INTRODUCTION Catatonia is a behavioral syndrome marked by an inability to move normally, and is associated with many underlying psychiatric, neurologic, and general medical disorders [ 1 ]. Within psychiatric nosology, catatonia is recognized as a descriptive modifier of mood episodes (analogous to psychosis), a subtype of schizophrenia, and a disorder due to a general medical condition [ 2,3 ]. Recognizing catatonia is important because it may be caused or exacerbated by treatment of the underlying disorder (eg, antipsychotic drugs used for mood or psychotic disorders may worsen catatonia)CLINICAL FEATURES The core feature of catatonia is a motor disturbance in which patients are unable to move normally despite full physical capacity in the limbs and trunk [ 1 ]. Starting, stopping, and planning movement can be impaired, and motor behavior may be repetitive, purposeless, impervious to external stimuli, and contrary to intent [ 10 ]. Small prospective studies of catatonia and case series have found that catatonia is marked by heterogeneous signs that are observed or elicited ( table 1 and table 2 ); the most common are [ 1,2,10,25 ]: Immobility (hypokinesis or akinesis) Mutism Stupor (decreased alertness and response to stimuli) Negativism (resistance to all instructions or all attempts to be moved) Waxy flexibility Posturing (catalepsy) Excessive motor activity (excitement) Staring Echophenomena (repeating another persons words or movements) Onset of catatonia can be either acute or insidious [ 1,8 ]. Following remission, some patients cannot recall their experience during the episode, whereas others describe an awareness of their activity and the inability to communicate [ 26 ]. Catatonia occurs in patients who are severely ill with an underlying psychiatric or general medical disorder, and is thus analogous to delirium [ 2,27 ]. (See 'Underlying disorders' below.) Subtypes There are several subtypes of catatonia, based upon the specific nature of the movement disturbance and other associated features [ 1,28,29 ]. The three principal forms in order of incidence are retarded, excited, and malignant. While a factor-analytic study of 314 psychotic patients supported separation of retarded and excited catatonia as subtypes [ 30 ], patients can exhibit signs of both subtypes concurrently [ 31 ]. Subtypes are not necessarily stable during a catatonic episode, and patients may transition from retarded to excited catatonia or vice versa [ 32,33 ]. In addition, retarded and excited catatonia can each progress to malignant catatonia; alternatively, malignant catatonia can occur de novo. Retarded catatonia The retarded form of catatonia is characterized by mutism, inhibited movement, posturing, negativism, and staring [ 1,9 ]. Postures may be mundane (eg, sitting or standing in the same position for hours) or unusual (eg, head raised above the bed as if on a pillow). Response to voice and noxious stimuli is decreased. Although speech and spontaneous movements are reduced, some patients appear to be alert and aware of the environment. In more severe cases, eating and drinking may cease and stupor and incontinence may occur [ 33 ]. Malignant catatonia Malignant catatonia (also called lethal catatonia) is a life-threatening condition that is characterized by fever (less likely in older patients), autonomic instability (labile or elevated blood pressure, tachycardia, tachypnea, and diaphoresis), delirium, and rigidity [ 1,15 ]. The syndrome is typically fulminant and progresses rapidly within a few days [ 34 ]. Common but nonspecific laboratory findings include leukocytosis, elevated creatine kinase, and low serum iron [ 15,35 ]. Signs of malignant catatonia overlap with signs of the neuroleptic malignant syndrome (NMS). (See 'Differential diagnosis' below.) Excited catatonia Excited catatonia is characterized by excessive and purposeless motor activity in both the upper and lower limbs (hyperkinesis), restlessness, stereotypy, impulsivity, frenzy, and combativeness, [ 1,9 ]. Delirium may occur in severe cases, and the excess motor activity may cause self-injury or harm to others. Other forms Other, infrequent forms of catatonia may occur [ 1 ]. One example is periodic catatonia, which is marked by waxing and waning of catatonic signs [ 28 ] or periods of retarded catatonia alternating with excited catatonia [ 1 ]. Subtypes There are several subtypes of catatonia, based upon the specific nature of the movement disturbance and other associated features [ 1,28,29 ]. The three principal forms in order of incidence are retarded, excited, and malignant. While a factor-analytic study of 314 psychotic patients supported separation of retarded and excited catatonia as subtypes [ 30 ], patients can exhibit signs of both subtypes concurrently [ 31 ]. Subtypes are not necessarily stable during a catatonic episode, and patients may transition from retarded to excited catatonia or vice versa [ 32,33 ]. In addition, retarded and excited catatonia can each progress to malignant catatonia; alternatively, malignant catatonia can occur de novo. Retarded catatonia The retarded form of catatonia is characterized by mutism, inhibited movement, posturing, negativism, and staring [ 1,9 ]. Postures may be mundane (eg, sitting or standing in the same position for hours) or unusual (eg, head raised above the bed as if on a pillow). Response to voice and noxious stimuli is decreased. Although speech and spontaneous movements are reduced, some patients appear to be alert and aware of the environment. In more severe cases, eating and drinking may cease and stupor and incontinence may occur [ 33 ]. Malignant catatonia Malignant catatonia (also called lethal catatonia) is a life-threatening condition that is characterized by fever (less likely in older patients), autonomic instability (labile or elevated blood pressure, tachycardia, tachypnea, and diaphoresis), delirium, and rigidity [ 1,15 ]. The syndrome is typically fulminant and progresses rapidly within a few days [ 34 ]. Common but nonspecific laboratory findings include leukocytosis, elevated creatine kinase, and low serum iron [ 15,35 ]. Signs of malignant catatonia overlap with signs of the neuroleptic malignant syndrome (NMS). (See 'Differential diagnosis' below.) Excited catatonia Excited catatonia is characterized by excessive and purposeless motor activity in both the upper and lower limbs (hyperkinesis), restlessness, stereotypy, impulsivity, frenzy, and combativeness, [ 1,9 ]. Delirium may occur in severe cases, and the excess motor activity may cause self-injury or harm to others. Other forms Other, infrequent forms of catatonia may occur [ 1 ]. One example is periodic catatonia, which is marked by waxing and waning of catatonic signs [ 28 ] or periods of retarded catatonia alternating with excited catatonia [ 1 Partial, temporary relief of signs 5 to 10 minutes after IV administration of lorazepam is consistent with a diagnosis of catatonia [ 1,28 ]. If there is no change and the patient remains awake with stable vital signs, a second dose is given, and the patient is examined within 5 to 10 minutes, although observation can continue for longer periods. A negative response does not rule out catatonia, and occurs in approximately 20 percent or more of catatonic patients. Reasonable alternatives to lorazepam are available. A randomized trial that compared a single dose of oral oxazepam 60 mg with a single dose of oral lorazepam 2 mg in 17 patients found that the benefit of each drug was comparable [ 44 ]. In case reports, oral zolpidem 10 mg was useful

DIAGNOSIS A minimum of two to four signs for at least several hours is required to make the diagnosis of catatonia ( table 1 and table 2 ) [ 1,11,25,38 ]. However, neither the number of catatonic features required for the diagnosis nor their duration is established, and no one sign is pathognomonicTreatment:Treatment algorithm First-line treatment for catatonia is a benzodiazepine or electroconvulsive therapy (ECT), depending upon the subtype of catatonia, clinical urgency, and availability of treatments [ 1,13,27-31 ]: For patients with malignant catatonia, we recommend a benzodiazepine plus immediate preparation to administer ECT as soon as possible. If the benzodiazepine provides a substantive response during the first 24 to 48 hours, it can be continued in lieu of ECT. For patients with retarded or excited catatonia, we recommend treatment with a benzodiazepine ( lorazepam is used most often). No randomized trials have evaluated benzodiazepines or ECT for acute catatonia. However, prospective open-label studies, cases series, and retrospective studies suggest that benzodiazepines alone, or benzodiazepines followed by ECT, lead to recovery in approximately 60 to 80 percent of patients [ 1,13,24,32,33 ]. Treatment guidelines from the American Psychiatric Association, United Kingdom National Institute for Health and Clinical Excellence, and World Federation of Societies of Biological Psychiatry recommend treating catatonia with either a benzodiazepine or ECT, depending upon the clinical urgency [ 27-31 ]. A review of open-label studies, case series, and case reports found that treatment of catatonia is the same regardless of the underlying disorder [ 12 ]. Malignant catatonia ECT is first-line treatment for patients with malignant catatonia [ 1,4,13,24 ]. We recommend that clinicians concurrently start a benzodiazepine and the process of obtaining informed consent and medical consultation for ECT. If the patient does not measurably respond to a benzodiazepine within the first day or two, ECT should commence. Reviews of case reports have found that mortality for progressive malignant catatonia increases if ECT does not begin within five days of symptom onset [ 24,34 ]. Another review of case reports found that in patients with malignant catatonia, response to ECT occurred in 9 of 11 patients (89 percent), whereas response to a benzodiazepine occurred in 2 of 5 patients (40 percent) [ 13 ]. During the first week, daily ECT may be needed. The safety and administration of benzodiazepines and ECT are discussed separately. (See 'Benzodiazepine safety and administration' below and 'Electroconvulsive therapy safety and administration' below.) Retarded or excited catatonia Based upon prospective open-label studies and case series, we recommend initial treatment with a benzodiazepine for patients with retarded or excited catatonia [ 1,13 ]. Lorazepam has been studied most frequently [ 1,10,13,32,35,36 ], but case reports also describe successful treatment with diazepam , clonazepam , clorazepate , midazolam , and alprazolam [ 37-46 ]. In a review of case reports of 104 catatonic episodes that were treated with benzodiazepine monotherapy, 70 percent remitted; among the 72 episodes treated with lorazepam, 79 percent remitted [ 13 ]. Other reviews estimate that 60 to 80 percent of patients with catatonia respond to lorazepam monotherapy [ 4,37,47 ]. Although amobarbital was significantly more effective than placebo in a randomized trial [ 48 ], most authorities consider benzodiazepines as first-line pharmacotherapy because they are generally effective and safer than barbiturates [ 1,3,4 ]. In addition, benzodiazepines have been studied more often, are familiar to clinicians, and an antagonist ( flumazenil ) is available. (See 'Benzodiazepine safety and administration' below.) Clinical factors may be associated with response to a benzodiazepine. Successful benzodiazepine treatment may be more likely in patients with a significant reduction of catatonic signs after the first dose of lorazepam or other benzodiazepine (positive lorazepam challenge test) [ 34 ]. Acutely catatonic patients with an underlying mood disorder may respond more favorably to a benzodiazepine than schizophrenic patients [ 11,49 ]. In addition, benzodiazepines at low doses do not appear to benefit chronic catatonia in schizophrenic patients. A randomized trial compared adjunctive lorazepam with placebo for treating slow-onset, long-standing (4 years) catatonic signs in severely disabled and treatment-resistant chronic schizophrenic patients; lorazepam 6 mg daily provided no benefit [ 50 ]. It is not clear whether a longer duration of catatonia prior to treatment is associated with a poorer response to treatment, due to contradictory study results [ 11,32 ]. Age, sex, and the number and pattern of catatonic signs do not appear to be associated with response to a benzodiazepine [ 4,9,24,32 ]. The lorazepam challenge test is discussed separately. (See "Catatonia in adults: Epidemiology, clinical features, assessment, and diagnosis", section on 'Lorazepam challenge' .) For patients with retarded or excited catatonia that does not respond to a benzodiazepine, ECT is the treatment of choice [ 1,4,24,32 ]. In addition, if the underlying cause of catatonia is a mood disorder, or for patients requiring a rapid treatment response, ECT is the most effective treatment option. Based upon open-label studies, case series, and retrospective studies, it is estimated that approximately 60 percent or more of catatonic patients achieve remission with ECT, including patients unresponsive to a benzodiazepine [ 4,27,32,33,35,51-53 ]. As an example, a review of case reports of 55 catatonic episodes that were treated with ECT alone found that 85 percent remitted [ 13 ]. A subsequent chart review of 27 catatonic patients treated with ECT found that 59 percent improved [ 33 ]. For patients with a mood disorder or acute psychosis, ECT can relieve both the catatonic syndrome and the underlying psychopathology [ 4,24 ]. (See 'Electroconvulsive therapy safety and administration' below.) There are no established predictors of response to ECT for patients with catatonia [ 3 ]. However, acutely catatonic patients with an underlying mood disorder may respond more favorably to ECT than schizophrenic patients [ 49 ], and ECT does not appear to benefit chronic catatonia in schizophrenic patients [ 54 ]. Benzodiazepine safety and administration Benzodiazepines are generally safe and well tolerated in this setting. At doses used for treating catatonia, benzodiazepines are not associated with respiratory depression in otherwise healthy adults. However, clinicians should be cognizant of concomitant drugs that can cause sedation or respiratory depression, eg, opioids. In addition, benzodiazepines cause varying degrees of motor incoordination and increase the risk of falls [ 10 ]. Benzodiazepines can be administered intravenously, intramuscularly, or orally ( lorazepam is available in all three formulations) [ 4,32 ]. Intravenous administration is preferred to assure adherence and rapid, complete absorption (intravenous access also permits administration of fluids for dehydration). Intravenous benzodiazepines should be injected or infused slowly. As patients improve, they should be switched to oral medication. Lorazepam has been studied most often, and is typically initiated at 1 to 2 mg three times per day. Close observation for a clinical response can substantiate the diagnosis of catatonia. The dose is then increased by 3 mg per day every one to two days, depending upon patient response, tolerability, 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 [ 1 ]. For patients with excited catatonia, lorazepam 1 to 2 mg is given at more frequent intervals until the patient is calm but awake.A more cautious approach is suggested for patients at risk of cardiorespiratory compromise or oversedation (eg, older, obese, or volume depleted patients; patients with cardiovascular or respiratory disease; patients receiving opioid analgesics). For patients with these risk factors, the initial dose may be reduced to 0.5 mg three times per day and closer monitoring provided [ 10,35 ]. (See "Catatonia in adults: Epidemiology, clinical features, assessment, and diagnosis", section on 'Lorazepam challenge' .) The duration of treatment required to achieve remission of catatonia with a benzodiazepine is typically 4 to 10 days [ 34 ]. The benzodiazepine is usually continued at the effective dose for three to six months to maintain recovery and is then slowly tapered and discontinued, although longer maintenance treatment may be necessary [ 55 ]. Additional information about the clinical use and pharmacology of benzodiazepines is discussed separately. (See "Sedatives and hypnotics abuse and dependence: Pharmacology and epidemiology" .) Electroconvulsive therapy safety and administration ECT is generally safe, even in patients whose general medical status is compromised [ 56 ]. However, safety concerns necessitate preprocedure medical consultation. ECT is typically administered with the same technique used for other indications. (See "Medical consultation for electroconvulsive therapy" and "Technique for performing electroconvulsive therapy (ECT) in adults" .) There are no absolute contraindications to ECT [ 57-61 ]. Underlying general medical conditions may increase the risk of adverse effects of ECT or general anesthesia, but modern ECT technique and preprocedure consultation to optimize the patients general medical status reduce these risks. As an example, catatonic patients with motor immobility and muscle damage are at increased risk for transient hyperkalemia associated with the muscle relaxant succinylcholine [ 3,12 ]. This increased risk is eliminated by using a nondepolarizing muscle relaxant (eg, rocuronium ) [ 62 ]. Electrode placement and other aspects of ECT technique for treating catatonia have not been standardized [ 12 ]. However, bilateral electrode placement and brief pulse current are generally preferred [ 1 ]. ECT is generally given three times per week on alternating days. However, clinical urgency may necessitate daily treatments for malignant catatonia until the patient is physiologically stable, which often occurs within two to five treatments [ 1 ]. At least six treatments are given regardless of the catatonia subtype to reduce the risk of sudden relapse. Most patients receiving ECT regardless of the indication remit with 6 to 12 treatments, but some patients may require 20 or more [ 56 ]. ECT is usually terminated after the acute catatonic episode has remitted, but one case report described maintenance ECT for a patient with recurrent catatonia [ 63 ]. Additional information about ECT is discussed separately. (See "Overview of electroconvulsive therapy (ECT) for adults" and "Technique for performing electroconvulsive therapy (ECT) in adults" .) Case reports describe catatonic patients who responded to ECT plus lorazepam [ 60,61 ]. The decision to continue a benzodiazepine during ECT is determined by the patients initial response to the medication and the modifications in ECT technique that are required. For patients with a partial but incomplete response to lorazepam, the drug may be continued during ECT to maintain the drugs therapeutic benefit. However, the benzodiazepine should be discontinued if it interferes with ECT (increases seizure threshold and shortens seizure duration) despite adjustments in the ECT technique. (See "Overview of electroconvulsive therapy (ECT) for adults", section on 'Concurrent medications' .) Other treatments Alternative treatments may be available for patients with catatonia who do not respond to benzodiazepines and either decline ECT or do not have access to it [ 4 ]. Case reports describe other treatments that were added to an existing pharmacotherapy regimen and may possibly be beneficial. These other treatments include carbamazepine [ 64 ], topiramate [ 65 ], valproate [ 66,67 ], zolpidem [ 4,68,69 ], memantine [ 70-73 ], and bromocriptine [ 74 ]. Amantadine has also been used, but has dopamine agonist activity that can potentially worsen an underlying psychosis [ 73 ]. Additional case reports describe treatment of catatonia with repeated transcranial magnetic stimulation [ 12 ]. LONG-TERM PROGNOSIS Although the long-term outcome of catatonia has not been rigorously studied, catatonia appears to have a generally favorable prognosis, especially the retarded and excited subtypes [ 4,75 ]. Long-term prognosis appears to be linked to the nature and severity of the underlying psychiatric or general medical disorder [ 3,24 ]. 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 [ 24 ]. However, catatonia may persist for years, particularly in patients with schizophrenia [ 50 ]. In addition, patients with malignant catatonia may be left with permanent morbidity (eg, cognitive deficits, apathy syndromes, and limb strictures), and death rates of up to 20 percent have been reported [ 34 ]. Case reports describe recurrent catatonic episodes [ 13,63 ]. One case series of five patients reported that the mean interval between consecutive episodes was 11 months (range 5 to 20 months) [ 76 ]. The motor signs were generally consistent across each patients two episodes. For cases with complete information, the same treatment worked in the two episodes