Neurocognitive intra-individual variability in mood disorders: effects on attentional response time distributions.

BACKGROUND: Attentional impairment is a core cognitive feature of major depressive disorder (MDD) and bipolar disorder (BD). However, little is known of the characteristics of response time (RT) distributions from attentional tasks. This is crucial to furthering our understanding of the profile and extent of cognitive intra-individual variability (IIV) in mood disorders. METHOD: A computerized sustained attention task was administered to 138 healthy controls and 158 patients with a mood disorder: 86 euthymic BD, 33 depressed BD and 39 medication-free MDD patients. Measures of IIV, including individual standard deviation (iSD) and coefficient of variation (CoV), were derived for each participant. Ex-Gaussian (and Vincentile) analyses were used to characterize the RT distributions into three components: mu and sigma (mean and standard deviation of the Gaussian portion of the distribution) and tau (the 'slow tail' of the distribution). RESULTS: Compared with healthy controls, iSD was increased significantly in all patient samples. Due to minimal changes in average RT, CoV was only increased significantly in BD depressed patients. Ex-Gaussian modelling indicated a significant increase in tau in euthymic BD [Cohen's d = 0.39, 95% confidence interval (CI) 0.09-0.69, p = 0.011], and both sigma (d = 0.57, 95% CI 0.07-1.05, p = 0.025) and tau (d = 1.14, 95% CI 0.60-1.64, p < 0.0001) in depressed BD. The mu parameter did not differ from controls. CONCLUSIONS: Increased cognitive variability may be a core feature of mood disorders. This is the first demonstration of differences in attentional RT distribution parameters between MDD and BD, and BD depression and euthymia. These data highlight the utility of applying measures of IIV to characterize neurocognitive variability and the great potential for future application.

Bouncing back: is the bipolar rebound phenomenon peculiar to lithium? A retrospective naturalistic study.

In bipolar disorder the discontinuation of lithium prophylaxis is associated with early episode precipitation. Is this ;rebound' phenomenon peculiar to lithium? This naturalistic retrospective case note review investigated the frequency of immediate recurrence after discontinuation of any prophylactic treatment. Bipolar patients who stopped at least one medication after at least 6 months of remission were studied. A total of 310 case notes were examined in a systematic search. A total of 53 cases of discontinuation in 48 subjects were found. Discontinued medications included lithium, valproate, carbamazepine, typical and atypical antipsychotics and antidepressants. Recurrence occurred within 3 months of medication withdrawal in 39 cases (74%). Over half of the discontinuation episodes involved lithium: recurrence occurred in 86% of these cases. In the groups stopping other prophylactic agents, a majority of subjects suffered recurrence: anticonvulsants (89%), antipsychotics (64%) and antidepressants (58%). However, these groups were small and the clarity of the data was undermined by the simultaneous withdrawal of other agents. Manic and hypomanic episodes were the most common form of recurrences. Depressive episodes occurred proportionately most frequently following antidepressant withdrawal. More than half of recurrences required hospital admission. This study provides preliminary naturalistic evidence that early episode recurrence in bipolar disorder is not peculiar to lithium withdrawal but may occur following withdrawal of medication from all classes recommended in prophylaxis. These findings, if replicated, have important implications for clinical practice and for research.

Oxcarbazepine in the maintenance treatment of bipolar disorder.

BACKGROUND: Some studies have suggested that oxcarbazepine has a role in preventing episode recurrence in bipolar affective disorder. This review attempted to investigate the existing evidence from randomised controlled trials for its use in the maintenance treatment of this illness. OBJECTIVES: To review the efficacy of oxcarbazepine, relative to placebo and other agents, in the prevention of affective episodes of bipolar affective disorder. The efficacy of oxcarbazepine was considered in terms of episode recurrence, general and social functioning. Adverse effects, overall acceptability to participants and mortality were also considered. SEARCH STRATEGY: CCDANCTR-Studies and CCDANCTR-References were searched on 7/11/2007. Medline, CENTRAL, EMBASE and PsycINFO were searched in March 2007. Specialist journals and conference proceedings were handsearched. Reference lists of relevant papers and major textbooks of affective disorder were checked. Authors, experts in the field and pharmaceutical companies were contacted requesting information on published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing oxcarbazepine with placebo or alternative agents, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder were sought. Participants with bipolar disorder, male and female, of all ages, were included. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports individually by two review authors. The methodological quality of included studies was assessed individually by two review authors. The main outcomes were the efficacy of oxcarbazepine maintenance treatment in preventing or attenuating further episodes of bipolar affective disorder (including its efficacy in rapid cycling disorder), the acceptability of oxcarbazepine treatment to participants, the prevalence of side-effects, and mortality, if any, on oxcarbazepine treatment. Where appropriate, data concerning outcome measures and adverse effects were to be extracted from the studies and analysed using Review Manager software. MAIN RESULTS: Two randomised controlled trials were found that met the methodological criteria for inclusion in the review. However, they did not report data with sufficient clarity to allow their confident extraction for inclusion in the meta-analysis. Findings from the two studies were presented descriptively. AUTHORS' CONCLUSIONS: There is an insufficient methodologically rigorous evidence base to provide guidance on the use of oxcarbazepine in the maintenance treatment of bipolar disorder. Given the need for more efficacious therapeutic agents, there is a need for good quality randomised controlled trials examining the therapeutic potential of this and related agents in bipolar disorder.

Global Precipitation Measurement (GPM) Mission Products and Services at the NASA Goddard Earth Sciences (GES) Data and Information Services Center (DISC).

This article describes NASA/JAXA Global Precipitation Measurement (GPM) mission products and services at the NASA Goddard Earth Sciences (GES) Data and Information Services Center (DISC). Built on the success of the Tropical Rainfall Measuring Mission (TRMM), the next generation GPM mission consists of new precipitation measurement instruments and a constellation of international research and operational satellites to provide improved measurements of precipitation globally. To facilitate data access, research, applications, and scientific discovery, the GES DISC has developed a variety of data services for GPM. This article is intended to guide users in choosing GPM datasets and services at the GES DISC.

Tiagabine in the treatment of acute affective episodes in bipolar disorder: efficacy and acceptability.

BACKGROUND: Bipolar disorder is a common recurrent illness with high levels of chronicity. Treatment resistance persists despite the use of established medications, such as lithium and valproate. New medications are required for the treatment of refractory cases. Some open-label reports have suggested that the anticonvulsant tiagabine may be efficacious in bipolar disorder. There is a need to clarify the evidence available, in the form of randomised controlled trials, for its use in the treatment of acute affective episodes in bipolar disorder OBJECTIVES: To review the evidence for the efficacy and acceptability of tiagabine in the treatment of acute mood episodes in bipolar disorder. SEARCH STRATEGY: The following databases were searched on 13-10-2005. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References),The Cochrane Controlled Clinical Trials Register (CCCTR),EMBASE,MEDLINE,LILACS,PsycLIT andPsyndex. Reference lists of relevant papers and major textbooks of mood disorder were searched. Handsearches were done (specialist journals and conference proceedings). Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials, which compared tiagabine with placebo or with active agents in the treatment of any acute mood episodes in bipolar disorder, were selected. Studies of participants with bipolar disorder were to be included. Subjects could be of either sex and of all ages. DATA COLLECTION AND ANALYSIS: Data extraction and methodological quality assessment were performed independently by two reviewers. For analysis, relative risk was used for binary efficacy outcomes and the weighted mean difference or standardised mean differerence was used for continuously distributed outcomes MAIN RESULTS: We did not find any studies which fulfilled the Cochrane criteria of randomised controlled trials. However, one uncontrolled open label study and one case series were found. There were also three case reports/series of acute treatment which were continued into maintenance therapy, and one open non-randomised study with this design. The results of these studies are inconsistent. AUTHORS' CONCLUSIONS: We found no randomised controlled trials of tiagabine in bipolar disorder. In the reported cases, a significant proportion of patients suffered episodes of syncope or seizure. There is a need for randomised controlled trials examining the efficacy and acceptability of tiagabine in the acute treatment of bipolar disorder, after the nature of these episodes has been clarified.

Tiagabine in the maintenance treatment of bipolar disorders.

BACKGROUND: Tiagabine, an anticonvulsant, has been reported to have efficacy in prophylactic treatment of bipolar disorder in case reports and in case series. OBJECTIVES: To review the efficacy and acceptability of tiagabine, relative to placebo, and other agents in the prevention and/or attenuation of episodes of bipolar affective disorder. The efficacy and acceptability of tiagabine were considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. SEARCH STRATEGY: The following databases were searched on 13-10-2005. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References),The Cochrane Controlled Clinical Trials Register (CCCTR),EMBASE,MEDLINE,LILACS,PsycLIT andPsyndex. Reference lists of relevant papers and major textbooks of affective disorder were examined.Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. Specialist journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomised controlled trials which compare tiagabine with placebo, alternative mood stabilisers or antipsychotics, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder, were sought. Bipolar patients, male and female, of all ages were to be included. DATA COLLECTION AND ANALYSIS: Data were to be extracted from the original reports if they met our inclusion criteria. The main outcomes to be assessed were:(1) The efficacy of tiagabine treatment in preventing or attenuating further episodes of bipolar affective disorder, including its efficacy in rapid cycling disorder.(2) The acceptability of tiagabine treatment to patients.(3) The prevalence of side effects.(4) Mortality, if any, on tiagabine treatment.Outcomes concerning relapse or recurrence were to be analysed excluding data from studies using discontinuation protocols, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of tiagabine treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were to be analysed using Review Manager version 4.2.8. MAIN RESULTS: No randomised controlled trials of tiagabine in the maintenance treatment of bipolar disorder were found. AUTHORS' CONCLUSIONS: There is an insufficient methodologically rigorous evidence base to provide guidance on the use of tiagabine in the maintenance treatment of bipolar disorder. There is a need for randomised controlled trials examining the therapeutic potential of this agent in bipolar disorder, after the nature of reported episodes of syncope or seizure in tiagabine-treated bipolar patients has been established.

Does 'rebound mania' occur after stopping carbamazepine? A pilot study.

Withdrawal of lithium prophylaxis in patients with bipolar affective disorder has been shown to precipitate 'rebound mania', an effect which may negate its benefits in the poorly compliant. No studies have looked for similar effects on withdrawal of carbamazepine, an alternative and adjunctive prophylactic treatment. This retrospective study examined the effects of withdrawal of carbamazepine prophylaxis in patients with bipolar disorder. A systematic search for patients with bipolar disorder who stopped carbamazepine therapy whilst in remission was conducted, followed by case note review and interview. In a case series of six patients who stopped carbamazepine, four remained well for at least 3 months, one developed an episode of moderate depression and one remained well before resuming treatment after 1 month. None required admission or suffered a manic episode in the 3 months following cessation. This study does not support the existence of a carbamazepine 'rebound' effect. It raises the possibility that recurrence after stopping carbamazepine may be less severe than the 'rebound mania' seen on lithium withdrawal. If this is the case, it may be a better choice of mood stabilizer in the poorly compliant. To date, there is insufficient evidence on which to base this choice. There is a need to examine this issue further through larger prospective and experimental studies on the effects of anticonvulsant withdrawal.

Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder.

BACKGROUND: Although lithium has been the most commonly used maintenance treatment in bipolar disorder for several decades, valproate is being used increasingly - especially in the United States of America. There is a need to clarify whether the increasingly prominent prophylactic role of valproate in bipolar disorder is justified. OBJECTIVES: To review the effectiveness of valproate, relative to placebo, other mood stabilisers and antipsychotics, in the prevention and/or attenuation of acute episodes of bipolar disorder. The effectiveness of valproate was considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. SEARCH STRATEGY: The CCDAN group search strategy was used. The following databases were searched: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), The Cochrane Controlled Clinical Trials Register (CCCTR), EMBASE, MEDLINE, LILACS, PsycLIT and Psyndex. Reference lists of relevant papers and major textbooks of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials which compared valproate with placebo, alternative mood stabilisers (including lithium and carbamazepine) or neuroleptics, where the stated intent of intervention was the maintenance treatment of bipolar disorder. Participants were males and females of all ages with a diagnosis of bipolar disorder however diagnosed, approximating to ICD 10 Code F31 and DSM IV 296, but including patients diagnosed as ICD-9 manic depressive psychosis and DSM-III and DSM-IIIR bipolar disorder. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports individually by two reviewers. The main outcomes to be assessed were: 1. The effectiveness of valproate treatment in preventing or attenuating further episodes of bipolar disorder, including its effectiveness in rapid cycling disorder. 2. The acceptability of valproate treatment to patients. 3. The prevalence of side-effects. 4. Mortality on valproate treatment. Outcomes concerning relapse/recurrence were analysed excluding data from discontinuation studies, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of valproate treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were analysed using Review Manager version 4.1. MAIN RESULTS: One trial of 12 months duration with 372 participants was identified comparing lithium, divalproex and placebo. It had several methodological limitations. The primary analysis of time to occurrence of mood episode described in the main trial report found no reliable difference between the treatments, although there was a trend for divalproex to be more effective than lithium. In the analysis in this review, patients taking divalproex who left the study because of the occurrence of an mood episode were significantly less in number than those on placebo (RRR 37%; RR 0.63; 95% CI 0.44 to 0.90). There was no significant difference in the numbers of patients in receipt of divalproex compared with those in receipt of lithium who left the study because they suffered any mood episode. (RRR 22%; RR 0.78; 95% C.I. 0.52 to 1.17). There was insufficient information to allow sub-group analyses of rapid-cycling disorder. The divalproex group had significantly more patients suffering tremor (RRI 223%; RR 3.23; 95% C.I. 1.85 to 5.62), weight gain (RRI 187%; RR 2.87; 95% C.I. 1.34 to 6.17) and alopecia (RRI 143%; RR 2.43; 95% C.I. 1.05 to 5.65) than the placebo group. In comparison with the lithium, divalproex was associated with more frequent sedation (RRI 58%; RR 1.58; 95% C.I. 1.08 to 2.32) and infection (RRI 107%; RR 2.07; 95% C.I. 1.16 to 3.68), but less suffered thirst (RRR 62%; RR 0.38; 95% C.I. 0.18 to 0.81) and polyuria (RRR 57%; RR 0.43; 95% C.I. 0.22 to 0.82). REVIEWER'S CONCLUSIONS: In view of the equivocal findings of this review, conclusions about the efficacy and acceptability of valproate compared to placebo and lithium cannot be made with any degree of confidence. With current evidence, patients and clinicians would probably wish to use lithium before valproate for maintenance treatment. At present, the observed shift of prescribing practice to valproate is not based on reliable evidence of efficacy

Valproate for acute mood episodes in bipolar disorder.

BACKGROUND: Bipolar disorder is a common debilitating illness, characterised by acute affective episodes with full or partial inter-episode remission. Effective and acceptable treatment of acute episodes is required. Valproate has become a leading adjunctive and alternative mood stabilising treatment to lithium in bipolar disorder. OBJECTIVES: To determine the efficacy and acceptability of valproate in the treatment of acute episodes of bipolar disorder. SEARCH STRATEGY: The search included the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registrar (CCDANCTR), the Cochrane Controlled Clinical Trials Register (CCTR), reference lists of relevant papers and books, and contact with authors of trials, experts and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing valproate with placebo, other mood stabilisers and antipsychotic medication in the treatment of any bipolar affective episode. Participants were of both sexes, of all ages, with a diagnosis of bipolar affective disorder approximating to ICD 10 Code F31 and DSM IV 296. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed independently by two reviewers blind to the authorship and source of papers. Ten randomised controlled trials were found comparing valproate with other interventions in mania. None was found examining its use in depression or mixed affective episodes. Data were extracted on the main outcome 'failure to respond by the end of the study' assessed by a less than 50% reduction in the Young Mania Rating Scale or the SADS-S mania scale. Three trials (316 participants) compared valproate with placebo. Three trials (158 participants) compared valproate with lithium. Two trials (363 participants) compared valproate with olanzapine. One trial (36 participants) compared valproate with haloperidol. Two trials (59 patients) compared valproate with carbamazepine. Acceptability of treatment was estimated using the outcome measure 'total number of subjects withdrawing from the study'. Three trials (321 patients) contributed to the comparison between valproate and placebo, two studies (144 patients) contributed to the comparison with lithium. One study (30 patients) provided data on this outcome in the comparison between valproate and carbamazepine. Pooled relative risks (with 95% confidence intervals) were calculated using fixed effect approaches. MAIN RESULTS: Valproate was more efficacious than placebo (RRR 38%; RR 0.62; 95% C.I. 0.51 to 0.77) in the treatment of mania. There was no significant difference between valproate and lithium (RRI 5%; RR 1.05; 95% C.I. 0.74-1.50) or between valproate and carbamazepine (RRR 34%; RR 0.66; 95% C.I. 0.38 to 1.16). Valproate was less effective than olanzapine (failure to achieve clinical response; RRI 25%; RR 1.25, 95% C.I. 1.01 to 1.54; average of 2.8 point less change on the Mania Rating Scale (95% CI 0.83 to 4.79). There were no significant differences in acceptability as measured by total number of subjects withdrawing from the study. There were significant differences in the side effect profiles of valproate and olanzapine, with more sedation and weight gain on olanzapine. REVIEWER'S CONCLUSIONS: There is consistent, if limited, evidence to suggest that valproate is an efficacious treatment for acute mania. Valproate may be less effective than olanzapine but may cause less sedation and weight gain. More well designed, randomised controlled trials investigating the relative efficacy and acceptability of valproate in the treatment of the full range of acute affective episodes occurring in bipolar disorder are required.

The evaluation of the rheological properties of lactose/microcrystalline cellulose and water mixtures by controlled stress rheometry and the relationship to the production of spherical pellets by extrusion/spheronization.

The consistency of wet powder masses produced from two ratios (7:3 and 8:2) of alpha-lactose monohydrate (L) and microcrystalline cellulose (MCC) mixed with a range of water contents has been assessed with a parallel plate controlled stress rheometer. The range of water contents, which could be studied, was restricted to those, which could be extruded uniformly by a ram extruder. In the creep mode, the instantaneous compliance increased as the water content increased for both L:MCC ratios illustrating the increasing deformability of the mixtures with increasing water content. The derived apparent viscosity of the mixtures as a function of shear rate, increased as the water content decreased and the values for all the systems fell on a common line. This indicates that the measurements are providing a reliable assessment of the mixtures and that the change in water content and L:MCC ratio provides systems, whose change of viscosity with rate of shear is consistent at low rates of shear. The values of the storage and loss moduli obtained from oscillatory measurements, increased with a decrease in water content but this time the two ratios of L:MCC were not on a common line when related to the water content of the mixtures. There was a range of water levels over which both the values of the storage and loss moduli were approximately constant. This corresponded to the level of water, which produced the pellets of the smallest diameter and range of diameters and were of the most spherical shape when produced by a ram extruder and spheronization. For 8:2 L:MCC ratio, there appeared to be a value for both the storage and the loss moduli above which the wet mass could not produce good pellets. For the 7:3 L:MCC these limiting levels were not achieved before extrusion with steady state conditions could be maintained without the mass being too wet or too dry. Instead, there appeared to be minimum levels of the moduli required to ensure that the mixtures were able to produce good pellets.

Parenteral nutrition outside hospital: psychosocial styles of adaptation.

Twenty subjects who had been on Long Term Parenteral Nutrition outside hospital for varying periods were studied. The study dealt with examination of factors which determined success or problems in adaptation to the regimen. Two subgroups with distinctive coping styles were identified. The first was characterized by a high degree of dependence on the external environment. The second, in contrast, was characterized by a behavioural pattern of assumption of personal responsibility for gratification of needs, less dependence on the external environment and a need to have life well organized and under control. Males in middle age appeared to adapt more readily than those in the younger or older age group. Women experienced a more profound disturbance of body image than men. Individuals in stable relationships with supportive families adapted better and had fewer complications and readmissions to hospital. The presence of chronic illness before the institution of LTPN appeared to facilitate a better adaptation to the regimen than that found after sudden bowel loss due to intra-abdominal castrastrophe in previously healthy individuals.

Intact parathyroid hormone concentration and cyclic AMP metabolism in thyroid disease.

In 35 thyrotoxic patients and 35 patients receiving thyroxine replacement therapy mean serum intact parathyroid hormone concentrations were lower than in euthyroid normal volunteer controls. In 20 hypothyroid patients intact PTH was increased relative to euthyroid controls. Mean serum adjusted calcium was increased in thyrotoxic patients relative to euthyroid controls and in 8 toxic patients with elevated serum adjusted calcium (greater than 2.60 mmol/l) intact PTH was below the assay detection limit (less than 0.5 pmol/l). Indices of PTH activity were consistent with intact PTH measurements in thyrotoxic patients with nephrogenous cyclic adenosine monophosphate lower, tubular maximum reabsorption of phosphate higher, and urinary calcium creatinine ratio higher than controls. In hypothyroid patients these indices of PTH activity suggest relative end organ resistance to PTH with nephrogenous cyclic adenosine monophosphate similar, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio lower than in controls. In treated hypothyroid patients nephrogenous cyclic adenosine monophosphate was higher, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio higher than in controls. These results are compatible with the hypothesis that thyroid status modifies the renal responses to PTH (1-84).