Thursday, 7 January 2021

Glutamate Antagonists for the Treatment of Catatonia

Because of its N-methyl-d-aspartic acid antagonist properties, amantadine (100–500mg three times a day), and its derivative memantine (5–20mg/day), have been tried in catatonia.

  1. Carroll and coworkers identified 25 cases of amantadine and memantine use in the treatment of catatonia. All cases improved, mostly after 1–7days.

  2. It should be noted, however, that six were unpublished, and that seven other were cases experiencing a “catatonia-parkinsonian syndrome” while under treatment with the high-potency neuroleptic drugs haloperidol or fluphenazine.
  3. The symptoms diminished when neuroleptics were tapered, and they added amantadine. Since then, they have published eleven additional cases describing the successful use of amantadine or memantine in catatonia.
  4. In one case, in an adolescent girl, catatonia that was resistant to ECT improved after the addition of amantadine.
  5. Only in a review of Hawkins and coworkers, they report a case in which the use of amantadine remained without effect. Should acknowledge, however, that negative cases are less likely to be published.
  6. Given these positive signals in the published literature, and evidence of its efficacy in treating the negative and cognitive symptoms of schizophrenia, amantadine should be further studied as a feasible treatment option for catatonia. There is anecdotal evidence from case reports on the use of various other pharmacological agents, such as bromocriptine and biperiden.
  7. Based on the GABA-hypothesis of catatonia, and the GABA-related working mechanism of several anti-convulsive mood stabilizers, these drugs have been proposed as a viable treatment option to treat catatonia in bipolar patients.
  8. Only a few cases have published reports.
  9. They used valproate in several case reports and found not only to have prophylactic effects but also “an improving effect on the catatonic symptoms”.
  10. In a solitary case report, they advocated levetiracetam as a treatment for catatonia in bipolar disorder, given its mood-stabilizing efficacy.
  11. It is of note, however, that levetiracetam has also been described to provoke catatonia.
  12. Using topiramate and carbamazepine have also been reported.
  13. Although lithium has been anecdotally reported to have a beneficial effect on acute catatonic symptoms, they mostly describe it to be of use in the prevention of recurrent catatonia, albeit with sometimes limited results.


  1. Carroll BT, Goforth HW, Thomas C, Ahuja N, McDaniel WW, Kraus MF, et al. Review of adjunctive glutamate antagonist therapy in the treatment of catatonic syndromes. J Neuropsychiatry Clin Neurosci (2007) 19(4):406–12.10.1176/appi.neuropsych.19.4.406  
  2. Gelenberg AJ, Mandel MR. Catatonic reactions to high-potency neuroleptic drugs. Arch Gen Psychiatry (1977) 34(8):947–50.10.1001/archpsyc.1977.01770200085010  
  3. 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):292–9.10.1097/01.pra.0000400268.60537.5e  
  4. Babington PW, Spiegel DR. Treatment of catatonia with olanzapine and amantadine. Psychosomatics (2007) 48(6):534–6.10.1176/appi.psy.48.6.534  
  5. Muneoka K, Shirayama Y, Kon K, Kawabe M, Goto M, Kimura S. Improvement of mutism in a catatonic schizophrenia case by add-on treatment with amantadine. Pharmacopsychiatry (2010) 43(4):151–210.1055/s-0029-1242821  
  6. Hervey WM, Stewart JT, Catalano G. Treatment of catatonia with amantadine. Clin Neuropharmacol (2012) 35(2):86–710.1097/WNF.0b013e318246ad34  
  7. de Lucena DF, Pinto JP, Hallak JE, Crippa JA, Gama CS. Short-term treatment of catatonia with amantadine in schizophrenia and schizoaffective disorder. J Clin Psychopharmacol (2012) 32(4):569–7210.1097/JCP.0b013e31825ebf6e  
  8. Ene-Stroescu V, Nguyen T, Waiblinger BE. Excellent response to amantadine in a patient with bipolar disorder and catatonia. J Neuropsychiatry Clin Neurosci (2014) 26(1):E43.10.1176/appi.neuropsych.13020038  
  9. Mahmood T. Bromocriptine in catatonic stupor. Br J Psychiatry (1991) 158:437–810.1192/bjp.158.3.437  
  10. Franz M, Gallhofer B, Kanzow WT. Treatment of catatonia with intravenous biperidene. Br J Psychiatry (1994) 164(6):847–810.1192/bjp.164.6.847b  
  11. DelBello MP, Foster KD, Strakowski SM. Case report: treatment of catatonia in an adolescent male. J Adolesc Health (2000) 27(1):69–7110.1016/S1054-139X(00)00109-9  
  12. Kruger S, Braunig P. Intravenous valproic acid in the treatment of severe catatonia. J Neuropsychiatry Clin Neurosci (2001) 13(2):303–410.1176/appi.neuropsych.13.2.303  
  13. Bowers R, Ajit SS. Is there a role for valproic acid in the treatment of catatonia? J Neuropsychiatry Clin Neurosci (2007) 19(2):197–810.1176/appi.neuropsych.19.2.197  
  14. Yoshida I, Monji A, Hashioka S, Ito M, Kanba S. Prophylactic effect of valproate in the treatment for siblings with catatonia: a case report. J Clin Psychopharmacol (2005) 25(5):504–510.1097/  
  15. Muneer A. Catatonia in a patient with bipolar disorder type I. J Neurosci Rural Pract (2014) 5(3):314–610.4103/0976-3147.133652 [PMC free article]  
  16. Chouinard MJ, Nguyen DK, Clement JF, Bruneau MA. Catatonia induced by levetiracetam. Epilepsy Behav (2006) 8(1):303–7.10.1016/j.yebeh.2005.04.016  
  17. McDaniel WW, Spiegel DR, Sahota AK. Topiramate effect in catatonia: a case series. J Neuropsychiatry Clin Neurosci (2006) 18(2):234–8.10.1176/appi.neuropsych.18.2.234  
  18. Rankel HW, Rankel LE. Carbamazepine in the treatment of catatonia. Am J Psychiatry (1988) 145(3):361–2.   
  19. Wald D, Lerner J. Lithium in the treatment of periodic catatonia: a case report. Am J Psychiatry (1978) 135(6):751–2.   
  20. Pheterson AD, Estroff TW, Sweeney DR. Severe prolonged catatonia with associated flushing reaction responsive to lithium carbonate. J Am Acad Child Psychiatry (1985) 24(2):235–710.1016/S0002-7138(09)60454-4  
  21. Gjessing LR. Lithium citrate loading of a patient with periodic catatonia. Acta Psychiatr Scand (1967) 43(4):372–510.1111/j.1600-0447.1967.tb05774.x  

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