotally reported, but in the few follow-up studies, the surviving patients return to their pre-MC level of functioning (35).
Although initially described by Kraepelin (36), periodic catatonia was studied prominently by Gjessing (37): he described patients to be in stupor alternating with excitement, waxing and waning for years without evident deterioration. They exhibited periods of mutism, posturing, negativism, rigidity, echophenomena, and stereotypy. Although considered a benign illness, about 3% of his patients had a more malignant form. Gjessing identified systematic metabolic changes in nitrogen balance with the changes in behavior. He attempted treatment with thyroid extract, iodine, and massive
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doses of nucleic acid, concluding that thyroid extracts were compensatory, but not curing the disorder. The nosology of Leonhard’s group (38) classifies periodic catatonia
as a separate, recurrent cycloid psychos is unrelated to manic-depressive illness or to schizophrenia, exhibiting a typical “bipolar” course with prominent grimacing,
stereotypes, impulsive actions, and negativism, alternating with stupor, posturing, mutism, and waxy flexibility. They preferred a trial with benzodiazepines followed, if unsuccessful, with ECT. First-degree relatives of patients with periodic catatonia are at substantial risk for the syndrome (39). Patterns of anticipation occurs, with the age of onset in probands earlier than the onset in their parents (40).
All these descriptive entities constitute a common syndrome, on the basis of rigorous examination protocols and quantitative rating scales that identify the signs of catatonia and facilitate syndrome recognition (3, 41). Several factor analytic and one cluster analytic study on available rating scales have delineated stable patterns among the catatonic features, indicating a high correlation between the catatonic symptoms and thus demonstrating that the syndrome exists. Despite differences in patient samples and a lack of uniformity in methods of assessment, two patterns – one consisting in catalepsy, posturing, mutism and negativism and a second consisting of echophenomena, automatic obedience, verbigeration and other stereotypies – have been abstracted (42-44). The first cluster, corresponding to the classic picture of catatonia, was unrelated to diagnosis, gender, age of onset, family history or treatment response. The second, however, showed a weak correlation with the diagnosis of mania (13, 45).
3. Catatonia can be delineated from other syndromes
Several hypo- and hyperkinetic psychomotor disturbances can be mistaken for catatonia (Table V).
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Table V. Differential diagnosis of catatonia (adapted from Bhati et al., 2007 (46))
Diagnosis Features similar to catatonia Distinguishing Features
Non catatonic-stupor Immobility, unresponsiveness, mutism, altered mental status
Clear precipitating cause (e.g. head trauma, anoxia, drug intoxication)
Encephalopathy Acute onset, bizarre behavior, altered mental status
Typically occurs in the context of medical illness, reversible with treatment of underlying medical condition
Stroke Acute onset, may present with immobility, mutism, and/or altered mental status
History of cerebrovascular disease, focal neurological signs, CT/MRI findings
Stiff-person syndrome Immobility, posturing Stiffness and spasms precipitated by surprise
Parkinson’s disease Immobility, altered mental status, comorbid affective disorder
Symptoms improved with dopamine agonists and anticholinergics, cogwheel rigidity
“Locked-in” syndrome Mutism, immobility Complete paralysis with preserved vertical eye movements and blinking, associated with lesions in pons and cerebral peduncles
Malignant hyperthermia Immobility, mutism, altered mental status, autonomic nervous system instability
Hyperthermia secondary to inhalation anesthetics, autosomal dominant, diagnosed with muscle biopsy
Status epilepticus Immobility, mutism, altered mental status, bizarre behavior
Epileptiform activity in EEG Autism Mutism, immobility, echophenomena Chronic with onset in childhood Severe obsessive-
compulsive disorder
Repetitive echophenomena, comorbid affective disorder
Anxiety, awareness of compulsive behavior
Elective mutism Mutism Possible underlying personality disorder or paranoia
Elective mutism is the failure to speak and respond to questions, occurring as a singular feature, associated with a pre-existing personality disorder or environmental stress. Mutism alone is not sufficient to diagnose catatonia, while at least one motor feature should also be present. Postictal mutism, occurring after a seizure, is characterized by short duration and the patient is amnestic for the event. The electroencephalography (EEG) is usually consistent with a seizure disorder. Mutism may follow a cerebrovascular stroke; in this case history of cardiovascular disease, sudden onset, and onset in late life are reported (47).
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The appearance of reduced arousal alone consistent with stupor is insufficient to diagnose catatonia. Stupor occurs with depression, intoxications, metabolic disorders, cerebrovascular stroke, post-seizure states, traumatic brain injury, encephalitis, and brain tumors. It may be associated with diffuse slowing of EEG frequencies, suggesting an encephalopathy (13).
Parkinson disease (PD) and parkinsonism is distinguished from catatonia by the presence of tremor, cog-wheel rigidity, pill-rolling finger movements, and short-stepping, shuffling gait disturbances. PD patients do not posture bizarrely. In akinetic parkinsonism the patient is rigid and mute, with abnormal postures. This condition usually follows years of illness with PD, and is typically accompanied by dementia. Sedative-hypnotics do not relieve the syndrome, but anticholinergic drugs have some benefit (48).
In patients with catatonia, the repetitive nature of their stereotypes, grimacing, and tics brings the diagnosis of obsessive–compulsive disorder (OCD) into the differential diagnosis. Mannerisms and rituals of catatonic patients can be misinterpreted as signs of OCD. Conversely, compulsions may become stereotypic and elaborately manneristic. In OCD mannerisms and stereotypes occur daily for many years rather than in episodes. A family history of OCD or tic disorder is often present. In patients with catatonia, a family history of mood disorders is more likely. One case report described the association between beta-hemolytic streptococcal infection and the development of obsessive-compulsive behavior that improved after treatment with lorazepam followed by plasmapheresis. The authors thus suggested that catatonia with OCD and tics may represent different aspects of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) (49).
Gilles de la Tourette’s disorder (GTD) is a disorder with prominent vocal and
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catatonia. GTD typically has a childhood age-of-onset and a preeminence of vocalizations (50).
Malignant hyperthermia is a rare autosomal-dominant genetic disorder in which the skeletal muscles respond to inhalation anesthetics and depolarizing muscle relaxants (succinylcholine) by hyper-metabolism, producing muscular rigidity and tremor, fever, and elevated CPK levels. The diagnosis is confirmed with a muscle biopsy (13).
The stiff-person syndrome (SPS) is a rare condition characterized by progressive symmetric rigidity of axial muscles with painful spasms precipitated by touch, passive stretching, startling noises, movement, and emotional stimuli. The symptoms are relieved during sleep, general anesthesia, myoneural blockade, peripheral nerve blockade, and with benzodiazepines and baclofen. Some patients exhibit increased cerebrospinal fluid antibodies against glutamic-acid-decarboxylase (51).
The locked-in syndrome (LIS) is characterized by total immobility except for vertical eye movements and blinking. Cortical functions are spared. The syndrome is caused by an acute lesion in the ventral pons with both cerebral peduncles involved paralyzing the cranial nerves. Consciousness is preserved and is demonstrated by voluntary blinking in response to questions. The patient tries to communicate, in contrast to catatonic subjects (52).
The DSM recognizes the possibility of catatonia due to medical illnesses, including disorders that can cause delirium. Nonetheless, diagnosis of catatonia cannot be made if its motor and behavioral symptoms presents only during the course of delirium. The correct distinction between the two syndromes has therapeutic implications as the administration of antipsychotics, indicated in cases of delirium, can worsen catatonic symptoms (53).
Among the hyperkinetic states, hypocalcaemia, acute dystonia, tardive dyskinesia, withdrawal dyskinesia and akathisia must be excluded.
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4. Catatonia is more often associated with mood disorders
Contrary to Kraepelin’s conception, catatonic symptoms occur more frequently
in association with mood disorders. Reports throughout the 20th Century link manic-depressive illness and catatonia. Of 700 manic-manic-depressive patients, Lange (54) found 25% to have several or more catatonic features. Bonner and Kent prospectively compared 100 consecutive patients diagnosed with manic excitement with 100 diagnosed with catatonic excitement. The two groups had overlapping features with 10% of the manic patients exhibiting several catatonic features. In a retrospective analysis of hospital records, Morrison (55, 56) found 20% of the catatonic patients to be ill with a mood disorder. Similarly, Abrams and Taylor (19) found 39 of 55 catatonic patients (70%) to have a mood disorder (mostly mania).
In three studies conducted since 1977, 28-31% of catatonic patient had mixed mania or mania. Conversely, more than 25% of manic patients show catatonic diagnostic symptoms. These authors concluded that manic patients with catatonia had a more severe form of mania, but were similar in all other clinical ways to manic patients without catatonia (57, 58). However, it is estimated that more than half of catatonic patients may have a mood disorder and 20-30% of bipolar patients may experience a catatonic episode in the course of their disease, most often as a manic manifestation (46). Patients with bipolar disorder and catatonic symptoms had more mixed episodes, more severe manic symptoms, more severe psychopathology, longer periods of hospitalization and a more severe course of illness than did the patients without catatonia (58).
Only 10-15% of catatonic patients have an underlying diagnosis of schizophrenia as measured in five studies dating from 1932 to 1986 (13, 59, 60); a recent prospective cohort study found catatonia in only 7.6% of patients with schizophrenia (61). Fein and McGrath (62) reported that of 12 patients with catatonia, eight were initially diagnosed
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as schizophrenic, but at a two-year follow-up, eight of the 12 were re-diagnosed as manic-depressive. All responded to lithium. The misdiagnoses were attributed to the failure to recognize the fluctuating presentations of mania, misidentifying the stuporous states of catatonia as emotional blunting, and assuming catatonic signs to represent schizophrenia. The liberal use of antipsychotic medicines for any psychotic patient results in drug-induced Parkinson-like features leading to the conclusion, that the patient is emotionally blunted and therefore suffering from schizophrenia (63). In young adults, the typical years of onset of schizophrenia, the challenge is great to distinguish emotional blunting of schizophrenia from the motor signs of catatonia or those that are drug-induced (3).
Northoff and his co-workers could find no differences in catatonia rating scale scores or sub-scores between catatonic patients with schizophrenia and those with mood disorders, supporting catatonia as a syndrome, not a disease, and not synonymous with schizophrenia (43).
5. Catatonia has a typical course
Kahlbaum stated that the course of catatonia has a cyclic pattern with a phase of gradual onset, a period of state, and then a remission phase. This progressive course and the view of catatonia as “a temporary stage or a part of a complex picture of various disease forms” need to be included into the concept of “unitary psychosis”, according to
which mental disorders constitute a continuum, where each disorder would represent a “stadium”(64).
In his nosological system, Leonhard (38) distinguished a non-systematic form of catatonia, characterized by an acute onset, a bipolar and polymorphous symptomatology, with hyperkinetic and akinetic phases. The Author emphasizes that
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these catatonias were more closely related to manic-depressive illness and cycloid psychosis rather than to schizophrenia (65).
Nowadays, most Authors agree that catatonia is a cyclic disorder. The deteriorative outcome, as described by Kraepelin for dementia praecox, is rare as treatments usually lead to remission of catatonic symptoms. Although the long-term outcome of catatonia has not been rigorously studied, long-term prognosis appears to be linked to the nature and severity of the underlying psychiatric or general medical disorder. Retarded or excited catatonia in patients with an underlying mood disorder or toxic-metabolic disorder usually resolves with treatment of the catatonic syndrome plus the underlying condition (46).
In a study of 1975, 10% of 2500 hospitalized patients at the University of Iowa met criteria for catatonia at their index admission: among those reexamined later, 40% had recovered completely. These are not schizophrenic patients (66). In fact catatonia may persist for years in patients with schizophrenia (67).
Case reports describe recurrent catatonic episodes. The motor signs were generally consistent across each patient’s two episodes. For cases with complete
information, the same treatment worked in the two episodes (68, 69).
In a review by B.T. Carroll the addition of data from Hoch (1921), Rachlin (1937), and Joyston-Bechal (1966) supports the argument that Kahlbaum’s observations about the course of catatonia were accurate (70).
6. Catatonia is the result of diverse etiologies
A diagnosis of catatonia “secondary to a general medical condition” is available in
both DSM-IV-TR and DSM-5. In fact, catatonia has been reported to result from a variety of medical conditions. The percentage of catatonia reported to be due to a
19
general medical condition ranges from 20% to 39%. Psychopathological picture does not differ in diverse etiologies (16). A wide variety of medical conditions, including viral infections (for example HIV), autoimmune diseases, metabolic, neurological and substance-induced disorders have been shown to cause catatonia.
The neurological conditions include strokes, tumors, inflammatory disorders, epilepsy, paraneoplastic syndrome. Metabolic, endocrine and nutritional disorders, which can cause catatonia, include diabetic ketoacidosis, hyponatremia, renal failure, hypo/hyperthyroidism, hyperparathyroidism, adrenal carcinoma, pellagra and vitamin B12 deficiency.
Catatonic signs can occur during both intoxication as well as withdrawal from drugs like alcohol, opioids, amphetamines, cannabis and hallucinogens. Neuroleptic agents, finally, can cause or aggravate pre-existing catatonia (71, 72).
A brand new type of autoimmune encephalitis involving anti-NMDA (N-methyl-D-aspartate) receptor is increasingly reported in current literature. It presents with neuro-psychiatric symptoms including catatonia, seizures and neuro-vegetative disturbances. An ovarian teratoma is found in 50-60% of affected females. Positive serum and cerebrospinal fluid antibodies are typical. MRI shows mild fronto-temporal atrophy, but is negative in up to half cases. A viral infection may trigger an inflammatory response that disrupts the blood-brain barrier. Anti-NMDA receptor antibodies can enter and bind specifically to an epitope located in the extracellular domain of NR1 subunit, whose physiological ligand is glycine. The antibodies lead to rapid and reversible removal of the receptors from synaptic sites, especially in the hippocampus. The first step of treatment is the removal of tumor. Recovery with immunotherapy (steroids, plasma exchange, immunosuppressive drugs and intravenous immunoglobulin), is described, but occurs slowly. Since catatonic symptoms are usually
20
prominent, some case reports of effective treatment with lorazepam and ECT dot the literature (73-75).
7. Catatonia by other names
Delirious mania is the acute onset of agitated, dreamy or delirious states with associated motor signs. Patients sleep poorly, and are disoriented. They confabulate, often with fantastic stories. The onset develops rapidly. Fever, rapid heart rate, elevated blood pressure, and rapid breathing are prominent. Garrulousness, flights of ideas, and rambling speech alternate with mutism, there is restlessness, agitation and self-harming. Catatonic features are usually obvious, suggesting that the condition is identical to that identified as excited catatonia. Delirious mania typically leads to prescription of intramuscular antipsychotic medicines. Such intervention, especially when patients are dehydrated and have an electrolyte imbalance, is likely to induce malignant catatonia. Benzodiazepines are effective alternatives to sedate the patient. Prior episodes of mood disorder or a family history of mood disorder are often reported.
Stupor presents difficulties for differential diagnosis because it is elicited by many neurologic and metabolic disorders. Also, unlike delirious mania, stupor is a specific DSM criterion for catatonia and a classic feature described by Kahlbaum and all other writers. Definitions of stupor in catatonia that are based on the simultaneous presence of other catatonic features skirt the issue of directly defining stupor (76). The term benign stupor is applied when patients recover from prolonged periods of stupor that were associated with severe depressive illnesses, in contrast with those who went on to the persistent illness of schizophrenia. Plum and Posner (77) define stupor as a state of unresponsiveness from which the patient can be aroused only by vigorous and
21
repeated stimuli and back into which the patient lapses as soon as the stimuli cease. This description is consistent with the literature on catatonia.
The acute onset of fever, autonomic instability, rigidity, and changes in mood and alertness, was described by Delay and colleagues in 1969 (78) during early trials of haloperidol. In 1980, the syndrome was labeled neuroleptic malignant syndrome (NMS)(79). The syndrome was occasionally fatal, with a mortality rate of 25% before 1984 that decreased to 12% by 1989. Reported incidence rates of NMS range between 0.07% and 0.9% in patients treated with neuroleptics. Although it typically develops within 24 to 72 hours of initiating antipsychotic treatment, it may also occur after 10 to 20 days (80, 81). More men than women are affected (3:2), but male patients typically receive higher drug doses, and this may explain their increased risk. Patients exhibited many signs of catatonia but the systemic manifestations dominated the syndrome (3). NMS is characterized by hyperthermia, severe ‘‘lead pipe’’ muscle rigidity,
rhabdomyolysis (resulting in an increase of CPK and myoglobin levels), autonomic dysregulation, and altered consciousness, ranging from simple disorientation to delirium. Autonomic changes (tachypnea, tachycardia, blood pressure instability, diaphoresis, urinary incontinence, flushing, or pallor) present a remittent course. Extrapyramidal symptoms or a positive Babinski sign may also be associated (82). Some alterations in laboratory tests, such as leukocytosis, elevated liver enzymes, and fluid and electrolyte imbalances (involving low iron, potassium, and calcium blood levels) are also features of NMS (83, 84). Possible risk factors described for the development of NMS include the presence of agitation, dehydration or physical restraints, concomitant administration of lithium, abrupt withdrawal of dopamine agonists, anticholinergics, or benzodiazepines, presence of organic brain syndromes or extrapyramidal symptoms, and iron deficiency (80, 85, 86). Excited manic patients seem to be at particular risk, probably because they are often dehydrated and receive
22
high doses of more than one antipsychotic drug at a time (3). Once neuroleptics are stopped, NMS is usually self-limited and lasts approximately 7 to 10 days; residual symptoms may persist, including cognitive deficits (87) or catatonic states (88). There is substantial clinical evidence of a frequent progression from catatonia to NMS. Many shared risk factors and specific treatment response suggest that these two distinct syndromes may belong to a spectrum of similar disorders (89, 90). To date, the pathophysiology of NMS and catatonia is not fully understood, but common etiological models have been proposed (91, 92). In support of the theory that catatonia predisposes to NMS, it has been speculated that the hypodopaminergic state associated with catatonia (93) may be aggravated by the blockade of dopamine D2 receptors determined by antipsychotics (94, 95). In psychotic conditions, the hyperdopaminergic mesolimbic dopamine system tries to adjust itself by the down-regulation of dopamine receptors. As Friedhoff (96) points out, this adjustment affects other brain regions, such as the mesostriatal and hypothalamic systems. If these areas become hypodopaminergic to a relatively large degree, catatonia may arise. The use of neuroleptics could further decrease dopaminergic transmission through dopamine blockade, leading to NMS (97). Because NMS occurred in response to anti-dopaminergic drugs, dopamine agonists have been recommended for treatment. The muscle relaxant dantrolene was frequently added. Interestingly NMS responds better to the same treatment proposed for malignant catatonia (3). Currently, benzodiazepines (especially lorazepam) are considered the most effective psychopharmacological treatment for catatonia. NMS may also benefit from treatment with benzodiazepines, presumably because of their ability to increase dopaminergic activity indirectly through an action on gamma-aminobutyric acid (GABA) receptors (98). Similarly, NMS can be also effectively treated with electroconvulsive therapy (ECT), a treatment of choice for catatonia, especially when drug treatment has failed (99, 100).
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A toxic serotonin syndrome (TSS) is described in patients exposed to a rapid increase in a selective serotonin reuptake inhibitor (SSRI) or when an SSRI is combined with other agents that affect the brain’s serotonin system (i.e. monoamine oxidase
inhibitors, lithium). The mechanism is dose-dependent. Patients are restless and sleep poorly. The sensorium is altered, the skin flushed, and the patient complains of sweating, tremor, shivering, lethargy, salivation, nausea, diarrhea, and abdominal pain. Temperature and blood pressure are elevated, tendon reflexes are hyperactive, movements ataxic, and myoclonus appears. Laboratory findings include leukocytosis, rhabdomyolysis with elevated CPK, myoglobinuria and renal failure. Hyponatremia, hypomagnesemia and hypercalcemia are also reported. Although most patients respond rapidly to withdrawal of the offending medicines and supportive care, ECT has also been used successfully (101). The overlap of the diagnosis of TSS and NMS is reported. The authors conclude that the two syndromes are conditions allied with catatonia (102).
8. Catatonia has a specific neurobiological correlate
Subjects with focal brain lesions rarely develop catatonic syndrome, and catatonic symptoms are more frequently observed in association with neurological pathologies that diffusely involve the central nervous system. This would seem to substantiate the hypothesis that catatonia is due to dysfunction of neural circuits with involvement of multiple structures rather than focal alterations (103).
In the pathophysiologic model by Northoff, catatonia is described as a psychomotor disorder while NMS is predominantly a motor disorder. In both, striatal D2 receptors and the basal ganglia are involved, but in contrast to the importance of striatal dopamine receptor blockade in NMS, alterations in γ-aminobutiric acid (GABA) transmission are central in catatonia. Northoff et al. analyzed the density of the
GABA-24
A receptor in the left sensorimotor cortex in catatonic patients. The binding of the radioligand, iomazenil, with the GABA-A receptor was significantly lower in catatonic patients compared to controls (104). Recent brain imaging has revealed predominantly cortical rather than subcortical anomalies in catatonia. On the contrary, NMS can be characterized as a disorder of the basal ganglia, with secondary involvement of cortical structures. Catatonia and NMS involve the same loops (orbitofrontal and motor), so there may be overlap in clinical phenomenology and treatment. However, catatonia and NMS may differ in terms of distinct kinds of modulation (105-107).
A disturbed functional connectivity between orbitofrontal and premotor/motor cortex may be closely related to generation of motor symptoms of catatonia. The lateral orbitofrontal cortex is strongly connected with the ventromedial caudate, as a part of the orbitofrontal loop involving lateral orbitofrontal cortex, caudate, pallidum, thalamus, and again orbitofrontal cortex (108). Consequently, catatonia arises from cortical-subcortical “top-down modulation”, where alterations in orbitofrontal cortex may
modulate cortical and subcortical motor structures, leading to down-regulation of striatal dopamine. Decreased inhibition by GABA renders the orbitofrontal cortex unable to exert its gating function on prefrontal and frontal cortical areas, so that prefrontal activity becomes dysregulated. Then, altered cortical GABA transmission down-regulates subcortical dopamine transmission, which may then account for rigidity in catatonia. Both orbitofrontal and motor loops may be down-regulated and thus vulnerable in the pre-catatonic state, and this vulnerability may be reinforced further by neuroleptics, resulting in the development of full-blown catatonia (106). Glutamate is involved since it has been hypothesized that hyperactivity of the N-methyl-D-aspartate (NMDA) receptor can determine dysfunction of GABA-A (109). Northoff further suggested that hyperactivity of glutamatergic system causes dysfunction of posterior
25
parietal lobe and thus explain bizarre posture and other catatonic symptoms observed in patients with lesions of the right parietal lobe (110).
Motor symptoms in NMS, characterized by primary subcortical origins, may be directly related to striatal D2 receptor blockade, that modulates the motor loop to the supplementary motor area and also the orbitofrontal loop. In contrast to cortical-subcortical modulation in catatonia, one may speak of cortical-subcortical-cortical “bottom-up modulation” in NMS, both taking place via the same orbitofrontal and motor loops
(111). Finally, hyperthermia and autonomic dysfunction in malignant catatonia and NMS may arise from disrupted transmission between orbitofrontal structures and lateral hypothalamus (91).
Other etiopathogenetic models involve: 1) an epileptic-like process where excitatory foci in brain areas involved in motor regulation can be expressed as catatonia when increasing numbers of neurons are recruited to fire synchronously (91); 2) a genetic susceptibility, supported by the observation of a family transmission in periodic catatonia (chromosome 15q15)(112), catatonic symptoms in the Prader-Willi syndrome (113), and the association of several polymorphisms of D2 receptor genes with an increased risk of NMS (114, 115); 3) an endocrine dysfunction where catatonia is associated to hyperparathyroidism, thyrotoxicosis, pheochromocytoma, or fluid/electrolyte imbalance (91); 4) an immunologic pathogenesis (e.g., catatonic patients with antiphospholipid antibody syndrome, cerebral localizations of systemic lupus erythematosus and the new anti-N-methyl-D-aspartate receptor encephalitis) (73, 116).
26 9. Catatonia has a specific diagnostic test
Lorazepam challenge test is the diagnostic test for catatonia. It is used also to
predict the response of catatonia to benzodiazepines. A syringe with 2 mg of lorazepam is prepared and a “butterfly” or similar intravenous setup established. The patient is
examined for signs of catatonia; 1 mg lorazepam is injected. The patient is observed for signs of catatonia and questioned. If, after five minutes, there has been no change, the second dose of 1 mg is given, the patient again observed and questioned. Favorable responses, with reduction in rigidity and the appearance of spontaneous movements and speech, usually occur within 10 minutes in at least two-third of patients, although they are observed for longer periods. The degree of change is recorded. If improvement is seen after the challenge test, treatment with increasing doses of lorazepam as high as 24 mg/day is recommended, with good response in 90% of cases. The negativity does not rule out a possible response to benzodiazepines, although higher dose are often necessary, but suggests a preferential response to ECT so that concurrent preparation should be initiated (25).
Zolpidem is a GABA-A agonist and has been reported in one case series to be effective in the treatment of catatonia. Zolpidem has a quick onset (15 to 30 minutes) which makes it a useful diagnostic tool. Zolpidem challenge test consists in administering 10 mg of zolpidem orally or through a nasogastric tube to achieve concentration between 80 and 150 ng/liter within 30 minutes of ingestion. Response usually occurs within 30 minutes and lasts 3 hours (117). It was reported to be effective in one case where lorazepam failed (21).
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10. Catatonia responds to specific treatments and is worsened by others
Catatonia is a treatable syndrome, once it is diagnosed. First effective treatment of catatonia were barbiturates. W.J. Bleckwenn in 1930 (118) reported that the intravenous administration of a 5% solution of amobarbital sodium, resulted in dramatic, though transient, effects in three catatonic patients. These examples encouraged the use of sodium amobarbital to treat catatonia. Barbiturates were associated with neurotoxic complications, dependence, and death by overdose. The development of the first benzodiazepine chlordiazepoxide in 1958, and diazepam, lorazepam, midazolam, provided alternatives with higher safety. In addition, benzodiazepines have studied more often, are familiar to clinicians, and an antagonist (flumazenil) is available. These agents soon became the preferred treatment for catatonia (119).
Nowadays, the most commonly used treatment is intravenous lorazepam, with a reported remission rate of catatonic manifestations of about 70%, regardless of the cause or of clinical manifestations (15). Intravenous administration is preferred to assure adherence and rapid, complete absorption. As patients improve, they should be switched to oral medication. The dosing schedule varies with the severity of catatonia and the presence of fever and vegetative signs. For stuporous patients, dosing starts at 3 mg daily (1 mg three times per day), increasing every one or two days to 6 mg, 9 mg, and 12 mg as tolerated, depending upon response and clinical urgency. A dose of 6 to 21 mg daily is effective for most patients, but a dose of 30 mg per day is occasionally necessary (22). For excited patients, lorazepam 1 to 2 mg is given at more frequent intervals until the patient is calm but awake; dosing may be often escalated more rapidly than in retarded forms. For patients with fever, hypertension, tachycardia, and tachypnea, intravenous dosing of 1 mg lorazepam, up to 6 mg, every two hours may be prescribed. A successful acute treatment course will take from 4–10 days (3, 35).
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Prolonged trials are not advised for severe catatonia, as complications have been reported (120). Comorbid schizophrenia may predict a less robust effect (67, 121).
ECT is effective in around 85% of patients. It works even when benzodiazepines fail to give adequate response (68). Since neither benzodiazepines nor ECT is considered a treatment for schizophrenia and since antipsychotic are usually ineffective or even dangerous in catatonia, catatonia appears to be pathophysiologically different from schizophrenia. Identification of catatonia with schizophrenia in clinical teaching results in unnecessary prescription of neuroleptic medications (16).
Clinicians should avoid antipsychotic and other dopamine-blocking drugs in patients with catatonia. First-generation antipsychotics do not appear to provide any benefit for treating catatonia. High potency antipsychotic drugs, especially haloperidol, are commonly used to reduce excited and aggressive behavior, but in these patients, such use risks the development of MC or NMS (3). There are reports that second-generation antipsychotics may treat catatonia since they have weak GABA-agonism and 5HT2 antagonism that could stimulate dopamine release in the prefrontal cortex and help alleviate catatonic symptoms. Moreover, all atypical antipsychotics have been found to precipitate and worsen catatonia, and to cause NMS. In addition, treating catatonia with an antipsychotic is a risk factor for NMS. In a recent review of the use of atypicals in the treatment of catatonia, Van Den Eede et al. advised using atypical antipsychotics in catatonic patients with caution, given the risk of NMS. They postulated that treatment with an antipsychotic might target the psychiatric illness that is driving the catatonia, rather than treating the catatonia itself (122). After catatonia has resolved and the patient is moving normally, eating and drinking, and autonomically stable, an antipsychotic drug may be used to treat an underlying psychotic disorder with undue risk of precipitating NMS. During this time, patients should be examined
29
regularly for recurrence of catatonic signs. If a benzodiazepine resolved the catatonic episode, it should be maintained during treatment with an antipsychotic (35).
Other therapeutic strategies are: the anticonvulsants topiramate and divalproex, glutamate antagonists, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)(109, 123, 124).
Benzodiazepines and ECT are also effective in patients with NMS, even when NMS has proved resistant to the more common protocol dopamine agonist/muscle relaxant, suggesting that catatonia and NMS belong to the same spectrum (99, 100).
The ECT in the treatment of catatonia will be better described in the next chapter.
11. Fink and Taylor’s criteria of Catatonia
The research team led by Max Fink and M.A. Taylor suggests new diagnostic criteria for catatonia (Table IV). They would address the poor specificity of DSM-IV-TR diagnosis. The absence of a duration criterion compromises reliability among observers, since echolalia and echopraxia come and go and other features can be quite variable. The non-specific features of immobility and excitement are sorted equally with the more specific features of catalepsy, waxy flexibility, negativism and mutism. While catalepsy and echophenomena are specific catatonic features, excessive motor activity and severe immobility are not. The excessive motor activity associated with catatonia is related to activity that is stimulus-bound, i.e. influenced by external stimuli. On the other hand, some catatonic patients seem purposeful in their mutism and negativism, and some manic patients seem purposeless in their excitement, limiting the utility of these descriptors. In addition, the DSM-IV-TR items 1, 3 and 4 (Table II) include postural immobility, creating a redundancy within the criteria. Patients who are stuporous (criterion 1) are also often mute (criterion 3). They would meet criteria 1 and
30
3 and could be labeled catatonic, although stuporous and mute patients are not all catatonic. Catalepsy often appears as posturing; thus, patients with this single sign fulfill criteria 1 and 4. Fink and Taylor’s criteria would strengthen the boundaries of the
syndrome, facilitating further study and the application of appropriate treatments (13). However, the changes proposed in DSM-5 (Table III) do not seem able to address the lack of specificity seen in DSM-IV-TR, since they present the same limitations in both overlapping of symptoms and absence of a duration criterion. Fink & Taylor (13) also proposed to delink completely catatonia from schizophrenia, defining catatonia as a separate entity with its own classification number, using the DSM-IV-TR coding of delirium as a model (Table VI). The Authors suggest including catatonia within the category “Movement Disorders”. For heuristic purposes, the Authors provide subtypes
for catatonia, following the classification model for other disorders. Such subtyping will encourage a closer look at symptomatology, course of illness, and more specific treatment algorithms. These subtypes also reflect differences in degrees of lethality, with the non-lethal forms responding to benzodiazepines. The delirious forms are worsened by neuroleptics, require higher doses of benzodiazepines and respond best to ECT. The malignant forms require life-support measures in addition to intensive ECT.
Table VI. Proposed categories for diagnostic classification of catatonia (adapted from Fink and Taylor, 2003 (13))
Classification element Category
DSM code XXX.0 Catatonia
DSM code xxx.1 Non-malignant catatonia (Kahlbaum syndrome) DSM code xxx.2 Delirious catatonia (delirious mania, excited catatonia)
DSM code xxx.3 Malignant catatonia (including neuroleptic malignant syndrome and serotonin syndrome)
Specifier
DSM code xxx.x1 Secondary to a mood disorder
DSM code xxx.x2 Secondary to a general medical condition or toxic state DSM code xxx.x3 Secondary to a neurological disease
31 12. Catatonic syndrome in DSM-5
Tandon and colleagues well summarize, in a recent update, DSM-5 changes in terms of catatonia (11). After careful consideration and several exchanges with the group of experts, it was decided not to create such an independent diagnosis of catatonia, completely uncoupled from psychiatric and general medical disorders (10). This change was not made because 1) the diagnostic condition in which catatonia occurs is more stable than catatonia itself over the longitudinal course of the illness in a given patient (e.g., patients with a major depressive disorder who exhibit catatonia in a particular depressive episode do not consistently do so in subsequent depressive episodes; patients with schizophrenia may exhibit catatonia at one time-point in the illness, but not others), thus, designation of catatonia as a specifier of the primary disorder in which it occurs seems appropriate; 2) making such a change would result in spurious comorbidity, with the requirement that patients concurrently receive two diagnoses of a catatonic syndrome plus a diagnosis of the primary psychiatric disorder (mania, major depressive disorder, schizophrenia, etc.); 3) although catatonia does share some important similarities across the different diagnostic conditions in which it occurs, there are some important distinctions as well (e.g. benzodiazepines and ECT are less effective in the treatment of catatonia when it occurs in the context of chronic schizophrenia in contrast to other disorders, some Authors consider antipsychotics to be effective in the treatment of catatonia when it occurs in the context of psychotic disorders)(125-127). In the final assessment, the prevailing opinion is that the changes made in the DSM-5 would be able to adequately address the limitations in DSM- IV-TR.
Fink’s research team has however expressed some concerns about the changes
implemented in the DSM-5. Of course, these Authors disagree with the persistence of a link between catatonia and schizophrenia. In addition, they observed that the application of a catatonia specifier for at least ten principal diagnoses concept serves no clinical
32
purpose and confuses treatment options. Then catatonia “due to another medical condition” and “unspecified catatonia” will justify the testing and treatment of catatonia
as a principal intervention, without deepen the etiology. Finally, because all the forms of catatonia are of systemic origin, it is probable that catatonia “due to another medical
condition” will have limited use, and the less restrictive “unspecified catatonia” will be applied for all forms of catatonia (128).
Undoubtedly, the changes made in the DSM-5 are helpful in improving the diagnosis and treatment of catatonia. However, the group of Fink, over the years, has carried increasingly convincing arguments for the autonomy of catatonia. Catatonia is a well-defined syndrome, deserving a home of its own in the psychiatric nomenclature as a specific psychopathology with many different facets. It has to be freed from schizophrenia and recognized his own right (129). Considering catatonia an independent syndrome would bring it back to the original Kahlbaum’s conception. It will ensure the most early recognition and application of the correct therapeutic procedure, avoiding serious consequences and potentially dangerous treatments.
33
E
LECTROCONVULSIVET
HERAPY FORC
ATATONIAAlthough electroconvulsive therapy (ECT) is an effective treatment for patients with mood and psychotic disorders, it is among catatonic patients that the most remarkable efficacy is observed (130). The first patients to benefit from ECT had catatonic symptoms, and the clinical experience of more than sixty years has shown that catatonia is the clinical condition with the most rapid, dramatic and often life-saving response to ECT.
1. A history
An intimate relationship of ECT and catatonia began with the very first research trials in 1934. Ladislas Von Meduna, a Hungarian neuropathologist, had observed paucity in the numbers of glial cells in the patients who died of schizophrenia and abundance in those with seizure disorders. At that time, it was thought that it was possible to ameliorate a psychiatric syndrome by inducing a systemic disease. After identifying intramuscular injections of camphor to be effective seizure-inducing agents in animal trials, Meduna was prepared to treat patients with schizophrenia. Meduna describes the first patient as Zoltan, a 37-year-old man who ‘‘…had been suffering from
a catatonic stupor for about four years. He never moved, never ate, never took care of his bodily needs, and had to be tube-fed daily…’’(131). After 9 injections, with 6
induced seizures, he recovered and was discharged to the community; after 3 months, he relapsed and was readmitted to the hospital. Of the first 11 patients treated by Meduna, 9 showed mutism, negativism, posturing, and stupors; 6 required daily tube-feeding (132). Although injections of camphor induced full grand mal seizures in less than half the injections, the relief of these symptoms encouraged further clinical trials. Within a few months, Meduna changed the induction method to intravenous pentylenetetrazol
