Tiihonen et al68 have reported evidence from a post-hoc analysis of patients from five trials involving lamotrigine augmentation of clozapine which suggested some significant effects, but interpretation remains difficult because of different designs and inclusion criteria. Further well-designed studies involving lamotrigine would be very valuable.

Since available antipsychotics generally have only limited efficacy for negative symptoms and since negative symptoms are Inhibitors,research,lifescience,medical closely related to functional outcomes, various augmentation strategies of antipsychotics have been tested in this domain. Despite positive results in initial, small scale trials with N-methyl-D-aspartate (NMDA) receptor agonistic treatments, such as glycine, d-alanine, d-serine, dcycloserine, the largest placebo-controlled study

of glycine and d-cycloserine was negative.69 However, recent trials of augmentation treatment with glycine transporter inhibitors have been positive,70 suggesting that this Dovitinib chemical structure mechanism may be more promising. In addition a meta-analysis of 5 smallscale trials Inhibitors,research,lifescience,medical of adjunctive treatment with antidepressants concluded that these agents may reduce negative symptoms in patients with a predominantly negative symptom profile.71 However, since depression can mimic negative symptoms and since these trials had only 16 or less patients in each treatment arm, more Inhibitors,research,lifescience,medical data are needed. Maintenance treatment Once the maximum degree of therapeutic response is achieved after an acute exacerbation, the challenge becomes maintaining those gains, preventing relapse and facilitating Inhibitors,research,lifescience,medical the ongoing application of appropriate psychosocial and vocational therapies. There is little question about the indications for continuing antipsychotic medication on an indefinite basis, except perhaps in patients who have only experienced Inhibitors,research,lifescience,medical one episode. Even there, however, relapse rates are 82% after 5 years,37 and discontinuing medication is associated with a five times higher

risk of relapse than staying on medication. This does suggest, however, that a small subgroup of patients might remain Cilengitide free of relapse, but at present we have no means to identify such individuals prior to making the decision to stop antipsychotic maintenance therapy. The choice of medication takes on particular importance when long-term treatment is the focus, as the benefitto-risk ratio may change substantially. Some drugs are associated with greater or lesser degrees of specific longterm risks, eg, tardive dyskinesia, weight gain, type 2 this research diabetes, dyslipidemia, etc. Risk not only varies by drug, but of course also from individual to individual. At present, taking a good history and appropriate ongoing monitoring is the best strategy to identify particular risk profiles, but it is hoped that in the not-too-distant future pharmacogenetics might help in informing choice of optimum treatment(s).