SS06-01 - Are we getting the most out of combination therapy in the short-term and long-term treatment of mania?

2011 ◽  
Vol 26 (S2) ◽  
pp. 2181-2181
Author(s):  
S. Kasper ◽  
E. Vieta ◽  
F. Bellivier ◽  
M. Frye
Keyword(s):  
Bipolar Disorder ◽  
Combination Therapy ◽  
Maintenance Treatment ◽  
Treatment Guidelines ◽  
Single Agent ◽  
First Line ◽  
Short Term ◽  
Long Term Treatment ◽  
Study Designs

The extensive research into the treatment of bipolar disorder over the last 20 years means that we, as clinicians, have never been in a better position to treat patients with bipolar disorder. Yet despite the availability of modern, evidence-based treatment guidelines, bipolar disorder remains an everyday treatment challenge. Newly diagnosed patients requiring treatment for the first time are not always adequately controlled with single-agent therapy and, similarly, combination therapy is also frequently necessary as maintenance treatment. But with this recognition comes the new challenge of identifying when monotherapy is not enough, which agents to combine, when and for how long? How do we know?Joined by an internationally respected faculty, Professor Siegfried Kasper chairs a discussion to help answer some of the key questions facing clinicians today:What response can be anticipated from recommended first-line monotherapies for acute mania?How do we know whether the response we observe when we prescribe a first-line treatment in a manic patient is adequate?To what extent can a partial non-response to monotherapy be improved by the addition of a second agent?What's the benefit of maintaining combination treatment once patients are stable and how long should I continue?Does adding an antipsychotic to a mood stabiliser increase the risk of adverse events, in the short term or in the long term?Drawing on latest guideline recommendations, recent clinical research, case studies and their extensive clinical experience, the panel will debate these interesting questions and shed light on how we can optimize both acute and maintenance treatment in this patient group.Although the design of maintenance studies in bipolar disorder has significantly evolved in recent years, individual study designs continue to differ in important ways, with important implications. What may appear to be small differences between study designs, such as the type of most recent episode experienced by the patients or the stabilisation criteria used in the trial, can have big implications for study outcome. It is thus becoming increasingly important to be able to evaluate the results of trials within the context of the design and determine what they mean for treatment practice. Our panel will therefore also discuss the extent to which the design of bipolar maintenance studies can influence the results achieved and share their views on what this means for treatment now, and in the future.Are we, and more importantly our patients, getting the most out of combination therapy for bipolar mania? Come and debate the issues with the panel, share your views and see what can be achieved.

Typical and atypical antipsychotics in bipolar disorder

2000 ◽  
Vol 12 (3) ◽  
pp. 115-119 ◽  
Author(s):  
R.W. Licht
Keyword(s):  
Bipolar Disorder ◽  
Atypical Antipsychotics ◽  
Treatment Guidelines ◽  
Bipolar Depression ◽  
Term Treatment ◽  
Advantages And Disadvantages ◽  
Long Term Treatment ◽  
Randomised Controlled ◽  
Typical Antipsychotics

ABSTRACTBackground: In clinical practice, typical antipsychotics are widely used in the treatment of bipolar disorder, albeit in treatment guidelines often considered as adjunctive agents only. Recently, focus has shifted towards the use of atypical antipsychotics. This paper reviews the advantages and disadvantages associated with the use of antipsychotics in bipolar disorder.Methods: Randomised controlled trials (RCTs) were selected for review. A few review articles were also cited.Results: Typical antipsychotics, at least some of them, are powerful antimanics, beneficial for severe agitation in particular. However, in the long term treatment, typical antipsychics may precipitate depression. Among the atypical antipsychotics, both risperidone and olanzapine are clearly antimanic alternatives, although olanzapine is the best studied. Clozapine seems to be useful when other treatments fail to work.Conclusions: Antipsychotics are beneficial for some clinical presentations of mania. To minimize side effets, atypical agents should be preferred before typical agents, unless parenteral administration is needed. Despite the lack of RCTs, antipsychotics also seem to be useful as adjunctive agents in the treatment of psychotic bipolar depression. For the long term treatment of bipolar disorder, typical antipsychotics should be used only under certain circumstances. The place of atypical antipsychotics in the long term treatment of bipolar disorder remains to be studied.

scholarly journals Study designs, duration, and choice of comparators including the use of placebo

2002 ◽  
Vol 4 (4) ◽  
pp. 463-469
Keyword(s):  
Maintenance Treatment ◽  
Medicinal Products ◽  
Methodological Issues ◽  
Short Term ◽  
Loss To Follow Up ◽  
Recent Debate ◽  
Study Designs ◽  
Prevention Of Relapse

This paper discusses some methodological issues that are relevant to the design of controlled trials of new medicinal products for use in the treatment of schizophrenia. Two issues are covered more generally and at greater length. The first is the use of placebo. Recent debate of this topic was stímulated by changes to the Declaratíon of Helsinki, The second is the design of studies to evaluate maíntenance treatment in the preventíon of relapse and recurrence. With respect to both of these issues, specifíc implications for trials in schizophrenia are considered. Addítional design topics addressed briefly are noninferiority designs, add-on designs, withdrawal designs, run-in periods on placebo, loss to follow-up, and short-term and long-term trials.

scholarly journals Barriers to stopping neuroleptic (antipsychotic) treatment in people with schizophrenia, psychosis or bipolar disorder

2020 ◽  
Vol 10 ◽  
pp. 204512532093791
Author(s):  
Joanna Moncrieff ◽  
Swapnil Gupta ◽  
Mark Abie Horowitz
Keyword(s):  
Bipolar Disorder ◽  
Adverse Effects ◽  
Psychosocial Support ◽  
Clinical Excellence ◽  
Patient Choice ◽  
Antipsychotic Treatment ◽  
Short Term ◽  
Major Barrier ◽  
Long Term Treatment

Most guidelines recommend long-term, indefinite neuroleptic (or antipsychotic) treatment for people with schizophrenia, recurrent psychosis or bipolar disorder, on the basis that these medications reduce the chance of relapse. However, neuroleptics have significant adverse effects, including sexual dysfunction, emotional blunting, metabolic disturbance and brain shrinkage, and patients often request to stop them. Evidence for the benefits of long-term treatment is also not as robust as generally thought. Short-term randomised trials show higher rates of relapse among those whose neuroleptic treatment is discontinued compared with those on maintenance treatment, but they are confounded by adverse effects associated with the withdrawal of established medication. Some longer-term studies show possible advantages of medication reduction and discontinuation in terms of improved social functioning and recovery. Therefore, there is a good rationale for supporting patients who wish to stop their medication, especially given the patient choice agenda favoured by The National Institute for Clinical Excellence (NICE). The major barrier to stopping antipsychotics is an understandable fear of relapse among patients, their families and clinicians. Institutional structures also prioritise short-term stability over possible long-term improvements. The risk of relapse may be mitigated by more gradual reduction of medication, but further research is needed on this. Psychosocial support for patients during the process of reducing medication may also be useful, particularly to enhance coping skills. Guidelines to summarise evidence on ways to reduce medication would be useful. Many patients want to try and stop neuroleptic medication for good reasons, and psychiatrists can help to make this a realistic option by supporting people to do it as safely as possible, with the best chance of a positive outcome.

scholarly journals Hamlet’s augury: how to manage discontinuation of mood stabilizers in bipolar disorder

2021 ◽  
Vol 11 ◽  
pp. 204512532110006
Author(s):  
Mutahira M. Qureshi ◽  
Allan H. Young
Keyword(s):  
Bipolar Disorder ◽  
Treatment Guidelines ◽  
Term Treatment ◽  
Mood Stabilizers ◽  
High Rate ◽  
Future Research ◽  
High Quality Research ◽  
Medication Discontinuation ◽  
Long Term Treatment

Research has generated good quality evidence about the treatment and management of bipolar disorder in acute and, to some degree, sub-acute/continuation phases. This has informed various guidelines about the treatment and management of bipolar disorder (BD). However, for the long-term or maintenance phase of illness, most guidelines peter out and, in the absence of sufficiently high-quality research evidence, remain vague. This is particularly evident for the important clinical question of discontinuing mood stabilizing pharmacological agents after a period of remission has been achieved. The aim of this review is to put together current existing evidence about discontinuing mood stabilizers after a period of remission in order to come up with a structured and coherent strategy for managing such discontinuation and to make recommendations for future research. To this end, we reviewed the main relevant treatment guidelines and subsequent evidence following the publication of these guidelines. The current recommended long-term treatment of BD is usually considered within the same principles applicable to any chronic health condition (e.g. hypertension or diabetes) where the focus is on continuing treatment at minimum effective medication dose often life-long, switching to alternative choice of medication due to side-effects and very few, if any, indications for complete cessation. However, in the absence of strong evidence on long-term treatment and the high rate of non-concordance in BD, medication discontinuation is a very important aspect of the treatment that should be given due consideration at every aspect of the treatment.

scholarly journals Momordica charantia (Bitter melon) in Combination with Metformin Potentiates Hypoglycemic and Hypolipidemic Effects in Alloxan-induced Diabetic Rats

2018 ◽  
Vol 21 (2) ◽  
pp. 109-117
Author(s):  
Monirul Islam ◽  
Md Saiful Islam ◽  
Shaheda Zannah ◽  
Golam Sadik ◽  
Mamunur Rashid
Keyword(s):  
Combination Therapy ◽  
Treatment Protocol ◽  
Liver Glycogen ◽  
Term Treatment ◽  
Fixed Dose ◽  
Control Group ◽  
Bitter Melon ◽  
Short Term ◽  
Long Term Treatment

The present study was designed to investigate the effects of bitter melon (Momordica charantia) in combination with a standard oral hypoglycemic agent metformin on alloxan induced diabetic rats (AIDRs). Both the plant extract and the drug, individually and in combination, were subjected in vivo for two weeks (short term) and four weeks (long term) treatment protocol to determine blood glucose level, lipid profile and liver glycogen level using Swiss Albino rats. In short term treatment protocol, bitter melon extract (BME) at a dose of 75, 150 and 300 mg/ kg body weight (bw) were administered in AIDRs by using oral gavages once daily and dose-dependent antihyperglycemic and antidyslipidemic effects were investigated. This short term study revealed that the most effective dose of BME was found as 300 mg/kg bw among the three doses. In long term treatment protocol, AIDRs in different groups received fixed dose monotherapy of BME (300 mg/kg bw) and metformin (15 mg/kg bw) and fixed dose BME (150 mg/kg bw) and metformin (7.5 mg/kg bw) combination therapy. The study showed that combination therapy significantly decreased the blood glucose level from 18.42 ± 0.95 to 6.80 ± 0.39 mmol/l in comparison to the control group after daily treatment for four weeks. In case of antidyslipidemic effect, combination therapy reduced total cholesterol (34.25%), triglycerides (11.92%) and LDL-cholesterol (57.73%) levels and increased HDL-cholesterol level (55.48%) in comparison with their respective control groups. Metformin, BME and their combination preserved the liver glycogen level by 35.21%, 22.54% and 49.01%, respectively in comparison to diabetic control group. These changes were significantly better than those of BME and metformin monotherapy. The results suggested that treatment with combination therapy was more effective than mono-therapy for preventing diabetes as bitter melon extract potentiates the effects of metformin on long term alloxan-induced diabetic rats.Bangladesh Pharmaceutical Journal 21(2): 109-117, 2018

scholarly journals Impact of topoisomerase IIα overexpression in the primary colon tumor on the prognosis of metastatic colorectal cancer

2018 ◽  
Vol 8 (3) ◽  
pp. 26-35 ◽  
Author(s):  
A. D. Darenskaya ◽  
N. V. Dobrova ◽  
E. V. Stepanova
Keyword(s):  
Primary Tumor ◽  
Term Treatment ◽  
Colon Tumor ◽  
First Line ◽  
Short Term ◽  
Topoisomerase Iiα ◽  
Long Term Treatment ◽  
Primary Colon ◽  
Line Chemotherapy

Background.The evaluation of clinical and morphological characteristics is not sufficient to predict the prognosis of metastatic colorectal cancer (mRCC). Tumor aggressiveness may vary significantly even in patients with similar clinical and morphological disease characteristics. These differences are believed to be associated with molecular tumor characteristics and can be used as additional prognostic factors for patient survival.Objective:to evaluate the effect of topoisomerase IIα overexpression (topoIIα) in primary colon tumor on the mRCC prognosis.Materials and methods. The study cohort included patients with mRCC that have not previously received treatment for disseminated disease. All participants had a morphologically verified diagnosis of colon adenocarcinoma and received first-line chemotherapy with oxaliplatin and capecitabine. We evaluated both short-term and long-term treatment outcomes. We also assessed the expression of topoIIα in primary colon tumors (biopsy/surgical specimens obtained prior to initiation of first-line treatment) using immunohistochemical methods. We aimed to evaluate the association between the level of topoIIα expression and short-term/long-term treatment outcomes. We analyzed the impact of topoIIα expression in the primary tumor on the efficacy of first-line chemotherapy, progression-free survival (PFS) and overall survival (OS) in patients with mRCC.Results. Immunohistochemical evaluation of topoIIα expression in the primary tumor was conducted for 39 patients with mRCC. We found no correlation between topoIIα expression and PFS, i.e. median PFS did not differ significantly between patients with topoIIα-positive and topoIIα-negative tumors (p >0.05). Individuals with low levels of topoIIα expression in the primary tumor and those with topoIIα-negative cancer demonstrated significantly higher OS than patients with topoIIα overexpression (median OS 16.30 ± 2.0 months; 95 % confidence interval 12.32–20.28 vs 7.7 ± 4.98 months; 95 % confidence interval 0.00–17.46; p = 0.007).Conclusion.Overexpression of topoIIα is a factor of poor prognosis associated with poorer OS in patients with mRCC that received first-line chemotherapy with oxaliplatin and capecitabine.

scholarly journals Maintenance Pharmacological Treatment of Juvenile Bipolar Disorder: Review and Meta-Analyses

2019 ◽  
Vol 22 (8) ◽  
pp. 531-540 ◽  
Author(s):  
Caitlin S Yee ◽  
Emily R Hawken ◽  
Ross J Baldessarini ◽  
Gustavo H Vázquez
Keyword(s):  
Bipolar Disorder ◽  
Clinical Response ◽  
Maintenance Treatment ◽  
Controlled Trial ◽  
Gastrointestinal Symptoms ◽  
Term Treatment ◽  
Placebo Control ◽  
Pharmacological Treatments ◽  
Long Term Treatment

Abstract Background Guidelines for maintenance treatment of juvenile bipolar disorder rely heavily on evidence from adult studies and relatively brief trials in juveniles, leaving uncertainties about optimal long-term treatment. We aimed to systematically review long-term treatment trials for juvenile bipolar disorder. Methods We analyzed data recovered by a systematic literature search using the PRISMA guidelines statement, through 2018, for peer-reviewed reports on pharmacological treatments for juvenile bipolar disorder lasting ≥24 weeks. Results Of 13 reports with 16 trials of 9 treatments (18.8% were randomized and controlled), with 1773 subjects (94.4% BD-I; ages 6.9–15.1 years), lasting 11.7 (6–22) months. Pooled clinical response rates were 66.8% (CI: 64.4–69.1) with drugs vs 60.6% (53.0–66.7) in 3 placebo-control arms. Random-effects meta-analysis of 4 controlled trials yielded pooled odds ratio (OR) = 2.88 ([0.87–9.60], P = .08) for clinical response, and OR = 7.14 ([1.12–45.6], P = .04) for nonrecurrence. Apparent efficacy ranked: combined agents >anticonvulsants ≥lithium ≥antipsychotics. Factors favoring response ranked: more attention deficit/hyperactivity disorder, polytherapy, randomized controlled trial design, nonrecurrence vs response. Adverse events (incidence, 5.50%–28.5%) notably included cognitive dulling, weight-gain, and gastrointestinal symptoms; early dropout rates averaged 49.8%. Conclusions Pharmacological treatments, including anticonvulsants, lithium, and second-generation antipsychotics, may reduce long-term morbidity in juvenile bipolar disorder. However, study number, quality, and effect magnitude were limited, leaving the status of scientific support for maintenance treatment for juvenile bipolar disorder inconclusive.

What is the optimal serum lithium level in the long-term treatment of bipolar disorder? A review

2007 ◽  
Vol 40 (06) ◽  
Author(s):  
E Severus ◽  
N Kleindienst ◽  
F Seemüller ◽  
S Frangou ◽  
HJ Möller ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Term Treatment ◽  
Lithium Level ◽  
Serum Lithium Level ◽  
Long Term Treatment
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