Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493)

Antioxidant treatment of the glutathione deficiency in bipolar disorder with n-acetyl cysteine: a double blind randomized placebo controlled trial

We present an approach which we call PSyKAl that is designed to achieve portable performance for parallel finite-difference, finite-volume, and finite-element earth-system models. In PSyKAl the code related to the underlying science is formally separated from code related to parallelization and single-core optimizations. This separation of concerns allows scientists to code their science independently of the underlying hardware architecture and for optimization specialists to be able to tailor the code for a particular machine, independently of the science code. We have taken the free-surface part of the NEMO ocean model and created a new shallow-water model named NEMOLite2D. In doing this we have a code which is of a manageable size and yet which incorporates elements of full ocean models (input/output, boundary conditions, etc.). We have then manually constructed a PSyKAl version of this code and investigated the transformations that must be applied to the middle, PSy, layer in order to achieve good performance, both serial and parallel. We have produced versions of the PSy layer parallelized with both OpenMP and OpenACC; in both cases we were able to leave the natural-science parts of the code unchanged while achieving good performance on both multi-core CPUs and GPUs. In quantifying whether or not the obtained performance is good we also consider the limitations of the basic roofline model and improve on it by generating kernel-specific CPU ceilings

N-acetilcisteína para o tratamento de episódios de depressão maior no transtorno bipolar

Objetivo: Neste relato, avaliamos o efeito da N-acetilcisteína (NAC) adjuvante em sintomas depressivos e desfechos funcionais no transtorno bipolar. Para isso, conduzimos uma análise secundária de todos os pacientes com critérios diagnósticos para um episódio depressivo em um ensaio clínico randomizado comparando NAC adjuvante com placebo no transtorno bipolar. Método: Ensaio clínico randomizado comparando NAC adjuvante com placebo para episódios depressivos no transtorno bipolar durante 24 semanas. Desfechos funcionais e sintomáticos foram coletados no período. Resultados: Dezessete participantes estavam disponíveis para esta análise. Tamanhos de efeito grandes foram encontrados para sintomas depressivos e desfechos funcionais. Oito dos dez participantes no grupo da NAC tiveram resposta clínica ao fim do tratamento. O mesmo ocorreu em apenas um dos sete que receberam placebo. Discussão: Esses resultados indicam que a NAC adjuvante pode ser útil para episódios de depressão maior no transtorno bipolar. Estudos desenhados para confirmar esta hipótese são necessários.Objective: In this report, we aimed to evaluate the effect of add-on N-acetylcysteine (NAC) on depressive symptoms and functional outcomes in bipolar disorder. To that end, we conducted a secondary analysis of all patients meeting full criteria for a depressive episode in a placebocontrolled trial of adjunctive NAC for bipolar disorder. Method: Twenty-four week randomised clinical trial comparing adjunctive NAC and placebo in individuals with bipolar disorder experiencing major depressive episodes. Symptomatic and functional outcome data were collected over the study period. Results: Seventeen participants were available for this report. Very large effect sizes in favor of NAC were found for depressive symptoms and functional outcomes at endpoint. Eight of the ten participants on NAC had a treatment response at endpoint; the same was true for only one of the seven participants allocated to placebo. Discussion: These results indicate that adjunctive NAC may be useful for major depressive episodes in bipolar disorder. Further studies designed to confirm this hypothesis are necessary

Effects of N-acetyl cysteine on cognitive function in bipolar disorder

AimsBipolar disorder is characterized by progressive changes in cognition with declines in executive functioning, memory and sustained attention. Current pharmacotherapies for bipolar disorder target mood symptoms but have not addressed these cognitive changes resulting in euthymic individuals who still experience cognitive deficits. N-acetyl cysteine (NAC) has been shown to have effects on antioxidant status, glutamate transmission, inflammation and neurogenesis. Adjunctive treatment with NAC improves the symptoms experienced by those with bipolar disorder, particularly depression, and it was hypothesized that cognition may also be improved following NAC treatment.MethodsAs part of a larger randomized, double-blind, placebo-controlled trial, participants in the current report were tested at baseline and 6 months to assess changes in cognitive function following either 2000&thinsp;mg of NAC daily or placebo.ResultsThis study failed to find changes in cognitive function following treatment with NAC compared to placebo.ConclusionsWhile an important pilot study, this study had a small sample size and included a limited battery of cognitive tests. Further investigations on the effects of NAC on cognitive performance in bipolar disorder are required.<br /

A preliminary investigation on the efficacy of <i>N</i>-acetyl cysteine for mania or hypomania

OBJECTIVE: Oxidative imbalance has emerged as a treatment target in bipolar disorder. As very limited data are available on the clinical use of antioxidants for mania, we report here results from a post hoc and exploratory subgroup analysis of a randomized, placebo-controlled trial of N-acetyl cysteine (NAC). METHODS: This was a placebo-controlled, randomized, clinical trial assessing the effect of NAC over 24 weeks in mania or hypomania. Symptomatic and functional outcomes were collected over the study period. RESULTS: Fifteen participants were available for this report; two participants in each group failed to complete all assessments. Within-group analyses pointed to an improvement in the NAC group on manic symptoms and worsening in the placebo group on depressive symptoms at endpoint. CONCLUSIONS: Although the sample size was small, these results indicated within-group efficacy for this glutathione precursor as compared to placebo. Future trials specifically designed to demonstrate the efficacy of NAC in mania are needed