Approximately two-thirds of patients will respond to treatment with benzodiazepines, although those with catatonic schizophrenia show reduced responsiveness. Catatonia sometimes re-emerges during transition from IV lorazepam to oral dosing. This may require reinstitution of IV lorazepam and an eventual higher oral dosing. There is no established guideline for how long benzodiazepine responders will require maintenance. We have had patients on benzodiazepines for weeks and even months, necessitating careful eventual taper. If decreased tolerance to benzodiazepines emerges (via increasing sedation), it is safe to gradually taper the benzodiazepine. After discontinuation, lorazepam may again be needed in cases of catatonic rebound.
If catatonia persists for more than 2 to 3 days or if malignant features are present, ECT remains the definitive treatment. ECT works synergistically with benzodiazepines and demonstrates response rates of up to 80%.13 Bitemporal placement is recommended, at a frequency of 3 times per week for at least 6 sessions. ECT may work by increasing cerebral blood flow to the orbitofrontal and parietal cortices, increasing GABA activity and GABA receptor expression, and by increasing dopamine release and modulation of dopamine receptors.
When benzodiazepines are ineffective or contraindicated and ECT is unavailable or refused, second-line treatments include glutamatergic agents, such as memantine (5-10 mg twice daily) or amantadine (400-600 mg daily in divided doses). These agents appear to be safe, well-tolerated, and effective in case reports, as monotherapy or in combination with a benzodiazepine. Other options include valproate or carbamazepine, which may be particularly useful if the catatonia is related to underlying mania. Valproic acid has demonstrated some effectiveness in excited catatonia.
A final option to consider is an atypical antipsychotic. These agents are the last step in the algorithm because of their potential to worsen catatonia or cause conversion to a malignant catatonia. Antipsychotics should be given in combination with a benzodiazepine, and low-potency atypical agents are preferred. Among antipsychotic agents, aripiprazole may be the safest choice given its partial-agonist activity. If the catatonia occurs in the setting of clozapine cessation, re-initiation of clozapine should be a first-line strategy. High-potency typical antipsychotics should generally be avoided in catatonic patients.
Supportive management is essential in cases of catatonia. In addition to treatment of the catatonic symptoms, full resolution often requires treatment of the underlying disorder. This can be challenging in cases of psychosis, which may require a careful balance of antipsychotics and benzodiazepines.
As a neuropsychiatric and general medical syndrome, catatonia represents an important diagnostic and treatment challenge for all clinicians given its morbidity and mortality. By examining the nature of cortico-striato-thalamo-cortical circuits and the effects of transmitters and modulating systems, we can better understand why such a wide array of etiologies can present with the catatonic syndrome and why the pharmacologic and electroconvulsive treatments can be very effective when provided expeditiously.
Dr Beach is Assistant Professor of Psychiatry and Residency Training Director, Massachusetts General Hospital, Harvard Medical School; Dr Francis is Professor of Psychiatry, Associate Director of Residency Training, and Director of Neuromodulation Services, Penn State Medical School, Hershey Medical Center, Hershey, PA; Dr Fricchione is Professor of Psychiatry, Mind Body Medical Institute and Associate Chief of Psychiatry, Massachusettes General Hospital, Harvard Medical School, Boston, MA. Drs Fricchione and Beach have received funding through the David Judah Fund for catatonia research.
1. Taylor MA, Fink M. Catatonia in psychiatric classification: a home of its own. Am J Psychiatry. 2003;160:1233-1241.
2. Fricchione GL. Neuroleptic catatonia and its relationship to psychogenic catatonia. Biol Psychiatry. 1985;20:304-313.
3. Carroll BT. The universal field hypothesis of catatonia and neuroleptic malignant syndrome. CNS Spectr. 2000;5:26-33.
4. Fisher CM. Honored guest presentation: abulia minor vs. agitated behavior. Clin Neurosurg. 1983;31:9-31.
5. Northoff G. What catatonia can tell us about “top-down modulation”: a neuropsychiatric hypothesis. Behav Brain Sci. 2002;25:555-577.
6. Northoff G. Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology. J Neural Transm. 2002;109:1453-1467.
7. Hirjak D, Kubera KM, Northoff G, et al. Cortical contributions to distinct symptom dimensions of catatonia. Schizophr Bull. February 2019; Epub ahead of print.
8. Fricchione G, Mann SC, Caroff SN. Catatonia, lethal catatonia, and neuroleptic malignant syndrome. Psychiatric Annals. 2000;30:347-355.
9. Tuerlings JH, van Waarde JA, Verwey B. A retrospective study of 34 catatonic patients: analysis of clinical care and treatment. Gen Hosp Psychiatry. 2010;32:631-635.
10. Fisher CM. “Catatonia” secondary to disulfiram toxicity. Arch Neurol. 1989;46:798-804.
11. Fricchione GL, Cassem NH, Hooberman D, Hobson D. Intravenous lorazepam in neuroleptic-induced catatonia. J Clin Psychopharmacol. 1983;3:338-342.
12. Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia. II. Treatment with lorazepam and electroconvulsive therapy. Acta Psychiatr Scand. 1996;93:137-143.
13. Petrides G, Divadeenam KM, Bush G, Francis A. Synergism of lorazepam and electroconvulsive therapy in the treatment of catatonia. Biol Psychiatry. 1997;42:375-381.
14. Fink M, Taylor MA. Catatonia: A Clinician’s Guide to Diagnosis and Treatment. New York, NY: Cambridge University Press; 2003.
15. Levenson JL. Medical aspects of catatonia. Prim Psychiatry. 2009;16:23-26.
16. Philbrick KL, Rummans TA. Malignant catatonia. J Neuropsychiatry Clin Neurosci. 1994;6:1-13.
17. Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia I: rating scale and standardized examination. Acta Psychiatr Scand. 1996;93:129-136.
18. Carroll BT, Goforth HW, Thomas C, et al: Review of adjunctive glutamate antagonist therapy in the treatment of catatonic syndromes. J Neuropsychiatry Clin Neurosci. 2007;19:406-412. ❒