In addition, the complex receptor binding profile of clozapine has suggested to

some that attempts to simulate this effect should involve combining multiple drugs. There are several reports indicating a high prevalence of antipsychotic polypharmacy in recent clinical practice.55 #PRT062607 randurls[1|1|,|CHEM1|]# Despite widespread use, there is relatively little evidence that this strategy is helpful, particularly when clozapine is not involved. Correll et al56 reviewed 19 randomized trials including 1216 subjects. Although the overall results could be interpreted Inhibitors,research,lifescience,medical as suggesting an advantage for combination therapy in comparison with monotherapy, the factors which appeared to contribute to this effect limit the conclusions that can be drawn for the present context. Combination therapy was more likely to be efficacious when administered from the start of treatment rather than waiting to identify poor or partial responders and when clozapine was involved. Studies which took place in China and studies which lasted longer than 10 weeks were also more likely to be positive. This leaves the question unresolved Inhibitors,research,lifescience,medical as to whether or not adding a second antipsychotic is likely to be helpful when a patient fails Inhibitors,research,lifescience,medical to derive an adequate response from an initial trial of monotherapy with drugs other than clozapine. Adding a second antipsychotic to mitigate adverse effects from another medication is a different situation, and there is some suggestion

that, for Inhibitors,research,lifescience,medical example, adding aripiprazole to clozapine can lead to a reduction in weight and/or lipid abnormalities.57,58 Clozapine Since the Kane et al6 study, clozapine has been considered the best established treatment for refractory patients. In addition, clozapine has been shown to be superior to second-generation Inhibitors,research,lifescience,medical antipsychotics even among patients who were only moderately ill7 and would not necessarily have met criteria for true treatment resistance. The superiority of clozapine has been demonstrated in subsequent individual studies59,28,24 and metaanalysis.60,61,62 However, as mentioned previously, in a recent metaanalysis by Leucht et al14 of 28 randomized, head-to-head comparisons of clozapine with other second-generation

antipsychotic drugs, clozapine did not show consistent superiority. Nevertheless, many if not most of these studies used low or very low doses Cytidine deaminase of clozapine or patients were not truly poor responders. Other pharmacologic classes in augmentation strategies Numerous other classes of agents have been studied to determine their ability to augment the effects of antipsychotics in the treatment of patients with schizophrenia, either in general or in poor or partial responders. Cochrane reviews of benzodiazipines,63 lithium,64 and valproate65 could find no clear evidence of efficacy. A systematic review of carbamazepine66 was also negative. Lamotrigine has been examined in a Cochrane review including five studies involving 537 participants.