Is There a Role for Valproic Acid in the Treatment of Catatonia?

“Ms. G” was a 46-year-old woman with a history of alcohol dependence who possibly suffered from a mood disorder for years based on her biopsychosocial history; however, she was never treated for her mood disorder. She presented with motor as well as affective signs of catatonia on multiple admissions to various hospitals within a span of 4 months. She was treated with benzodiazepines with improvement in catatonic motor signs. Ms. G was placed on various antipsychotics for her catatonic affective symptoms, which failed to improve, with her motor signs invariably returning. She was transferred to our institution for further evaluation and after several weeks with no improvement was placed on a regimen of valproic acid, 1000 mg, and within 3 to 4 days her catatonic symptoms dissipated. The patient was discharged on this regimen with no subsequent catatonic episodes.

Case reports using valproic acid in the treatment of catatonia successfully have documented neuroimaging studies showing a GABA-A receptor density reduction in the brains of catatonic patients. 2 These data further support a GABAergic deficit in catatonic patients. The relationship between catatonia and mood disorders is well established, where approximately a quarter to half the patients with catatonia also meet criteria for a mood disorder. 3 Plasma GABA levels have also been noted to be low in approximately 40% of patients with mood disorders, which further supports the hypothesis of a GABAergic deficit in catatonia and bipolar disorder. 4 Extrapolating from the above, we suggest that GABA modulation may be a significant factor involved in illness ranging from mood disorders to catatonia. The number of patients with catatonic schizophrenia has declined, yet the number of patients with catatonia associated with mood disorders has remained stable. 3 This may, in part, be due to use of antipsychotics and involvement of a GABAergic mechanism (animal studies have shown GABA modulation of GABA receptors in animals treated on antipsychotics for a period of time). 5 This may support a greater preponderance for GABAergic deficit in mood disorder patients then in schizophrenia patients. The mechanism is not clear on how valproic acid works, but it is clear that it increases CNS GABA. Studies have shown that valproic acid enhances GABA level and neuronal GABA responsiveness. The use of valproic acid should be considered an option for treatment of catatonic patients, particularly those with mood disorders.