Search

Background Clozapine was the widely accepted gold standard treatment for treatment resistant psychotic symptoms. Clozapine has efficacy of about 50% and some responding patients have to discontinue it due to serious adverse effects. The search for novel agents to use for clozapine-non-responders continues. One such possible agent is the non-dopaminergic antipsychotic pimavanserin, an inverse agonist of serotonin 5-HT2A receptors which was recently approved for the hallucinations and delusions of Parkinson's Disease Psychosis. We report here the successful results of using pimavanserin in patients with refractory hallucinations and delusions who failed to respond to clozapine. We also report similar results in refractory psychosis patients who did not receive clozapine. Methods We present ten cases of patients with schizophrenia and schizoaffective disorder with refractory hallucinations and delusions who received a trial of pimavanserin when clozapine or multiple antipsychotics failed. Six of ten patients had not responded to a clozapine trial. The subjects' ages ranged between 21 and 77 years and were followed up for several months. Results All 10 patients with refractory hallucinations and delusions showed marked response to pimavanserin 34 mg/day within 4–8 weeks, with continuation of the response for several months of follow-up. Improvements in negative symptoms and social functioning were also observed in several patients. Discussion This series of 10 cases of patients with refractory psychosis who responded to pimavanserin is an important new finding that has never been reported before. Controlled studies comparing clozapine and pimavanserin in refractory schizophrenia are warranted to confirm these clinical observations.

Background Pharmaceutical companies conduct clinical trials to show the efficacy and safety of new medications for the treatment of schizophrenia. After the new medications are marketed, clinicians treating patients with schizophrenia discover that a considerable number of patients do not respond to these new medications. The goals of the review are to examine the methodology and design of recent antipsychotic clinical trials, identify common flaws, and propose guidelines to fix the flaws and improve the quality of future clinical trials of antipsychotic medications. Methods A review of recent antipsychotic clinical trials was conducted using a PubMed search. Ten recent trials published in the past four years were reviewed and their methods analyzed and critiqued. Results The authors identified six major methodological flaws that may explain the suboptimal response in many patients after a drug is approved. Most of the flaws are related to eligibility criteria, the misuse of the Positive and Negative Syndromes Scale (PANSS) and the lack of consensus on how to define remission, response and exacerbation in schizophrenia. Proposed guidelines for a more rigorous use of the PANSS are presented and recommendations are proposed for using uniform criteria for remission, response and exacerbation in schizophrenia. Conclusions The authors recommend using standardized diagnostic interviews to screen patients for eligibility criteria and using the PANSS according to the author's recommendations and the proposed guidelines. Uniform criteria to define remission, response and exacerbation are recommended for clinical trials examining the efficacy and safety of antipsychotic drugs in schizophrenia.

Introduction In addition to being a critical component of the visual system, the retina provides the opportunity for an accessible and noninvasive probe of brain pathology in neuropsychiatric disorders. Several studies have reported various retinal abnormalities in schizophrenia, some primary and others iatrogenic. There is now increasing evidence supporting the existence of retinal anomalies in schizophrenia across structural, neurochemical and physiological parameters. Here, we review the types of retinal pathology in schizophrenia and discuss how these findings may provide novel insights for future research into the neurodevelopmental neurobiology of this syndrome, and possibly as useful biomarkers. Methods Using the keywords schizophrenia, retina, pathology, electroretinogram (ERG), and/or optical coherence tomography (OCT) on PubMed, all studies using the English language within 30 years were reviewed. Methods were examined, and common themes were identified, tabulated, and discussed. Results We classified the reports of retinal pathology into primary and secondary. The major secondary retinal pathology is related to the iatrogenic effects of a once widely prescribed first generation antipsychotic (thioridazine), which was found to be associated with retinal pigment deposits, decreased visual acuity, and suppression of dark adapted ERG responses. The primary retinal findings were obtained via different measures primarily using ERG, OCT, and microvascular imaging. The most consistent findings were 1) decreased ERG wave amplitudes, 2) reduced macular volume, 3) thinning of retinal nerve fiber layer, and 4) widened venule caliber. Conclusion The abnormal pathobiological findings of the retina in schizophrenia may represent an important avenue for elucidating some of the neurodevelopmental aberrations in schizophrenia. The well replicated retinal anomalies could serve as biomarkers for schizophrenia and perhaps an endophenotype that may help identify at-risk individuals and to facilitate early intervention.