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Despite being present in up to 1% of the population, few controlled trials have examined the efficacy of treatments for bipolar II depression. Pooled data are presented from four placebo-controlled studies (BOLDER I [5077US/0049] and II [D1447C00135]; EMBOLDEN I [D1447C00001] and II [D1447C00134]) that evaluated the efficacy of quetiapine monothera...
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Context 1
... separation from placebo was observed from week 1 for both doses of quetiapine and was maintained through week 8 (Figure 2). Effect sizes, based on MADRS scores, were moderate for both quetiapine 300 and 600 mg/day (MMRM: 0.44 and 0.47, respect- ively, p < 0.001 vs placebo; Figure 3). The effect sizes in the bipolar I population in the four trials were 0.58 for quetiapine 300 mg/day and 0.64 for quetiapine 600 mg/day (Figure 3 ...
Context 2
... sizes, based on MADRS scores, were moderate for both quetiapine 300 and 600 mg/day (MMRM: 0.44 and 0.47, respect- ively, p < 0.001 vs placebo; Figure 3). The effect sizes in the bipolar I population in the four trials were 0.58 for quetiapine 300 mg/day and 0.64 for quetiapine 600 mg/day (Figure 3 ...
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Citations
... 172 However, caution should be exercised when considering the use of antidepressants without a mood stabilizer in patients with BD-II who might also experience high rates of mood instability and rapid cycling. Such individuals can instead respond better to newer second generation antipsychotic agents such as quetiapine 173 and lumateperone, 93 which are supported by post hoc analyses of these more recent clinical trials with more BD-II patients. In addition, despite the absence of randomized controlled trials, open label studies have suggested that lithium and other mood stabilizers can have similar efficacy in BD-II, especially in the case of lamotrigine. ...
Bipolar disorders (BDs) are recurrent and sometimes chronic disorders of mood that affect around 2% of the world’s population and encompass a spectrum between severe elevated and excitable mood states (mania) to the dysphoria, low energy, and despondency of depressive episodes. The illness commonly starts in young adults and is a leading cause of disability and premature mortality. The clinical manifestations of bipolar disorder can be markedly varied between and within individuals across their lifespan. Early diagnosis is challenging and misdiagnoses are frequent, potentially resulting in missed early intervention and increasing the risk of iatrogenic harm. Over 15 approved treatments exist for the various phases of bipolar disorder, but outcomes are often suboptimal owing to insufficient efficacy, side effects, or lack of availability. Lithium, the first approved treatment for bipolar disorder, continues to be the most effective drug overall, although full remission is only seen in a subset of patients. Newer atypical antipsychotics are increasingly being found to be effective in the treatment of bipolar depression; however, their long term tolerability and safety are uncertain. For many with bipolar disorder, combination therapy and adjunctive psychotherapy might be necessary to treat symptoms across different phases of illness. Several classes of medications exist for treating bipolar disorder but predicting which medication is likely to be most effective or tolerable is not yet possible. As pathophysiological insights into the causes of bipolar disorders are revealed, a new era of targeted treatments aimed at causal mechanisms, be they pharmacological or psychosocial, will hopefully be developed. For the time being, however, clinical judgment, shared decision making, and empirical follow-up remain essential elements of clinical care. This review provides an overview of the clinical features, diagnostic subtypes, and major treatment modalities available to treat people with bipolar disorder, highlighting recent advances and ongoing therapeutic challenges.
... Die höchste Evidenz bei der Behandlung der BD existiert für Quetiapin, für das die beste Wirksamkeit und Verträglichkeit bei 300 mg/Tag in der unretardierten und retardierten Form bei der BD gezeigt wurde [19,20]. Der Einsatz von Quetiapin ist in Schwangerschaft und Stillzeit relativ sicher. ...
... Weight gain and metabolic changes with long-term use of quetiapine have been demonstrated in several studies [39]. Young et al. (2013) showed a signi cant increase (> 7%) in body weight of 6.4%, 9.4%, and 4.0% in patients receiving 300, 600 mg, and placebo, respectively, with a median increase of 0.8 kg for the group receiving 600 mg and decreases of 0.1 and 0.6 kg for quetiapine 300 mg and placebo, respectively [36]. In our sample, although we did not observe weight gain in the acute phase, there was a signi cant weight gain at the last visit of the maintenance phase compared to the baseline of the study. ...
Background: Bipolar disorder type I is a chronic disorder with a polymorphic and plastic presentation. Most clinical trials limit the evaluation of treatment to one of the poles of the acute phase. The ARIQUELI study aimed to evaluate the efficacy and tolerability of quetiapine monotherapy as a treatment for bipolar disorder overall, regardless of clinical presentation in the acute phase and in the maintenance phase.
Method: The ARIQUELI study was divided into two phases: Phase I, to investigate the treatment of bipolar disorder with quetiapine monotherapy, and Phase II, to compare two augmentation strategies in the treatment of quetiapine-refractory patients. Patients aged 18 to 40 years with type I bipolar disorder received quetiapine monotherapy between 300 to 800 mg for eight weeks regardless of clinical presentation. Responders were included in a maintenance phase of up to 22 months. The primary outcome was achievement and maintenance of response scores. Outcomes for Phase I were compared between the three clinical presentation groups in the acute phase (depression/mania/mixed).
Results: 105 patients were included, and although some differences in tolerability and depressive symptoms scores were observed, no difference between the groups was observed regarding primary outcome.
Conclusions: Quetiapine is equally effective in treating all forms of bipolar disorder I, with smaller differences in side effects and depressed patients showing a greater reduction in depressive symptoms.
Limitations: High prevalence of rapid cycling in the sample limits the comparison with other studies. Sample size was determined based on the results of the augmentation phase.
... Quetiapine immediate-release (IR) and extended-release (XR) were approved by the Food and Drug Administration (FDA) in 2006 and 2008, respectively, for treating adults with bipolar depression [6,7]. It has been used as an off-label medication for bipolar depression in children, even though it is not FDA-approved in the pediatric population. ...
Quetiapine is a second-generation antipsychotic (SGA) approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia, mania, and aggression in children and adolescents. It is also commonly used as an off-label medication to treat children and adolescents with bipolar depression, although the FDA has not approved quetiapine for this purpose. We conducted a systematic review of randomized clinical trials (RCTs) using the MEDLINE database and included two studies that met our inclusion criteria. Both RCTs were eight-week short-term studies that involved patients of 10-18 years of age with a Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of bipolar disorder, depressed type. The mean difference in the Children's Depression Rating Scale-Revised (CDRS-R) score and the response and remission rates in the quetiapine group were not statistically significant when compared to the placebo group. A high placebo response rate proved that quetiapine was no better than the placebo in treating pediatric bipolar depression. Quetiapine proved to be a relatively safe drug with the most common side effects being headache, somnolence, gastric upset, and weight gain. There was a significant increase in triglyceride levels, but no other metabolic effects were reported. This calls for future studies with larger sample sizes and improved methodology to explore the efficacy of quetiapine and other SGAs for the management of pediatric bipolar depression.
... For example, as reviewed in Chapter 13, the second-generation antipsychotic quetiapine has been studied in at least six well-designed placebo-controlled RCTs for those with BP II depression, with a total sample of well over 1,000 patients, and in two reasonably large maintenance studies. Pooled analyses of these trials demonstrated that quetiapine was more effective than placebo in managing BP II depression, equally effective in managing BP I and BP II depression, and at least as effective as a maintenance treatment for managing BP I patients (Datto et al., 2016;Young et al., 2013Young et al., , 2014. In addition, head-to-head comparisons of antidepressants against lithium showed them to be as effective (sertraline) or more effective (venlafaxine) in treating acute depression, and more effective during maintenance treatment (venlafaxine, fluoxetine) (Altshuler et al., 2017;Amsterdam et al., 2016Amsterdam et al., , 2015Amsterdam and Shults, 2010). ...
... Pooled analyses of five identically designed trials demonstrated that quetiapine was superior to placebo, and moreover was equally effective for acute depression in BDI and BDII. 243,437 The latter finding must be reconciled with the fact that quetiapine beat placebo in only three of the five individual trials in patients with BDII, compared to all five in patients with BDI. 253,290,[438][439][440] This is probably because the smaller sample of BDII patients-only about half as many patients with BDII as BDI were enrolled in each ...
The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.
... Although there was no statistically significant difference, it is notable that the placebo group included a higher number of patients with bipolar disorder type II. The studies investigating the treatment response in bipolar depression, obtained contradictory results between bipolar I and II in terms of treatment response rates and treatment resistance (McElroy et al., 2010;Thase et al., 2006;Young et al., 2013). Low response rates in the placebo group of this study may be a result of the higher number of patients with bipolar II in the placebo group compared to the study group. ...
For 30 years, bright light therapy (BLT) has been considered as an effective, well-tolerated treatment for seasonal affective disorder (SAD). Because of low response rates, new treatment strategies are needed for bipolar depression (BD), which resembles SAD in certain respects. Few placebo-controlled studies of BLT efficacy have been carried out for BD. Accordingly, this study evaluates the efficacy and safety of BLT as an add-on treatment for BD. Thirty-two BD outpatients were randomly assigned to BLT (10000lx) or dim light (DL, < 500lx). During a two-week period, light was administered each morning for 30min. The Hamilton Rating Scale for Depression and the Montgomery-Ǻsberg Depression Rating Scale assessed clinical outcome, and the UKU Side Effects Rating Scale evaluated side effects. No significant difference was observed in baseline depression scores in the two groups. Response rates for BLT and DL were 81% and 19%, and remission rates were 44% and 12.5%, respectively. Analyses showed statistically significant reductions in depression scores for the BLT group compared with the DL group on all scales. Side effects were similar in both groups, with headache as the most common side effect. The results suggest that BLT is an effective and safe add-on treatment for BD.
... Terms were included in the model for treatments, center, and bipolar diagnosis strata as well as a term for the baseline total score as a covariate. For the current analyses of pooled data from the five clinical trials, mean and SD or SE values are provided for baseline data and response to treatment, with pooling of 300 and 600 mg dose groups for quetiapine IR in the BOLDER and EMBOLDEN studies (both quetiapine doses were significantly superior to placebo in the individual studies and in pooled analyses [35]). Efficacy of treatment was assessed in the pooled intent-to-treat (ITT) population (i.e., patients who received at least one dose of study medication and had at least one post-baseline efficacy assessment), using last observation carried forward (LOCF) methodology. ...
Bipolar I and II represent the most common and severe subtypes of bipolar disorder. Although bipolar I disorder is relatively well studied, the clinical characteristics and response to treatment of patients with bipolar II disorder are less well understood.
To compare the severity and burden of illness of patients with bipolar II versus bipolar I disorder, baseline demographic, clinical, and quality of life data were examined in 1900 patients with bipolar I and 973 patients with bipolar II depression, who were enrolled in five similarly designed clinical placebo-controlled trials of quetiapine immediate-release and quetiapine extended-release. Acute (8 weeks) response to treatment was also compared by assessing rating scale scores, including Montgomery–Åsberg depression rating scale, Hamilton rating scale for anxiety, Young mania rating scale, and clinical global impression-severity scores, in the bipolar I and II populations in the same pooled database.
Patients with bipolar I and bipolar II depression were similar in demographics, baseline rating scale scores (depression, anxiety, mania, and quality of life), and mood episode histories. Symptom improvements in response to quetiapine were greater versus comparators (lithium, paroxetine, and placebo) at 4 and 8 weeks in both bipolar I and II patients. Patients with the bipolar II subtype initially showed slower responses to all treatments, but, by 8 weeks, attained similar symptom improvement as patients with bipolar I depression.
Pooled analysis of five clinical trials of quetiapine demonstrated that patients with bipolar II depression have a similar burden of illness and quality of life to patients with bipolar I. Bipolar II patients consistently showed a slower response to treatments than bipolar I patients, but, after 8 weeks of treatment with quetiapine, symptom improvements were similar between bipolar I and II disorder subtypes.
... Reducing the minimum duration threshold for hypomania from ≥4 to <4 days has the potential advantage of increasing sensitivity and capturing more patients who may benefit from bipolar disorder-specific treatment approaches. Although evidence-based strategies for managing bipolar II disorder are limited [21,22], with more research being needed in this area, there is general agreement among experts that antidepressants should be used cautiously (if at all) for individuals with bipolar II disorder, and mood stabilizing treatments may prove more beneficial than antidepressants for such patients [23,24]. Thus, different treatment approaches are warranted for bipolar II disorder compared to unipolar MDD patients, and broadening the diagnostic criteria for bipolar II disorder may alert clinicians to the need to consider mood stabilizers, and perhaps avoid antidepressants, for susceptible individuals. ...
Current diagnostic criteria for a hypomanic episode, as outlined in both the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and DSM-5), require a minimum duration of four consecutive days of symptoms of mood elevation. The 4-day criterion for duration of hypomania has been challenged as arbitrary and lacking empirical support, with many arguing that shorter-duration hypomanic episodes are highly prevalent and that those experiencing these episodes are clinically more similar to patients with bipolar disorder than to those with unipolar major depressive disorder. We review the current evidence regarding the prevalence, diagnostic validity, and longitudinal illness correlates of shorter-duration hypomanic episodes and summarize the arguments for and against broadening the diagnostic criteria for hypomania to include shorter-duration variants. Accumulating findings suggest that patients with major depressive episodes and shorter-duration hypomanic episodes represent a complex clinical phenotype, perhaps best conceptualized as being on the continuum between those with unipolar depressive episodes alone and those with DSM-5-defined bipolar II disorder. Further investigation is warranted, ideally involving large prospective, controlled studies, to elucidate the diagnostic and treatment implications of depression with shorter-duration hypomanic episodes.
... Young et al. [38], data compared the efficacy and tolerability of QTP and lithium monotherapy with that of placebo for a major depressive episode in BD and the results showed that the mean MADRS total score change from the baseline at 8 ...
Quetiapine (QTP) is an is an atypical antipsychotic, that was approved in 1997 by American Food and Drug Administration (FDA) for schizophrenia, both in adults and adolescents (13-17 years). Since 2003 this drug was approved also for the treatment of maniac episode in bipolar adults and adolescents (10-17 years) then in 2006 FDA extended the use of QTP to bipolar depression episodes and in 2008 to the maintenance treatment of bipolar disorder. In 2009 QTP starts to be used also as add on therapy of major depressive disorder combined to antidepressants, without FDA consent. Actually this drug, in "off label" use, is employed also for monotherapy of unipolar depression. QTP treatment was generally well tolerated. The incidence of treatment-emergent mania/hypomania was lower with QTP compared with the antidepressant paroxetine and placebo.
