Asian Journal of Psychiatry 7 (2014) 69

Contents lists available at ScienceDirect

Asian Journal of Psychiatry

journal homepage: www.elsevier.com/locate/ajp

Review

The catatonia conundrum: Controversies and contradictions

Susanta Kumar Padhy *, Preeti Parakh 1, M. Sridhar
Department of Psychiatry, PGIMER (Post Graduate Institute of Medical Education and Research), Chandigarh, India

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 29 March 2013
Received in revised form 21 July 2013
Accepted 23 July 2013

Although catatonia is known to psychiatrists for more than a century, it is still poorly understood, often
under recognized, have inspired debate and criticism about nosological status of the catatonic syndrome
in recent times without reaching its conclusion. It can present with a number of psychiatric and medical
illnesses and is easily treatable, though treatment response varies depending upon the underlying
condition and can lead on to a multitude of complications, if not treated. Some issues are more than forty
catatonic signs are available to scientic audience for diagnosis; threshold number for labelling varies
according to the nosological system followed and the underlying condition; and mood stabilizers like
carbamazepine and lithium are helpful in some cases of idiopathic periodic catatonia. Researchers have
been asking for a separate diagnostic category for catatonia since long and the debate has gained pace
over the last few years, with new editions of both DSM and ICD coming up. Therefore, this paper looks at
the controversies associated with the diagnosis and classication of catatonia, the arguments and
counter-arguments and future directions, in crisp.
2013 Elsevier B.V. All rights reserved.

Keywords:
Catatonia
Controversies
Classicatory system
Nosology
Periodic catatonia

Contents
1.
2.
3.
4.

5.
6.
7.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The origin of the controversy . . . . . . . . . . . . . . . . . . . . . . . . . . .
Renewal of the controversy. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Current issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Catatonia is common . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
Catatonia is an identiable syndrome . . . . . . . . . . . . . . .
4.2.
Catatonia of diverse etiologies is treated the same way .
4.3.
Catatonia is under-recognized and under-researched . . .
4.4.
Better treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.5.
Counterarguments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Contradictions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion and future directions . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction
The catatonic syndrome has been known to psychiatrists for
more than a century now. However, it still remains poorly
understood and often under-recognized. Although it can present
with a number of psychiatric and medical illnesses and is easily
treatable, the diagnosis is often missed, leading to a multitude of

* Corresponding author. Tel.: +91 172 2756811/8872016158;

mobile: +91 8054831604.
E-mail addresses: susanta.pgi30@yahoo.in (S.K. Padhy), drpreeti9@yahoo.co.in
(P. Parakh), drsridhar2@gmail.com (M. Sridhar).
1
Tel.: +91 9814803639.
1876-2018/$ see front matter 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ajp.2013.07.006

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complications. It has been proposed that the failure of the

psychiatric diagnostic classication systems to give catatonia its
due place has resulted in under-recognition, poor treatment
choices and a high morbidity and mortality (Fink et al., 2010).
Since its rst appearance in scientic literature, catatonia has
inspired debate and criticism. This review looks at the controversies associated with the diagnosis and classication of catatonia,
the arguments and counter-arguments and future directions.
2. The origin of the controversy
The German clinician Karl Ludwig Kahlbaum (1874) was the
rst to formulate the concept of catatonia. Although others before

S.K. Padhy et al. / Asian Journal of Psychiatry 7 (2014) 69

him had reported patients with psychomotor signs, Kahlbaum

described these signs as the manifestations of a single disease
entity, which he named catatonia. He considered it an independent
clinical entity, characterized by psychomotor alterations, cyclical
in course and generally with a good prognosis (Kahlbaum, 1874).
The patients he described would have currently met the criteria for
bipolar disorder, depressive disorder, schizophrenia, and delirium.
While many clinicians endorsed Kahlbaums concept and
presented similar cases, Kraepelin (1896) had different ideas.
Kraepelin believed that catatonia was a phase of a progressively
deteriorating condition which he called dementia praecox. Unlike
Kahlbaum, he considered catatonic signs to be a manifestation of
mental blocking, rather than primarily psychomotor disturbances
(Kraepelin, 1896). Kraepelins concept also found supporters and
with time, was adopted by the modern classicatory systems like
Diagnostic and Statistical Manual of Mental Disorders (DSM) and
the International Statistical Classication of Diseases and Related
Health Problems (ICD).
ICD recognized catatonic schizophrenia as a subtype of
schizophrenia as early as 1949 (World Health Organization,
1949), while DSM included a diagnosis of schizophrenic reaction:
catatonic type in its rst edition in 1952 (American Psychiatric
Association, 1952). Schizophrenic reaction was renamed as schizophrenia in the second edition in 1968 (American Psychiatric
Association, 1968) and catatonia became a subtype of schizophrenia.

autism and mental retardation among other disorders (Dhossche

and Bouman, 1997).
Catatonia has also been reported to result from a variety of
medical conditions. The percentage of catatonia reported to be due
to a general medical condition in studies on catatonic patients has
been reported to range from 20% to 39% (Barnes et al., 1986; Bush
et al., 1996a; Smith et al., 2012; Wilcox, 1986). A wide variety of
medical conditions, including metabolic, neurological and substance induced disorders have been shown to cause catatonia
(Ahuja, 2000; Carroll et al., 1994). The neurological conditions
include strokes, tumours, inammatory disorders, epilepsy, paraneoplastic syndrome and others (Ahuja, 2000; Carroll et al., 1994).
Metabolic, endocrine and nutritional disorders that can cause
catatonia include diabetic ketoacidosis, hyponatremia, renal
failure, hypothyroidism, hyperthyroidism, hyperparathyroidism,
adrenal carcinoma, pellagra and vitamin B12 deciency (Ahuja,
2000; Carroll et al., 1994). Catatonic signs can occur both during
intoxication as well as withdrawal from drugs of dependence, like
alcohol, opioids, amphetamines, cannabis and hallucinogens
(Ahuja, 2000). Neuroleptic agents can cause or aggravate preexisting catatonia. Neuroleptics are also associated with the
occurrence of neuroleptic malignant syndrome, which is considered by some to be a subtype of catatonia (Fink, 1996; Mann et al.,
1986). With such a ubiquitous presentation, catatonia should not
be subsumed under schizophrenia but deserves to be an
independent entity like delirium.

3. Renewal of the controversy

4.2. Catatonia is an identiable syndrome
The following years saw renewal of the debate with many
studies reporting that catatonia was more common among
depressed and manic patients than in those with schizophrenia
(Abrams and Taylor, 1976; Morrison, 1975; Taylor and Abrams,
1977). Catatonia was also described in patients with neurologic
and general medical illnesses (Gelenberg, 1991). In spite of these
developments, there was no change in the nosology of catatonia in
the next edition of DSM (1980), where catatonia was again
described as a subtype of schizophrenia. The debate continued,
with researchers asking for a revision of the nosological status of
catatonia (Fink and Taylor, 1991). It was only in 1994, in the fourth
edition of DSM, that catatonia was additionally recognized as a
disorder due to a general medical condition and as a specier in
mood disorders, apart from being a subtype of schizophrenia.

In spite of having a varied presentation with more than forty

signs and symptoms, catatonia is identiable as a syndrome.
Published rating scales are available that facilitate the syndromes
recognition (Braunig et al., 2000; Northoff et al., 1999). Inter-rater
reliability individually and across instruments has been shown to
be good. Factor analytic studies have delineated a pattern among
the catatonic features, indicating that a syndrome exists (Ungvari
et al., 2009).
4.3. Catatonia of diverse etiologies is treated the same way

Researchers have been asking for a separate diagnostic category

for catatonia since long and the debate has gained pace over the
last few years, with both the fth edition of DSM and the eleventh
edition of ICD coming up. The arguments given in favour of
catatonia as an independent entity are discussed below.

About 70% of catatonic patients respond to lorazepam alone,

regardless of the cause of catatonia (Fink et al., 2010). Electroconvulsive therapy (ECT) is another effective treatment that works
even when benzodiazepines fail to give the desired response (Bush
et al., 1996b). Since neither benzodiazepines nor ECT is considered
a treatment for schizophrenia and since response to antipsychotic
agents is poor in catatonia, catatonia appears to be pathophysiologically different from schizophrenia. Though, there are some
reports of efcacy of mood stabilizers like carbamazepine and
lithium in idiopathic recurrent catatonia (Padhy et al., 2011).

4.1. Catatonia is common

4.4. Catatonia is under-recognized and under-researched

Catatonia has been described in association with many

disorders. Among psychiatric conditions, catatonia is commonly
seen in bipolar disorder, depressive disorder, schizophrenia and
substance-induced disorders amongst others. In psychiatric
inpatients, catatonia has been observed in 7%17% of cases,
commonly in those with mood or substance abuse disorders
(Chalasani et al., 2005; Fink and Taylor, 2006). Around 28%31%
of patients with catatonia present with a manic or mixed
episode while catatonia is associated with a schizophrenic
disorder in only 1015% of cases (Taylor and Fink, 2003). A
recent prospective cohort study found catatonia in only 7.6% of
patients with schizophrenia (Kleinhaus et al., 2012). Catatonia is
seen in the paediatric population as well, in association with

In a Dutch study, clinicians could identify catatonia in only 2% of

139 inpatients, but the research team was able to identify catatonia
in 18% (van der Heijden et al., 2005), indicating that the diagnosis
of catatonia is often missed. The researchers advocating a separate
diagnostic category for catatonia argue that it will help in better
recognition of catatonia as well as encourage research to improve
our understanding of the neurobiological mechanisms of catatonia
(Fink et al., 2010).

4. Current issues

4.5. Better treatment

Catatonia is treatable once it is diagnosed (Ungvari et al., 1994).
But non-identication of catatonia with schizophrenia in clinical

S.K. Padhy et al. / Asian Journal of Psychiatry 7 (2014) 69

teaching results in unnecessary prescription of antipsychotic

medications, which may even worsen catatonia. If not recognized
and treated, catatonia can result in several complications like
malnutrition, infections, contractures, permanent disability and
even death. Delinking catatonia from schizophrenia can help in
early recognition and better treatment of catatonia from other
causes, especially medical ones.
5. Counterarguments
The opponents of an independent diagnosis for catatonia argue
that catatonic schizophrenia is different from catatonia due to
other causes, both in phenomenology and treatment. There is
evidence to suggest that catatonic schizophrenia is more likely to
be associated with stereotypies, mannerisms, automatic movements and bizarre postures than other catatonic disorders (Kruger
et al., 2003). Catatonia associated with schizophrenia is also less
likely to respond to benzodiazepines and ECT than catatonia with
mood or medical disorders (Rohland et al., 1993) but ECT is still
superior to benzodiazepines in these patients (Suzuki et al., 2003).
Ungvari et al. (2010) have argued that chronically abnormal
psychomotor behaviour is a core feature of schizophrenia and
dissociation of catatonia completely from the major psychotic and
mood disorders may lead to further marginalization of catatonia as
a nonspecic syndrome and may hamper research on the
signicance of psychomotor phenomena as a symptom dimension
of psychotic and mood disorders.
6. Contradictions
The catatonic syndrome is associated with many contradictions
which must be addressed if the controversies are to be resolved.
The description of catatonia is confusing as it includes some
seemingly contradictory clinical signs. For example, catatonic signs
include motor immobility as well as excessive motor activity,
negativism as well as automatic obedience, mutism as well as
verbigeration. DSM IV Text Revision (American Psychiatric
Association, 2000) mentions 11 catatonic signs and symptoms
while ICD 10 (World Health Organization, 1992) lists 9 signs and
symptoms for catatonia. Even catatonia rating scales differ not only
in the nature and number of included items, but even in the
denition of these items (Sienaert et al., 2011).
Currently, DSM IV Text Revision (American Psychiatric Association, 2000) recognizes catatonia as a distinct diagnostic category
(catatonia due to organic mental disorder), a subtype of a major
diagnostic entity (schizophrenia), as an episode specier of two
major diagnostic entities (major depression and bipolar disorder)
and also as an adverse effect of a treatment (neuroleptic malignant
syndrome). The number of signs and symptoms needed for the
diagnosis also vary according to the pathological condition
underlying the suspect catatonic syndrome. At least two signs
are required for the diagnosis of catatonic schizophrenia subtype
and for catatonic manifestations of mood disorders, while a single
motor symptom is needed for diagnosis of catatonia due to general
medical condition. Assessment of severity or duration of symptoms is not required.
7. Conclusion and future directions
Whether catatonic signs and symptoms constitute a subtype of
schizophrenia or a separate syndrome is still not clear. There is a
need for prospective and comprehensive studies in large samples
to address the lack of conceptual clarity in catatonia and to
determine its nosological position. Genetic and neuroimaging
studies can also add to our knowledge of the pathophysiology of
catatonia. With substantial gaps still present in our understanding

of catatonia, it is unlikely that the coming editions of Diagnostic

and Statistical Manual of Mental Disorders (DSM) and the
International Statistical Classication of Diseases and Related
Health Problems (ICD) will be able to put the controversy to rest.
Conict of interest
None.
References
Abrams, R., Taylor, M.A., 1976. Catatonia, a prospective clinical study. Archives of
General Psychiatry 33, 579581.
Ahuja, N., 2000. Organic catatonia: a review. Indian Journal of Psychiatry 42, 327
334.
American Psychiatric Association, 1952. Diagnostic and Statistical Manual of Mental Disorders, 1st ed. American Psychiatric Association, Washington, DC.
American Psychiatric Association, 1968. Diagnostic and Statistical Manual of Mental Disorders, 2nd ed. American Psychiatric Association, Washington, DC.
American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental
Disorders, 4th ed., text rev. American Psychiatric Association, Washington, DC.
Barnes, M.P., Saunders, M., Walls, T.J., Saunders, I., Kirk, C.A., 1986. The syndrome of
Karl Ludwig Kahlbaum. Journal of Neurology, Neurosurgery and Psychiatry 49,
991996.
Braunig, P., Kruger, S., Shugar, G., Hofer, J., Borner, I., 2000. The catatonia rating
scale I: development, reliability, and use. Comprehensive Psychiatry 41 (2)
147158.
Bush, G., Fink, M., Petrides, G., Dowling, F., Francis, A., 1996a. Catatonia. I. Rating
scale and standardized examination. Acta Paediatrica Scandinavica 93, 129
136.
Bush, G., Fink, M., Petrides, G., Dowling, F., Francis, A., 1996b. Catatonia. II. Treatment with lorazepam and electroconvulsive therapy. Acta Paediatrica Scandinavica 93, 137143.
Carroll, B.T., Annson, T.J., Kennedy, J.C., Yendrek, R., Boutros, M., Bilon, A., 1994.
Catatonic disorder due to general medical conditions. Journal of Neuropsychiatry and Clinical Neurosciences 6, 122133.
Chalasani, P., Healy, D., Morriss, R., 2005. Presentation and frequency of catatonia in
new admissions to two acute psychiatric admission units in India and Wales.
Psychological Medicine 35, 16671675.
Dhossche, D., Bouman, N., 1997. Catatonia in children and adolescents. Journal of
the American Academy of Child and Adolescent Psychiatry 36, 870871.
Fink, M., Taylor, M.A., 1991. Catatonia: a separate category for DSM-IV? Integrated
Psychiatry 7, 210.
Fink, M., 1996. Neuroleptic malignant syndrome and catatonia: one entity or two?
Biological Psychiatry 39, 14.
Fink, M., Shorter, E., Taylor, M.A., 2010. Catatonia is not schizophrenia: Kraepelins
error and the need to recognize catatonia as an independent syndrome in
medical nomenclature. Schizophrenia Bulletin 36, 314320.
Fink, M., Taylor, M.A., 2006. Catatonia: A Clinicians Guide to Diagnosis and
Treatment. Cambridge University Press, New York, NY.
Gelenberg, A.J., 1991. The catatonic syndrome. Lancet 1, 13391341.
Kahlbaum, K.L., 1874. Die Katatonie oder das Spannungsirresein. Verlag August
Hirshwald, Berlin.
Kleinhaus, K., Harlap, S., Perrin, M.C., Manor, O., Weiser, M., Harkavy-Friedman, J.M.,
Lichtenberg, P., Malaspina, D., 2012. Catatonic schizophrenia: a cohort prospective study. Schizophrenia Bulletin 38, 331337.
Kraepelin, E., 1896. Psychiatrie: ein Lehrbuch f ur Studierende und Arzte, 6th ed. J.
Ambrosius Barth, Leipzig.
Kruger, S., Bagby, R.M., Hofer, J., Braunig, P., 2003. Factor analysis of the catatonia
rating scale and catatonic symptom distribution across four diagnostic groups.
Comprehensive Psychiatry 44, 472482.
Mann, S.C., Caroff, S.N., Bleier, H.R., Welz, W.K., Kling, M.A., Hayashida, M., 1986.
Lethal catatonia. American Journal of Psychiatry 143, 13741381.
Morrison, J.R., 1975. Catatonia: diagnosis and treatment. Hospital & Community
Psychiatry 26, 9194.
Northoff, G., Koch, A., Wenke, J., Eckert, J., Boker, H., Pug, B., Bogerts, B., 1999.
Catatonia as a psychomotor syndrome. Movement Disorders 14, 404416.
Padhy, S.K., Subodh, B.N., Bharadwaj, R., Arun, K., Suresh, K., Srivastava, M.K., 2011.
Recurrent catatonia treated with lithium and carbamazepinea series of 2
cases. Primary Care Companion for CNS Disorders 13 (1) .
Rohland, B.M., Carroll, B.T., Jacoby, R.G., 1993. ECT in the treatment of the catatonic
syndrome. Journal of Affective Disorders 29, 255261.
Sienaert, P., Rooseleer, J., De Fruyt, J., 2011. Measuring catatonia: a systematic
review of rating scales. Journal of Affective Disorders 135, 19.
Smith, J.H., Smith, V.D., Philbrick, K.L., Kumar, N., 2012. Catatonic disorder due to a
general medical or psychiatric condition. Journal of Neuropsychiatry and
Clinical Neurosciences 24, 198207.
Suzuki, K., Awata, S., Matsuoka, H., 2003. Short-term effect of ECT in middle-aged
and elderly patients with intractable catatonic schizophrenia. Journal of ECT 19,
7380.
Taylor, M., Fink, M., 2003. Catatonia in psychiatric classication: a home of its own.
American Journal of Psychiatry 160, 19.

S.K. Padhy et al. / Asian Journal of Psychiatry 7 (2014) 69

Taylor, M.A., Abrams, R., 1977. Catatonia: prevalence and importance in the manic
phase of manic-depressive illness. Archives of General Psychiatry 34, 12231225.
Ungvari, G.S., Caroff, S.N., Gerevich, J., 2010. The catatonia conundrum: evidence of
psychomotor phenomena as a symptom dimension in psychotic disorders.
Schizophrenia Bulletin 36, 231238.
Ungvari, G.S., Goggins, W., Leung, S.K., Lee, E., Gerevich, J., 2009. Schizophrenia with
prominent catatonic features (catatonic schizophrenia). III: latent class analysis of the catatonic syndrome. Progress in Neuro-Psychopharmacology and
Biological Psychiatry 33, 8185.
Ungvari, G.S., Leung, C.M., Wong, M.K., Lau, J., 1994. Benzodiazepines in the
treatment of catatonic syndrome. Acta Psychiatrica Scandinavica 89, 285288.

van der Heijden, F.M., Tuinier, S., Arts, N.J., Hoogendoorn, M.L., Kahn, R.S., Verhoeven,
W.M., 2005. Catatonia: disappeared or under-diagnosed? Psychopathology 38,
38.
Wilcox, J.A., 1986. Organic factors in catatonia. British Journal of Psychiatry 149,
782784.
World Health Organization, 1949. Manual of the International Statistical Classication of Diseases, Injuries, and Causes of Death, 6th rev. World Health
Organization, Geneva.
World Health Organization, 1992. The ICD-10 Classication of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. World
Health Organization, Geneva.