Long-term Treatment Of Bipolar Disorder Research Articles

Clinical vignette – Aripiprazol long acting injection monotherapy as long-term treatment for bipolar disease

IntroductionOver the last decade a number of effective maintenance treatments for bipolar disorder (BPD) have been developed. Lithium remains the best-established option, but valproic acid, lamotrigine, olanzapine, and quetiapine are also effective maintenance drugs. However, oral administration contributes to lower adherence rates with these drugs. In the United States and Europe, aripiprazole is approved for the acute management of manic and mixed episodes and maintenance in BPD. It presents the advantage of a low risk of metabolic side effects, sexual dysfunction, and sedation, which can facilitate treatment adherence and help improve clinical outcomes.ObjectivesThe authors present an illustrative case on which aripiprazol long acting injection monotherapy was effective as maintenance treatment in a patient with long history of BPD with several hospital inpatient admissions and very poor therapeutic adherence.MethodsCase report based on the patient's file. Narrative review of articles available in PubMed about the use of aripiprazol in BPD.ResultsFor this patient, aripiprazol long acting injection has proved to be an excellent choice for long-term treatment of BPD. The once-a-month injection promotes therapeutic adherence, which in this case was combined with involuntary outpatient treatment, ensuring therapeutic compliance.ConclusionsAripiprazol has been shown to be safe and effective in the maintenance treatment in BPD. It shows similar efficacy and a superior tolerability profile when compared with other well-established treatments. Further studies are needed, warranted by its potential advantages, particularly on patients with poor insight and adherence.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Defining the role of SGAs in the long-term treatment of bipolar disorder.

Defining the role of SGAs in the long-term treatment of bipolar disorder.

Maintenance treatment trends, therapeutic outcomes and their association with clinical features in remitted bipolar disorder

The evidence base data regarding long-term treatment of bipolar disorder (BD) is less than satisfactory. With the first-line rank of lithium and valproate; antipsychotics (AP) and anticonvulsants (AC) considered options for prolonged treatment in remitted bipolar patients. Literature demonstrates various treatment options in remitted patients with different clinical features. The aim of this study to present and assess clinical outcomes of maintenance treatment for BD with various clinical features. In total 186 bipolar patients in remission were enrolled in this study. All the patients were evaluated with SCID-I (Structured Clinical Interview for DSM-IV) ; and lifelong psychiatric comorbidities were determined. Sociodemographical and clinical features, and lifelong pharmacological treatment of the patients were assessed. Semi-structured interview schedules were filled. 71% lithium, 44% AC, 18% AP monotherapies and 23% lithium-AC, 15% lithium-AP, 25% AC-AP combination therapies were used as maintenance treatment. 61% and 62% of the patients were responders of lithium and AC monotherapies respectively. AC and AP combination had the highest response level. The predictors on the probability of treatment response for lithium were being married, non-psychotic, to show seasonal pattern and less severe episodes. Anticonvulsants were effective in males, divorces, suicide attempters, and the patients with predominance of mixed features in periods. Obsessive-compulsive disorder was the most common comorbid diagnosis in study group. Lithium monotherapy was tended to use in prevention, however treatment combinations which contain APs might be effective alternative to monotherapy. Individualized medication ought to be administered for each patient, with the consideration of clinical features and tolerability.

Lityumun İndüklediği Nefrojenik Diyabetes İnsipitus ve Böbrek Yetmezliği: Bir Olgu Sunumu

Lithium is used for long-term treatment of bipolar disorder. Lithium can cause nephrogenic diabetes insipidus (NDI) in up to 20 to 40 percent of patients and less frequently it can cause chronic tubulointerstitial nephritis and renal failure. Most of NDI cases usually resolve after discontinuation of lithium treatment. In a minority of cases, the NDI may be permanent. Here we present a case using lithium due to bipolar disorder and then developing NDI and renal failure and treated with indomethacin. Key wORdS: Acute kidney injury, Lithium, Nephrogenic diabetes insipidus

Clinical vignette – aripiprazol long acting injection monotherapy as long-term treatment for bipolar disease

Introduction Over the last decade a number of effective maintenance treatments for bipolar disorder (BPD) have been developed. Lithium remains the best-established option, but valproic acid, lamotrigine, olanzapine, and quetiapine are also effective maintenance drugs. However, oral administration contributes to lower adherence rates with these drugs. In the United States and Europe, aripiprazole is approved for the acute management of manic and mixed episodes and maintenance in BPD. It presents the advantage of a low risk of metabolic side effects, sexual dysfunction, and sedation, which can facilitate treatment adherence and help improve clinical outcomes. Objectives/aims The authors present an illustrative case on which aripiprazol long acting injection monotherapy was effective as maintenance treatment in a patient with long history of BPD with several hospital inpatient admissions and very poor therapeutic adherence. Methods Case report based on the patient's file. Narrative review of articles available in PubMed about the use of aripiprazol in BPD. Results For this patient, aripiprazol long acting injection has proved to be an excellent choice for long-term treatment of BPD. The once-a-month injection promotes therapeutic adherence, which in this case was combined with involuntary outpatient treatment, ensuring therapeutic compliance. Conclusions Aripiprazol has been shown to be safe and effective in the maintenance treatment in BPD. It shows similar efficacy and a superior tolerability profile when compared with other well-established treatments. Further studies are needed, warranted by its potential advantages, particularly on patients with poor insight and adherence.

Childhood trauma and treatment outcome in bipolar disorder

ABSTRACTThe aim of the present study was to investigate the potential influence of childhood trauma on clinical presentation, psychiatric comorbidity, and long-term treatment outcome of bipolar disorder. A total of 135 consecutive patients with bipolar disorder type I were recruited from an ongoing prospective follow-up project. The Childhood Trauma Questionnaire and the Structured Clinical Interview for DSM–IV Axis I Disorders were administered to all participants. Response to long-term treatment was determined from the records of life charts of the prospective follow-up project. There were no significant differences in childhood trauma scores between groups with good and poor responses to long-term lithium treatment. Poor responders to long-term anticonvulsant treatment, however, had elevated emotional and physical abuse scores. Lifetime diagnosis of posttraumatic stress disorder (PTSD) was associated with poor response to lithium treatment and antidepressant use but not with response to treatment with anticonvulsants. Total childhood trauma scores were related to the total number of lifetime comorbid psychiatric disorders, antidepressant use, and the presence of psychotic features. There were significant correlations between all types of childhood abuse and the total number of lifetime comorbid psychiatric diagnoses. Whereas physical neglect was related to the mean severity of the mood episodes and psychotic features, emotional neglect was related to suicide attempts. A history of childhood trauma or PTSD may be a poor prognostic factor in the long-term treatment of bipolar disorder. Whereas abusive experiences in childhood seem to lead to nosological fragmentation (comorbidity), childhood neglect tends to contribute to the severity of the mood episodes.

Illness history: Not associated with remission during treatment of major depression in 515 mood disorder patients

BackgroundThere is suggestive evidence that prior illness history may have little association with response to long-term treatment in bipolar disorder (BD) or recurrent major depressive disorder (MDD), but relationships of illness-history to treatment-response in acute episodes of depression require further testing. MethodsWe tested for associations of selected measures of illness history with remission during treatment of an acute index episode of major depression in 515 mood-disorder patients (327 MDD, 188 BD), using bivariate and multivariate methods. ResultsRemission of depression was more likely with lesser initial symptom-severity and bipolar diagnosis, but not related to years since illness-onset, previous depressions or episodes (based on counts, yearly rates, or %-of months ill), or other indices of illness-severity (hospitalization, co-morbidity, suicide attempt). ConclusionsLikelihood of response to standard treatments for acute major depressive episodes in MDD or BD appeared to be largely independent of prior illness-history.

The effect of lithium on hematopoietic, mesenchymal and neural stem cells.

Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone for the long-term treatment of bipolar disorder. A number of biological properties of lithium have been discovered, including its hematological, antiviral and neuroprotective effects. In this article, a systematic review of the effect of lithium on hematopoietic, mesenchymal and neural stem cells is presented. The beneficial effects of lithium on the level of hematopoietic stem cells (HSC) and growth factors have been reported since 1970s. Lithium improves homing of stem cells, the ability to form colonies and HSC self-renewal. Lithium also exerts a favorable influence on the proliferation and maintenance of mesenchymal stem cells (MSC). Studies on the effect of lithium on neurogenesis have indicated an increased proliferation of progenitor cells in the dentate gyrus of the hippocampus and enhanced mitotic activity of Schwann cells. This may be connected with the neuroprotective and neurotrophic effects of lithium, reflected in an improvement in synaptic plasticity promoting cell survival and inhibiting apoptosis. In clinical studies, lithium treatment increases cerebral gray matter, mainly in the frontal lobes, hippocampus and amygdala. Recent findings also suggest that lithium may reduce the risk of dementia and exert a beneficial effect in neurodegenerative diseases. The most important mediators and signaling pathways of lithium action are the glycogen synthase kinase-3 and Wnt/β-catenin pathways. Recently, to study of bipolar disorder pathogenesis and the mechanism of lithium action, the induced pluripotent stem cells (iPSC) obtained from bipolar patients have been used.

Management of adverse effects of mood stabilizers.

Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management.

Patient-Important Outcomes in the Long-Term Treatment of Bipolar Disorder: A Mixed-Methods Approach Investigating Relative Preferences and a Proposed Taxonomy.

In patient-centered healthcare, the assessment and selection of treatment should be based on outcomes important to patients and the relative importance patients place on these outcomes. The evidence base on long-term treatment outcomes important to patients with bipolar disorder is inconclusive. The aim of this study was to investigate the relative importance of patient-important outcomes in bipolar disorder, and to construct a holistic and logically sound shortlist of treatment outcomes relevant in the evaluation and selection of pharmacological treatment in bipolar disorder. Overall, 22 outpatients from southern and eastern Norway participated in four focus groups, and suggested outcomes important in treatment decisions. Quantitative, relative importance weights for treatment outcomes identified in literature reviews were elicited from each participant, employing a self-explicated approach (SEA). The method combined a ranking- and rating-stated preference exercise and resulted in a 0-100 SEA-score for each outcome. Outcomes from the literature accommodated the outcomes suggested in the focus groups. Mean age in the sample was 42 years and 64% were women. All patients completed the exercises with consistent results. The most important outcomes were severe depression (median SEA 95 [interquartile range 26]), severe mania (76 [40]), quality of life (65 [53]), work/school functioning (58 [48]), and social functioning (54 [50]). Avoiding severe mania was significantly more important to patients with bipolar disorder type I compared with patients with type II. Outcome scores correlated strongly (p < 0.01) across the ranking and rating exercises. Based on the results, a simplified and consistent set of outcomes was constructed. Patients' preferences for outcomes in the long-term treatment of bipolar disorder vary considerably. To advance patient-centered healthcare, we propose that researchers, clinical guideline producers, and patient-clinician dyads integrate a taxonomy of patient-important outcomes, such as constructed in this study, when assessing treatment options.

Tratamiento a largo plazo del trastorno bipolar: papel de los antipsicóticos

Therapy of the patient suffering bipolar disorder requires continuation beyond the acute phases to prevent new episodes. The objective of this non-systematic review is to analyze the role of antipsychotic drugs in long-term therapy of bipolar disorder. Clinical practice guidelines (CPG) published between 2009 and 2014 have been reviewed. Several atypical antipsychotic drugs (aripiprazole, olanzapine, quetiapine, long-acting risperidone, and ziprasidone) are recommended, as monotherapy or combined with a mood-stabilizing drug, as first line long-term treatment in several CPG. Most drugs have an indication for prevention of manic episodes, and only quetiapine is recommended to prevent depressive episodes as well. Considering long-term treatment of bipolar disorder with antipsychotic drugs is adequate, but risk/benefit ratio of these drugs has to be kept in mind, given the limitations of available studies and the possible side effects of prolonged treatment.

Efficacy and Safety of Long-term Treatment with Lurasidone in Older Adults with Bipolar Depression: Results of a 6 Month Open-label Study

Long-term treatment of bipolar disorder in the elderly has not been well-studied. This secondary analysis evaluated the safety and efficacy of 6 months of treatment with lurasidone in patients over 55 years with bipolar depression.

More robust evidence for the efficacy of lithium in the long-term treatment of bipolar disorder: should lithium (again) be recommended as the single preferred first-line treatment?

With two recent systematic reviews and meta-analyses on the efficacy of lithium compared to placebo and other treatment options, it can now be concluded that lithium is the only drug that has been shown efficacious in the prevention of any mood episodes, manic episodes and depressive episodes in randomised trials not enriched for prior response to and tolerance of lithium. It is argued that lithium should be recommended as the single preferred first-line drug in the long-term treatment of bipolar disorder.

Lithium for prevention of mood episodes in bipolar disorders: systematic review and meta-analysis.

BackgroundIn a previous meta-analysis of randomized controlled trials comparing lithium with placebo as a long-term treatment in bipolar disorders, we observed a clear preventative effect for manic episodes; however, the effect was equivocal for depressive episodes. Since then, the evidence base has grown further. In this update, we furthermore present the data on efficacy of lithium in comparison to alternative drug treatments. In addition, we analyze the data comparing lithium with placebo and other treatments regarding drop-outs due to reasons other than a mood episode and completion of study (no mood episode and no drop-out to reasons other than a mood episode).MethodsRandomized controlled trials (RCTs) were sought comparing lithium with placebo and lithium with an alternative treatment in bipolar disorders where the stated intent of treatment was prevention of mood episodes. To this purpose, the Cochrane Central Register of Controlled Trials (CENTRAL) was searched. Reference lists of relevant papers and major textbooks of mood disorders were examined. Authors, other experts in the field, and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished.ResultsFor the comparison of lithium with placebo, seven trials (1,580 participants) were included. Lithium was more effective than placebo in preventing overall mood episodes (random effects RR 0.66, 95% CI 0.53 to 0.82), manic episodes (random effects RR 0.52, 95% CI 0.38 to 0.71), and, dependent on the type of analyses applied, depressive episodes (random effects RR 0.78, 95% CI 0.59 to 1.03; fixed effect RR 0.73, 95% CI 0.60 to 0.88). Lithium was inferior to placebo in leading to drop-outs for reasons other than a mood episode (random effects RR 1.33, 95% CI 1.07 to 1.65) but superior to placebo on study completion (random effects RR 1.69, 95% CI 1.12 to 2.55).For the comparison of lithium with anticonvulsants, seven trials were included (n = 1,305). In prevention of manic episodes, lithium showed superiority compared to anticonvulsants (random effects RR 0.66, 95% CI 0.44 to 1.00). However, there was no significant difference regarding prevention of overall mood episodes, depressive episodes, dropping-out to reasons other than a mood episode, or study completion.ConclusionsThe evidence base for lithium in the long-term treatment of bipolar disorders has strengthened. With no other drug available having such ample and consistent evidence for its efficacy lithium remains the most valuable treatment option in this indication.

Comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: a systematic review and network meta-analysis

Lithium is the established standard in the long-term treatment of bipolar disorder, but several new drugs have been assessed for this indication. We did a network meta-analysis to investigate the comparative efficacy and tolerability of available pharmacological treatment strategies for bipolar disorder. We systematically searched Embase, Medline, PreMedline, PsycINFO, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before June 28, 2013, that compared active treatments for bipolar disorder (or placebo), either as monotherapy or as add-on treatment, for at least 12 weeks. The primary outcomes were the number of participants with recurrence of any mood episode, and the number of participants who discontinued the trial because of adverse events. We assessed efficacy and tolerability of bipolar treatments using a random-effects network meta-analysis within a Bayesian framework. We screened 114 potentially eligible studies and identified 33 randomised controlled trials, published between 1970 and 2012, that examined 17 treatments for bipolar disorder (or placebo) in 6846 participants. Participants assigned to all assessed treatments had a significantly lower risk of any mood relapse or recurrence compared with placebo, except for those assigned to aripiprazole (risk ratio [RR] 0·62, 95% credible interval [CrI] 0·38-1·03), carbamazepine (RR 0·68, 0·44-1·06), imipramine (RR 0·95, 0·66-1·36), and paliperidone (RR 0·84, 0·56-1·24). Lamotrigine and placebo were significantly better tolerated than carbamazepine (lamotrigine, RR 5·24, 1·07-26·32; placebo, RR 3·60, 1·04-12·94), lithium (RR 3·76, 1·13-12·66; RR 2·58, 1·33-5·39), or lithium plus valproate (RR 5·95, 1·02-33·33; RR 4·09, 1·01-16·96). Although most of the drugs analysed were more efficacious than placebo and generally well tolerated, differences in the quality of evidence and the side-effect profiles should be taken into consideration by clinicians and patients. In view of the efficacy in prevention of both manic episode and depressive episode relapse or recurrence and the better quality of the supporting evidence, lithium should remain the first-line treatment when prescribing a relapse-prevention drug in patients with bipolar disorder, notwithstanding its tolerability profile. None.

Long-term treatment of bipolar disorder

Long-term treatment of bipolar disorder

Pharmacokinetics of Lithium in Egyptian Bipolar Patients: Dosage Adjustment Approach

Due to its proven clinical effectiveness, lithium has been considered as a corner stone for the long-term treatment of Bipolar Disorder (BPD) for more than half a century. The objective of this study was to evaluate the effect of patients’ different co-variables on lithium pharmacokinetics and the development of a pharmacokinetic model for the estimation of lithium clearance in Egyptian bipolar patients; this model can be used afterwards during dosage adjustment to achieve target’s steady-state plasma concentrations in similar settings. The study was conducted on 65 adult Egyptian bipolar patients of both genders, in both the in- and out-patient settings in the Institute of Psychiatry, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Patients’ full profiles were prepared, containing all their data. Single daily dose regimen was followed by all patients and one blood sample was drawn 12 ± 0.5 hours post dose for steady-state lithium concentration, sodium level and serum creatinine determinations. Lithium trough levels were determined using Flame Emission Photometry technique. Data analysis and regression modeling revealed a significant correlation between total body weight (TBW), body surface area (BSA) and lithium clearance. Due to multicollinearity, BSA was excluded from the basic non-linear regression equation and TBW was found to be the only covariate affecting lithium clearance. Mean lithium clearance was found to be 0.243 ± 0.097 Lit/Kg/day, ranging from 0.091 to 0.71 Lit/Kg/day.

Treatment of Bipolar Disorder

We review recent developments in the acute and long-term treatment of bipolar disorder and identify promising future routes to therapeutic innovation. Overall, advances in drug treatment remain quite modest. Antipsychotic drugs are effective in the acute treatment of mania; their efficacy in the treatment of depression is variable with the clearest evidence for quetiapine. Despite their widespread use, considerable uncertainty and controversy remains about the use of antidepressant drugs in the management of depressive episodes. Lithium has the strongest evidence for long-term relapse prevention; the evidence for anticonvulsants such as divalproex and lamotrigine is less robust and there is much uncertainty about the longer term benefits of antipsychotics. Substantial progress has been made in the development and assessment of adjunctive psychosocial interventions. Long-term maintenance and possibly acute stabilisation of depression can be enhanced by the combination of psychosocial treatments with drugs....

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

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

S.05.01 Lithium: still a cornerstone in the long-term treatment of bipolar disorder?

S.05.01 Lithium: still a cornerstone in the long-term treatment of bipolar disorder?