Intravenous Valproate Treatment: Some Observations

Dear Editor:

Norton (1) highlights the utility of intravenous (IV) valproate treatment in psychiatry. At the Central Institute of Psychiatry, Ranchi, India, we have used IV valproate, and I would like to share some observations and describe difficulties encountered while using this formulation. Initially, we used IV valproate to treat acute manic exacerbation in 2 patients—one with bipolar disorder and the other with schizoaffective disorder, manic type (diagnosed according to the ICD-10 criteria) (2). Both patients showed a dramatic improvement in manic as well as in psychotic symptoms, without taking concomitant antipsychotics. Moreover, the fact that IV valproate effectively treated schizoaffective disorder was a novel observation, in contrast to a previous report (3).

Encouraged by these results, we have initiated a study comparing oral and IV valproate loading in patients with an acute manic episode. The protocol being followed for administering IV valproate is as described by Norton and Quarles (4). Despite the good response of manic symptoms to IV valproate, however, we have encountered some problems with this treatment modality. We wish, not to discourage psychiatrists from trying this preparation, but to caution them. First, the infusion was not possible in highly agitated patients, even with physical restraints in some cases: these patients became more combative, and the infusion had to be discontinued to avoid exhaustion. Thus, although we recommend this treatment for acutely agitated patients, the patient’s cooperation may be a prerequisite. Second, we also encountered nausea and vomiting in doses ranging from 20 to 30 mg/kg, both during and immediately following the infusion (the total dosage not exceeding 1500 mg daily, in divided doses). Although IV valproate causes less nausea (1), one has to bear in mind that the patient must ultimately be switched to oral valproate, and those not tolerating IV valproate also may not tolerate oral valproate. Third, in a few cases we had to reduce the dosage after switching to an oral preparation, because patients developed more adverse effects after receiving the oral formulation in the same dosage. This reduction led to reemergence of symptoms in one patient, who had to be started on a second mood stabilizer. Fourth, although we had kept the patients only on valproate and lorazepam (as needed) during the study, one patient was inadvertently administered 10 mg of IV haloperidol. This patient developed marked dizziness, ataxia, and sedation and had to be dropped from the study. Thus, potential drug interactions with IV valproate require further exploration. Finally, although the initial response to IV valproate was dramatic, it tended to slow down, or even plateau, by day 3 of the infusion. Additional antipsychotics were then required, especially in patients with predominant psychosis. Because most data on the use of IV vaproate derive from patients with epilepsy, we encourage more studies of psychiatric patients to gain insights into the appropriate dosing strategies and the adverse-effect profile.

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Harpreet S Duggal, MD
Pittsburgh, Pennsylvania