World Psychiatric Association Pharmacopsychiatry Section statement on comparative effectiveness of antipsychotics in the treatment of schizophrenia

Data from two major government-funded studies of comparative antipsychotic effectiveness in schizophrenia contradict the widely prevalent belief that the newer second-generation medications are vastly superior to the older first-generation drugs. This has caused uncertainty among patients, clinicians and policy-makers about the relative utility of first- and second- generation antipsychotic agents in its treatment. To reduce confusion and provide a contextual understanding of the new data, the World Psychiatry Association Section on Pharmacopsychiatry comprehensively reviewed the literature on the comparative effectiveness of different antipsychotic treatments for schizophrenia and developed this update. Utilizing data from the approximately 1,600 randomized controlled trials of antipsychotic treatment in schizophrenia, we applied the two indirect and one direct method to comparing the effectiveness of 62 currently-available antipsychotic agents. The subclasses of 51 first-generation and 11 second-generation antipsychotics were both found to be very heterogeneous, with substantial differences in side-effect profiles among members. Second-generation antipsychotic agents were found to be inconsistently more effective than first-generation agents in alleviating negative, cognitive, and depressive symptoms and had a lower liability to cause tardive dyskinesia; these modest benefits were principally driven by the ability of second-generation antipsychotics to provide equivalent improvement in positive symptoms along with a lower risk of causing extrapyramidal side-effects. Clozapine was found to be more efficacious than other agents in treatment-refractory schizophrenia. There were no consistent differences in efficacy among other second-generation antipsychotic agents; if such differences exist, they are likely small in magnitude. Dosing was found to be a key variable in optimizing effectiveness of both first- and second- generation antipsychotic agents. There was enormous individual variability in antipsychotic response and vulnerability to various adverse effects. In contrast to their relatively similar efficacy in treating positive symptoms, there were substantial differences among both first- and second- generation antipsychotic agents with regard to their propensity to cause extrapyramidal, metabolic and other adverse effects; second-generation agents have a lower liability to cause acute extrapyramidal symptoms and tardive dyskinesia along with a tendency to cause greater metabolic side-effects than first-generation agents. Based on these data about the comparative effectiveness of different antipsychotic treatment options, we summarize elements of current best antipsychotic practice for the treatment of schizophrenia and discuss the role of government and the pharmaceutical industry in obtaining and disseminating information which can facilitate best practice.     

Neurocognition in first-degree healthy relatives (siblings) of bipolar affective disorder patients

Aim:  Cognitive deficits have been presupposed to be endophenotypic markers in bipolar disorder, but few studies have ascertained the cognitive deficits in healthy relatives of bipolar disorder patients. The aim of the present study was to assess the cognitive functions of first-degree relatives of patients with bipolar disorder and compare them with healthy controls.
Methods:  Ten first-degree apparently healthy relatives of patients with bipolar disorder were compared with 10 age- and education-matched control subjects on computer-based cognitive tests.
Results:  As compared to the control group, the relatives group performed significantly poorly on tests for executive function and vigilance, while on the test for working memory the performance was not significantly different on most of the parameters.
Conclusions:  Executive functioning and vigilance could be potential markers of the endophenotype in bipolar patients.     

Intraventricular occurrence of a melanocytoma

Melanocytomas are rare tumors of the central nervous system that are believed to arise from leptomeningeal melanocytes. A young girl presented with a contrast-enhancing cystic mass in the temporal horn of the left lateral ventricle. Microsurgical resection of a black-colored vascular tumor supplied by the anterior choroidal artery was performed. Appropriate immunohistochemical staining and electron microscope evaluations were used to confirm the pathological diagnosis. The patient made an excellent recovery; follow-up imaging revealed no recurrent or residual tumor. This is the first documented primary occurrence of a melanocytoma in an intraventricular location. The intraventricular occurrence of this tumor suggests that melanocytes may migrate into the choroidal fissure and may infrequently undergo neoplastic proliferation in that location. This case contains implications for the differential diagnosis of intraventricular tumors.     

Rheolytic percutaneous thrombectomy for acute pulmonary embolism in a pediatric patient.

Acute massive pulmonary embolism can have significant hemodynamic effects in both adults and children. We describe the case of a 10-year-old boy who developed cardiogenic shock after suffering a massive pulmonary embolism. A significant thrombus burden was removed using a catheter-based strategy of rheolytic thrombectomy, leading to stabilization of the patient.     

Management of cancer‐associated thrombotic microangiopathy: What is the right approach?

A 49-year-old Caucasian woman presented with features suggestive of thrombotic microangiopathy (TMA). She did not respond to treatment with repeated plasma exchange and corticosteroids. A bone marrow biopsy revealed presence of metastatic carcinoma. A limited autopsy revealed presence of breast cancer with rib metastases. Though severe deficiency of von Willebrand factor-cleaving protease was initially proposed as a key pathogenetic factor for thrombotic thrombocytopenic purpura, subsequent studies involving patients with cancer-associated TMA did not find as severe a deficiency of von Willebrand factor-cleaving protease as is seen in idiopathic cases of thrombotic thrombocytopenic purpura. Here we address one approach of management of these patients with cancer-associated TMA.