Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: A meta-analysis of placebo-controlled trials

Background

The literature on the treatment mixed episodes in Bipolar Disorder [BD] is sparse. Second generation antipsychotics [SGA] have documented efficacy in mania, but not mixed episodes. The objective of this meta-analysis was to ascertain the efficacy of SGA, either as mono- and/or adjunctive therapy, in the treatment of acute mixed episodes of BD, compared to placebo.

Methods

A MEDLINE search for English language publications of randomized controlled trials [RCTs] comparing SGA with placebo in the treatment of an acute manic/mixed episode of BD, during the period 1990–2012, was performed using the terms ‘atypical antipsychotics’, ‘SGA’, ‘mixed episodes’, ‘dysphoric mania’ and each SGA independently. 9 RCTs reporting data on 1289 mixed episode patients treated with aripiprazole, asenapine, olanzapine, paliperidone-ER, risperidone, and ziprasidone, either as monotherapy or as adjunctive therapy, versus placebo, for 3–6 weeks, were included in the meta-analysis. We extracted data on the number of patients, SGA, duration of study and mean change in mania and depression scores from baseline to endpoint. Standardized mean difference between SGA and placebo for the mean baseline-to-endpoint change in mania and depression rating scores was calculated, with a 95% confidence limit.

Results

SGA, either alone or in combination with mood stabilizers, had superior efficacy in treating manic symptoms of mixed episodes compared to placebo (−0.41, 95% CI −0.53, −0.30; overall effect p<0.00001). SGA were equally effective for manic symptoms in mixed episodes and pure mania (p=0.99). SGA had superior efficacy in treating depressive symptoms of mixed episodes (−0.30, 95% CI −0.47, −0.13; p<0.001) compared to placebo in two trials reporting this information.

Limitations

Thirteen relevant studies could not be included as data for mixed-episodes were not presented separately.

Conclusions

SGA are effective in treating acute mixed episodes of BD, with predominant manic symptoms. Their efficacy in treating depressed mixed episodes remains unclear.     

Double-blind randomized controlled study showing symptomatic and cognitive superiority of bifrontal over bitemporal electrode placement during electroconvulsive therapy for schizophrenia

BackgroundSeveral studies show that bifrontal electrode placement produces relatively fewer cognitive adverse effects than bitemporal placement during electroconvulsive therapy (ECT) in depression. There are no reports comparing these electrode placements in schizophrenia.ObjectivesThis study compared the clinical and cognitive effects of bifrontal and bitemporal electrode placements in schizophrenia patients referred for electroconvulsive therapy (ECT).Methods122 schizophrenia patients who were prescribed ECT were randomized to receive ECT with either bifrontal (BFECT; n = 62) or bitemporal (BTECT; n = 60) placement. Their concomitant anti-psychotic medications and the number of ECT sessions were not controlled. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS), Bush-Francis Catatonia Rating Scale (BFCRS), and the Nurse Observation Scale for Inpatient Evaluation (NOSIE). Cognitive functions were assessed 24-h after the final ECT using a battery of tests. Clinical improvement was compared using chi-square test, repeated measures ANOVA and analysis of covariance (ANCOVA). Cognitive adverse effects were compared using t-test.ResultsAt the end of 2 weeks (after 6 ECT sessions) 63% and 13.2% of BFECT and BTECT patients respectively had met the response criterion for BPRS (40% reduction in total score; OR = 20.8; 95% CI = 3.61–34.33). BFECT patients showed significantly faster clinical response on BPRS (Time × Group interaction effect: P = 0.001), BFCRS (P < 0.001) and the NOSIE total assets score (P = 0.003). ANCOVA using baseline scores as covariates and treatment-resistance status as between-subject factor showed that BFECT patients had significantly greater improvement in all measures. BFECT patients had significantly higher PGI-memory-scale total score than BTECT patients (t = 5.16; P < 0.001). They also showed superior performance in other cognitive measures.ConclusionsBFECT results in superior clinical and cognitive outcomes than BTECT in schizophrenia patients referred for ECT.     

Post-irradiation Modification of Oxygen-dependent and Independent Damage by Catalase in Barley Seeds

Summary

If H₂O₂ is one of the major mediators of the ‘oxygen effect’ in biological systems then catalase, which enzymically decomposes H₂O₂ should have a significant influence on radiation damage, particularly under oxygenated conditions. The post-irradiation (300 Gy gamma rays) effect of catalase was, therefore, assessed on barley seeds of about 4 per cent moisture content under oxygenated and oxygen-free conditions at varying temperatures.

Catalase affords concentration-dependent radioprotection under oxygenated condition at both 25°C and 4°C. The level of protection at 4°C is less than at 25°C. This is obviously due to a decrease in catalase activity at low temperature. Under oxygen-free conditions, catalase enhances radiation damage at 4°C while at 25°C it has no effect. This has been substantiated by data on the frequency of chromosomal aberrations and on peroxidase activity. Sodium azide, a catalase inhibitor, was found to eliminate the radioprotective action of catalase.

The study supports the view that the ‘oxygen effect’ is mediated largely through peroxides in irradiated biological systems. However, the observations made particularly at 4°C under oxygen-free condition seem to involve physicochemical reactions.     

Cervicofacial nocardiosis in an immunocompetent child

Nocardiosis occurs primarily as an opportunistic infection in an immunocompromised host. The infection may on rare occasion occur in a normal host confounding the diagnosis. It is also notably an uncommon infection in children. We report a 1-y-old girl with cervicofacial nocardial infection who presented with acute suppurative otitis media and lymphadenitis. This child did not have any predisposing risk factors for this infection and responded well to treatment with co-trimoxazole and chloramphenicol. She is doing well on follow-up. CONCLUSION: Nocardiosis in an immunocompetent small child is reported.     

Strain analysis of flexing blood pump diaphragms.

Blood pumps usually use elastomer diaphragms that undergo repeated small-strain flexing (deformation). The stresses and strains that develop in the mechanically actuated diaphragms dictate the useful life and fluid-solid interactions of the diaphragm. A knowledge of these stresses and strains is essential for proper design of the pump's elastomer diaphragm. A nonlinear axisymmetric finite-element stress-strain analysis has been carried out on a Hexsyn rubber diaphragm used in a blood pump to illustrate a finite-element modeling technique. A situation involving the application of an axial deformation load on the diaphragm has been considered. In particular, the strains developed in a blood pump diaphragm during pumping have been quantified to illustrate the analysis technique.