Effects of pioglitazone on metabolic abnormalities,psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication: A randomized double-blind study

BackgroundSchizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose–lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP.Methods54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides ≥ 120 mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3 month treatment with Pioglitazone (30–45 mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis.ResultsIn the total sample there was an overall effect (P's < .05 to < .01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3 month values also showed significant (P < .05) decreases in fasting insulin, 2 h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F = 3.99, P = 0.02), improved insulin sensitivity (lower H0MA-IR, F = 6.24, P = .002), lower triglycerides (F = 2.68, P = .06) and increased HDL (F = 6.50, P = .001). By the end of the study 52% of the pioglitazone treated patients compared to 15% of the placebo patients had fasting glucose in the normal range (Fisher's exact test P = .02). Pioglitazone also significantly improved PANSS depression factor scores (F = 2.82, P = 0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings.ConclusionsIn the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients.     

The concept of violent suicide,its underlying trait and neurobiology: A critical perspective

Suicide is one of the leading causes of death and represents a significant public health problem world-wide. Individuals who attempt or die by suicide represent a highly heterogeneous population. Recently, efforts have been made to identify sub-populations and variables to categorize them. A popular dichotomy in suicide research of the past years is violent versus non-violent suicide - based on the method. This dichotomy is important given that there is an association between method of attempted suicide and risk of subsequent death by suicide. The differentiation concerning suicide methods is also critical regarding preventive efforts. In this review, we have tried to approach the concept of violent suicide from different perspectives, including a discussion about its definition and overlapping categories. In addition, we have critically discussed aggression as underlying trait, the question of intent to die, and sociodemographic, environmental, neuropsychological, and neurobiological factors potentially associated with violent suicide.     

Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States

The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection.