Intravenous Valproic Acid in the Treatment of Severe Catatonia

M.T. is a 38-year-old man who had been diagnosed with catatonic schizophrenia at age 18. He required, on average, 10 admissions per year. The acute phases were characterized by motor excitement; impulsive aggression; groping; stereotypies; iterations; impulsive behaviors such as binge eating, pica, and public nudity and masturbation; grimacing; vocal utterances (screaming); negativism; and gegenhalten. Neurological and medical disorders had been excluded. In the short intervals between acute phases, he exhibited severe negative symptoms accompanied by mannerisms and bizarre behaviors. The patient had been treated unsuccessfully with typical and atypical neuroleptics during previous hospitalizations and had shown minimal sedation on up to 12 mg/day of lorazepam both orally and intravenously. His legal representative had not agreed to ECT treatment.

During the index admission, oral administration of medication had not been possible because the patient was unable to open his mouth or to swallow due to extreme rigidity, negativism, and gegenhalten. Because of the previous treatment failures, we started a regimen of high-dose intravenous valproic acid monotherapy. On day 1, the patient received 4,000 mg/day of valproic acid, followed by a reduction of catatonic symptoms of 30% (measured by a systematic rating scale for catatonia⁴). On day 2, the patient received 3,000 mg/day of lorazepam followed by an additional 20% symptom reduction. On day 3, the dose was reduced to 2,500 mg/day, and on day 4, 1,800 mg/day were administered, resulting in a symptom reduction of 90%. The patient tolerated the treatment well and was finally able to take medication orally. He was maintained on 900 mg/day of valproate (plasma level 60 μg/l) and has not required any admissions for acute catatonic symptoms for 6 months.

This is the first report of successful intravenous valproic acid monotherapy in severe catatonic schizophrenia. We have since successfully treated 3 more cases with a similar regimen.

Although the etiology of the complex catatonic syndrome is not known, some symptoms have been associated with deficiency of gamma-aminobutyric acid (GABA).⁵ Valproic acid increases central GABAergic transmission by inhibiting GABA catabolism, stimulation of GABA synthesis, and potentiation of postsynaptic GABAergic effects⁶ and may thus lead to amelioration of catatonic symptoms. It would certainly be worthwhile to investigate the use of valproic acid in the acute and even prophylactic treatment of catatonia more systematically, as this agent may provide an effective and safe alternative in treatment nonresponders with a severe catatonic syndrome.