Dr. Carroll is clinical assistant professor of Psychiatry at Ohio University College of Osteopathic Medicine in Athens, and chief of Psychiatry Service at the Chillicothe Veteran’s Affairs (VA) Medical Center in Ohio. Dr. Lee is clinical associate professor at the University of Western Australia in Perth. Dr. Appiani is assistant professor of Pharmacology at  Universidad de Buenos Aires, Facultad de Medicina, and Director of the Association for the Study and Development of the Neurosciences in Buenos Aires, Argentina. Dr. Thomas is clinical pharmacy specialist in Psychiatry at the Chillicothe VA Medical Center.

Disclosure: Dr. Carroll is a consultant to Neuroleptic Malignant Syndrome Information Service; is on the speaker’s bureaus of Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, Pfizer, and Janssen; and receives grant support from Pfizer. Dr. Lee is consultant to Eli Lilly and Pfizer, and is on the speaker’s bureaus and receives grant support from Janssen-Cilag. Dr. Appiani reports no affiliation with or financial interest in any organization that may pose a conflict of interest. Dr. Thomas is on the speaker’s bureau of AstraZeneca.

Please direct all correspondence to: Brendan T. Carroll, MD, Chief, Psychiatry Service, MHCL, Chillicothe VA Medical Center, 116A, 17273 State Route 104, Chillicothe, OH 45601; Tel: 740-773-1141, x7871; Fax: 740-772-7179; E-mail: btcarroll1@cs.com.



Catatonia is an important clinical syndrome that occurs in affective, psychotic, autistic, developmental, and medical disorders. The pharmacotherapy of catatonia is complex because of multiple and varied therapeutic agents. The proposed pathophysiology of catatonia includes: g-aminobutyric acid (GABA)A hypoactivity, dopamine-2 hypoactivity, glutamate N-methyl-d-aspartate hyperactivity, serotonin-2 hyperactivity, and cholinergic hyperactivity. The pharmacotherapy of catatonia includes benzodiazepines, GABA promoters, certain anticonvulsants, glutamate inhibitors, and second-generation antipsychotics. The role of first-generation antipsychotics remains unclear. Catatonia, a treatable syndrome, occurs in a variety of psychiatric, medical, and neurologic illnesses. Physicians may benefit from learning about these pharmacologic treatment options.

Focus Points

• Multiple pharmacologic agents have been used in the treatment of catatonia.
• The proposed pathophysiology of catatonia involves gabaergic, dopaminergic, glutamatergic, and other neurochemical systems.
• The primary treatments for catatonia have mechanisms of action that involve one or more of these neurochemical systems.
• The alternative pharmacologic treatments of catatonia are important when benzodiazepines and electroconvulsive therapy are not effective treatment options.
• The application of pharmacologic treatment for catatonia is illustrated in case vignettes.



The clinician should approach catatonia as a diagnosable and treatable disorder. One approach is that catatonia is a psychiatric disorder and the clinician should treat the primary psychiatric disorder.1 However, another view is that, since catatonia is found in non-psychiatric medical disorders, it is a neuropsychiatric illness and treatment should focus on the medical disorder.2 The authors of this article favor the concept of catatonia as a neuropsychiatric syndrome with an identified set of etiologies, core features, pathophysiology, and treatment response.3 Catatonia constitutes a neurobiologic syndrome and is a constellation of symptoms reliably associated with disturbance that is functional, structural, neurochemical, or neuropathologic in a circumscribed structural location or neural circuit. The clinician is charged with the detection and diagnosis of catatonia. Thus, when catatonia becomes the focus of treatment, there is an urgent need to explore the different pharmacologic treatments. This heuristic approach may be helpful in many cases where the clinician begins with treatment and works backwards toward diagnosis.


Mechanisms Of Catatonia

There are multiple theories regarding the neurochemical etiology for catatonia. This article provides a brief mechanistic overview of catatonia; a more comprehensive review of specific theories of catatonia can be found elsewhere.4 In general, there are three major theories, namely, dopamine hypoactivity, g-aminobutyric acid (GABA) hypoactivity, and glutamate hyperactivity,4 along with the two minor theories of serotonin hyperactivity and cholinergic hyperactivity.4,5 Dopamine (D) hypoactivity, specifically at the D2 receptor, is thought to be the predominate mechanism that leads to catatonia. To further support the hypoactive D2 receptor theory, several case reports exist that demonstrate a relationship with high-potency typical antipsychotics either causing or worsening catatonia. This phenomenon is known as neuroleptic-induced catatonia (NIC). The decrease in activity at the D2 receptor then causes an abundant release of glutamate, the major excitatory neurotransmitter, hence, the physiologic attempt to increase dopamine activity via glutamate. Glutamate is known to regulating the catecholamine release and is directly involved in dopamine regulation.4 However, glutamate is known to be excitotoxic, thereby, causing neuronal damage, and may produce symptoms similar to catatonia.4,5 GABA, the major inhibitory neurotransmitter in the central nervous system, has an inverse relationship with glutamate. In environments with high glutamate, GABA acts to shut down glutamate release. Therefore, to further support the high glutamate activity and hypodopamine receptor theory, drugs that potentiate GABA (benzodiazepines) or act as GABA agonists (anticonvulsants) will have a benefit in treating catatonia.

These general neurochemical theories are supported by pharmacologic treatment because clinical studies of neurochemical mechanisms are difficult to obtain in these patients. These mechanisms will be reviewed further in the pharmacotherapy section of this article. Animal studies of catalepsy do provide some information on the actions of pharmacologic agents. However, there is no suitable model for catatonia in humans. Electroconvulsive therapy has been a very important treatment for catatonia and also contributes to these neurochemical theories.

Furthermore, catatonia is not a unitary syndrome and there may be subtypes that respond favorably to one type of medication. Catatonia is probably a heterogeneous condition with subtypes different in treatment responses and pathophysiology. Therefore, multiple agents may be required to not only treat acute catatonia, but maintain or prevent the reoccurrence of chronic catatonia.


Types Of Catatonia 

Catatonia is derived from a term for “tension insanity” by Kahlbaum and colleagues.6 Since this original description, additional signs have been observed and described by Dhossche and colleagues.7 Physicians working in different settings may encounter different forms of catatonia. A heuristic approach is to classify catatonia into acute and chronic types. Patients who present in an acute psychiatric setting and for a follow-up appointment in an outpatient clinic may both meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,8 criteria for the catatonia specifier. However, there are differences in the level of functional impairment and the severity of the syndrome (Table 1). This separation may help in selecting treatment for patients with catatonia.9


Rating Scales For Catatonia

Clinicians detect and diagnose catatonia with greater frequency with the use of a larger number of catatonic signs and a rating scale for catatonia.10,11 Furthermore, the treatment of catatonia is enhanced by the use of a rating scale handled by an experienced clinician with skill in administering the chosen rating scale. Rating scales include: one by Rosebush and colleagues,12 the Modified Rogers Scale,13 the Bush-Francis Catatonia Rating Scale,14 the Northoff Catatonia Scale,15 the Braunig Catatonia Rating Scale,16 and the KANNER Catatonia Rating Scale.17 Carroll and colleagues17 provide a review of catatonia rating scales. In North America, the Bush-Francis Catatonia Rating Scale is used most frequently.14


The Catatonia Dilemma

Catatonic signs may appear or worsen with antipsychotic pharmacotherapy.18 This “catatonic dilemma” illustrates the role of dopamine blockers on the pathogenesis of catatonia. NIC has been described with first-generation antipsychotics (FGAs) and, albeit less frequently, with second-generation antipsychotics (SGAs). SGAs tend not to worsen catatonia and have been recommended. NIC may emerge during pharmacologic treatment and can mimic acute or chronic catatonia. Thus, the physician may need to obtain a history of all meds administered and even toxicology for occult FGAs and SGAs.19 This modern “catatonic dilemma” must be considered by the clinician in a case by case basis.



Carroll and colleagues20 and Lee and Carroll21 reviewed several authoritative texts and review articles on the subject of catatonia response. They divided the drugs into their known classes and identified their mechanism of action. They also reviewed 49 cases that were rated with the Bush-Francis Rating Scale as part of clinical care at a neuropsychiatric institution between 1995 and 2005.8 Thirty-five patients (66%) met the description of schizophrenia with catatonic features. Ten patients (19%) had catatonia due to a general medical condition. Bipolar and unipolar mood disorders were a minority (four patients; 9%). Some improvement in catatonia and function occurred with medication treatment in 16 of the 49 cases. This included: SGAs (two), clozapine (two), lorazepam (four), bromocriptine (one), memantine (adjunct; six), and memantine (monotherapy; one).20

Meanwhile, Lee and Carroll21 reviewed treatments used in 71 episodes of catatonia (58 acute, 13 chronic) with schizophrenia (according to the DSM-IV; most of them were seen in two psychiatric intensive care facilities respectively from 1996 to 2002).4 All met restrictive criteria for catatonia according to Rosebush and colleagues22 and Lohr and Wisenewski.23 They were first treated with benzodiazepines (oral lorazepam or intramuscular clonazepam). Those who failed benzodiazepines received other treatments for their catatonic symptoms. The efficacy of benzodiazepines in acute catatonia in schizophrenia was seen in 40 of 58 episodes (69%). Despite the decent response in acute catatonia, this response was not sustained and catatonia returned in the majority of patients. The response rate in chronic catatonia in schizophrenia with benzodiazepines was 8%, thus, a much lower response rate versus response in acute catatonia. Response rates with amantadine, selegeline, lithium, and SGAs occurred in nine of 13 (69%), yielding a response rate similar to benzodiazepines in acute catatonia.21

These diverse medications have been reported to help improve catatonia (Tables 2–6; Figures 1–4). Lorazepam and other GABAA promoters (ie, benzodiazepines, zolpidem) increase GABA activity as their mechanism of action. Anticonvulsants may be helpful by increasing activity at GABA or modest anti-glutaminergic effects with some reports of benefit from carbamazepine and valproic acid. In neuroleptic-induced catatonia an anticholinergic might be helpful, suggesting a role for the cholinergic system in catatonia. Clozapine and other SGAs have been reported to improve catatonia in psychosis, perhaps via a greater “pass-though” of dopamine to the D2 receptor. Perhaps the most promising finding is that N-methyl-d-aspartate antagonists may improve schizophrenia with catatonic features.



Case 1

The authors describe the case of a 64-year-old female patient who came for psychiatric treatment accompanied by her son. According to her son’s description, the patient became mute. She could not perform her usual activities, and spent nearly the whole day in bed with akinesia. During this time the patient lost 15 lb and ate once a day and only if she was assisted. The patient had a history of two depressive episodes that, according to clinical records, were mild and produced by family conflicts. She was diagnosed by her former psychiatrist with dysthymia and was treated with venlafaxine 75 mg/day with partial response. At this time she was also under psychotherapy treatment. She had one venlafaxine-induced manic episode. 

This catatonic syndrome developed 10 days after the patient was started with risperidone 3 mg/day. In the clinical examination, the patient had immobility, she answered questions only with “yes” or “no”, and she had a marked delay of many seconds to answer. Physical examination revealed no fever, blood pressure of 125/75 Hg mm, and cardiac frequency of 85 beats per minute. She had catalepsy and cogwheel rigidity in both arms. Head computerized tomography scan showed an old small infarct in the subcortical zone of the right frontal lobe. The diagnosis of NIC was made. After the initial evaluation, risperidone was stopped. Treatment with lorazepam began at 2.5 mg/day gradually titrated to 2.5 mg BID. After 48 hours of this pharmacologic treatment the catatonic symptoms began to resolve. This was especially seen in an increase on verbal fluency and feeding habits. After 2 weeks of treatment, the patient was almost without catatonic symptoms, and in the physical examination she had mild cogwheel in both arms. She was started on quetiapine 25 mg/day titrated to 150 mg/day in a month. This drug was given to treat bipolar disorder. With this regimen of quetiapine 150 mg/day and lorazepam 5 mg/day the patient remained asymptomatic for 6 months until she decided to stop taking lorazepam. Immediately after lorazepam discontinuation the patient developed a clinical state of mutism, akinesia with a marked anxiety state. Lorazepam was administered again and symptoms resolved in hours. The diagnosis of this episode was catatonic symptoms due to benzodiazepine withdrawal. After this episode the patient remained stable and continued with lorazepam 5 mg/day and quetiapine 150 mg/day, without catatonic symptoms. Lithium 600 mg/day was added for the treatment of the bipolar disorder, with a favorable response.



Case 2

A 31-year-old female was admitted to a general hospital with immobility, waxy flexibility, negativism, mutism, rigidity, and decreased blinking. Her husband had reported that 10 days prior to the admission her behavior changed, she acted with increased suspiciousness, auditory hallucinations, and mystical delusions. She refused to drink and eat and had episodes of impulsivity without provocation. Weight loss was evident. The patient had no prior history of psychiatric disorder. She lived with her husband and three sons.

Laboratory studies were normal range except for a mild anemia with hemoglobin 9.2 g/dl and hematocrit 32.1 %.

A slow intravenous dose of lorazepam 2 mg was initiated. After 20 minutes of lorazepam administration the patient started to give brief delayed responses, with perseveration, movement improvement, exhibiting facial gestures, and giving minimal response to external stimuli.

After the lorazepam test, oral lorazepam 5 mg/day and zolpidem 10 mg/day was started. After 24 hours, there was improvement of catatonic signs, although posturing persisted. Due to the mystical delusions and hallucinations, the patient was also treated with quetiapine 200 mg. Four days after the admission the patient had abdominal distention and steatorrhea. Abdominal ecography was normal. Coprocultive results showed non-pathogenic non-enterohemorragic escherichia coli. A videoendoscopy of the upper digestive tract showed findings associated with a high specificity for celiac disease. The diagnosis and dietary treatment for celiac disease commenced. Along with the improvement of gastrointestinal symptoms, the patient showed an evident decrease of catatonic and psychotic symptoms.


Case 3

A 56-year-old woman was admitted to a general hospital with negativism, immobility, bizarre postures, waxy flexibility, fixed gaze, and mutism. Her family referred that 40 days prior to the admission the patient presented depressive symptoms, isolation tendency, and somatic delusions (she believed that she had terminal cancer of the spinal cord) with ideas of prejudice and damnation. She was treated in that opportunity with haloperidol 15 mg/day, prometazine 50 mg/day, and sertraline 100 mg/day. With this pharmacologic treatment, the patient improved her clinical state but complained about extrapyramidal symptoms (motor slowness and tremor). Then, she refused to see her doctor again and stopped taking the medication. One week later, the patient relapsed with mood, psychotic, and catatonic symptoms, as above.

The clinical exam showed no findings and the neurological exam showed cogwheel especially in the left arm, waxy flexibility in both arms, and posturing.

Upon rehospitalization, the patient was started on sertraline 50 mg/day and thioridazine 100 mg/day.

During the next 4 days the catatonic signs increased. Sertraline increased to 100 mg/day and thioridazine 200 mg/day. Three days later, the patient started to give monosyllabic responses, followed simple commands, and had brief episodes of immobility.

Fourteen days later, the patient had a global improvement in catatonic, psychotic, and mood symptoms. She could collaborate during the examination, spoke without delay, and had no bizarre postures or waxy flexibility. She was euthymic and with normal volition. Due to sedation, thioridazine was reduced to 50 mg/day. Three weeks after the admission the patient remained stable and was discharged from the inpatient unit. At 1-year follow-up she was stable without acute psychiatric symptoms.

This case is an example of a catatonic syndrome produced in the context of a mood disorder that had a good resolution without the use of benzodiazepines. In this case, the treatment of depressive symptoms with sertraline may have led to catatonic symptoms resolution. Thioridazine has a better side effect profile because of less extrapyramidal symptoms and perhaps a lower likelihood of NIC.


Case 4

A 24-year-old male, with a diagnosis of schizophrenia, paranoid type, was admitted to a general hospital presenting delusions of reference, visual and auditory hallucinations, and disorganized speech and behavior associated with a febrile state. The patient was sent from a psychiatric institution for clinical evaluation. He was treated with quetiapine 200 mg/day. He presented an episode of aspiration during sleep 3 days before the admission. After clinical evaluation the diagnosis of pneumonia was made. Chest X-ray confirmed pneumonia. He also had 11,100 white blood cells. The rest of the lab test were between normal ranges.

Two days later, the patient present immobility, rigidity, waxy flexibility, fixed gaze, decreased blinking, selective mutism, negativism, and refusal to eat and drink. A slow intravenous dose of lorazepam 2 mg was administrated. Five minutes later the patient started having facial gestures and gave responses with perseveration and terminal echolalia.

After this response, the patient was treated with memantine 5 mg/day and lorazepam 5 mg/day. With this regimen, the patient showed a clear clinical improvement with decrease of catatonic signs 24 hours after the introduction of these two drugs. The patient had no mutism and negativism. He could follow objects with his eyes and was able to answer simple questions without delay. After 4 days of treatment the patient remained with low verbal fluency and his memantine was increased to 10 mg/day. Two days after the memantine increase the patient showed improved verbal fluency and was without catatonic signs. He was able to walk, communicate, and feed himself.

After 10 days of treatment in the clinical unit he was transferred to the psychiatric unit where he continued treatment. Quetiapine was gradually titrated to 500 mg/day and he continued with memantine 5 mg/day and lorazepam 5 mg/day without acute psychotic and catatonic signs.



As seen with the above cases, catatonia is often difficult to assess secondary to multiple etiologies, both medical and psychiatric, along with complicated medication regimens that could further worsen the clinical diagnosis of catatonia. In this article, several different pharmacologic mechanisms were discussed, along with treatment options that have been published for the treatment of catatonia. Nevertheless, multiple agents may be required to satisfactorily treat acute catatonia, along with attempting to prevent a relapse in both catatonic and psychiatric symptoms.  PP



1.    Abrams R, Taylor MA. Catatonia. A prospective clinical study. Arch Gen Psychiatry. 1976;33(5):579-581.
2.    Ahmed I, Fujii D, eds. The Spectrum of Psychotic Disorders, Neurobiology, Etiology & Pathogenesis. New York, NY: Cambridge University Press; 2007.
3.    Barnes MP, Saunders M, Walls TJ, Saunders I, Kirk CA. The syndrome of Karl Ludwig Kahlbaum. J Neurol Neurosurg Psychiatry. 1986;49(9):991-996.
4.    Northoff G. What catatonia can tell us about “top-down modulation”: a neuropsychiatric hypothesis. Behav Brain Sci. 2002;25(5):555-577.
5.    Yeh AW, Lee JW, Cheng TC, Wen JK, Chen WH. Clozapine withdrawal catatonia associated with cholinergic and serotonergic rebound hyperactivity: a case report. Clin Neuropharmacol. 2004;27(5):216-218.
6.    Kahlbaum KL; Levij Y, Pridon T, trans. Catatonia. Baltimore, MD: Johns Hopkins University Press; 1973.
7.    Dhossche DM, Wilson  C, Wachtel  LE. Catatonia in childhood and adolescence: implications for the DSM-5. Primary Psychiatry. 2010;17(4):35-39.
8.    Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washinton, DC: American Psychiatric Association; 1994.
9.    Ungvari GS, Chiu HF, Chow LY, Lau BS, Tang WK. Lorazepam for chronic catatonia: a randomized, double-blind, placebo-controlled cross-over study. Psychopharmacology (Berl). 1999;142(4):393-398.
10.   van der Heijden F, Tuinier S, Arts N, Hoogendoorn M, Kahn R, Verhoeven W. Catatonia: disappeared or under-diagnosed? Psychopathology. 2005;38(1):3-8.
11.    Stompe T, Ortwein-Swoboda G, Ritter K, Schanda H, Friedmann A. Are we witnessing the disappearance of catatonic schizophrenia? Compr Psychiatry. 2002;43(3):167-174.
12.    Rosebush PI, Mazurek MF. Catatonia: re-awakening to a forgotten disorder. Mov Disord. 1999;14(3):395-397.
13.     Lund CE, Mortimer AM, Rogers D, McKenna PJ. Motor, volitional and behavioural disorders in schizophrenia. I. Assessment using the Modified Rogers Scale. Br J Psychiatry. 1991;158:323-327,333-336.
14.    Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia. I. Rating scale and standardized examination. Acta Psychiatr Scand. 1996;93(2):129-136.
15.    Northoff G, Koch A, Wenke J, et al. Catatonia as a psychomotor syndrome: a rating scale and extrpyramidal motor symptoms. Mov Disord. 1999;14(3):404-416.
16.    Bräunig P, Krüger S, Shugar G, Höffler J, Börner I. The catatonia rating scale I–development, reliability and use. Compr Psychiatry. 2000;41(2):147-158.
17.    Carroll BT, Kirkhart R, Ahuja N, et al. Katatonia: a new conceptual understanding of catatonia and a new rating scale. Psychiatry (Edgemont). 2008;5(12):42-50.
18.    Brenner I, Rheuban WJ. The catatonic dilemma. Am J Acta Psychiatry. 1978;135(10):1242-1243.
19.    Lee JW. Neuroleptic-induced catatonia: clinical presentation, response to benzodiazepines, and relationship to neuroleptic malignant syndrome. J Clin Psychopharmacol. 2010;30(1):3-10.
20.    Carroll BT, Carroll TD, Lee JW, et al. Why are some medications effective against catatonia? Int J Neuropsychopharmacology. 2006;9(suppl 1):S253.
21.    Lee JW, Carroll BT. Amantadine in the treatment of chronic catatonic schizophrenia. Int J Neuropsychopharmacology. 2006;9(suppl 1):S270.
22.    Rosebush PI, Hildebrand AM, Furlong BG, Mazurek MF. Catatonic syndrome in a general psychiatric population: frequency, clinical presentation, and response to lorazepam. J Clin Psychiatry. 1990;51(9):357-362.
23.    Lohr JB, Wisenewski AA. Movement Disorders: A Neuropsychiatric Approach. New York, NY: Guilford Press; 1987.