Conventional Mood Stabilizers Research Articles

Body composition in Japanese patients with psychiatric disorders: A cross-sectional study.

AimThis study aimed to investigate body composition in Japanese patients with psychiatric disorders.MethodsA cross‐sectional study was conducted to assess the body composition in Japanese patients with psychiatric disorders and healthy controls. InBody470 was used to measure the body composition of the participants. For the primary analysis, measures of body composition between patients and healthy controls were compared. Moreover, the following patient subgroups were also compared with the healthy controls: (a) patients with psychotic disorders only, (b) patients with mood disorders only, (c) patients receiving antipsychotics, (d) patients receiving conventional mood stabilizers, (e) patients receiving antidepressants only but not any antipsychotics and/or mood stabilizers, and (f) patients receiving hypnotics/anxiolytics.ResultsThis study included 205 individuals (105 patients and 100 healthy controls). It was found that patients had a significantly higher body mass index, waist‐hip ratio, body fat mass, and percent body fat compared with the healthy controls. Moreover, significant differences were noted in the waist‐hip ratio, body fat mass, and percent body fat between all patient subgroups other than patients receiving conventional mood stabilizers subgroup and healthy controls.ConclusionThis is the first cross‐sectional study to examine body composition in Japanese patients with psychiatric disorders. No difference in the skeletal muscle volume was noted although patients had higher body fat than healthy controls. A longitudinal and large cohort study in the future, controlling for medication and diagnosis, will need to determine why body fat is increased in Japanese patients with psychiatric disorders.

Prescription patterns in clinically stable patients with bipolar disorder: Findings from the Bipolar Disorder Course and Outcome from India (BiD-CoIN) study.

To evaluate the prescription pattern of patients with BD, currently in clinical remission. Additional aim of the study was tocompare the prescription pattern across different study centres. Prescription of 773 patients, currently in clinical remission, recruited from the outpatient setting of 14 General Hospital Tertiary Care Units of tertiary care centres in the country were evaluated. Almost all (98.1 %) participants were on medications at the time of assessment. In terms of conventional mood stabilizers, those receiving valproate (44.2 %), out-numbered those receiving lithium (38.9 %). A small proportion (7.4 %) was receiving a combination of both valproate and lithium. About two-third (62.5 %) were receiving at least one antipsychotic medication, with olanzapine (31.7 %) being the most commonly prescribed antipsychotic, followed by quetiapine (11.1 %), and risperidone (9.6 %). About one-third (34.4 %) of the participants were receiving antidepressants, with sertraline (22.6 %) forming bulk of the prescription. Less than half (43.9 %) of the participants were also receiving a benzodiazepine medication at the time of assessment, with chlordiazepoxide (18 %) being the most common agent, followed by clonazepam (14.5 %). There was variation in the prescription patterns across different centres, in terms of monotherapy, polypharmacy, use of preferred conventional mood stabilizers, use of various antipsychotics and antidepressants. Besides conventional mood stabilizers, about two-third of patients with bipolar disorder received concomitant antipsychotics, one-third received concomitant antidepressants and less than half received benzodiazepines.

Conventional mood stabilizers and/or second-generation antipsychotic drugs in bipolar disorders: A population-based comparison of risk of treatment failure

BackgroundThe study compared treatment failure when using three therapeutic strategies in bipolar disorders: (i) mood stabilizers (MSs: lithium, valpromide, divalproate, carbamazepine, lamotrigine) without second-generation antipsychotic (SGAP); (ii) SGAPs (aripiprazole, olanzapine, risperidone, quetiapine) without MS; (iii) combination of MSs and SGAPs. MethodsA historical cohort study was conducted using the French national healthcare databases in 20,086 outpatients aged 21+, newly treated with one of the three treatment strategies in 2011–2012, and diagnosed with a bipolar disorder. A composite outcome was based on indicators of treatment failure identified over 12 months: treatment discontinuation, switch or addition, psychiatric hospitalisation, suicide attempt, and death. For each strategy, the cumulative incidence of treatment failure was calculated while adjusting for covariates by propensity score weighting. ResultsA total of 8,225 patients (40.9%) were newly dispensed MSs, 9,342 (46.5%) SGAPs, and 2,519 (12.5%) both MSs and SGAPs. The one-year adjusted cumulative incidence of treatment failure was 75.7% (95%CI 74.9;76.3) in patients using MSs, 75.3% (74.6;76.0) in patients using SGAPs, and 60.5% (58.3;62.6) in patients with the combination. The adjusted difference in incidence for SGAPs compared with MSs was −0.40% (-1.4;0.6 p = 0.4) in the whole population, −2.2% (-3.3; −1.2 p < 0.002) in patients under 65 years and +6.7% (4.1;9.1 p < 0.002) in patients 65 years and over. LimitationsCombinations of MSs and SGAPs could not be directly compared with MS or SGAP monotherapies. ConclusionsOne-year treatment failure was high. Overall, no difference in treatment failure was observed between MS or SGAP strategy but differences might exist depending on age.

Relationship between bipolar disorder and attention deficit hyperkinetic disorder: An exploratory study.

This study aimed to evaluate the impact of comorbid attention deficit hyperkinetic disorder (ADHD) on Bipolar disorder (BD). Patients aged 13-40 years with diagnosis of BD with ADHD (N = 30) were compared to those with BD without ADHD (N = 69) for clinical course, functional outcome and quality of life. Those with BD + ADHD had significantly lower age of onset of BD (p < 0.001), a significantly higher number of total lifetime episodes (p = 0.002), higher number of lifetime manic episodes (p = 0.008), higher number of hospitalizations (p = 0.004) and higher prevalence of family history of BD as compared to those with BD without ADHD (p = 0.043). BD + ADHD group had poor response to conventional mood stabilizers and significantly higher prescriptions of atypical antipsychotics (p = 0.001) and higher rates of antidepressant-induced switch. Also, BD + ADHD group had significantly lower level of functioning in personal, occupational and social domains and reduced quality of life. In the BD + ADHD group, 40% patients had persistence of ADHD into adulthood. Comorbid current ADHD had more negative impact on the course and outcome of BD, when compared with those with ADHD in the past. Comorbid ADHD has negative impact on the course and outcome of BD.

A pragmatic approach to the diagnosis and treatment of mixed features in adults with mood disorders.

Mixed features specifier (MFS) is a new nosological entity defined and operationalized in the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th Edition. The impetus to introduce the MFS and supplant mixed states was protean, including the lack of ecological validity, high rates of misdiagnosis, and guideline discordant treatment for mixed states. Mixed features specifier identifies a phenotype in psychiatry with greater illness burden, as evidenced by earlier age at onset, higher episode frequency and chronicity, psychiatric and medical comorbidity, suicidality, and suboptimal response to conventional antidepressants. Mixed features in psychiatry have historical, conceptual, and nosological relevance; MFS according to DSM-5, is inherently neo-Kraepelinian insofar as individuals with either Major Depressive Disorder (MDD) or Bipolar Disorder (BD) may be affected by MFS. Clinicians are encouraged to screen all patients presenting with a major depressive episode (or hypomanic episode) for MFS. Although "overlapping symptoms" were excluded from the diagnostic criteria (eg, agitation, anxiety, irritability, insomnia), clinicians are encouraged to probe for these nonspecific symptoms as a possible proxy of co-existing MFS. In addition to conventional antidepressants, second generation antipsychotics and/or conventional mood stabilizers (eg, lithium) may be considered as first-line therapies for individuals with a depressive episode as part of MDD or BD with mixed features.

Lithium or Valproate Adjunctive Therapy to Second-generation Antipsychotics and Metabolic Variables in Patients With Schizophrenia or Schizoaffective Disorder.

People with schizophrenia are at greater risk for cardiovascular disease and their overall mortality rate is elevated compared to the general population. The metabolic side effects of antipsychotic medications have been widely studied; however, the effect of adding conventional mood stabilizers, such as lithium and valproate, to antipsychotic medication has not been assessed in terms of metabolic risk. The primary purpose of this secondary analysis was to examine whether treatment with lithium or valproate in addition to a second-generation antipsychotic is associated with poorer metabolic outcomes than treatment with a second-generation antipsychotic without lithium or depakote. Baseline data from 3 studies, which included measurement of body mass index, waist circumference, fasting glucose, insulin, homeostatic model assessment of insulin resistance, insulin sensitivity index, glucose utilization, and acute insulin response to glucose, were included in the analysis. No differences were found between those taking lithium or valproate and those who were not in terms of fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance. Insulin sensitivity was lower among participants taking lithium or valproate. Participants taking lithium or valproate had a higher body mass index than those not taking conventional mood stabilizers, although the difference did not reach statistical significance. These cross-sectional findings suggest it may be beneficial to monitor insulin sensitivity and body mass index in patients taking lithium or valproate in combination with a second-generation antipsychotic.

Pharmacotherapy of bipolar disorder with quetiapine: a recent literature review and an update.

Bipolar disorder is a chronic, recurrent condition with the usual onset during adolescence or early adulthood. In the Diagnostic and Statistical Manual of Mental Disorders 5th edition, it is conceptualized as a spectrum disorder usually associated with such comorbidities as anxiety disorders and substance use disorders. It is a relatively prevalent condition often complicated by mixed episodes, rapid cycling, subsyndromal symptoms, and treatment refractoriness. In spite of carrying substantial morbidity and mortality, effective treatments are few and far between and conventional mood stabilizers are often unsuccessful in controlling the various manifestations of the disorder. In this scenario, second generation antipsychotics are emerging as treatments with valid efficacy in all phases of bipolar disorder. Quetiapine is a versatile atypical antipsychotic which was first approved for the treatment of schizophrenia, but latter on the basis of controlled studies earned United States Food and Drug Administration’s approval for acute as well as maintenance treatment of this difficult to treat condition. In this review, recently published studies in the last 10 years were examined to update the knowledge about the efficacy and safety of quetiapine in the treatment of bipolar disorder. The medication’s clinical pharmacology was first considered followed by a literature review summarizing its uses in bipolar disorder. The conclusion was that quetiapine was efficacious in manic, mixed and depressive episodes and as a maintenance agent with a good tolerability profile.

Pharmacotherapy of Bipolar Affective Disorder: A Hospital based Study from Sub Himalayan Valley of Nepal.

In Bipolar disorder the mood of the patients fluctuates between depression and mania. The main objective of the study was to find out the commonest mood stabilizers used for the treatment of Bipolar affective disorders in Western Nepal in hospitalized patients in an actual clinical set up. This was a cross-sectional study which was conducted between October 2009 and September 2010 at Psychiatric ward at Manipal teaching hospital, Pokhara, Nepal, a tertiary care hospital situated in Western Nepal. The diagnosis of the disease was based on ICD-10 (Tenth revision) Classification of mental and Behavioural disorders, Diagnostic Criteria for Research. We calculated odds ratio and their 95% confidence intervals (95% CI). p< 0.05 was considered as statistically significant. 62.1% of the patients were less than 40 yrs, 56.3% were male, 72.4% were unemployed and 75.9% of the patients were having monthly income <10,000/month. As far as ethnicity is concerned 37.9% of the cases were Brahmin and by occupation 29.9% of the patients were students followed by housewife 25.3%, labour 17.2%, retired 13.8% respectively. Drugs and Psychotherapy [OR 1.4, 95% (CI 0.575, 3.4017)] was prescribed in age <40 years as compared to age>40 yrs. Male patients [OR 7.22, 95% (CI 0.862, 60.499)] and [OR 2.353, 95% (CI 0.857, 6.455)] received drugs by trade names and drugs not from the national drug list of Nepal as compared to females. Monthly income <10,000/month and [OR 2.8, 95% (CI 0.742, 10.56)] tendency of receiving drugs by trade names. Among the mood elevators Sodium valproate was the commonest drug to be prescribed in 51/87(58.6%) patients followed by Lithium in 30/87 (34.5%) cases and Carbamazepine in 6/87 (6.9%) cases. Sodium valproate was prescribed at 1,000 mg/day, Lithium was prescribed at 900 mg/day in and Carbamazepine was prescribed at 800 mg/day. Among all the mood elevators Sodium valproate is the commonest drug prescribed for the treatment of bipolar affective disorder, recommended that there is a trend of using newer drugs like sodium valproate rather than the conventional mood stabilizers like Lithium for bipolar affective disorder in Western Development region of Nepal.

A comparative study of olanzapine versus asenapine in acute treatment of manic episode: A 3-week prospective study

Introduction: Treatment of bipolar disorders has evolved over the years from conventional mood stabilizers to second-generation antipsychotics. Among the atypical antipsychotics, few have been approved by Food and Drug Administration as treatment of bipolar disorders. Aim: To study the efficacy and tolerability of olanzapine and asenapine in the acute treatment of bipolar disorder-manic episode in a 3-week randomized prospective study. Materials and Methods: A 3-week randomized, prospective, comparative, flexible doses of olanzapine (5-30 mg/day) and asenapine (10-20 mg/day) for acute treatment of bipolar disorder-current manic episode with or without psychotic symptoms in hospitalized patients. Results: The end-point reduction in mean score of Young Mania rating scale in the olanzapine group was 15.82 in comparison to 6.88 in the asenapine group. Mean score on clinical global impression for bipolar disorder and positive and negative syndrome scale was significantly less in the olanzapine group at the end of the study. 81.81% patients in olanzapine group and 17.60% patients in asenapine group had clinical response. There was significant average weight gain in the olanzapine group - 1.9 kg in comparison to 0.87 kg in asenapine group. Conclusion: The clinical response with olanzapine is significantly higher than the asenapine in the treatment of bipolar disorder-manic episode with or without psychotic symptoms. However, there is significant weight gain in olanzapine-treated patients.

Observational study to evaluate the clinical benefit of lamotrigine add-on therapy in bipolar patients in a naturalistic treatment setting

The objective of the current study was to assess, in a naturalistic treatment setting, the clinical benefits of lamotrigine add-on therapy for patients with bipolar disorder. This was an open-label, prospective, naturalistic, 12-week, observational study that included 98 bipolar patients treated with lamotrigine add-on therapy, in addition to mood stabilizers or atypical antipsychotics for 1-4 weeks. The clinical benefits of lamotrigine augmentation were evaluated using the Clinical Global Impression-Clinical Benefit (CGI-CB) Scale, and the Clinical Global Impression of Bipolar Disorder-Severity scale was used to evaluate the severity of the patients' conditions. According to paired t-test analyses, the mean CGI-CB score significantly decreased from 7.2 ± 2.7 at baseline to 3.8 ± 2.5 at Week 12. Likewise, the mean score for Clinical Global Impression of Bipolar Disorder-Severity scale significantly decreased from 4.7 ± 0.9 at baseline to 3.1 ± 1.2 at Week 12. Analysis of covariance showed that the extent to which CGI-CB scores changed from baseline to Week 12 did not significantly differ between patients with bipolar I and II disorder. However, the change in CGI-CB scores between Weeks 4 and 12 was significantly smaller in bipolar II patients than bipolar I patients. A total of 21 (21.4%) patients dropped out during the course of the study, and 30 patients (30.6%) reported 82 adverse events. The results of this study demonstrated that the use of lamotrigine in patients with bipolar disorder, especially those whom conventional mood stabilizers or antipsychotics are insufficiently effective or intolerable, can be beneficial regardless of the type of bipolar disorder.

Surveillance métabolique biologique après initiation d’un traitement antipsychotique chez des personnes traitées par lithium ou anticonvulsivants

To assess the rate of metabolic testing after initiation of second-generation antipsychotics (SGA) prescription in persons initially treated by conventional mood-stabilizers (lithium or anticonvulsants, as a proxy of bipolar disorder diagnosis) and to compare the rates of metabolic testing in these persons with those in persons with initiation of first-generation antipsychotics (FGA) prescription or with no antipsychotic prescription. Data were anonymously extracted from the 2004 to 2006 French national health database of the Régime Social des Travailleurs Indépendants (RSI). Patients aged 18 years and over were included in the cohort if they fulfilled the following criteria over a three-month inclusion period: refunding of lithium or anticonvulsant over the 3 months without discontinuation (as a proxy of bipolar disorder diagnosis), no concomitant refunding over the 3months of antipsychotic, and no concomitant refunding over the 3 months of an anti-diabetic drug (as a marker of diabetes) or a lipid-lowering drug (as a marker of hyperlipidemia). Metabolic testing was assessed using information collected in the RSI database on the reimbursement of glucose-specific serum tests (glycaemia) and lipid-specific serum tests (total cholesterol). Serum glucose and lipid testings were assessed at baseline and at 12-week follow-up for the first episode of antipsychotic dispensing. Multivariate analyses were performed to compare the rate of metabolic testing in users of SGA to those of users of FGA and to those of non-users of antipsychotics. Three thousand one hundred and seventy patients were included. Of the 490 (15.4%) persons with a first episode of antipsychotic dispensing after the index date, 138 (4.3%) were dispensed only FGA over the first episode and 352 (11.1%) SGA (including 37 patients with both SGA and FGA dispensing). Metabolic testing at baseline and at 12-week follow-up was performed for 14% of persons with initiation of FGA and 12% with initiation of SGA. Almost no patient had both baseline and follow-up testing. Testing rates were lower for lipid testing than for glucose testing. Compared to persons with no antipsychotic, persons with SGA were significantly more likely to have metabolic testing at baseline and at follow-up, independently from other characteristics (adjusted OR=0.24, 95% CI 0.16 to 0.36). No difference was found between persons with SGA and those with FGA (adjusted OR=1.12, 95%CI 0.62 to 2.0). Regarding the other characteristics associated with likelihood of metabolic testing (irrespective of the treatment group), women were more likely than men to have metabolic testing at baseline but not at follow-up. Elderly persons and persons with low occupational status were more likely to have metabolic testing at follow-up. From a public health point of view, such findings indicate that the metabolic risks associated with SGA use in real-life conditions are widely underestimated. Regarding the temporal trends of antipsychotic prescription, with the dramatic rise of SGA use observed in most countries, it is a public health priority to improve metabolic monitoring in SGA users, irrespective of the underlying diagnosis. Since it is more complex to modify pre-existing inadequate practices than to initiate correct ones in new prescribers, great attention should be paid to the need for delivering strong messages regarding the metabolic risks associated with SGA prescription during the initial training of physicians.

Treatment and outcomes of an Australian cohort of outpatients with bipolar I or schizoaffective disorder over twenty-four months: implications for clinical practice

BackgroundThe Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with ‘real-world’ treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.MethodsParticipants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale – Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.ResultsOn average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts.ConclusionsParticipants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.

Influence of the drug exposure definition on the assessment of the antipsychotic metabolic impact in patients initially treated with mood‐stabilizers

• Metabolic disturbances represent a well-known side effect of second generation antipsychotics. However, studies comparing second generation antipsychotic drugs (SGAPs) and first generation antipsychotic drugs (FGAPs) through administrative databases have shown contrasting findings, which may be attributable to methodological differences. • The definition of antipsychotic exposure impacts on the association between antipsychotics and metabolic risk in studies carried out through administrative databases. • Considering cumulative exposure to antipsychotics or including patients exposed to an antipsychotic drug for months or years is likely to over-represent patients who tolerate the drug well with a depletion of susceptible effects. • Antipsychotic drug exposure is a time-varying determinant and episodes of no use, past use and current use should be distinguished over the study period to avoid any misclassification bias that might lead to misleading findings. To assess the influence of three definitions of antipsychotic exposure on the comparison between first generation (FGAP) and second generation (SGAP) antipsychotic drugs and 'conventional' mood stabilizers towards the risk of metabolic events using (i) a dichotomous measure (exposed/non-exposed over the follow-up), (ii) a categorical measure taking into account the chronology of exposure at the time of the metabolic event (current, recent and no use) and (iii) a continuous measure (cumulative duration). A historical fixed cohort was identified from the 2004-2006 claims database of the French health insurance programme for self-employed workers, including 3172 patients aged 18 years and over who used conventional mood stabilizers over a 3 month period. A metabolic event was defined as an incident dispensing of an anti-diabetic or lipid-lowering drug. A metabolic event occurred in 367 patients (11.6%). At least one FGAP had been prescribed in 29% of patients who did not develop a metabolic event and in 22% of patients who developed a metabolic event. In addition, at least one SGAP had been prescribed in 12% of patients who did not develop a metabolic event and in 7% of patients who developed a metabolic event. Compared with conventional mood stabilizers, the risk of a metabolic event was negatively associated with exposure to SGAPs over the follow-up period (HR 0.53, 95% CI 0.34, 0.82, P= 0.004), positively associated with recent, but not current, exposure to SGAPs (HR 2.1, 95% CI 1.2, 3.7, P= 0.006) and not associated with cumulative duration of SGAPs (HR 1.001, 95% CI 0.999, 1.003, P= 0.20). The definition of exposure to antipsychotics in epidemiological studies exploring their metabolic impact is of paramount importance in understanding this association. Different definitions can lead to opposite and seemingly nonsensical results. Not taking into account past exposure, in order to minimize the depletion of susceptible effects, may lead to absurd results.

Efficacy of antimanic treatments in mixed states

To review the efficacy of pharmacological agents in bipolar mixed states. We conducted a PubMed search of all English-language articles involving Food and Drug Administration (FDA)-approved agents for manic/mixed states in adults with bipolar I disorder. We also included names of agents established as efficacious in acute mania/mixed states that have not received FDA approval for bipolar disorder. Bibliographies from relevant articles were also searched. The efficacy of each agent in the mixed state subpopulation was reviewed, as evidenced by change from baseline on total scores of mania [e.g., Young Mania Rating Scale (YMRS)] and depression [e.g., Montgomery-Åsberg Depression Rating Scale (MADRS)] measures. No available study is dedicated exclusively to the evaluation of mixed state populations. Although key inclusion and exclusion criteria are similar across treatment studies, mixed states have been variably defined and measured. The use of conventional manic and depressive metrics in bipolar mixed states perpetuates the unproven notion that mixed states are the consequence of coexisting depression and mania. Notwithstanding the methodological limitations, there are numerically more studies that exist for atypical antipsychotic agents than for any other class. On the basis of symptomatic improvement, recommendations for and/or strong admonishments against any established antimanic agents (e.g., lithium) cannot be made. An emergent signal supports combination treatment strategies (e.g., atypical antipsychotic plus divalproex) over mood stabilizer monotherapy (e.g., divalproex). Available evidence does not empirically support the hypothesis that conventional antipsychotics engender and/or amplify depressive symptoms in bipolar mixed states. All proven antimanic agents (including lithium), can be recommended in the treatment of mixed/dysphoric states. The totality of evidence with attention paid to the therapeutic index of each agent would suggest that atypical antipsychotics and divalproex be considered as first-line treatment, with lithium and carbamazepine as second-line. Most individuals will require combination therapy for the treatment of mixed states; variable combinations of atypical antipsychotics and conventional mood stabilizers have the most replicated evidence.

Bipolar Disorder and Complementary Medicine: Current Evidence, Safety Issues, and Clinical Considerations

Bipolar disorder (BD) is a debilitating syndrome that is often undiagnosed and undertreated. Population surveys show that persons with BD often self-medicate with complementary and alternative medicine (CAM) or integrative therapies in spite of limited research evidence supporting their use. To date, no review has focused specifically on nonconventional treatments of BD. The study objectives were to present a review of nonconventional (complementary and integrative) interventions examined in clinical trials on BD, and to offer provisional guidelines for the judicious integrative use of CAM in the management of BD. PubMed, CINAHL,(®) Web of Science, and Cochrane Library databases were searched for human clinical trials in English during mid-2010 using Bipolar Disorder and CAM therapy and CAM medicine search terms. Effect sizes (Cohen's d) were also calculated where data were available. Several positive high-quality studies on nutrients in combination with conventional mood stabilizers and antipsychotic medications in BD depression were identified, while branched-chain amino acids and magnesium were effective (small studies) in attenuating mania in BD. In the treatment of bipolar depression, evidence was mixed regarding omega-3, while isolated studies provide provisional support for a multinutrient formula, n-acetylcysteine, and l-tryptophan. In one study, acupuncture was found to have favorable but nonsignificant effects on mania and depression outcomes. Current evidence supports the integrative treatment of BD using combinations of mood stabilizers and select nutrients. Other CAM or integrative modalities used to treat BD have not been adequately explored to date; however, some early findings are promising. Select CAM and integrative interventions add to established conventional treatment of BD and may be considered when formulating a treatment plan. It is hoped that the safety issues and clinical considerations addressed in this article may encourage the practice of safety-conscious and evidence-based integrative management of BD.

Long‐acting injectable risperidone in a bipolar patient submitted to bariatric surgery and intolerant to conventional mood stabilizers

Long‐acting injectable risperidone in a bipolar patient submitted to bariatric surgery and intolerant to conventional mood stabilizers

Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature.

To review extant literature implicating inflammation in the pathophysiology of bipolar disorder. Furthermore, we review evidence regarding the anti-inflammatory actions of mood-stabilizing medication, the putative reciprocal association of inflammation with behavioral parameters and medical burden in bipolar disorder, and the potential role of anti-inflammatory agents in the treatment of bipolar disorder. MEDLINE and PubMed searches were conducted of English-language articles published from 1950 to April 2008 using the search terms bipolar disorder, manic, or mania, cross-referenced with inflammation, inflammatory, interleukin, cytokine, C-reactive protein, or tumor necrosis factor. The search, which was conducted most recently on August 20, 2008, was supplemented by manually reviewing reference lists from the identified publications. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. Studies were reviewed for statistical comparisons of cytokines among persons with and without bipolar disorder, during symptomatic and non-symptomatic intervals and before and after pharmacologic treatment. Significant and nonsignificant findings were tabulated. Available evidence indicates that bipolar disorder and inflammation are linked through shared genetic polymorphisms and gene expression as well as altered cytokine levels during symptomatic (i.e., mania and depression) and asymptomatic intervals. However, results are inconsistent. Several conventional mood stabilizers have anti-inflammatory properties. The cyclooxygenase-2-selective anti-inflammatory celecoxib may offer antidepressant effects. Inflammation is closely linked with behavioral parameters such as exercise, sleep, alcohol abuse, and smoking, as well as with medical comorbidities including coronary artery disease, obesity and insulin resistance, osteoporosis, and pain. Methodological limitations precluding definitive conclusions are heterogeneity in sample composition, cytokine assessment procedures, and treatment regimens. The inclusion of multiple ethnic groups introduces another source of variability but also increases the generalizability of study findings. Inflammation appears relevant to bipolar disorder across several important domains. Further research is warranted to parse the reciprocal associations between inflammation and symptoms, comorbidities, and treatments in bipolar disorder. Studies of this topic among youth are needed and may best serve this purpose.

Update and long-term clinical management of rapid cycling

Rapid cycling is a course specifier for bipolar disorder associated with increased morbidity and treatment refractoriness. Although there are problems arising from its definition, rapid cycling occurs in 10-20% of bipolar patients, predominating in women and in patients with bipolar II disorder. In addition, the predominant clinical manifestation is depressive symptoms, a factor that should be considered in treatment. Several hypotheses have been put forward to explain the occurrence of rapid cycling at some point in the course of a bipolar patient (hypothyroidism, antidepressant use, female hormone cycle, drugs, etc.). There are few long-term controlled studies on the treatment of rapid cycling. The majority obtained a reduced response to conventional mood stabilizers such as lithium and valproate. Combinations of mood stabilizers with agents effective in the depressive phases, such as lamotrigine, are the alternatives to be considered as long-term management strategies for bipolar patients with rapid cycling.

Bipolar disorder and comorbid alcoholism: prevalence rate and treatment considerations

Classic Kraepelian observations and contemporary epidemiological studies have noted a high prevalence rate between bipolar disorder and alcoholism. The extent to which these two illnesses are comorbid (i.e., two distinct disease processes each with an independent course of illness), genetically linked, or different phenotypic expressions of bipolar illness itself continues to be investigated. It is increasingly clear that co-occurring alcohol abuse or dependence in bipolar disorder phenomenologically changes the illness presentation with higher rates of mixed or dysphoric mania, rapid cycling, increased symptom severity, and higher levels of novelty seeking, suicidality, aggressivity, and impulsivity. It is very encouraging that interest and efforts at evaluating pharmacotherapeutic compounds has substantially increased over the past few years in this difficult-to-treat patient population. This article will review the clinical studies that have evaluated the effectiveness of conventional mood stabilizers (lithium, carbamazepine, divalproex, and atypical antipsychotics) in the treatment of alcohol withdrawal and relapse prevention in patients with alcoholism and in the treatment of bipolar disorder with comorbid alcoholism. A number of add-on, adjunctive medications, such as naltrexone, acamprosate, topiramate, and the atypical antipsychotics quetiapine and clozapine, may be candidates for further testing.

Pharmacotherapy of bipolar depression: An update

Bipolar affective disorder is a virulent illness with high rates of recurrence, disability, social impairment, and suicide. Although the manic or hypomanic episodes define the disorder, the depressions are more numerous and less responsive to treatment. As the initial depressive episodes are commonly misdiagnosed, initiation of therapy with mood stabilizers is often delayed, increasing the likelihood of treatment-emergent affective switches on antidepressant monotherapy. The empirical basis for selecting treatments for people with bipolar depression is weak, and only the combination of olanzapine and fluoxetine has received US Food and Drug Administration (FDA) approval. Conventional mood stabilizers are preferred for first-line therapies, although atypical antipsychotics are increasingly used, and FDA approval of quetiapine is pending. Antidepressants--particularly selective serotonin reuptake inhibitors and bupropion--are indicated when mood stabilizers are ineffective and for "breakthrough" depressions.