The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and ...presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence ...and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made.
Objective
An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and ...previous meta‐analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view.
Method
Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task.
Results
Impairments were found for all 11 test‐measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26–0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test‐measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression.
Conclusion
This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta‐analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.
A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to ...update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.
Previous studies of neurocognitive performance in bipolar disorder (BD) have focused predominantly on euthymia. In this study we aimed to compare the neurocognitive profile of BD patients when ...depressed with healthy controls and explore the component structure of neurocognitive processes in these populations.
Cognitive tests of attention and executive function, immediate memory, verbal and visuospatial learning and memory and psychomotor speed were administered to 53 patients with a SCID-verified diagnosis of BD depression and 47 healthy controls. Test performance was assessed in terms of statistical significance, effect size and percentile standing. Principal component analysis (PCA) was used to explore underlying cognitive factor structure.
Multivariate analysis revealed an overall group effect, depressed BD patients performing significantly worse than controls. Patients performed significantly worse on 18/26 measures examined, with large effect sizes (d > 0.8) on tests of speed of processing, verbal learning and specific executive/working memory processes. Almost all tests produced at least one outcome measure on which ∼25-50% of the BD sample performed at more than 1 standard deviation (s.d.) below the control mean. Between 20% and 34% of patients performed at or below the fifth percentile of the control group in working memory, verbal learning and memory, and psychomotor/processing speed. PCA highlighted overall differences between groups, with fewer extracted components and less specificity in patients.
Overall, neurocognitive test performance is significantly reduced in BD patients when depressed. The use of different methods of analysing cognitive performance is highlighted, along with the relationship between processes, indicating important directions for future research.
Late-life depression (LLD) is associated with a decline in physical activity. Typically this is assessed by self-report questionnaires and, more recently, with actigraphy. We sought to explore the ...utility of a bespoke activity monitor to characterize activity profiles in LLD more precisely.
The activity monitor was worn for 7 days by 29 adults with LLD and 30 healthy controls. Subjects underwent neuropsychological assessment and quality of life (QoL) (36-item Short-Form Health Survey) and activities of daily living (ADL) scales (Instrumental Activities of Daily Living Scale) were administered.
Physical activity was significantly reduced in LLD compared with controls (t = 3.63, p < 0.001), primarily in the morning. LLD subjects showed slower fine motor movements (t = 3.49, p < 0.001). In LLD patients, activity reductions were related to reduced ADL (r = 0.61, p < 0.001), lower QoL (r = 0.65, p < 0.001), associative learning (r = 0.40, p = 0.036), and higher Montgomery-Åsberg Depression Rating Scale score (r = -0.37, p < 0.05).
Patients with LLD had a significant reduction in general physical activity compared with healthy controls. Assessment of specific activity parameters further revealed the correlates of impairments associated with LLD. Our study suggests that novel wearable technology has the potential to provide an objective way of monitoring real-world function.
Sudden unexplained death in psychiatric patients may be due to drug-induced arrhythmia, of which lengthening of the rate-corrected QT interval (QTc) on the electrocardiogram is a predictive marker. ...We estimated the point prevalence of QTc lengthening in psychiatric patients and the effects of various psychotropic drugs.
Electrocardiograms were obtained from 101 healthy reference individuals and 495 psychiatric patients in various inpatient and community settings and were analysed with a previously validated digitiser technique. Patients with and without QTc lengthening, QTc dispersion, and T-wave abnormality were compared by logistic regression to calculate odds ratios for predictive variables.
Abnormal QTc waas defined from the healthy reference group as more than 456 ms and was present in 8% (40 of 495) of patients. Age over 65 years (odds ratio 3·0 95% CI 1·1–8·3), use of tricyclic antidepressants (4·4 1·6–12·1), thioridazine (5·4 2·0–13·7), and droperidol (6·7 1·8–24·8) were robust predictors of QTc lengthening, as was antipsychotic dose (high dose 5·3 1·2–24·4; very high dose 8·2 1·5–43·6). Abnormal QT dispersion or Twave abnormalities were not significantly associated with antipsychotic treatment, but were associated with lithium therapy.
Antipsychotic drugs cause QTc lengthening in a dose-related manner. Risks are substantially higher for thioridazine and droperidol. These drugs may therefore confer an increased risk of drug-induced arrhythmia.
Neurocognitive impairment is a well-recognized feature of depression that has been reported in younger and older adults. Similar deficits occur with ageing and it is unclear whether the greater ...deficits in late-life depression are an ageing-related phenomenon or due to a difference in the nature of late-life depression itself. We hypothesized that ageing alone would not fully explain the increased neurocognitive impairment in late-life depression but that differences in the illness explain the greater decrements in memory and executive function.
Comparison of the neuropsychological performance of younger (<60 years) and older (60 years) adults with major depressive disorder (MDD) and healthy comparison subjects. Scores for each depression group were normalized against their respective age-matched control group and the primary comparisons were on four neurocognitive domains: (i) attention and executive function; (ii) verbal learning and memory; (iii) visuospatial learning and memory; and (iv) motor speed.
We recruited 75 subjects with MDD <60 years (n=44), 60 years (n=31) and 82 psychiatrically healthy comparison subjects <60 years (n=42), 60 years (n=40). The late-life depression group had greater impairment in verbal learning and memory and motor speed but not in executive function. The two depressed groups did not differ in depression severity, global cognitive function, intelligence or education.
Late-life depression is associated with more severe impairment in verbal learning and memory and motor speed than depression in earlier adult life and this is not due to ageing alone.
Objective
Cognitive dysfunction is an established feature of major depressive disorder (MDD). However, it remains unclear whether deficits in different cognitive domains are relatively independent or ...originate from a circumscribed ‘primary deficit’. This study tested the hypothesis that a deficit in attention represents a primary deficit in depression.
Method
Neuropsychological function was assessed in 30 depressed patients with MDD and 34 control participants. Cognitive composites were derived from a minimum of three tests and included attention, executive function, visuospatial memory and verbal memory. A multivariate analysis of variance was used to assess group differences in overall cognitive performance, and multiple regression models were used to evaluate the role of attention in deficits in other domains.
Results
The cognitive deficit in the depressed sample was found to be characterized by poorer performance in attention and executive function. When evaluating the interrelationship between the two deficits, the attentional deficit was found to persist when variability in executive function was statistically accounted for, whilst the executive deficit was eliminated when attention was accounted for.
Conclusion
The results demonstrated that the attentional deficit could not be explained by deficits in executive function, which provides support for a primary attention deficit in depression.
Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various ...diagnostic categories in current use identify cases that are particularly helpful for biological-genetic research.
To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case-control bipolar disorder sample.
We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM-IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type.
The RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42 x 10(-7)). Biological systems implicated included gamma amniobutyric acid (GABA)(A) receptors. Genes having at least one associated polymorphism at P<10(-4) included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12.
Our findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes.
PDF
