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Catatonia is not schizophrenia and it is treatable
SCHRES-07320; No of Pages 5 Schizophrenia Research xxx (2017) xxx–xxx
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Catatonia is not schizophrenia and it is treatable Francisco J. Appiani a,⁎, Gonzalo S. Castro b a
Program of Pharmacology, Direction of Teaching and Research, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina Fellowship in abnormal movements, Program of Abnormal Movements and Parkinson disease, Neurology Division, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina
b
a r t i c l e
i n f o
Article history: Received 26 March 2017 Received in revised form 20 May 2017 Accepted 25 May 2017 Available online xxxx Keywords: Catatonia Lorazepam Electroconvulsive therapy
a b s t r a c t Catatonia is a cluster of motor features that appears in many recognized psychiatric illnesses, that according to the DSM-5 it is not linked as a subtype to schizophrenia anymore. The classic signs are mutism, a rigid posture, fixed staring, stereotypic movements, and stupor, which are all part of a broad psychopathology that may be found in affective, thought, neurological, toxic, metabolic and immunological disorders. Despite the many etiologies, catatonia may be a life-threatening condition with a specific treatment. Benzodiazepines are the first line therapeutic option for catatonia, being lorazepam the first-choice drug. Eighty percent of the patients are relieved by the use of barbiturates or benzodiazepines, while in those who fail, an improvement is achieved by electroconvulsive therapy (ECT). With more than 60 years of use in catatonic patients, ECT has proven to be an effective and safe tool for the treatment of this frequent and sometimes forgotten syndrome. © 2017 Elsevier B.V. All rights reserved.
1. Introduction Psychomotor symptoms in psychiatric disorders have been a controversial issue in modern psychiatry. Karl Ludwig Kahlbaum (1828–1899) was the first psychiatrist to clearly associate psychomotor symptoms to psychiatric disorders. Since Kahlbaum's first description of catatonia there were many different positions about this entity (Caroff et al., 2004). Kahlbaum syndrome refers to the most common presentation of retarded catatonia, generally with a favorable outcome, named “Atonic melancholia”. According to his descriptions, the patient has a melancholic prodromal state, followed by impairment of thought, associated to choreiform movements that limit his ability to carry out voluntary movements (Fink and Taylor, 2003). Emil Kraepelin inserted catatonia as a subtype of his Dementia praecox classification. Despite the clinical reality of Catatonia syndrome, the inclusion in Dementia Praecox and then in Schizophrenia nearly erased the original concept of Kahlbaum's catatonia and remained associated to schizophrenia during many decades. As presented below, this situation was not only a nosography dilemma but it has therapeutic implications. Other authors like Karl Wernicke put Catatonia closer to neurology nosology. He was convinced that the whole pathology of mental patients consists of nothing else but the peculiarities of their motor behavior. He coined the term psychomotor disturbances referring to ⁎ Corresponding author. E-mail address: [email protected] (F.J. Appiani).
abnormalities of motion and speech which were independent from thought and will (Pfuhlmann and Stüber, 2001). Karl Leonhard and Karl Kleist were clinicians who continued and delineated Wernicke's ideas. They established a new nosology of what they called “endogenous psychosis” with emphasis in catatonic symptoms as “motility symptoms”. K. Leonhard described acute (and benign) catatonia (Cycloid Psychosis) separated from those chronic and refractory to treatment (systematic schizophrenias) (Teichmann, 1990). This clinical observation is relevant, because there are descriptions of treatment refractory patients in those with chronic catatonia presentations (Ungvari et al., 1999). Nowadays a group of scholars led by Fink et al. had been working in the recognition of catatonia syndrome as a different clinical entity. According to clinical and basic research, catatonia is a cluster of motor features that appears in many recognized psychiatric illnesses. The classic signs are mutism, a rigid posture, fixed staring, stereotypic movements, and stupor, which are all part of a broad psychopathology that includes most of the major diagnostic classes (Bleckwenn, 1930). Psychomotor symptoms may be found in affective, thought, neurological, toxic, metabolic and immunological disorders. Clinical forms may be transient or “benign”, with a good response to specific treatment, and it can also have a malignant course like in Stauder's catatonia, neuroleptic malignant syndrome and toxic serotonin syndrome (Fink and Taylor, 2003). It is necessary to highlight that the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM 5), published by the American Psychiatric Association, removed the diagnosis of catatonic schizophrenia. Instead catatonia is a specifier for schizophrenia as it is for mood disorders.
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Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030
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DSM 5 also added catatonia as a specifier for brief psychotic disorder, schizophreniform disorder, schizoaffective disorder and in substanceinduced psychotic disorder. Before DSM-5, Catatonia was restricted to sections of the psychotic, affective, or medical disorders in adult patients. During the last few years, progress has been made in delineating this syndrome in children and adolescents across a wide range of disorders. Dirk Dhossche and his group have showed that catatonia may be present in children and adolescents with autistic, developmental, and tic disorders, and in its idiopathic form, with a similar response to treatment like in adult patients. Finally DSM-5 included catatonia as a specifier in autistic spectrum disorders. The study of pediatric catatonia supports a home of its own for catatonia in DSM-5. (Dhossche et al., 2010a). (Dhossche et al., 2010b). Catatonia can also be diagnosed as a consequence of medical condition and as catatonia not otherwise specified NOS (American Psychiatric Association, 2013). In summary, catatonia is a treatable syndrome secondary to many etiologies that it is not linked as a subtype to schizophrenia anymore. 1.1. Treatment of catatonic syndrome Despite the many etiologies, catatonia has a specific treatment. Today, benzodiazepines are among first line treatment options for catatonia. The effectiveness of these compounds in the treatment of catatonic syndrome was first reported in 1930. W. J. Bleckwenn found that intravenous administration of amobarbital sodium produced a transient response in three catatonic patients (Bleckwenn, 1930). Barbiturates, according to a study done in 1992 (McCall et al., 1992), have a response rate of 50% in patients with catatonia, but due to its narrow therapeutic index they are not used anymore. Today, benzodiazepines are considered as an alternative with higher safety margins and are the first line treatment for this clinical entity. 1.2. Benzodiazepines Though several hypotheses have been proposed, the molecular mechanism of catatonia remains unknown. Given the efficacy of BZD (a GABA-A agonist), in relieving catatonia, hypoactivity at GABA-A receptors was one of the most discussed molecular mechanisms involved in the pathogenesis of catatonia (Northoff et al., 1999). Lorazepam is used at doses between 8 and 24 mg daily (https:// dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype = all&query = lorazepam, 2017), and is generally well tolerated without causing sedation, especially when daily incremental doses are performed. In case a higher dosage is chosen, the patient should be monitored for excessive sedation, which tends to occur earlier than respiratory compromise (Sienaert et al., 2014). Most authors suggest starting lorazepam at 1–2 mg every 4 to 12 h so as to avoid sedation (Daniels, 2009), and response is usually seen within 3–7 days, although might be gradual and slow. It appears certain benzodiazepines are more effective for catatonia, and thus lorazepam is accepted to be a first-choice drug, with highest frequency of use. Successful use of diazepam, oxazepam or clonazepam has also been reported (Dhossche et al., 2014) (Table 1). 1.3. Indications and efficacy The dramatic experience that established lorazepam as an effective drug for catatonia took place in 1983, when Gregory Fricchione described the rapid relief of neuroleptic malignant syndrome (NMS) by intravenous lorazepam at Massachusetts General Hospital. After various treatment options failed to produce any improvement, intravenous lorazepam in 2-mg doses was administered. NMS tended to resolved within a day, with some symptoms resolving within hours.
By 1996, a systematic study established the lorazepam sedative test as a diagnostic verification of catatonia (Bush et al., 1996a).The patient should be first examined for catatonic sigs, and then 1 or 2 mg of lorazepam should be administered intravenously. After 5 min, a re-examination of the patient must be done, and a second dose should be given in case no changes were observed (Bush et al., 1996b). The authors suggested as a clinical guide that a positive response to treatment may be considered when a reduction of at least 50% of catatonic signs and symptoms are observed using the Bush Francis catatonia Rating Scale (BFCRS) standardize rating scale, which usually occurs within 10 min (Fink and Taylor, 2003) unless the administration is via intramuscularly or per os, when the interval should be around 150 and 300 min respectively (Bush et al., 1996b). Nowadays treatment with lorazepam is considered highly effective, easy and safe, and more than 80% of the patients are relieved by the use of barbiturates or benzodiazepines, while in those who fail, an improvement is achieved by ECT (Bush et al., 1996b; Fink and Taylor, 2003). This was described using high doses of lorazepam (6–16 mg/day) for 3–5 days, but in some cases dosages up to 30 mg/day may be necessary (Fink and Taylor, 2009). Hung et al. reported remission rates as high as 79% in seven catatonic patients suffering from major depression (Hung and Huang, 2006), while in another major study (n:107) two thirds responded but only half of them remitted (Tibrewal et al., 2010). According to Lin Chin-Chuen, describing intramuscular lorazepam or intravenously diazepam response in 68 instances of relapses and recurrences of catatonia, a full recovery was shown in most instances (79.4%) (Lin et al., 2016). There is no consensus on how long benzodiazepines should be continued, and generally they are maintained until the underlying illness has remitted. Relapse into a catatonic state can occur if benzodiazepines are discontinued before the underlying disorder is resolved (Rasmussen et al., 2016; Rosebush et al., 1994). 1.4. Poor outcome predictors Several studies have shown that benzodiazepines are effective on acute catatonia and in those cases of retarded catatonia related to diverse psychiatric, neurologic or medical disorder, but less when associated with schizophrenia. In a 5-year follow-up study, Beckmann et al. found benzodiazepines ineffective in the treatment of chronic catatonic schizophrenia (Beckmann et al., 1992), and similar outcomes were published in a randomized double-blind, placebo-controlled trial in 18 patients with chronic catatonia in schizophrenia (Ungvari et al., 1999). The poorer prognosis in patients with schizophrenia under treatment with lorazepam may be related to the chronicity of symptomatology, or it may suggest a distinct underlying pathophysiology, perhaps reflecting the prominence of psychosis affecting their motor behavior, like in systematic schizophrenias described by Karl Leonhard (Beckmann et al., 1992; Leonhard, 1986; Rasmussen et al., 2016; Rosebush et al., 1994). According to Fink, prognosis is particularly favorable when catatonic syndrome is dominated by hyperactivity, rapid and pressured speech, stupor and lability of mood, as well as the history of a previous episode with complete recovery, rapid onset of the catatonic state and good social functioning before the episode (Fink, 2001; Fink and Taylor, 2003). Table 1 Rates to response to lorazepam treatment in catatonic patients with various underlying diagnoses22. Diagnosis
Patients responding (%)
Bipolar disorders (n = 31) Unipolar depression (n = 30) Other psychoses (n = 24) Medical/neurological conditions (n = 11) Schizophrenia (n = 22)
97 93 92 82 59
Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030
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A higher number of episodes were recognized as a condition to worse prognosis according to Urstein, in a monograph published in 1912 (Urstein, 1912). László Meduna recognized a longer illness duration to predict a worse outcome on eleven patients (Gazdag et al., 2009) and so did Tibrewal et al. when analyzing 107 inpatients, who included as predictors of poor response the presence of mutism, third-person auditory hallucinations and ‘made phenomena’ (in which the individual feels he is being made to do something) (Tibrewal et al., 2010). 1.5. Zolpidem Zolpidem is a positive allosteric modulator of GABA-A receptors and was first described to be effective by Mastain as a treatment of a catatonic patient who was previously not responsive to benzodiazepines nor ECT (Mastain et al., 1995; Rascle et al., 1997). Moreover, he continued to demonstrate its efficacy in a larger group of patients (seven patients), with a mean response starting within 15–30 min and lasting between 2 and 5 h. Although this short-last acting may lead scientific community to consider it an impractical option, zolpidem was shown to be effective even after treatment with benzodiazepines and/or ECT had failed according to a few case reports, and what is more, longterm treatment has also been described, as it reduces risk of respiratory depression. Although evidence on zolpidem appears to lack well design, controlled studies with numerous patients, the diagnostic and therapeutic test with zolpidem seems to be a credible alternative to increasing lorazepam doses (Cottencin et al., 2007; Thomas et al., 1997). 10 mg of zolpidem is first administered per os and after 30 min the patient is re-examined. It is considered a positive response when a reduction of at least 50% of the BFCRS-score is observed. 2. Electroconvulsive therapy 2.1. Indications, safety and efficacy When benzodiazepines and other pharmacological treatments fail, electroconvulsive therapy (ECT) is the next step (Table 2). Electroconvulsive therapy is one of the most controversial therapeutic approaches in psychiatry and is the treatment of choice when benzodiazepines have failed. It is also indicated in cases when a decisive and rapid response is required like in malignant catatonia (with high fever, and dysautonomia). Catatonia may be a life-threatening condition, with medical consequences as thrombosis, pulmonary embolism, and eventually death. In malignant and prolonged cases, patients can develop infections, especially pneumonia. Patients with catatonia are three times more likely to die than age-matched individuals in the general population (Fink and Taylor, 2003). If we consider a risk-benefit balance, ECT is the preferred treatment of catatonia in those patients who have no response to benzodiazepines. It is safe and effective, even in the medically compromised, the elderly,
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and in all trimesters of pregnancy (Anderson and Irving, 2009; Turek and Hanlon, 1977). ECT has no absolute contraindication to its use, making it the preferred treatment for catatonia, of any severity, in the widest range of patients, and with virtually any comorbidity when pharmacological treatment failed (Fink and Taylor, 2003; Turek and Hanlon, 1977). The efficacy of ECT in catatonia is generally acknowledged, even in the absence of randomized controlled evidence (Greenberg and Charles, 2005). Response rates in ECT are not systematically studied, but its efficacy is described in hundreds of case reports and some small studies. Hawkins et al. reported an 85% (47/55) of complete response rate (Hawkins et al., 1995). Hatta et al. in a sample 50 consecutive patients with catatonic symptoms admitted to a university hospital during a 32-month period, found a response rate to ECT of 100% (Hatta et al., 2007). In a review of 121 publications made by Van der Wuff et al., no negative studies were found regarding efficacy (Van der Wurff et al., 2003). It is important to consider that there may be a bias regarding the efficacy of ECT because it is not frequent to publish negative results of medical treatments. Table 3. ECT has also shown efficacy in malignant catatonia (neuroleptic malignant syndrome, Stauder's catatonia and in toxic serotonin syndrome). The delay in applying ECT in malignant catatonia increases medical complications and mortality. According to Fink et al., malignant catatonia cases should be treated within the first five days of hospital admission (Fink and Taylor, 2003). 2.2. NMS as a catatonia subtype Based on clinical symptomatology, course, and the treatment response, NMS must be viewed as a subtype of catatonia (Fink, 1996). NMS is a malignant form of catatonia triggered by neuroleptics with many treatment options, among which dantrolene, bromocriptine and amantadine have been repeatedly tried and published without strong evidence and probably lacking theoretical basis. As there are no studies comparing the efficacy of these treatments between them, the authors suggest that if safety and efficacy is in consideration, ECT should be the option when benzodiazepines have failed. In a revision published by Mann et al., 23 of 27 (85%) patients with NMS responded to ECT within two days and most symptoms were relieved by three days (Ghaziuddin et al., 2002; Mann et al., 1990). Haloperidol is commonly used to reduce excited and aggressive behavior, but in catatonic patients raise the risk of MC/NMS. More than half of MC/NMS cases occur with haloperidol and most of the remainder are associated with other high-potency antipsychotic agents. The manic patients who are febrile or who have had a prior episode of catatonia are even more susceptible to develop MC/NMS with haloperidol and other high potency antipsychotic drugs. Atypical antipsychotics are being frequently prescribed in disorders that can be associated with catatonia. However, randomized controlled trials are needed to evaluate the effect of these drugs, and caution is advisable, since cases of NMS have been
Table 2 Percentage of response to catatonia. Authors
Number of patients treated with ECT
Clinical measure evaluated with
ECT applied after ineffective pharmacological treatment
Percent response to ECT
Mean number of ECT sessions
Raveendranathan et al., 2012 Van Waarde et al., 2010 Bush et al., 1996a, 1996b Rohland et al., 1993 Suzuki et al., 2004
63 27 4 28 11
+ + + − +
88.89 59 100 93 100 (acute)
7.25 ± 2.54. 15 4,5 12 9.9 ± 1.3.
Hatta et al., 2007. Payee et al., 1999. Medda et al., 2015.
50 9 26
BFCRS CGI-I BFCRS Kahlbaum criteria BPRS. GAF DSM IV criteria BFCRS BFCRS CGI-I
+ + +
100 89 80,8
8,8 6,33 (3–9) 10.2 ± 3.0
BFCRS: Bush Francis Catatonia Rating Scale. CGI-I: Clinical Global Impression - Improvement. GAF: Global Assessment of Functioning.
Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030
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Table 3 Possible causes of treatment resistant catatonic patients. Possible causes of treatment resistant catatonic patients Chronic symptoms. Delay in recognition. ECT procedure: unilateral application. Not enough number of sessions. Short ECT seizure duration (less than 40 s). Patient high seizure threshold.
linked to treatment with these drugs (Fink and Taylor, 2003; Hawkins et al., 1995; Van Den Eede et al., 2005). 2.3. Patophysiology hypothesis Exact pathophysiological characterization of both NMS and catatonia remains unclear. However, it is possible to speculate that since neuroleptics may produce NMS and acts through dopamine blockade receptor, dopamine may be involved in the patophysiology of catatonia. On the other hand, the response to benzodiazepine treatment allows speculation that the gabaergic system may be involved as well. George Northoff published in 2002 a research about patophysiology of this entity. He found that subcortical D2 blockade neuroleptics may dysregulate circuits between motor/premotor cortex and basal ganglia. In addition, he found that a premotor/motor cortex circuit may be dysregulated by gabaergic abnormalities in orbitofrontal cortex. He concluded that catatonia may be characterized as a cortical “psychomotor syndrome” while NMS may rather be regarded as subcortical “motor syndrome” (Northoff, 2002). 2.4. Causes of ECT treatment resistance in catatonic patients a) Not enough number of sessions One of the causes of resistance to treatment may be due to insufficient number of ECT sessions. Sometimes ECT improves psychomotor symptoms, often within two or three treatments (it is generally accepted at least six sessions) and family members or practitioners ask to stop the treatment. It is a very frequent situation influenced by public opinion, even in medical settings. Discontinuation increases the risk of quick relapse. Suzuki and co-workers studied long-term efficacy of ECT. They found a recurrence rate of 63.6% after 1 year of ECT, despite continuation pharmacotherapy (Suzuki et al., 2004). It is reported that if the etiology is secondary to a chronic disease (mood, psychotic or somatic), maintenance treatment and perhaps indefinite prophylactic treatment will be needed (Fink and Taylor, 2003). b) Procedural failures ECT effectiveness is associated to procedural technique. Many patients may be considered refractory to treatment when the procedure has not been performed correctly. Bi-temporal localization of electrodes and initial energies estimated at half the patient's age (US devices calibrated to a maximum 500 mC) are generally effective as the preferred initial procedure. According to Fink, ECT clonic seizure should have a length of at least 40 s for an optimal clinical response, although ECT is too complex a treatment to allow a simple scheme for a sham control (Fink, 1979). Only empirical conclusions can be made, as studies that document a relationship between duration and outcome are few, and have major design flaws such as selection bias, uncontrolled medication use, and an inability to distinguish between seizure time and number of treatments (American Psychiatric Association, 1990; Lalla and Milroy, 1996). Despite correct technical procedures, it must be taken in account idiosyncratic differences in seizure threshold among patients. In patients with a high seizure threshold (for example elderly patients), etomidate anesthesia, sinusoidal ECT device, hyperventilation maneuvers, caffeine and teophiline suppositories may be of help (Fink and Taylor, 2003).
c) Concomitant use of benzodiazepines Benzodiazepines have the capacity to increase the convulsive threshold and therefore reduce the effectiveness of ECT. This is a very frequent situation because as we discussed before, benzodiazepines are the first line treatment for catatonic symptoms. ECT combined with benzodiazepines has been associated with reduced efficacy and efficiency of ECT. On the other side, Petrides et al. and Swarts et al. reported that the combination of lorazepam with ECT could produce a potentiation synergism, superior to monotherapy, although any formal conclusion can be made both are report cases with four and five patients respectively (Petrides et al., 1997; Swartz et al., 2003). In cases of concomitant use of benzodiazepines, it is recommended to use flumazenil (a specific competitive antagonist at benzodiazepine receptors) in the induction process (Whitwam and Amrein, 1995). Etomidate is gabaergic anesthetic which has the added property of increasing seizure duration (Khalid et al., 2006). The pharmacological properties of these compounds raise the question about their influence in treatment response with ECT. Anyway, adequate induction of seizure is the key in catatonia response, as it was described before the introduction of anesthetics in ECT. d) Delay in recognizing psychomotor symptoms and in applying treatment A delay in applying ECT decreases the response to treatment and it can also increase medical complications and mortality rates in catatonia. In a research made by Hawkins et al. it was found a response rate to ECTof 59%. This response rate is well below of what is usually reported in catatonic patients treated with bi-temporal ECT. The authors highlight that one of the reasons could be that a significant treatment delay (a mean time interval of 2 months) may have negatively influenced treatment response (Hawkins et al., 1995; Levenson, 2009). e) Chronic catatonic symptoms According to Malur et al., ECT may improve prolonged catatonia with complex medical comorbidities, but may require many treatment sessions (between 15 and 30 sessions). Although only three cases were evaluated, gross cerebral pathology may predict a less robust response, but they conclude that as for acute catatonia, ECT may resolve prolonged catatonia after benzodiazepines have failed (Malur et al., 2001). Research is needed regarding ECT response in chronic catatonic patients. We believe that it is necessary to differentiate cases of chronic catatonic symptoms in the context of a chronic psychosis of those secondary to CNS pathology. It is possible that chronic symptoms should be refractory to treatment, while cases with CNS lesions need more treatment sessions compared to acute catatonic syndromes. 2.5. Augmentation strategy in ECT refractory patients When ECT and lorazepam have failed or produced a partial response, clozapine may be associated with ECT in delirious catatonic mania. Many clinical trials showed that it may be a safe alternative when it is associated to ECT (Havaki-Kontaxaki et al., 2006; Kupchik et al., 2000; Petrides et al., 2015). Unfortunately, this is a speculation, because there are no reports of this treatment in catatonic patients. Clozapine have been used alone in delirious mania with some controversial results. There are reports of positive effects in this entity and there also reports of catatonia and NMS probably induced by this drug (Barbini et al., 1997; Lee and Robertson, 1997; Vasudev and Grunze, 2010). In summary, the combination of clozapine and ECT needs further investigation in catatonic patients who do not respond to gabaergic agonists and ECT alone.
Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030
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3. Conclusion Catatonia is a frequent psychomotor manifestation of psychiatric and non-psychiatric diseases with specific therapeutic approaches. First line treatment is based in gabaergic drugs, especially benzodiazepines. Lorazepam has a response rate of almost 80% of the cases. It is usually useful with doses between 8 and 24 mg daily, and is generally well tolerated without causing sedation. A useful diagnostic and therapeutic test is known as lorazepam sedative test, which may reveal a significant improvement on catatonic signs after 1 or 2 mg of lorazepam are administered intravenously. Although further research is needed, zolpidem appears to be useful as an augmentation strategy when there is not full response to lorazepam. Apparently chronic and malignant cases (NMS, Stauder's catatonia and TSS) may have a lower response to these compounds. In these cases and in those who do not respond to lorazepam, electroconvulsive therapy is indicated. Despite public concern and legal regulations imposed in many countries, ECT is a safe and effective alternative. Treatment resistance to ECT may be due to many causes: it may be related to technical procedures, insufficient amount of sessions, concomitant medication, not recognition of clinical entity and time of evolution. In those cases of ECT treatment resistance, we speculate that the combination with clozapine could be an alternative option in delirious catatonic mania patients, but this strategy needs further investigation. Acknowledgments
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Proceedings of the 147th Annual Meeting of the American Psychiatric Association. 129 USA: Philadelphia. Sienaert, et al., 2014. A clinical review of the treatment of catatonia. Front. Psych. 5, 181. Suzuki, et al., 2004. One-year outcome after response to ECT in middle-aged and elderly patients with intractable catatonic schizophrenia. J. ECT. 20 (2), 99–106. Swartz, et al., 2003. Diminished ECT response in catatonia due to chronic neurologic condition. J. ECT. 19 (2), 110–114. Teichmann, 1990. The influence of Karl Kleist on the nosology of Karl Leonhard. Psychopathology 23, 267–276. Thomas, et al., 1997. Test for catatonia with zolpidem. Lancet 349 (9053), 702. Tibrewal, et al., 2010. Response rate of lorazepam in catatonia: a developing country's perspective. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 34 (8), 1520–1522. Turek, Hanlon, 1977. The effectiveness and safety of electroconvulsive therapy (ECT). J. Nerv. Ment. Dis. 64 (6), 419–431. Ungvari, et al., 1999. 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Schizophrenia Research journal homepage: www.elsevier.com/locate/schres
Catatonia is not schizophrenia and it is treatable Francisco J. Appiani a,⁎, Gonzalo S. Castro b a
Program of Pharmacology, Direction of Teaching and Research, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina Fellowship in abnormal movements, Program of Abnormal Movements and Parkinson disease, Neurology Division, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina
b
a r t i c l e
i n f o
Article history: Received 26 March 2017 Received in revised form 20 May 2017 Accepted 25 May 2017 Available online xxxx Keywords: Catatonia Lorazepam Electroconvulsive therapy
a b s t r a c t Catatonia is a cluster of motor features that appears in many recognized psychiatric illnesses, that according to the DSM-5 it is not linked as a subtype to schizophrenia anymore. The classic signs are mutism, a rigid posture, fixed staring, stereotypic movements, and stupor, which are all part of a broad psychopathology that may be found in affective, thought, neurological, toxic, metabolic and immunological disorders. Despite the many etiologies, catatonia may be a life-threatening condition with a specific treatment. Benzodiazepines are the first line therapeutic option for catatonia, being lorazepam the first-choice drug. Eighty percent of the patients are relieved by the use of barbiturates or benzodiazepines, while in those who fail, an improvement is achieved by electroconvulsive therapy (ECT). With more than 60 years of use in catatonic patients, ECT has proven to be an effective and safe tool for the treatment of this frequent and sometimes forgotten syndrome. © 2017 Elsevier B.V. All rights reserved.
1. Introduction Psychomotor symptoms in psychiatric disorders have been a controversial issue in modern psychiatry. Karl Ludwig Kahlbaum (1828–1899) was the first psychiatrist to clearly associate psychomotor symptoms to psychiatric disorders. Since Kahlbaum's first description of catatonia there were many different positions about this entity (Caroff et al., 2004). Kahlbaum syndrome refers to the most common presentation of retarded catatonia, generally with a favorable outcome, named “Atonic melancholia”. According to his descriptions, the patient has a melancholic prodromal state, followed by impairment of thought, associated to choreiform movements that limit his ability to carry out voluntary movements (Fink and Taylor, 2003). Emil Kraepelin inserted catatonia as a subtype of his Dementia praecox classification. Despite the clinical reality of Catatonia syndrome, the inclusion in Dementia Praecox and then in Schizophrenia nearly erased the original concept of Kahlbaum's catatonia and remained associated to schizophrenia during many decades. As presented below, this situation was not only a nosography dilemma but it has therapeutic implications. Other authors like Karl Wernicke put Catatonia closer to neurology nosology. He was convinced that the whole pathology of mental patients consists of nothing else but the peculiarities of their motor behavior. He coined the term psychomotor disturbances referring to ⁎ Corresponding author. E-mail address: [email protected] (F.J. Appiani).
abnormalities of motion and speech which were independent from thought and will (Pfuhlmann and Stüber, 2001). Karl Leonhard and Karl Kleist were clinicians who continued and delineated Wernicke's ideas. They established a new nosology of what they called “endogenous psychosis” with emphasis in catatonic symptoms as “motility symptoms”. K. Leonhard described acute (and benign) catatonia (Cycloid Psychosis) separated from those chronic and refractory to treatment (systematic schizophrenias) (Teichmann, 1990). This clinical observation is relevant, because there are descriptions of treatment refractory patients in those with chronic catatonia presentations (Ungvari et al., 1999). Nowadays a group of scholars led by Fink et al. had been working in the recognition of catatonia syndrome as a different clinical entity. According to clinical and basic research, catatonia is a cluster of motor features that appears in many recognized psychiatric illnesses. The classic signs are mutism, a rigid posture, fixed staring, stereotypic movements, and stupor, which are all part of a broad psychopathology that includes most of the major diagnostic classes (Bleckwenn, 1930). Psychomotor symptoms may be found in affective, thought, neurological, toxic, metabolic and immunological disorders. Clinical forms may be transient or “benign”, with a good response to specific treatment, and it can also have a malignant course like in Stauder's catatonia, neuroleptic malignant syndrome and toxic serotonin syndrome (Fink and Taylor, 2003). It is necessary to highlight that the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM 5), published by the American Psychiatric Association, removed the diagnosis of catatonic schizophrenia. Instead catatonia is a specifier for schizophrenia as it is for mood disorders.
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Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030
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DSM 5 also added catatonia as a specifier for brief psychotic disorder, schizophreniform disorder, schizoaffective disorder and in substanceinduced psychotic disorder. Before DSM-5, Catatonia was restricted to sections of the psychotic, affective, or medical disorders in adult patients. During the last few years, progress has been made in delineating this syndrome in children and adolescents across a wide range of disorders. Dirk Dhossche and his group have showed that catatonia may be present in children and adolescents with autistic, developmental, and tic disorders, and in its idiopathic form, with a similar response to treatment like in adult patients. Finally DSM-5 included catatonia as a specifier in autistic spectrum disorders. The study of pediatric catatonia supports a home of its own for catatonia in DSM-5. (Dhossche et al., 2010a). (Dhossche et al., 2010b). Catatonia can also be diagnosed as a consequence of medical condition and as catatonia not otherwise specified NOS (American Psychiatric Association, 2013). In summary, catatonia is a treatable syndrome secondary to many etiologies that it is not linked as a subtype to schizophrenia anymore. 1.1. Treatment of catatonic syndrome Despite the many etiologies, catatonia has a specific treatment. Today, benzodiazepines are among first line treatment options for catatonia. The effectiveness of these compounds in the treatment of catatonic syndrome was first reported in 1930. W. J. Bleckwenn found that intravenous administration of amobarbital sodium produced a transient response in three catatonic patients (Bleckwenn, 1930). Barbiturates, according to a study done in 1992 (McCall et al., 1992), have a response rate of 50% in patients with catatonia, but due to its narrow therapeutic index they are not used anymore. Today, benzodiazepines are considered as an alternative with higher safety margins and are the first line treatment for this clinical entity. 1.2. Benzodiazepines Though several hypotheses have been proposed, the molecular mechanism of catatonia remains unknown. Given the efficacy of BZD (a GABA-A agonist), in relieving catatonia, hypoactivity at GABA-A receptors was one of the most discussed molecular mechanisms involved in the pathogenesis of catatonia (Northoff et al., 1999). Lorazepam is used at doses between 8 and 24 mg daily (https:// dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype = all&query = lorazepam, 2017), and is generally well tolerated without causing sedation, especially when daily incremental doses are performed. In case a higher dosage is chosen, the patient should be monitored for excessive sedation, which tends to occur earlier than respiratory compromise (Sienaert et al., 2014). Most authors suggest starting lorazepam at 1–2 mg every 4 to 12 h so as to avoid sedation (Daniels, 2009), and response is usually seen within 3–7 days, although might be gradual and slow. It appears certain benzodiazepines are more effective for catatonia, and thus lorazepam is accepted to be a first-choice drug, with highest frequency of use. Successful use of diazepam, oxazepam or clonazepam has also been reported (Dhossche et al., 2014) (Table 1). 1.3. Indications and efficacy The dramatic experience that established lorazepam as an effective drug for catatonia took place in 1983, when Gregory Fricchione described the rapid relief of neuroleptic malignant syndrome (NMS) by intravenous lorazepam at Massachusetts General Hospital. After various treatment options failed to produce any improvement, intravenous lorazepam in 2-mg doses was administered. NMS tended to resolved within a day, with some symptoms resolving within hours.
By 1996, a systematic study established the lorazepam sedative test as a diagnostic verification of catatonia (Bush et al., 1996a).The patient should be first examined for catatonic sigs, and then 1 or 2 mg of lorazepam should be administered intravenously. After 5 min, a re-examination of the patient must be done, and a second dose should be given in case no changes were observed (Bush et al., 1996b). The authors suggested as a clinical guide that a positive response to treatment may be considered when a reduction of at least 50% of catatonic signs and symptoms are observed using the Bush Francis catatonia Rating Scale (BFCRS) standardize rating scale, which usually occurs within 10 min (Fink and Taylor, 2003) unless the administration is via intramuscularly or per os, when the interval should be around 150 and 300 min respectively (Bush et al., 1996b). Nowadays treatment with lorazepam is considered highly effective, easy and safe, and more than 80% of the patients are relieved by the use of barbiturates or benzodiazepines, while in those who fail, an improvement is achieved by ECT (Bush et al., 1996b; Fink and Taylor, 2003). This was described using high doses of lorazepam (6–16 mg/day) for 3–5 days, but in some cases dosages up to 30 mg/day may be necessary (Fink and Taylor, 2009). Hung et al. reported remission rates as high as 79% in seven catatonic patients suffering from major depression (Hung and Huang, 2006), while in another major study (n:107) two thirds responded but only half of them remitted (Tibrewal et al., 2010). According to Lin Chin-Chuen, describing intramuscular lorazepam or intravenously diazepam response in 68 instances of relapses and recurrences of catatonia, a full recovery was shown in most instances (79.4%) (Lin et al., 2016). There is no consensus on how long benzodiazepines should be continued, and generally they are maintained until the underlying illness has remitted. Relapse into a catatonic state can occur if benzodiazepines are discontinued before the underlying disorder is resolved (Rasmussen et al., 2016; Rosebush et al., 1994). 1.4. Poor outcome predictors Several studies have shown that benzodiazepines are effective on acute catatonia and in those cases of retarded catatonia related to diverse psychiatric, neurologic or medical disorder, but less when associated with schizophrenia. In a 5-year follow-up study, Beckmann et al. found benzodiazepines ineffective in the treatment of chronic catatonic schizophrenia (Beckmann et al., 1992), and similar outcomes were published in a randomized double-blind, placebo-controlled trial in 18 patients with chronic catatonia in schizophrenia (Ungvari et al., 1999). The poorer prognosis in patients with schizophrenia under treatment with lorazepam may be related to the chronicity of symptomatology, or it may suggest a distinct underlying pathophysiology, perhaps reflecting the prominence of psychosis affecting their motor behavior, like in systematic schizophrenias described by Karl Leonhard (Beckmann et al., 1992; Leonhard, 1986; Rasmussen et al., 2016; Rosebush et al., 1994). According to Fink, prognosis is particularly favorable when catatonic syndrome is dominated by hyperactivity, rapid and pressured speech, stupor and lability of mood, as well as the history of a previous episode with complete recovery, rapid onset of the catatonic state and good social functioning before the episode (Fink, 2001; Fink and Taylor, 2003). Table 1 Rates to response to lorazepam treatment in catatonic patients with various underlying diagnoses22. Diagnosis
Patients responding (%)
Bipolar disorders (n = 31) Unipolar depression (n = 30) Other psychoses (n = 24) Medical/neurological conditions (n = 11) Schizophrenia (n = 22)
97 93 92 82 59
Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030
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A higher number of episodes were recognized as a condition to worse prognosis according to Urstein, in a monograph published in 1912 (Urstein, 1912). László Meduna recognized a longer illness duration to predict a worse outcome on eleven patients (Gazdag et al., 2009) and so did Tibrewal et al. when analyzing 107 inpatients, who included as predictors of poor response the presence of mutism, third-person auditory hallucinations and ‘made phenomena’ (in which the individual feels he is being made to do something) (Tibrewal et al., 2010). 1.5. Zolpidem Zolpidem is a positive allosteric modulator of GABA-A receptors and was first described to be effective by Mastain as a treatment of a catatonic patient who was previously not responsive to benzodiazepines nor ECT (Mastain et al., 1995; Rascle et al., 1997). Moreover, he continued to demonstrate its efficacy in a larger group of patients (seven patients), with a mean response starting within 15–30 min and lasting between 2 and 5 h. Although this short-last acting may lead scientific community to consider it an impractical option, zolpidem was shown to be effective even after treatment with benzodiazepines and/or ECT had failed according to a few case reports, and what is more, longterm treatment has also been described, as it reduces risk of respiratory depression. Although evidence on zolpidem appears to lack well design, controlled studies with numerous patients, the diagnostic and therapeutic test with zolpidem seems to be a credible alternative to increasing lorazepam doses (Cottencin et al., 2007; Thomas et al., 1997). 10 mg of zolpidem is first administered per os and after 30 min the patient is re-examined. It is considered a positive response when a reduction of at least 50% of the BFCRS-score is observed. 2. Electroconvulsive therapy 2.1. Indications, safety and efficacy When benzodiazepines and other pharmacological treatments fail, electroconvulsive therapy (ECT) is the next step (Table 2). Electroconvulsive therapy is one of the most controversial therapeutic approaches in psychiatry and is the treatment of choice when benzodiazepines have failed. It is also indicated in cases when a decisive and rapid response is required like in malignant catatonia (with high fever, and dysautonomia). Catatonia may be a life-threatening condition, with medical consequences as thrombosis, pulmonary embolism, and eventually death. In malignant and prolonged cases, patients can develop infections, especially pneumonia. Patients with catatonia are three times more likely to die than age-matched individuals in the general population (Fink and Taylor, 2003). If we consider a risk-benefit balance, ECT is the preferred treatment of catatonia in those patients who have no response to benzodiazepines. It is safe and effective, even in the medically compromised, the elderly,
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and in all trimesters of pregnancy (Anderson and Irving, 2009; Turek and Hanlon, 1977). ECT has no absolute contraindication to its use, making it the preferred treatment for catatonia, of any severity, in the widest range of patients, and with virtually any comorbidity when pharmacological treatment failed (Fink and Taylor, 2003; Turek and Hanlon, 1977). The efficacy of ECT in catatonia is generally acknowledged, even in the absence of randomized controlled evidence (Greenberg and Charles, 2005). Response rates in ECT are not systematically studied, but its efficacy is described in hundreds of case reports and some small studies. Hawkins et al. reported an 85% (47/55) of complete response rate (Hawkins et al., 1995). Hatta et al. in a sample 50 consecutive patients with catatonic symptoms admitted to a university hospital during a 32-month period, found a response rate to ECT of 100% (Hatta et al., 2007). In a review of 121 publications made by Van der Wuff et al., no negative studies were found regarding efficacy (Van der Wurff et al., 2003). It is important to consider that there may be a bias regarding the efficacy of ECT because it is not frequent to publish negative results of medical treatments. Table 3. ECT has also shown efficacy in malignant catatonia (neuroleptic malignant syndrome, Stauder's catatonia and in toxic serotonin syndrome). The delay in applying ECT in malignant catatonia increases medical complications and mortality. According to Fink et al., malignant catatonia cases should be treated within the first five days of hospital admission (Fink and Taylor, 2003). 2.2. NMS as a catatonia subtype Based on clinical symptomatology, course, and the treatment response, NMS must be viewed as a subtype of catatonia (Fink, 1996). NMS is a malignant form of catatonia triggered by neuroleptics with many treatment options, among which dantrolene, bromocriptine and amantadine have been repeatedly tried and published without strong evidence and probably lacking theoretical basis. As there are no studies comparing the efficacy of these treatments between them, the authors suggest that if safety and efficacy is in consideration, ECT should be the option when benzodiazepines have failed. In a revision published by Mann et al., 23 of 27 (85%) patients with NMS responded to ECT within two days and most symptoms were relieved by three days (Ghaziuddin et al., 2002; Mann et al., 1990). Haloperidol is commonly used to reduce excited and aggressive behavior, but in catatonic patients raise the risk of MC/NMS. More than half of MC/NMS cases occur with haloperidol and most of the remainder are associated with other high-potency antipsychotic agents. The manic patients who are febrile or who have had a prior episode of catatonia are even more susceptible to develop MC/NMS with haloperidol and other high potency antipsychotic drugs. Atypical antipsychotics are being frequently prescribed in disorders that can be associated with catatonia. However, randomized controlled trials are needed to evaluate the effect of these drugs, and caution is advisable, since cases of NMS have been
Table 2 Percentage of response to catatonia. Authors
Number of patients treated with ECT
Clinical measure evaluated with
ECT applied after ineffective pharmacological treatment
Percent response to ECT
Mean number of ECT sessions
Raveendranathan et al., 2012 Van Waarde et al., 2010 Bush et al., 1996a, 1996b Rohland et al., 1993 Suzuki et al., 2004
63 27 4 28 11
+ + + − +
88.89 59 100 93 100 (acute)
7.25 ± 2.54. 15 4,5 12 9.9 ± 1.3.
Hatta et al., 2007. Payee et al., 1999. Medda et al., 2015.
50 9 26
BFCRS CGI-I BFCRS Kahlbaum criteria BPRS. GAF DSM IV criteria BFCRS BFCRS CGI-I
+ + +
100 89 80,8
8,8 6,33 (3–9) 10.2 ± 3.0
BFCRS: Bush Francis Catatonia Rating Scale. CGI-I: Clinical Global Impression - Improvement. GAF: Global Assessment of Functioning.
Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030
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Table 3 Possible causes of treatment resistant catatonic patients. Possible causes of treatment resistant catatonic patients Chronic symptoms. Delay in recognition. ECT procedure: unilateral application. Not enough number of sessions. Short ECT seizure duration (less than 40 s). Patient high seizure threshold.
linked to treatment with these drugs (Fink and Taylor, 2003; Hawkins et al., 1995; Van Den Eede et al., 2005). 2.3. Patophysiology hypothesis Exact pathophysiological characterization of both NMS and catatonia remains unclear. However, it is possible to speculate that since neuroleptics may produce NMS and acts through dopamine blockade receptor, dopamine may be involved in the patophysiology of catatonia. On the other hand, the response to benzodiazepine treatment allows speculation that the gabaergic system may be involved as well. George Northoff published in 2002 a research about patophysiology of this entity. He found that subcortical D2 blockade neuroleptics may dysregulate circuits between motor/premotor cortex and basal ganglia. In addition, he found that a premotor/motor cortex circuit may be dysregulated by gabaergic abnormalities in orbitofrontal cortex. He concluded that catatonia may be characterized as a cortical “psychomotor syndrome” while NMS may rather be regarded as subcortical “motor syndrome” (Northoff, 2002). 2.4. Causes of ECT treatment resistance in catatonic patients a) Not enough number of sessions One of the causes of resistance to treatment may be due to insufficient number of ECT sessions. Sometimes ECT improves psychomotor symptoms, often within two or three treatments (it is generally accepted at least six sessions) and family members or practitioners ask to stop the treatment. It is a very frequent situation influenced by public opinion, even in medical settings. Discontinuation increases the risk of quick relapse. Suzuki and co-workers studied long-term efficacy of ECT. They found a recurrence rate of 63.6% after 1 year of ECT, despite continuation pharmacotherapy (Suzuki et al., 2004). It is reported that if the etiology is secondary to a chronic disease (mood, psychotic or somatic), maintenance treatment and perhaps indefinite prophylactic treatment will be needed (Fink and Taylor, 2003). b) Procedural failures ECT effectiveness is associated to procedural technique. Many patients may be considered refractory to treatment when the procedure has not been performed correctly. Bi-temporal localization of electrodes and initial energies estimated at half the patient's age (US devices calibrated to a maximum 500 mC) are generally effective as the preferred initial procedure. According to Fink, ECT clonic seizure should have a length of at least 40 s for an optimal clinical response, although ECT is too complex a treatment to allow a simple scheme for a sham control (Fink, 1979). Only empirical conclusions can be made, as studies that document a relationship between duration and outcome are few, and have major design flaws such as selection bias, uncontrolled medication use, and an inability to distinguish between seizure time and number of treatments (American Psychiatric Association, 1990; Lalla and Milroy, 1996). Despite correct technical procedures, it must be taken in account idiosyncratic differences in seizure threshold among patients. In patients with a high seizure threshold (for example elderly patients), etomidate anesthesia, sinusoidal ECT device, hyperventilation maneuvers, caffeine and teophiline suppositories may be of help (Fink and Taylor, 2003).
c) Concomitant use of benzodiazepines Benzodiazepines have the capacity to increase the convulsive threshold and therefore reduce the effectiveness of ECT. This is a very frequent situation because as we discussed before, benzodiazepines are the first line treatment for catatonic symptoms. ECT combined with benzodiazepines has been associated with reduced efficacy and efficiency of ECT. On the other side, Petrides et al. and Swarts et al. reported that the combination of lorazepam with ECT could produce a potentiation synergism, superior to monotherapy, although any formal conclusion can be made both are report cases with four and five patients respectively (Petrides et al., 1997; Swartz et al., 2003). In cases of concomitant use of benzodiazepines, it is recommended to use flumazenil (a specific competitive antagonist at benzodiazepine receptors) in the induction process (Whitwam and Amrein, 1995). Etomidate is gabaergic anesthetic which has the added property of increasing seizure duration (Khalid et al., 2006). The pharmacological properties of these compounds raise the question about their influence in treatment response with ECT. Anyway, adequate induction of seizure is the key in catatonia response, as it was described before the introduction of anesthetics in ECT. d) Delay in recognizing psychomotor symptoms and in applying treatment A delay in applying ECT decreases the response to treatment and it can also increase medical complications and mortality rates in catatonia. In a research made by Hawkins et al. it was found a response rate to ECTof 59%. This response rate is well below of what is usually reported in catatonic patients treated with bi-temporal ECT. The authors highlight that one of the reasons could be that a significant treatment delay (a mean time interval of 2 months) may have negatively influenced treatment response (Hawkins et al., 1995; Levenson, 2009). e) Chronic catatonic symptoms According to Malur et al., ECT may improve prolonged catatonia with complex medical comorbidities, but may require many treatment sessions (between 15 and 30 sessions). Although only three cases were evaluated, gross cerebral pathology may predict a less robust response, but they conclude that as for acute catatonia, ECT may resolve prolonged catatonia after benzodiazepines have failed (Malur et al., 2001). Research is needed regarding ECT response in chronic catatonic patients. We believe that it is necessary to differentiate cases of chronic catatonic symptoms in the context of a chronic psychosis of those secondary to CNS pathology. It is possible that chronic symptoms should be refractory to treatment, while cases with CNS lesions need more treatment sessions compared to acute catatonic syndromes. 2.5. Augmentation strategy in ECT refractory patients When ECT and lorazepam have failed or produced a partial response, clozapine may be associated with ECT in delirious catatonic mania. Many clinical trials showed that it may be a safe alternative when it is associated to ECT (Havaki-Kontaxaki et al., 2006; Kupchik et al., 2000; Petrides et al., 2015). Unfortunately, this is a speculation, because there are no reports of this treatment in catatonic patients. Clozapine have been used alone in delirious mania with some controversial results. There are reports of positive effects in this entity and there also reports of catatonia and NMS probably induced by this drug (Barbini et al., 1997; Lee and Robertson, 1997; Vasudev and Grunze, 2010). In summary, the combination of clozapine and ECT needs further investigation in catatonic patients who do not respond to gabaergic agonists and ECT alone.
Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030
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3. Conclusion Catatonia is a frequent psychomotor manifestation of psychiatric and non-psychiatric diseases with specific therapeutic approaches. First line treatment is based in gabaergic drugs, especially benzodiazepines. Lorazepam has a response rate of almost 80% of the cases. It is usually useful with doses between 8 and 24 mg daily, and is generally well tolerated without causing sedation. A useful diagnostic and therapeutic test is known as lorazepam sedative test, which may reveal a significant improvement on catatonic signs after 1 or 2 mg of lorazepam are administered intravenously. Although further research is needed, zolpidem appears to be useful as an augmentation strategy when there is not full response to lorazepam. Apparently chronic and malignant cases (NMS, Stauder's catatonia and TSS) may have a lower response to these compounds. In these cases and in those who do not respond to lorazepam, electroconvulsive therapy is indicated. Despite public concern and legal regulations imposed in many countries, ECT is a safe and effective alternative. Treatment resistance to ECT may be due to many causes: it may be related to technical procedures, insufficient amount of sessions, concomitant medication, not recognition of clinical entity and time of evolution. In those cases of ECT treatment resistance, we speculate that the combination with clozapine could be an alternative option in delirious catatonic mania patients, but this strategy needs further investigation. Acknowledgments
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Please cite this article as: Appiani, F.J., Castro, G.S., Catatonia is not schizophrenia and it is treatable, Schizophr. Res. (2017), http://dx.doi.org/ 10.1016/j.schres.2017.05.030