Can Intravenous Drugs have Rapid Effects on Mania?

By Prof. Levine

In these two research trials we explored whether very high dose intravenous valproate or fosphenytoin might have rapid effects [within 20 minutes] on mania equivalent to the effects reported with these drugs in status epilepticus.

Phrolov K, Applebaum J, Levine J, Miodovnick H, Belmaker RH. Single-dose intravenous valproate in acute mania. J Clin Psychiatry. 2004 Jan;65(1):68-70

OBJECTIVE: High-dose loading with oral and intravenous valproate has been reported to be therapeutic in mania over 48 to 72 hours. We hypothesized that very high dose intravenous (IV) valproate might have even more rapid effects equivalent to effects in status epilepticus that occur within 20 minutes.

METHOD: Seven patients with mania (Young Mania Rating Scale score > 20) and minimal prior drug treatment were given valproate 20 mg/kg IV over 30 minutes.

RESULTS: No antimanic effects were observed during 120 minutes of observation. There were no side effects.

CONCLUSION: Slowly evolving biochemical changes, perhaps at the gene level, may be required for the antimanic effect of anticonvulsants.

Applebaum J, Levine J, Belmaker RH. Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9

OBJECTIVES: Since several anticonvulsants are therapeutic in mania and since acute mania requires rapid and intensive treatment, we hypothesized that intravenous high-dose phenytoin might be acutely antimanic. A new prodrug of phenytoin, fosphenytoin, which has few cardiac or local vein side effects, was used to test this hypothesis.

METHOD: Seven patients with a DSM-IV manic episode and minimal prior drug treatment were given intravenous fosphenytoin and were assessed at baseline and after 15, 30, 45, and 60 minutes with the Young Mania Rating Scale, the Clinical Global Impressions scale, and the Mini-Mental State Examination. Data were gathered in 2002.

RESULTS: No antimanic effects were observed. No subject had any clear improvement in manic symptoms on the YMRS at any timepoint assessed.

CONCLUSION: Intravenous fosphenytoin at doses that are effective in status epilepticus appears to be ineffective in acute mania.

Stanley Research Center, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.