CLINICAL HANDBOOK OF SCHIZOPHRENIA

188 III. SOMATIC TREATMENTtolerated, produced a faster onset of action in the combination group, and indicated reducedhostility and core psychotic symptoms. This advantage for valproate augmentationwas not sustained, however, beyond the first week of treatment.Based on the randomized trial–derived evidence currently available, therefore, nodata support or refute the use of valproate as an adjunctive agent in the long-term treatmentof schizophrenia. However, it may be reasonable to consider valproate for acutelyill inpatients with agitation in the first weeks of treatment and when more rapid improvementis important. We also support the use of valproate in patients with unstable moodswhen an antipsychotic alone fails to lead to mood stability.CarbamazepineA review of the available literature by Leucht et al. (2002) determined that carbamazepinemonotherapy has not been shown to be effective in the treatment of schizophrenia whencompared to placebo or antipsychotic. Some studies have shown a trend indicating a benefitfrom carbamazepine as an adjunct to antipsychotics in the treatment of schizophrenia,but the trials have had small numbers of subjects, and a review of the available datahas indicated inconsistent and inconclusive results.Some preliminary data show that carbamazepine may be useful in treating affectivesymptoms of schizophrenia, and may decrease violent behavior in psychotic patients.However, the studies are extremely limited, and further research is warranted on the useof carbamazepine in patients with excitement, aggression, mania with psychosis, and bipolar-typeschizoaffective disorder.Furthermore, it is important to note that because carbamazepine induces metabolicactivity and can therefore lower the dose of certain antipsychotics (e.g., haloperidol,thiothixene) when administered adjunctively, when it is withdrawn, a corresponding increaseof the antipsychotic may occur. Indeed, studies of patients on haloperidol demonstratedthat the adjunctive use of carbamazepine was associated with a dramatic fall inhaloperidol plasma levels and a worse clinical outcome compared to the monotherapygroup.Thus, at present, neither carbamazepine monotherapy nor augmentation can be recommendedon the basis of the available evidence for routine use in the treatment ofschizophrenia.LamotrigineSeveral lines of evidence suggest that glutamate may be involved in schizophreniapathophysiology. Postmortem studies have revealed a lower density of glutamatergic receptorsin patients with schizophrenia; and lower levels of cerebrospinal fluid (CSF) glutamatehave been found in patients with schizophrenia compared to normal controls. Themost compelling evidence is provided by the psychomimetic effects of the N-methyl-dasparticacid (NMDA) antagonists phencyclidine and ketamine. When administered tonormal controls, both agents can induce positive, negative, and cognitive symptoms similarto those observed in patients with schizophrenia. Hence, there has been much interestand speculation about the role of lamotrigine, which acts on the glumatate system, in thetreatment of schizophrenia.Despite this, there are few studies in the literature about the effects of lamotriginein the treatment of schizophrenia. There are no reported randomized, controlled clinicaltrials of lamotrigine monotherapy in schizophrenia, and few trials of adjunctivetreatment.