August 08, 2004

A review of Valproate (Depakote) as a booster medicine for schizophrenia

Valproate as an adjunct to antipsychotics for schizophrenia: a systematic review of randomized trials.
Basan A, Kissling W, Leucht S.
Schizophr Res. 2004 Sep 1;70(1):33-7.

This article takes a systematic look at the literature regarding the efficacy of using valproic acid (Depakote) as an adjunctive (additional to an antipsychotic) medication for schizophrenia. This medicine is a mood stabilizer and is typically a first line drug for treating bipolar disorder. However, it has properties that may make it useful in people with schizophrenia. It targets a neurotransmitter (chemical in the brain that turns on or off neurons or brain cells) called GABA which is a neurotransmitter that typically has a turning-off effect on brain cells. Some of these cells are involved in the production of dopamine which is a neurotransmitter that is associated, when in too high of a level, with the positive symptoms of schizophrenia (hallucinations, delusions, paranoia, bizarre thinking) and when in too little concentration, with the movement side effects seen with certain medications, like haloperidol/Haldol.

These authors searched the literature and came up with several articles that seemed relevant. Upon applying certain standards, five articles met the eligibility requirement to be included in the review and meta-analysis. (A meta-analysis is where the data from several studies are compiled together and analyzed as a group.) The results presented in this paper are equivocal at best. There are upsides and downsides to polypharmacy (the use of more than one medication to treat a particular condition.) On the one hand, the more meds you have someone take, the greater risk there is for side effects and drug interactions. Valproic acid has problems with weight gain and liver toxicity and that is true with other antipsychotics which can make for a problem. However, there is some minor evidence that valproic acid may help speed up the initial recovery of someone when starting or restarting them on antipsychotic medication. That can be useful if they only have a short time in the hospital and cannot afford to wait the couple of weeks to get full effect by the antipsychotic alone. However, the benefit wears out and was gone by the end of the study that showed this benefit, so it is unclear whether it means that the valproic acid should be continued or stopped after the acute situation resolves. Small trials have suggested that there may be a general decrease in negative symptoms (flat affect, constricted emotions, low energy, low motivation, poor hygiene) that is sometimes the most debilitating aspect of schizophrenia for many people. It does seem though, that valproic acid is useful in the case of schizoaffective disorder when there is a need for mood stability. It also seems to have a place for the aggressive or violent patient who has frequent outbursts and can benefit from some stabilization of their mood.

Overall, should you ask the doctor to start valproic acid for you or your loved one? Well, if they are already stable on medication, it is not something that they need to have. If they aren't doing well, it might be worth a try to add it if there are no strong reasons to stay away from it (poor liver function, pregnancy or intent to become pregnant or history of weight gain or nonresponse to valproic acid.) The data currently is inconclusive to the benefit for valproic acid augmentation and therefore it is not possible to give a blanket recommendation one way or the other. However, if things are not working, it might be worth a try if it hasn't been tried in the past.

link to abstract on pubmed

Author: Jacob Ballon


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