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It was first described in 1875 by Kahlbaum (1) who reported 25 patients with a “brain disease” characterized by four of the following signs: long periods of immobility, mutism alternating with verbigeration, staring, withdrawal and refusal to eat or drink, negativism, posturing and grimacing, echolalia, echopraxia, stereotypy, and waxy flexibility (see Table 1). Kahlbaum observed that these otherwise immobile patients could become very agitated or excited and were often found to have extremes of mood disturbance in the form of “melancholy” or “mania.” This phenomenon of marked, polar alterations in the predominant psychomotor state eventually led to division of the syndrome into retarded and excited types (2). The excited form has been much more difficult to characterize and distinguish from mania (3). In rare instances, patients with severe motor excitement develop fever, autonomic disturbances, stupor, and rhabdomyolysis and may succumb to cardiovascular collapse. This clinical state has been referred to as lethal or malignant catatonia (4,5) and the clinical and laboratory similarities to neuroleptic malignant syndrome (NMS) has generated considerable interest and discussion (6,7). This chapter focuses on retarded catatonia including clinical, laboratory and autonomic features, diagnosis, complications, treatment, and underlying diagnoses. THE CURRENT STATUS OF CATATONIA Whereas catatonia seemed to “disappear” from the clinical landscape for many years (8,9) recent studies reported the incidence to be between 9 and 15% of admissions to acute-care psychiatric units (10–13). This suggests that the term may simply have fallen into disuse and that the clinical phenomenon of immobile, mute, staring, withdrawn, and rigid patients has been with us all the time. Whether or not one used the term catatonia to describe this particular constellation of signs may, at one time, have been of only academic interest, but the situation changed once it became clear that the syndrome is exquisitely responsive to treatment with benzodiazepines (BZPs) (14). This ability to treat the condition easily and effectively is, perhaps, the most compelling reason for “re-awakening” physi- cians to a “forgotten disorder” (15). This is particularly true for neurologists who are often called on to assess patients with catatonic signs. From: Current Clinical Neurology: Psychiatry for Neurologists Edited by: D.V. Jeste and J.H. Friedman © Humana Press Inc., Totowa, NJ MAKING THE DIAGNOSIS OF CATATONIA The first and most essential step in recognizing catatonia is to think of the diagnosis when presented with a particular constellation of clinical signs. The most common catatonic signs are immobility, staring, mutism, and withdrawal with refusal to eat or drink, each of which has been observed in more than 75% of patients who presented to either our acute-care inpatient psychiatric unit or our consultation-liaison service. The diagnosis in these cases was based on the following: the presence of four or more of the catatonic signs described by Kahlbaum, and the resolution of the catatonia in response to treatment with BZP medication. The frequency of individual signs in 165 consecutive cases is shown in Fig. 1. In contrast to the core catatonic features of mutism, immobility, staring, withdrawal, and refusal to eat, the more bizarre signs are comparatively less common. Patients are often incontinent and, depending on the duration of untreated illness, may be cachectic and dishevelled as well. Catatonic immobility can be so profound that at times it is difficult to see respirations. Whereas the absence of meaningful responses to those around them suggests a disturbance of consciousness, these patients are typically hyper-alert, aware of their surroundings, and able to recall their catatonic state in detail once recovered. Awareness and consciousness are reflected in the finding of normal electroen- cephalograms (EEGs) in almost all catatonic patients, a quality of gaze that belies unawareness, and the “ability” of these patients to do the exact opposite of what is requested (negativism) or to engage in echoing another’s words or gestures. CONDITIONS ASSOCIATED WITH CATATONIA The majority of patients who develop catatonia do so in the context of another illness. In fact, catatonia has been described in association with a wide range of conditions, which often become apparent only after the catatonia resolves. A final common pathway for the wide spectrum of disorders and 82 Rosebush and Mazurek Table 1 Catatonic Signs Described by Kahlbaum in 1874 Sign Definition Immobility Paucity or absence of spontaneous movements Staring Decreased frequency of blinking Mutism Inaudible whisper or absence of spontaneous speech Rigidity Increased muscle tone during passive movement of limbs Withdrawal and refusal to eat Turning away from examiner, avoidance of eye contact, refusal of food or drink when offered Posturing Voluntary assumption and maintenance of an inappropriate or bizarre posture Grimacing Unusual or exaggerated spontaneous facial expressions; Kahlbaum also referred to these as “snout spasms,” “convulsive-type spasms,” and “tics” Negativism Active resistance to instruction, e.g., patient asked to close or open eyes or mouth does the opposite Waxy flexibility (catalepsy) The maintenance of a limb in any position in which it is placed by the examiner Echolalia or echopraxia The repetition or mimicking of the examiner’s actions or words Stereotypy Aimless repetitive movements, often bizarre in nature Verbigeration The continuous and directionless repetition of single words or phrases Catatonia 83 diseases said to cause or give rise to catatonia has not yet been identified. One possible unifying mech- anism is the experience of overwhelming anxiety and preoccupation with death, reported by many patients who have been catatonic (11,16). One suspects, for example, that this might have been oper- ative in reports of catatonia occurring in the context of severe burns (17). A minority of individuals appears to simply have catatonia and no other underlying disorder. Underlying Diagnoses Despite Kahlbaum’s original observation that his catatonic patients suffered from disturbances of mood, Kraepelin, and later Bleuler, considered catatonia to be a subtype of schizophrenia. In his Lectures on Clinical Psychiatry, Kraepelin wrote that “the descriptions of disease summed up by [Kahlbaum] as katatonia are only special forms of dementia praecox” and he emphasized the difference between catatonia and manic-depressive illness (18). For many years to follow, the subject of catatonia could be found only in reference to schizophrenia. Then, in the 1970s, the sole association of catatonia with schizophrenia was questioned as studies revealed that these patients ultimately enjoyed a more favorable outcome than generally expected with schizophrenia (19,20). Later, prospective studies found that the majority of catatonic patients admitted to acute-care psychiatric units had mood disorders (20,21), confirming Kahlbaum’s impression. These findings are reflected in the inclu- sion of catatonia in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a modifier of certain mood disorders and general medical conditions in addition to being a subtype of schizophrenia (22). In our prospective study and 15-year follow-up of more than 100 patients admitted to our inpatient psychiatry service or seen on the medical units in a catatonic state, both unipolar and bipolar affective disorders have been the most common underlying diagnoses, accounting for approx 44% of cases. Fig. 1. Frequency of individual signs in 165 episodes of catatonia. This is followed in frequency by schizophrenia (17%), other psychoses (e.g., brief reactive psychosis, atypical psychosis, paranoid disorders [7%]), cocaine intoxication (7%), and identifiable medical or neurological conditions (9%) (see Table 2). The vast majority of patients with catatonia are found to be psychotic once they are treated and able to speak. Except for the patient with normal pressure hydrocephalus and one of the individuals with a posterior fossa tumor, all these patients responded to treatment with lorazepam. A very important and readily treatable cause of catatonia, which accounted for 16% of our cases, is BZP withdrawal. Our first case is a striking illustration of the phenomenon. One of us was called on an emergency basis to admit an 88-year-old man who was thought by his physician to be suffering from the consequences of an apparent brainstem stroke. The patient was, until a few days earlier, cognitively intact and in semi-independent living because of blindness resulting from glaucoma. He had no other medical history. Because of his age, his family did not want him transferred to the hospital and subjected to investigations so we assessed him at the retirement home. On examination, he was found to be mute, staring, immobile, extremely rigid, and incontinent. He had not taken anything by mouth for several days and appeared very dehydrated. We learned that his clonazepam, which he had been taking at a dose of 1.5 mg for 15 years for sleep, had been tapered and finally discontinued just days before his deterioration. His family declined blood work or other investigations but gave per- mission for the intramuscular administration of 2 mg of lorazepam. Within 45 minutes he began to speak and take fluids by mouth. His rigidity lessened. Another 2 mg was given 6 hours later at bed- time and by the morning he had recovered fully. On a maintenance regimen of lorazepam he lived for another 6 years without any medical events. Patients admitted to the hospital for any reason are often reluctant to report their use of this com- monly prescribed agent. Shortly after, they experience withdrawal, one manifestation of which can be catatonia. Hauser (23) described catatonia precipitated by BZP withdrawal in 1989 and in 1996 we reported five patients in our series whose catatonia had occurred in this context (24). Since that time, other similar reports have appeared in the literature (25,26). Neurological Conditions That Can Mimic Catatonia Parkinsonism We have been asked to see patients with a tentative diagnosis of catatonia who, upon examination, are found to be parkinsonian. In 1998 (27), we described a 37-year-old woman who had been hospitalized at another center with a diagnosis of catatonia. On examination, she had profound psychomotor 84 Rosebush and Mazurek Table 2 Underlying Neurological and Medical Disorders Found in 16 of 137 Prospectively Studied Patients With Catatonia Presenting to a Psychiatry Service Neurological/medical disorder N Brain tumor (Posterior Fossa n = 2, Frontal n = 1) 3 AIDS 2 Viral encephalitis 2 Spongiform encephalopathy (CJD) 2 GM 2 gangliosidosis 1 Mitochondrial disorder (Kearne-Sayres) 1 Paraneoplastic syndrome (limbic encephalitis) 1 Frontal lobe dementia 1 Multi-infarct dementia 1 Normal pressure hydrocephalus 1 Temporal lobe dysrythmia 1 retardation with a stare and flat facial expression. Her “posturing” consisted of periods of freezing— a very stooped posture and flexed arms. She had no spontaneous speech and on further examination was found to have a shuffling gait, cogwheel rigidity, and micrographia. We subsequently learned that, prior to hospitalization, she had been treated with high-dose antipsychotic agents for anxiety and insomnia. We therefore diagnosed parkinsonism secondary to these drugs and she eventually recovered, albeit slowly, from their withdrawal. The most common causes of parkinsonism in the patients we see are either idiopathic disease or extrapyramidal side effects secondary to antipsychotic drug treatment. Wilson’s disease, a disorder of copper metabolism that results in copper deposition in the eye, liver, and basal ganglia, should always be considered in patients who present with any form of movement disorder at a young age and have concomitant psychiatric disturbances. Unlike catatonic patients, those suffering from parkinsonism are usually cooperative and eager to interact with the physician rather than withdrawn and negativistic. Mutism, a key feature of catatonia, is uncommon with parkinsonism, although patients may be hypophonic. Rigidity characterizes both conditions, but parkinsonian patients often have a tremor, which is not part of the syndrome of catatonia. Furthermore, the bizarre behavioral features of catatonia, such as posturing and echophe- nomena, are absent. It is important to be alert to the possibility that a patient with parkinsonism can have superimposed catatonia, a situation we have observed a number of times. Akinetic Mutism (28) Akinetic mutism refers to patients who are fully aware but appear to have a profound lack of drive or motivation to speak or move. Rigidity and staring are typically absent, as are the more bizarre clinical features of catatonic state. A key point of differentiation from catatonia is the absence of negativism in patients with akinetic mutism. Despite this, the two conditions can be difficult to distinguish, as illustrated by an anecdote reported by Fisher (29) regarding a case of disulfuram-induced catatonia. He described a conference at the Massachusetts General Hospital in Boston during which 90 neurologists were presented with a mute, immobile patient who had, 2 weeks earlier, suffered rupture of an anterior communicating artery aneurysm. According to Fisher, the neurologists on hand were equally divided as to whether the patient should be regarded as having catatonia or akinetic mutism. “Locked-In” Syndrome (30) In locked-in syndrome, which typically reflects pontine pathology, patients are aware but unable to move, speak, or respond to their environment because of interruption of motor pathways and spar- ing of the reticular-activating system. Their alert gaze is similar to that observed in patients with catatonia. An important difference is that once the “locked-in” patient learns to use blinking to respond to questions, there is almost invariably a desire to communicate. As with catatonic patients, the EEG is typically normal and sleep–wake cycles are preserved. Neuroleptic Malignant Syndrome (31,32) This serious and life-threatening reaction to dopamine D 2 -blocking agents is characterized by immobility, staring, rigidity, and mutism. The presence of diaphoresis, fever, and a labile blood pressure, as well as the absence of negativism, echolalia, echopraxia, grimacing or posturing, distin- guishes NMS from catatonia. Additionally, NMS is typically associated with leukocytosis, low serum iron, and high levels of creatine phosphokinase not found in most cases of uncomplicated catatonia. Persistent Vegetative State (33–35) In persistent vegetative state, which typically follows a severe cerebral injury, patients are inattentive and mute with no apparent awareness of their surroundings. Whereas patients with catatonia may, at first blush, appear unaware of what is going on around them, the quality of their staring gaze indi- cates intense awareness and vigilance. The EEG in vegetative states is almost always abnormal in Catatonia 85 contrast to the normal results found in catatonic patients who also generally have excellent recall of events that took place when they were catatonic. Nonconvulsive Status Epilepticus (36–39) Patients with absence or partial complex status epilepticus (SE) can present in a state that is clinically indistinguishable from catatonia. They are immobile, mute, unresponsive, often rigid, and unable to eat, drink, or cooperate with an examination. Myoclonic jerking, automatisms, or semi- purposeful movements, eyelid fluttering or rhythmic twitching of the eyes, face, or jaw, if present, can be clues to the diagnosis. The EEG, which we believe is an important investigative tool in the diagnostic work-up of catatonia, is crucial in distinguishing nonconvulsive SE from catatonia. Stiff-Man Syndrome (40,41) This uncommon condition, now referred to as “stiff-person syndrome” (SPS), appropriately so given that women are affected more often than men, is very frequently misdiagnosed as a psychiatric condition such as conversion or catatonia. The clinical presentation of SPS often appears bizarre and exaggerated. Exacerbations or episodes can be triggered by emotional stress and the disorder is responsive to BZPs. Patients with SPS develop extensor muscle spasms of the spine and legs that can render them immobile and cause catatonia-like dystonic “posturing.” The rigidity can be extremely severe and has been described as “stony,” “board-like,” and “rock-hard” (40). In contrast to the mute state of catatonic patients, however, these individuals will indicate that they are in extreme pain. It now appears that SPS may be an autoimmune disease resulting from antibodies directed against glutamic acid decarboxylase, the rate-limiting enzyme in the production of γ-aminobutyric acid (GABA) (42). Other autoimmune diseases such as diabetes and thyroiditis often afflict these individuals and in this respect, the medical history can alert one to the possible presence of the condition. The diagnosis of SPS is strongly supported by the presence of high serum levels of glutamic acid decarboxylase antibodies. The EEG in these patients will be normal and electomyographic studies will typically show continuous motor unit activity (40). EXAMINATION AND INVESTIGATION OF THE CATATONIC PATIENT The very nature of catatonia means that the patient is unable to cooperate with many aspects of a physical examination, especially a detailed neurological assessment. The parts of the neurological exam that can usually be carried out on the catatonic patient and that can be helpful in differentiating catatonia from other conditions, include the pupillary reaction, ocular movements, the corneal reflex, reaction to pain, the presence of drooling, blink response to threat, reactions to light or sound, frontal release signs, assessment of tone, deep tendon reflexes, and the plantar responses (29). All patients with catatonia should have an EEG. Frequent determination of vital signs can assist in the early detection of infection or incipient NMS. In uncomplicated catatonia, patients are afebrile and normotensive, although they often have tachycardia. Hematological investigations should include a complete blood count, blood urea nitrogen, creatinine, muscle and hepatic enzymes, electrolytes, blood glucose, and urinalysis, all of which should be normal unless the patient is markedly dehydrated or has an intercurrent infection or illness. Fever and an elevated white blood cell count in a patient with apparent catatonia should raise concerns about possible encephalitis or, if antipsychotics have been administered, NMS. COMPLICATIONS OF CATATONIA Catatonia can be associated with considerable morbidity, particularly if the immobility, poor oral intake, and muscle rigidity are prolonged and develop in a patient who is alone and in a warm environment. Complications that can quickly arise under such circumstances include dehydration, mal- nutrition, pneumonia, deep vein thrombosis, pulmonary embolism, skin breakdown, contractures, and acute renal failure (43). 86 Rosebush and Mazurek There is evidence that patients are at increased risk of developing NMS if antipsychotic drugs (APDs) are administered when they are catatonic (7,44,45). This is of considerable clinical relevance, given that catatonia affects approx 10% of patients hospitalized with acute psychiatric illness, the majority of whom are psychotic and in apparent need of APDs. The three patients on our inpatient unit who have developed NMS over the past 15 years were all catatonic prior to the administration of APDs. How then, is one to proceed with such patients? We recommend treating the catatonia with BZPs before APDs are prescribed. If this proves ineffective, electroconvulsive therapy (ECT) may be considered. It is our experience that once the catatonic syndrome has resolved, APDs may be introduced without undue risk of precipitating NMS. If a patient is judged to require APDs prior to resolution of the catatonia, we feel it is prudent to maintain BZPs during treatment with the APDs. Lethal or malignant catatonia (4) is an extreme form of excited catatonia that bears remarkable simi- larity to NMS both in its clinical features and high mortality if untreated. Indeed it may be indistinguishable except for the absence of antecedent use of APDs and the history of rapidly increasing psychomotor activity. Early descriptions indicate that these patients develop psychosis, followed by uncontrollable motor activity. Fever, diaphoresis, dehydration, tachycardia, labile blood pressure, alterations in consciousness, and eventually cardiovascular collapse ensue. TREATMENT In 1990, following a number of individual case studies (46–48), we reported that catatonia of the retarded type is exquisitely responsive to the administration of low-dose BZPs (11). These agents have a paradoxical effect of rapidly activating the mute, immobile patient, making the treatment of catatonia one of the more memorable clinical experiences, akin to that of treating Parkinson’s disease with L-dopa. Within a matter of hours of receiving the medication, a patient who previously may have been mistaken for dead, begins to move, talk, and eat. Yassa (49) described 10 patients, all of whom responded to low-dose lorazepam either by mouth or intramuscular injection. Seven had dramatic resolution of their catatonic state within hours of receiving BZP treatment. Immobility or severe psychomotor retardation, mutism, and withdrawal with refusal to eat or drink were the most common clinical features. Ungvari et al. (50) used low-dose lorazepam to treat 18 patients with catatonia that had been present for 2–22 days. Fifteen (83%) of these patients had virtually complete resolution of their catatonic state within hours. A literature review of 72 episodes of catatonia treated with BZPs (51) found a response rate of almost 80%. More recently, Lee et al. reported that 16 of 24 catatonic patients (73%) remitted fully with either lorazepam or clonazepam. In our ongoing prospective study that now involves 165 episodes of catatonia, predominantly of the retarded type (52), we have continued to observe a robust response in approx 85% of patients following treatment with lorazepam. In our study, all catatonic patients admitted to the psychiatry unit are observed for 24 hours prior to treatment, in order to exclude those who recover spontaneously. The median duration of the catatonia has been 3 days with a range of 1–180 days. Catatonia had been present for 10 days or more in 19 cases. The one diagnostic subgroup that does not enjoy a robust response to lorazepam is schizophrenia. In our prospective study, patients suffering from an underlying schizophrenic process responded 20–30% of the time, compared with an overall response rate of approx 90% in the other diagnostic subgroups, including those with underlying medical and neurological disorders (53). Ungvari et al. (54) observed a similar lack of responsiveness in catatonic patients with underlying schizophrenia. In a randomized double-blind, placebo-controlled, crossover study of lorazepam 6 mg per day for 6 weeks in 17 patients with chronic schizophrenia and chronic catatonia, no significant differences were found on any measure between those who received lorazepam or those who received placebo, in contrast to the 83% response rate to lorazepam they had observed in their original study of patients with acute catatonia. Lee et al. (13) reported that patients who responded only partially to lorazepam were invariably schizophrenic. This poor responsiveness to BZPs, in patients with underlying schizophrenia, may be related to the nature of the core illness with more prominent psychosis and less anxiety, the nature Catatonia 87 of the particular catatonic symptoms that were present at the time of treatment or the chronicity that characterizes both the catatonia and the primary illness. In the unresponsive schizophrenic patients studied by Ungvari et al., the typical catatonic signs included posturing, grimacing, stereotypy, and waxy flexibility; whereas in our series, in which there has been a high rate of response, the most frequent findings were immobility, mutism, staring, and withdrawal. It is well recognized that chronic symptoms of any kind generally respond less robustly to treatment than do acute symptoms. The less robust effect of BZPs observed in patients with chronic catatonia should not, however, preclude a trial of therapy. Gaind et al. (55) reported success in a 29-year-old man with chronic schizophrenia and chronic severe catatonia, who responded slowly but completely to monotherapy with low-dose lorazepam. This patient went from a state of prolonged and profound incapacitation that lasted 5 years and required continuous hospitalization, to semi-independent living, which he had maintained at 8-year follow-up. We have also reported the effectiveness of lorazepam in the treatment of a long-standing catatonic state in a patient with late-onset Tay Sachs disease (56). The ideal treatment of any condition is one that is easily administered, produces a rapid response, and has a wide margin of safety. BZPs meet all three requirements and can be given orally, intramuscularly, or intravenously (57). Low-dose lorazepam, which has been the most well studied BZP, produces a response within 1–3 hours and has a wide margin of safety even at high doses. Its speed of action decreases the time during which a patient is at risk of the complications that result from poor oral intake and immobility. The rapid response of catatonia to BZPs results in patients being able to cooperate with a full examination and any required investigations. It could be argued that, unless there is a clear contraindication to the use of BZPs, all mute, rigid, and immobile patients should be given a trial of this agent as a way to differentiate catatonia from clinically similar conditions. Even if another primary diagnosis is suspected, the patient may also be catatonic (58). Davis and Borde (59) described a 12-year-old boy who presented with immobility, mutism, severe rigidity, double incontinence, reduced blinking, way flexibility, and “posturing.” He was eventually diagnosed with Wilson’s disease and treated with penicillamine. His “catatonia,” however, improved little over 2 months until diazepam was administered. Within 2 days he was eating, speaking, and walking. To take another case in point, an 86-year- old woman was sent to the hospital from her nursing home with a tentative diagnosis of rapidly deteriorating Parkinson’s disease. Over 1 month she had become mute, immobile, rigid, and appeared frightened. We considered catatonia in the differential and prescribed lorazepam 1 mg. Within 1 hour of the first dose, the patient had a “miraculous” full recovery from her worsening “parkinsonism.” Although ECT is also an effective treatment of catatonia, it is a more complicated intervention and requires clear consent from either the patient or a designated surrogate. By virtue of their mutism and withdrawal, catatonic patients are unable to engage in a discussion of ECT or consent to its administration. Surrogate consent is usually much more difficult to obtain for ECT because of the associated stigma. Furthermore, surrogate caregivers may not have full knowledge of the patient’s medical history or medication use, making it difficult for them to be fully apprised of the risk–benefit ratio of anesthesia and the procedure itself. Often, a knowledgeable family member or caretaker is not available. Given that an initial dose of lorazepam is completely effective in quickly resolving catatonia in 85% of cases, it should be the first line of treatment. ECT should be considered after several days of lorazepam administration have been ineffective and the conditions for accepting consent from a fully competent, informed surrogate have been met (60). In the case of lethal catatonia, high doses of a BZP or ECT are the safest and most effective forms of treatment (60). RECOMMENDED TREATMENT REGIMEN We recommend that most patients be treated initially with 2 mg of lorazepam intramuscularly. In the young, elderly, obese, or medically compromised patient, we suggest reducing each dosage to 88 Rosebush and Mazurek 1 mg. The possibility that lorazepam may be more effective than other BZPs such as Oxazepam (48,61) may relate to the fact that GABA-A receptors are made up of varying combinations of 16 different subunits, resulting in some diversity among the GABA-A receptors themselves. The different BZPs may differentially affect these various GABA-A receptor subtypes, thereby potentially producing “pharmacological diversity” and heterogeneity of response (62). Whereas lorazepam can be given orally or sublingually, patient negativism is often manifested in a refusal to open the mouth, making oral administration impractical. Even when the patient appears to have accepted the tablet, it is often difficult to ascertain whether it has been ingested. The dehydration that is often present further reduces a patient’s ability to absorb or swallow medication. For all these reasons, intramuscular injection is the preferred route of administration for the initial dose. Response to the initial injection usually occurs within 1–3 hours. If there is no response or only minimal change, the same dosage should be repeated after 3 hours and again after another 3 hours if the catatonia has not resolved. Although the intravenous route is effective, as well as practical if a patient is being rehydrated with intravenous fluids, the duration of action is very short unless the medication is given in the form of a continuous infusion. BZPs not only bring about rapid resolution of the presenting catatonic state but seem to be required for maintenance of this effect until treatment of the primary disorder has been instituted. Discontinuation, immediately after the initial response, appears to put the patient at high risk of relapse. Once treatment of the patient’s underlying illness has been established, BZPs can be tapered and discontinued in most cases. We have encountered a small subset of patients in whom long-term use of BZPs appears to be required. These individuals have responded robustly to acute treatment but appear to relapse into a catatonic state whenever the drugs are discontinued, despite the use of anti- depressant medication or mood stabilizers. They appear to require long-term maintenance treatment with a BZP, raising the interesting question of whether catatonia in such cases might be considered a diagnosis in its own right and not simply a manifestation of another underlying disorder. COMPLICATIONS OR SIDE EFFECTS OF BZP TREATMENT Unsteadiness of Gait Following BZP Administration This is a concern in the elderly or anyone with an underlying gait disturbance, especially when the therapeutic goal of treatment is motoric activation. Staff should be advised that treatment often takes effect rapidly and consideration should be given to using bed-side rails, making a walker available, and providing close supervision for vulnerable patients during the initial period of mobilization when they are up and about. Respiratory Depression With BZP Use BZPs depress alveolar ventilation and reduce hypoxic drive. These effects are more marked in patients with chronic obstructive pulmonary disease (COPD). At lower dosages, BZDs may worsen any sleep-related respiratory disorders like obstructive sleep apnea secondary to their effects on the upper airway musculature. This may result in reduced ventilatory response to carbon dioxide. One should, therefore, use a lower dosage of lorazepam and carry out more frequent monitoring of vital signs in any catatonic individual who is obese or known to have COPD or sleep apnea. Measurement of oxygen saturation is appropriate in these situations and provides an easy, noninvasive, and readily available tool for monitoring. Precipitation of Agitation or Excitement Following Treatment BZPs have the potential to disinhibit behavior, although this is felt to occur uncommonly. Patients with retarded catatonia, especially those with an underlying bipolar affective disorder, may become markedly agitated or excited following resolution of the catatonia. This can be associated with destruc- tion of property and aggression toward others. It is, therefore, important for staff to be aware of, and prepared for, this eventuality. This would include maintaining the patient on close observation, being Catatonia 89 [...]... Medical aspects of the persistent vegetative state (1) N Engl J Med 1994 ;33 0: 1499–1508 35 Kennard C, Illingworth R Persistent vegetative state J Neurol Neurosurg Psychiatry 1995;59 :34 7 34 8 36 Walls MJ, Bowers TC, Dilsaver SC, Swann AC Catatonia associated with depression secondary to complex partial epilepsy J Clin Psychiatry 19 93; 54: 73 37 Kirubakaran V, Sen S, Wilkinson CB Catatonic stupor: unusual manifestation... treatment issues J Clin Psychiatry 1995;56 :34 7 35 3 57 Rosebush PI, Hildebrand AM, Mazurek MF The treatment of catatonia: benzodiazepines of ECT? 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