Consecutively, Simhandl et al119 reported a significant effect in chronic schizophrenia for adjunctive carbamazepine treatment in an 8-week double-blind, placebocontrolled study. However, the use of carbamazepine may also diminish serum levels of some antipsychotics, eg, risperidone or haloperidol, and thus lead to worsening of psychosis.120 A recent Cochrane meta-analysis also came to the conclusion that carbamazepine cannot be recommended for routine clinical use for the treatment of augmentation

of antipsychotic treatment of schizophrenia.121 The widespread use of valproate – especially Inhibitors,research,lifescience,medical in the US – in schizophrenic patients is backed up by at least 6 open positive studies including difficult-to-treat

late-life schizophrenia,122 and two double-blind add-on studies.123,124 A meta-analysis including all randomized studies, however, again gave no unambiguous evidence in favor of valproate.125 The antiglutamatergic actions of lamotrigine and topiramate may be of particular interest because of hypothesized Inhibitors,research,lifescience,medical glutamatergic mechanisms in schizophrenia. They may be capable of reducing excessive glutamatergic hyperactivity due to selective NMDA receptorblocka.de of interneurons.126 Inhibitors,research,lifescience,medical A well-controlled experimental study observed protective effects of lamotrigine against ketamine-induced psychosis127 followed by three blinded, placebo-controlled studies in which lamotrigine was shown to be effective (in combination with clozapine or other atypical antipsychotics) in treatment-refractory schizophrenic patients.128,130 However, again, a meta-analysis including all randomized studies was not able to support, lamotrigine’s effectiveness,

Inhibitors,research,lifescience,medical mostly due to the poor quality of reporting of every single trial.131 For topiramate, a small (n=26) but placebo-controlled add-on Inhibitors,research,lifescience,medical study of ongoing atypical antipsychotics was suggestive of effects on general psychopathology,but was unable to show a significant, improvement in positive or negative symptoms.132 Affective disorders Unipolar depression Although large randomized, placebo-controlled monotherapy Casein kinase 1 trials failed,133 lamotrigine may be of interest for the treatment of refractory unipolar depression. DAPT solubility dmso Retrospective chart reviews (eg, ref 134) open135 and randomized open-label,136 and controlled augmentation studies137,138 are supportive of an antidepressant effect of lamotrigine add-on in treatment-resistant major depressive disorder (MDD). In a double-blind, placebo-controlled study, topiramate appeared to be an effective agent in the reduction of depressive symptoms and anger in moderately depressed women,139 but these results have not yet been replicated. Of the older anticonvulsants, carbamazepine has shown limited evidence in open studies for an acute antidepressant140-143 and prophylactic effect.