Treatment Of Acute Manic Episodes Research Articles

Lithium: The best current treatment for the well-informed bipolar patient.

Lithium is the gold standard in the maintenance treatment of bipolar disorders. When used properly, lithium can bring about dramatic improvements in the course of this disease, with, in general, good tolerability, also in comparison with other approved treatment options. However, it's not a panacea for every individual patient at every stage of the disease. There is a significant number of patients who do not respond to or do not tolerate the usually recommended therapeutic serum concentrations of 0.6 - 0.8 mmol/l. Given its potential toxicity, lithium is a drug for the informed cooperating patient, who has developed an acceptance regarding his illness and the need for long-term medication and regular check-ups. High-quality group psychoeducation may greatly help for the majority of patients for successful long-term treatment with lithium, based on "shared decision making" with an openness to flexible patient-centered solutions with regard to dosage issues, side effect management and stand-by add-on/combination treatment. Under the above conditions, lithium should be offered and recommended to every patient with bipolar disorders early in the course of the disease as the mainstay of long-term treatment. Against this background, lithium should also be used more often in the acute treatment of manic episodes, if needed in combination with other mood stabilizing drugs that are approved for this purpose and may have a more rapid onset of action, in order to facilitate the path to successful long-term treatment with lithium.

Prescription of Valproate-Containing Medicines in Women of Childbearing Potential who have Psychiatric Disorders: Is It Worth the Risk?

Valproate-containing medicines have long been used in psychiatric practice, principally in the treatment of acute manic episodes, as augmentation agents in the treatment of bipolar and unipolar depressive episodes, and in the prophylaxis of bipolar affective disorder. Many babies are still being born with the adverse consequences of valproate exposure in utero, which include congenital malformations, neurodevelopmental delay, and increased risks of attention-deficit hyperactivity disorder and autism spectrum disorder. Previous measures designed to better inform women about the risks associated with valproate have not been sufficiently effective. This review highlights recent recommendations from influential regulatory and advisory bodies, summarises the relative efficacy and tolerability of valproate preparations in the psychiatric conditions for which they have often been prescribed, and offers practical guidance for the withdrawal and replacement of valproate-containing medicines in women with psychiatric disorders.

Effectiveness and Cognitive Changes With Ultrabrief Right Unilateral and Other Forms of Electroconvulsive Therapy in the Treatment of Mania.

Electroconvulsive therapy (ECT) is an effective treatment in mania. However, there is little evidence regarding the use of ultrabrief right unilateral (RUL-UB) ECT in treatment of acute manic episodes. The aim of this study was to report on the effectiveness and cognitive profile of ECT in bipolar mania, including a sample who received RUL-UB ECT. This naturalistic study retrospectively collected data in 33 patients who received ECT with concurrent antipsychotics for mania between October 1, 2014, and July 30, 2016. Electroconvulsive therapy was given using RUL-UB, brief-pulse right unilateral, or brief-pulse bitemporal approaches, dosed according to the patient's seizure threshold. The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS) score, and the Montreal Cognitive Assessment (MoCA) were administered to patients before and after the ECT course. For the whole sample, there was a significant improvement in BPRS (total score and manic subscale), YMRS, and MoCA total scores across the ECT treatment course. The overall BPRS response rate was 84%, and mean scores decreased from 42.1 (SD, 12.0) to 26.0 (SD, 4.0). The 13 patients who received RUL-UB ECT also showed significant improvement in BPRS, YMRS, and MoCA scores over the treatment course. Electroconvulsive therapy in general and also specifically RUL-UB ECT were effective in treating mania and also led to global cognitive improvement.

Use of Lithium in Severe Acute Manic Episodes: Retrospective Prescription Practice From a Tertiary Inpatient Unit.

A retrospective chart review was performed to investigate the common preferences of clinicians for the pharmacological treatment of acute manic episodes, with particular regard to lithium use, and to assess the adherence of clinical practice to established guidelines. Cases of manic episodes in patients admitted to Bakirköy Mazhar Osman Mental Health and Neurological Diseases Education and Research Hospital were retrospectively reviewed. Length of stay, medication data, serum levels, and adverse effects were evaluated for patients who received lithium therapy (N=98). On the first day of lithium treatment, 81 patients received 900 to 1200 mg of lithium. In total, 44 patients were discharged with the same dose as that given on the first day of treatment. With the exception of 1 patient, the dose was increased by 300 to 600 mg in the remaining patients within the first 10 days on the basis of serum drug concentrations. The mean serum concentrations of lithium in the first week were 0.67±0.17 mEq/L in patients with no dose increase, and 0.51±0.15 mEq/L in patients who did receive a dose increase. In total, 94 patients received at least 1 antipsychotic medication in addition to lithium. Clinicians attempted to maintain serum lithium levels above 0.60 mEq/L at the time of acute treatment initiation, consistent with established guidelines. Clinical practice in large inpatient settings may force clinicians to use lithium in combination with antipsychotics for the treatment of acute mania; the delayed action of lithium and the need for rapid stabilization may drive these practices.

P.2.f.030 Are there differences in treatment of acute manic episodes in bipolar patients with or without comorbid borderline personality disorder?

P.2.f.030 Are there differences in treatment of acute manic episodes in bipolar patients with or without comorbid borderline personality disorder?

C.04.01 Early treatment of acute manic episodes in bipolar disorder

Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10–20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly in low-income and middle-income countries. Targeting medical and psychiatric comorbidity, integrating adjunctive psychosocial treatments, and involving caregivers have been shown to improve health outcomes for people with bipolar disorders. The aim of this Seminar, which is intended mainly for primary care physicians, is to provide an overview of diagnostic, pathogenetic, and treatment considerations in bipolar disorders. Towards the foregoing aim, we review and synthesise evidence on the epidemiology, mechanisms, screening, and treatment of bipolar disorders.

P.3.c.012 Intramuscular and orodispersable olanzapine efficiency in the acute treatment of manic episodes

P.3.c.012 Intramuscular and orodispersable olanzapine efficiency in the acute treatment of manic episodes

Pharmacoeconomics of quetiapine for the management of acute mania in bipolar I disorder

Bipolar disorder (or manic depression) is a lifelong, severe and complex psychiatric illness characterized by recurrent episodes of depression and mania. The aim of this study is to explore the cost–effectiveness of quetiapine compared with other alternatives for the treatment of acute manic episodes in bipolar I disorder, with a specific focus on serious side effects. Four trials investigating quetiapine monotherapy and adjunctive therapy were performed to investigate the efficacy of quetiapine in patients with bipolar I disorder. Data were derived from The Netherlands Mental Health Survey and Incidence Study and used to construct a study population for the model. To assess the cost–effectiveness of quetiapine in the management of acute mania in bipolar I disorders, a discrete event simulation model of seven monotherapy and combination treatment options was developed. A comparison of the total costs demonstrates that all of the monotherapy options and placebo are more costly than the combination therapy options. The combinations of lithium with risperidone (€2365) and with olanzapine (€2429) are estimated to be less costly per patient than the combination of lithium with quetiapine (€2555). A group of 10,000 patients switching from olanzepine/lithium to quetiapine/lithium would involve extra costs of €1,260,000, but would prevent an estimated number of 362 serious side effects. Switching from risperidone/lithium to quetiapine/lithium would cost an additional €1,900,000 and would prevent 1580 serious side effects. In terms of serious side effects, the combination of lithium/quetiapine was superior to the combination of lithium with olanzapine or risperidone. It must be considered whether the decreased likelihood of developing a severe side effect is worth the extra costs incurred with the combination of quetiapine/lithium.

Risperidone may be the most cost-effective atypical antipsychotic for the treatment of acute manic episodes in bipolar I disorder,

Risperidone may be the most cost-effective atypical antipsychotic for the treatment of acute manic episodes in bipolar I disorder,

Risperidone may be the most cost-effective atypical antipsychotic for the treatment of acute manic episodes in bipolar I disorder,

Risperidone may be the most cost-effective atypical antipsychotic for the treatment of acute manic episodes in bipolar I disorder,

Behandlung manischer Episoden bei bipolaren Störungen mit Risperidon

In patients with bipolar disorder antipsychotics are frequently used for the treatment of acute manic episodes, either in monotherapy, in addition to a mood stabilizer or in patients refractory to lithium or other mood stabilizers. However, a number of studies demonstrated that the use of conventional neuroleptics is restricted -- particularly for long-term treatment and relapse prevention in bipolar disorder -- due to their side effect profile and their potential to induce or worsen depressive symptoms. In contrast, atypical antipsychotics have a better tolerability profile and fewer extrapyramidal side effects. A number of clinical studies showed that the atypical antipsychotic risperidone was effective and well tolerated in the treatment of bipolar mania. This was reported both for the treatment of acute episodes and for the maintenance therapy. Recent data suggest that risperidone can be used effectively either in addition to or even instead of a mood stabilizer. This review summarizes the available literature on risperidone in the treatment of bipolar disorders.

Bipolar disorder: historic perspective, current pharmacologic treatment options and a review of quetiapine

Bipolar disorder is a complex mental illness that is frequently both under-diagnosed and under-treated. The symptoms of bipolar disorder can be confused with other medical illnesses or drug effects or may even be overlooked entirely as extreme character traits. The consequences of delayed diagnosis or misdiagnosis are potentially devastating, including loss of employment, impaired relationships and a severely impaired quality of life. This article will review the historic perspectives of bipolar disorder, the diagnostic criteria for the phases of the illness, and the pharmacologic options available to treat this condition. Quetiapine, an atypical antipsychotic, will be reviewed indepth. Based on extensive trial data, reviewed in this article, quetiapine is approved by the US Food and Drug Administration for use as monotherapy or as adjunctive therapy with other mood stabilizers for the treatment of acute manic episodes of bipolar I disorder. Clinical trials describing the efficacy of quetiapine in other phases of bipolar disorder and in other patient populations are also reviewed. A discussion of the drug profile of quetiapine includes its chemistry, availability, pharmacodynamics, pharmacokinetics and metabolism. Preclinical studies, postmarketing surveillance, safety, tolerability and regulatory issues are also evaluated. Finally, potential future directions for quetiapine are discussed, together with a review of key issues in bipolar disorder management and details of the information resources used in preparing this article.

Suicide Risk in Placebo-Controlled Trials of Treatment for Acute Manic Episode and Prevention of Manic-Depressive Episode

The authors' goal was to investigate whether there is a greater suicide risk in the placebo arms of placebo-controlled studies of active medication for the treatment of acute manic episode and the prevention of manic/depressive episode. If so, this would be a strong ethical argument against the conduct of such studies. All placebo-controlled, double-blind, randomized trials of medication for the treatment of acute manic episode and the prevention of manic/depressive episode that were part of a registration dossier submitted to the regulatory authority of the Netherlands, the Medicines Evaluation Board, between 1997 and 2003, were reviewed for occurrence of suicide and attempted suicide. In 11 placebo-controlled studies of the treatment of acute manic episode, including 1,506 patients (117 person-years) in the combined active compound group and 1,005 patients (71 person-years) in the combined placebo group, no suicides and no suicide attempts occurred. In four placebo-controlled studies of the prevention of manic/depressive episode, including 943 patients (406 person-years) in the combined active compound group and 418 patients (136 person-years) in the combined placebo group, two suicides (493/100,000 person-years of exposure) and eight suicide attempts (1,969/100,000 person-years of exposure) occurred in the combined active compound group, but no suicides and two suicide attempts (1,467/100,000 person-years of exposure) occurred in the combined placebo group. Concern about greater risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials for these indications, provided that appropriate precautions are taken.

Spotlight on Olanzapine in Bipolar I Disorder1

Olanzapine is an atypical antipsychotic that is approved in the US and Europe for the oral treatment of acute manic episodes in patients with bipolar I disorder and for maintenance therapy to prevent recurrence in responders. Oral olanzapine is effective in the treatment of bipolar mania, both as single agent therapy and as adjunctive therapy in combination with lithium or valproate semisodium. In the treatment of acute episodes, olanzapine is superior to placebo and at least as effective as lithium, valproate semisodium, haloperidol and risperidone in reducing the symptoms of mania and inducing remission. Additional comparative studies are required to determine the efficacy of olanzapine relative to newer atypical antipsychotics such as quetiapine, ziprasidone and aripiprazole. Olanzapine is also effective at delaying or preventing relapse during long-term maintenance therapy in treatment responders and is currently the only atypical antipsychotic approved for this indication. Current evidence suggests that olanzapine may be more effective than lithium in preventing relapse into mania, but not relapse into depression or relapse overall. Olanzapine is generally well tolerated and, although it is associated with a higher incidence of weight gain than most atypical agents, it has a low incidence of extrapyramidal symptoms. Therefore, oral olanzapine is a useful first-line or adjunctive agent for both the acute treatment of manic episodes and the long-term prevention of relapse into manic, depressive or mixed episodes associated with bipolar I disorder.

Mood Stabilizers Target Cellular Plasticity and Resilience Cascades: Implications for the Development of Novel Therapeutics

Bipolar disorder is a devastating disease with a lifetime incidence of about 1% in the general population. Suicide is the cause of death in 10 to 15% of patients and in addition to suicide, mood disorders are associated with many other harmful health effects. Mood stabilizers are medications used to treat bipolar disorder. In addition to their therapeutic effects for the treatment of acute manic episodes, mood stabilizers are useful as prophylaxis against future episodes and as adjunctive antidepressant medications. The most established and investigated mood-stabilizing drugs are lithium and valproate but other anticonvulsants (such as carbamazepine and lamotrigine) and antipsychotics are also considered as mood stabilizers. Despite the efficacy of these diverse medications, their mechanisms of action remain, to a great extent, unknown. Lithium's inhibition of some enzymes, such as inositol monophosphatase and glycogen synthase kinase-3, probably results in its mood-stabilizing effects. Valproate may share its anticonvulsant target with its mood-stabilizing target or may act through other mechanisms. It has been shown that lithium, valproate, and/or carbamazepine regulate numerous factors involved in cell survival pathways, including cyclic adenine monophospate response element-binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen-activated protein kinases. These drugs have been suggested to have neurotrophic and neuroprotective properties that ameliorate impairments of cellular plasticity and resilience underlying the pathophysiology of mood disorders. This article also discusses approaches to develop novel treatments specifically for bipolar disorder.

Predictors of Response to Treatment of Acute Bipolar Manic Episodes With Divalproex Sodium or Placebo in 2 Randomized, Controlled, Parallel-Group Trials

Identification and control of factors that are associated with placebo and drug response in acute mania may influence the design and analysis of future trials in this condition. We analyzed pooled data from 2 multicenter, placebo-controlled, randomized trials of divalproex sodium for the treatment of acute manic episodes, using linear and logistic regression to search for common and treatment-specific predictors of response. In both treatment groups, patients with greater numbers of prior hospitalizations, more severe baseline symptoms, or younger age at onset of illness were found to be significantly less likely to respond. The effect sizes associated with these factors were of comparable magnitude to the effect size associated with divalproex treatment. Stratification on the basis of these prognostic factors may improve the power of future trials for the treatment of acute mania and may help explain patient response to treatment.

Seizure Drug Combats Antipsychotic Side Effects

Seizure Drug Combats Antipsychotic Side Effects

Med Check

Med Check

Olanzapine

Olanzapine is an atypical antipsychotic that is approved in the US and Europe for the oral treatment of acute manic episodes in patients with bipolar I disorder, and for maintenance therapy to prevent recurrence in responders. Oral olanzapine is effective in the treatment of bipolar mania, both as single agent therapy and as adjunctive therapy in combination with lithium or valproate semisodium. In the treatment of acute episodes, olanzapine is superior to placebo and at least as effective as lithium, valproate semisodium, haloperidol and risperidone in reducing the symptoms of mania and inducing remission. Additional comparative studies are required to determine the efficacy of olanzapine relative to newer atypical antipsychotics, such as quetiapine, ziprasidone and aripiprazole. Olanzapine is also effective at delaying or preventing relapse during long-term maintenance therapy in treatment responders, and is currently the only atypical antipsychotic approved for this indication. Current evidence suggests that olanzapine may be more effective than lithium in preventing relapse into mania, but not relapse into depression or relapse overall. Olanzapine is generally well tolerated, and although it is associated with a higher incidence of weight gain than most atypical agents, it has a low incidence of extrapyramidal symptoms (EPS). Therefore, oral olanzapine is a useful first-line or adjunctive agent for both the acute treatment of manic episodes and the long-term prevention of relapse into manic, depressive or mixed episodes associated with bipolar I disorder.

Lithium in bipolar disorder: can drug concentrations predict therapeutic effect?

The evidence is reviewed for effective serum lithium concentrations for the acute and prophylactic treatment of mania and depression in patients with bipolar disorder. The efficacy of lithium in the treatment of acute manic episodes has been recognised for several decades, primarily using concentrations in the range of 0.8 to 2 mmol/L. The number of patients responding increases as the serum lithium concentration increases, although individual patients may respond at lower concentrations (<0.8 mmol/L). Lithium doses and serum concentrations similar to those used to treat acute mania have been studied in bipolar depression, with no evaluation of a relationship between concentration and clinical response. Several prospective controlled trials have evaluated this relationship in the prophylactic treatment of bipolar disorder. Maintaining higher serum lithium concentrations (0.8 to 1 mmol/L) improves the likelihood of good effect in prophylactic treatment, although individual patients may do well on lower concentrations. Despite the paucity of evidence to specifically support the efficacy of lithium at lower serum lithium concentrations in the elderly, lower target ranges (0.5 to 0.8 mmol/L) are commonly recommended due to an increased sensitivity to adverse effects, particularly neurotoxicity. The serum lithium concentrations recommended in adults have been applied to children; however, this has not been studied. Overall, the evidence suggests a relationship between serum lithium concentration and therapeutic effect, although the exact nature of this relationship is not clear. For example, it is not known why some people respond to lower concentrations and others do not. There are many factors that influence studies trying to elucidate this relationship. Many of these factors are related to the interpretation of the serum lithium concentration. In summary, patients have an increased chance of responding to lithium if 12-hour serum lithium concentrations at steady state are above 0.8 mmol/L. Many patients will respond to lower concentrations (0.4 to 0.7 mmol/L), but we are unable to identify these patients a priori. The relationship between serum lithium concentrations and adverse effects is also very important in determining appropriate target lithium concentrations. The current best advice is to individualise the target serum lithium concentrations based on efficacy and tolerability and to optimise the interpretation of these concentrations by ensuring within-patient consistency with respect to dosage schedule, lithium preparation and the timing of blood sampling.