Review of Pharmacotherapy in the Treatment of the Catatonic Syndrome: First-Line, Adjunctive/Combination and Novel Options

Main Article Content

David Spiegel


Catatonia is a clinical syndrome characterized by a range of psychomotor abnormalities that occur in the context of a wide variety of both psychiatric and medical conditions.  It occurs in affective, psychotic, autistic, developmental and medical disorders. Catatonia may present with unusual stereotypies and medical comorbidities. Despite these various etiologies, treatment has been convergent on the gamma aminobutyric acid agonists (i.e., benzodiazepines), and glutamate antagonists, corresponding with the known pathophysiology on this syndrome. Treatment refractory and emergent cases are often referred to electroconvulsive therapy. The focus of this manuscript will be to review these known treatments in montherapy, adjunctive, combined, and potential novel pharmacotherapy.

Article Details

How to Cite
SPIEGEL, David. Review of Pharmacotherapy in the Treatment of the Catatonic Syndrome: First-Line, Adjunctive/Combination and Novel Options. Medical Research Archives, [S.l.], v. 4, n. 7, nov. 2016. ISSN 2375-1924. Available at: <>. Date accessed: 20 jan. 2018.
Catatonia; Gamma aminobutyric acid; Glutamate
Review Articles



1. Spiegel DR, Klaiber N. A Case of Catatonia Status-Post Left Middle Cerebral Artery Cerebrovascular Accident, Treated Successfully With Olanzapine. Clin Neuropharmacol. 2013;36(4):135-137. doi:10.1097/WNF.0b013e3182956d4d.

2. Babington PW, Spiegel DR. Treatment of catatonia with olanzapine and amantadine. Psychosomatics.
2007;48(6):534-536. doi:10.1176/appi.psy.48.6.534.

3. 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(4):406-412. doi:10.1176/appi.neuropsych.19.4.406.

4. Thomas P, Rascle C, Mastain B, Maron M, Vaiva G. Test for catatonia with zolpidem. Lancet (London, England). 1997;349(9053):702. doi:10.1016/S0140-6736(05)60139-0.

5. Dhossche D, Wilson C, Wachtel L. Catatonia in Childhood and Adolescence: Implications for the DSM-5. Prim Psychiatry. 2010:1723-1726.

6. Northoff G. Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology. J Neural Transm. 2002;109:1453-1467. doi:10.1007/s00702-002-0762-z.

7. Fink M, Taylor M. Neuroleptic malignant syndrome is malignant catatonia, warranting treatments efficacious for catatonia. Prog Neuropsychopharmacol Biol. 2006 Aug 30;30(6):1182-3; author reply 1184-5.

8. Francis A. Catatonia: Diagnosis, Classification, and Treatment. Curr Psychiatry Rep. 2010;12(3):180-185. doi:10.1007/s11920-010-0113-y.

9. Fink M, Kellner CH, McCall WV. Optimizing ECT Technique in Treating Catatonia. J ECT. 2016;32(3):149-150. doi:10.1097/YCT.0000000000000345.

10. Chang CH, Hsiao YL, Hsu CY, Chen ST. Treatment of catatonia with olanzapine: a case report. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1559-60.

11. Bowers R, Ajit SS. Is there a role for valproic acid in the treatment of catatonia? J Neuropsychiatry Clin Neurosci. 2007;19(2):197-198. doi:10.1176/jnp.2007.19.2.197.

12. Kritzinger PR, Jordaan GP. Catatonia: an open prospective series with carbamazepine. Int J Neuropsychopharmacol. 2001;4(3):251-257. doi:doi:10.1017/S1461145701002486.

13. Hosák L, Libiger J. Antiepileptic drugs in schizophrenia: a review. Eur Psychiatry. 2002;17(7):371-378.

14. Crestani F, Martin JR, Möhler H, Rudolph U. Mechanism of action of the hypnotic zolpidem in vivo. Br J Pharmacol. 2000;131(7):1251-1254. doi:10.1038/sj.bjp.0703717.

15. García-Santos G, Herrera F, Martín V, et al. Antioxidant activity and neuroprotective effects of zolpidem and several synthesis intermediates. Free Radic Res. 2004;38(12):1289-1299. doi:10.1080/10715760400017343.

16. Bastiampillai T, McGovern V, Lloyd B, Hittur Lingappa S, Nelson A. Treatment refractory chronic catatonia responsive to zolpidem challenge. Aust N Z J Psychiatry. 2016;50(1):98. doi:10.1177/0004867415582232.

17. Mastain B, Vaiva G, Guerouaou D, Pommery J. Favourable effect of zolpidem on catatonia. Rev Neurol (Paris). 1995 Jan;151(1):52-6.

18. Rasele C, Thomas P, Maron M, et al. Catatonia relief with zolpidem: An open study. Eur Neuropsychopharmacol. 1997;7:S277. doi:10.1016/S0924-977X(97)88920-1.

19. Thomas P, Cottencin O, Rascle C, Vaiva G. A case of agitated catatonia. Pharmacopsychiatry. 1999 Jan;32(1):38-40.

20. Polasek T, Sadagopal J, Elliot D. In vitro-in vivo extrapolation of zolpidem as a perpetrator of metabolic interactions involving CYP3A. Eur J Clin Pharmacol. 2010 Mar;66(3):275-83.

21. Williams ST, Conte MM, Goldfine AM, et al. Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury. Elife. 2013;2:e01157. doi:10.7554/eLife.01157.

22. Sallin K, Lagercrantz H, Evers K, Engström I, Hjern A, Petrovic P. Resignation Syndrome: Catatonia? Culture-Bound? Front Behav Neurosci. 2016;10:7. doi:10.3389/fnbeh.2016.00007.

23. Taylor MA, Fink M. Catatonia in psychiatric classification: a home of its own. Am J Psychiatry. 2003;160(7):1233-1241. doi:10.1176/appi.ajp.160.7.1233.

24. Akeju O, Brown EN, Brefel-Courbon C, et al. Awakened by a sleeping pill. Elife. 2013;2:e01658. doi:10.7554/eLife.01658.

25. Coyle J. The GABA-glutamate connection in schizophrenia: which is the proximate cause? Biochem Pharmacol. 2004 Oct 15;68(8):1507-14.

26. Gianutsos G, Chute S, Dunn J. Pharmacological changes in dopaminergic systems induced by long-term administration of amantadine. Eur J Pharmacol. 1985 Apr 16;110(3):357-61.

27. Goetz M, Kitzlerova E, Hrdlicka M. Combined use of electroconvulsive therapy and amantadine in adolescent catatonia precipitated by cyber-bullying. J Child Adolesc Psychopharmacol. 2013 Apr;23(3):228-31.

28. Bleidner WE, Harmon JB, Hewes WE, Lynes TE, Hermann EC. Absorption, distribution and excretion of amantadine hydrochloride. J Pharmacol Exp Ther. 1965;150(3):484-490.

29. Gualtieri T, Chandler M, Coons T. Amantadine: a new clinical profile for traumatic brain injury. Clin Neuropharmacol. 1989 Aug;12(4):258-70.

30. Zafonte RD, Lexell J, Cullen N. Possible applications for dopaminergic agents following traumatic brain injury: part 2. J Head Trauma Rehabil. 2001 Feb;16(1):112-6.

31. Vargus-Adams J, McMahon M, Michaud L, Bean J. Pharmacokinetics of amantadine in children with impaired consciousness due to acquired brain injury: preliminary findings using a sparse-sampling technique. PM & R. 2010 Jan;2(1):37-42.

32. Obregon DF, Velasco RM, Wuerz TP, Catalano MC, Catalano G, Kahn D. Memantine and catatonia: a case report and literature review. J Psychiatr Pract. 2011;17(4):292-299. doi:10.1097/01.pra.0000400268.60537.5e.

33. McDaniel WW, Spiegel DR, Sahota AK. Topiramate effect in catatonia: a case series. J Neuropsychiatry Clin Neurosci. 2006;18:234-238. doi:10.1176/appi.neuropsych.18.2.234.

34. Muneer A. Catatonia in a patient with bipolar disorder type I. J Neurosci Rural Pract. 2014;5(3):314-316. doi:10.4103/0976-3147.133652.

35. Lee C-Y, Chen C-C, Liou H-H. Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus. Br J Pharmacol. 2009;158(7):1753-1762. doi:10.1111/j.1476-5381.2009.00463.x.

36. Sienaert P, Dhossche DM, Vancampfort D, De Hert M, Gazdag G. A clinical review of the treatment of catatonia. Front Psychiatry. 2014;5:181. doi:10.3389/fpsyt.2014.00181.

37. Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011;36(2):78-86. doi:10.1503/jpn.100057.

38. Baker DA, Xi Z-X, Shen H, Swanson CJ, Kalivas PW. The origin and neuronal function of in vivo nonsynaptic glutamate. J Neurosci. 2002;22(20):9134-9141.

39. Munoz C, Yulan N, Achaval V, Appiani F, Carroll BT. Memantine in major depression with catatonic features. J Neuropsychiatry Clin Neurosci. 2008;20(1):119-120. doi:10.1176/jnp.2008.20.1.119.

40. Yoshida I, Monji A, Hashioka S, et al. Prophylactic effect of valproate in the treatment for siblings with catatonia: a case report. J Clin Psychopharmacol. 2005 Oct;25(5):504-5.

41. Soltanianzadeh Y, Greene E, Slootsky V. A 32-Year-Old Man with Chest Pain, Confused Mental State, and Muscle Rigidity. Psychiatr Ann. 2016;46(5):274-276.

42. Spiegel DR, Thanam S., and Rayamajhi U. In: Catatonia on the Consultation Liaison Service and Other Clinical Settings. Ed. Carroll BT and Spiegel DR., Nova Science Publishers, New York, 2016.

Most read articles by the same author(s)

Obs.: This plugin requires at least one statistics/report plugin to be enabled. If your statistics plugins provide more than one metric then please also select a main metric on the admin's site settings page and/or on the journal manager's settings pages.