Commentary on strategies for switching antipsychotics

Both the new generation of antipsychotics and the more traditional antipsychotic drugs produce an important and meaningful improvement in patients with schizophrenia, but most patients are neither cured nor free of symptoms. As a consequence, it is common to switch from one drug to another in the hope of obtaining a better response. All antipsychotic drugs produce some side effects, so switching can also be a tolerance issue. There are reports in the literature on the tactics of switching: abrupt discontinuation, cross tapering, starting a patient on a new drug while continuing with the old drug until the new drug has reached a steady state, or some variation on these tactics. In this issue, Ganguli et al. have carried out a randomized switching study, the data from which indicates the tactics that might be optimal. We put this paper into context, provide a critique and describe indications for switching

Cost-effectiveness of nurse-led self-help for recurrent depression in the primary care setting: design of a pragmatic randomized trial

<p>Abstract</p> <p>Background</p> <p>Major Depressive Disorder is a leading cause of disability, tends to run a recurrent course and is associated with substantial economic costs due to increased healthcare utilization and productivity losses. Interventions aimed at the prevention of recurrences may reduce patients' suffering and costs. Besides antidepressants, several psychological treatments such as preventive cognitive therapy (PCT) are effective in the prevention of recurrences of depression. Yet, many patients find long-term use of antidepressants unattractive, do not want to engage in therapy sessions and in the primary care setting psychologists are often not available. Therefore, it is important to study whether PCT can be used in a nurse-led self-help format in primary care. This study sets out to test the hypothesis that usual care plus nurse-led self-help for recurrent depression in primary care is feasible, acceptable and cost-effective compared to usual care only.</p> <p>Design</p> <p>Patients are randomly assigned to ‘nurse-led self-help treatment plus usual care’ (134 participants) or ‘usual care’ (134 participants). Randomisation is stratified according to the number of previous episodes (2 or 3 previous episodes versus 4 or more). The primary clinical outcome is the cumulative recurrence rate of depression meeting DSM-IV criteria as assessed by the Structured-Clinical-Interview-for-DSM-IV- disorders at one year after completion of the intervention. Secondary clinical outcomes are quality of life, severity of depressive symptoms, co-morbid psychopathology and self-efficacy. As putative effect-moderators, demographic characteristics, number of previous episodes, type of treatment during previous episodes, age of onset, self-efficacy and symptoms of pain and fatigue are assessed. Cumulative recurrence rate ratios are obtained under a Poisson regression model. Number-needed-to-be-treated is calculated as the inverse of the risk-difference. The economic evaluation is conducted from a societal perspective, both as a cost-effectiveness analysis (costs per depression free survival year) and as a cost-utility analysis (costs per quality adjusted life-year).</p> <p>Discussion</p> <p>The purpose of this paper is to outline the rationale and design of a nurse-led, cognitive therapy based self-help aimed at preventing recurrence of depression in a primary care setting. Only few studies have focused on psychological self-help interventions aimed at the prevention of recurrences in primary care patients.</p> <p>Trial registration</p> <p>NTR3001 (<url>http://www.trialregister.nl</url>)</p

Disrupting the rhythm of depression: design and protocol of a randomized controlled trial on preventing relapse using brief cognitive therapy with or without antidepressants

Background: Maintenance treatment with antidepressants is the leading strategy to prevent relapse and recurrence in patients with recurrent major depressive disorder (MDD) who have responded to acute treatment with antidepressants (AD). However, in clinical practice most patients (up to 70-80%) are not willing to take this medication after remission or take too low dosages. Moreover, as patients need to take medication for several years, it may not be the most cost-effective strategy. The best established effective and available alternative is brief cognitive therapy (CT). However, it is unclear whether brief CT while tapering antidepressants (AD) is an effective alternative for long term use of AD in recurrent depression. In addition, it is unclear whether the combination of AD to brief CT is beneficial.Methods/design: Therefore, we will compare the effectiveness and cost-effectiveness of brief CT while tapering AD to maintenance AD and the combination of CT with maintenance AD. In addition, we examine whether the prophylactic effect of CT was due to CT tackling illness related risk factors for recurrence such as residual symptoms or to its efficacy to modify presumed vulnerability factors of recurrence (e.g. rigid explicit and/or implicit dysfunctional attitudes). This is a multicenter RCT comparing the above treatment scenarios. Remitted patients on AD with at least two previous depressive episodes in the past five years (n = 276) will be recruited. The primary outcome is time related proportion of depression relapse/recurrence during minimal 15 months using DSM-IV-R criteria as assessed by the Structural Clinical Interview for Depression. Secondary outcome: economic evaluation (using a societal perspective) and number, duration and severity of relapses/recurrences.Discussion: This will be the first trial to investigate whether CT is effective in preventing relapse to depression in recurrent depression while tapering antidepressant treatment compared to antidepressant treatment alone and the combination of both. In addition, we explore explicit and implicit mediators of CT.Trial registration: Netherlands Trial Register (NTR): NTR1907

Significant Association of Estrogen Receptor Binding Site Variation with Bipolar Disorder in Females

Major depression is nearly twice as prevalent in women compared to men. In bipolar disorder, depressive episodes have been reported to be more common amongst female patients. Furthermore, periods of depression often correlate with periods of hormonal fluctuations. A link between hormone signaling and these mood disorders has, therefore, been suggested to exist in many studies. Estrogen, one of the primary female sex hormones, mediates its effect mostly by binding to estrogen receptors (ERs). Nuclear ERs function as transcription factors and regulate gene transcription by binding to specific DNA sequences. A nucleotide change in the binding sequence might alter the binding efficiency, which could affect transcription levels of nearby genes. In order to investigate if variation in ER DNA-binding sequences may be involved in mood disorders, we conducted a genome-wide study of ER DNA-binding in patients diagnosed with major depression or bipolar disorder. Association studies were performed within each gender separately and the results were corrected for multiple testing by the Bonferroni method. In the female bipolar disorder material a significant association result was found for rs6023059 (corrected p-value = 0.023; odds ratio (OR) 0.681, 95% confidence interval (CI) 0.570–0.814), a single nucleotide polymorphism (SNP) placed downstream of the gene coding for transglutaminase 2 (TGM2). Thus, females with a specific genotype at this SNP may be more vulnerable to fluctuating estrogen levels, which may then act as a triggering factor for bipolar disorder

Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature

A systematic search of the literature reveals limited evidence to support use of aripiprazole, a second-generation antipsychotic medication, in maintenance therapy of bipolar disorder, despite widespread use

Postpartum psychiatric disorders

Pregnancy is a complex and vulnerable period that presents a number of challenges to women, including the development of postpartum psychiatric disorders (PPDs). These disorders can include postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. In addition, other PPDs can include obsessive–compulsive disorder, post-traumatic stress disorder and eating disorders. The aetiology of PPDs is a complex interaction of psychological, social and biological factors, in addition to genetic and environmental factors. The goals of treating postpartum mental illness are reducing maternal symptoms and supporting maternal–child and family functioning. Women and their families should receive psychoeducation about the illness, including evidence-based discussions about the risks and benefits of each treatment option. Developing effective strategies in global settings that allow the delivery of targeted therapies to women with different clinical phenotypes and severities of PPDs is essential

Postpartum psychosis in bipolar disorder: no evidence of association with personality traits, cognitive style or affective temperaments

Background: Bipolar disorder has been associated with several personality traits, cognitive styles and affective temperaments. Women who have bipolar disorder are at increased risk of experiencing postpartum psychosis, however little research has investigated these traits and temperaments in relation to postpartum psychosis. The aim of this study is to establish whether aspects of personality, cognitive style and affective temperament that have been associated with bipolar disorder also confer vulnerability to postpartum psychosis over and above their known association with bipolar disorder. Methods: Personality traits (neuroticism, extraversion, schizotypy and impulsivity), cognitive styles (low self-esteem and dysfunctional attitudes) and affective temperaments (including cyclothymic and depressive temperaments) were compared between two groups of parous women with DSM-IV bipolar I disorder: i) 284 with a lifetime history of postpartum psychosis within 6 weeks of delivery (PP group), ii) 268 without any history of mood episodes with onset during pregnancy or within 6 months of delivery (no perinatal mood episode, No PME group). Results: After controlling for current mood state, and key demographic, clinical and pregnancy-related variables, there were no statistically significant differences between the PP and No PME groups on any of the personality, cognitive style or affective temperament measures. Conclusions: Personality traits, cognitive styles and affective temperaments previously shown to be associated with bipolar disorder in general were not specifically associated with the occurrence of postpartum psychosis. These factors may not be relevant for predicting risk of postpartum psychosis in women with bipolar disorder