Pharmacotherapy For Bipolar Disorder Research Articles

Lithium, the gold standard drug for bipolar disorder: analysis of current clinical studies.

Lithium is the gold standard drug in the treatment of bipolar disorder. Despite increasing scientific interest, relatively few patients with bipolar disorder receive lithium therapy. Lithium is the only drug that is effective in the prophylaxis of manic, depressive, and suicidal symptoms. Lithium therapy is also associated with a variety of adverse drug reactions and the need for therapeutic drug monitoring. Numerous studies have focussed on the efficacy and safety of both lithium-monotherapy and lithium-add-on therapy. The aim of this study is to provide a systematic overview of clinicalstudies on lithium therapy for bipolar disorder from the last 7 years and to present a critical analysis of these studies. The results provide an up-to-date overview of the efficacy, tolerability, and safety of lithium therapy for bipolar disorder and thus improve the pharmacotherapy of bipolar disorder. A total of 59 studies were analysed using various analysis parameters. The studies were also categorised into different subgroups. These are lithium-monotherapy, lithium vs. placebo/drug, and lithium + adjunctive therapy. The majority of the studies (N = 20) had a duration of only 3-8 weeks. Only 13 studies lasted for > 40 weeks. Lithium was superior to aripiprazole, valproic acid, and quetiapine in terms of improving manic symptoms. Lithium therapy resulted in a lower relapse rate compared to valproic acid therapy. Lithium was more neuroprotectively effective than quetiapine. Fourteen of the 22 add-on therapies to lithium showed a predominantly positive effect on the treatment outcome compared to lithium-monotherapy. Only the add-on therapy with sertraline led to a higher rate of study discontinuations than lithium-monotherapy. Lithium is a safe and effective treatment option for children. However, risperidone and quetiapine were superior to lithium in some aspects, which is why these drugs should be considered as an alternative treatment option for children. Collectively, current clinical studies highlight the relevance of lithium in the treatment of bipolar disorder.

The Effects of Standard Pharmacotherapy on Oxidative Stress Markers in Bipolar Patients: A Systematic Review

Background: Bipolar disorder is a complex mental disorder with a multifactorial pathology. Meta-analyses have shown that bipolar disorder is associated with imbalanced oxidative status, which can contribute to disease progression. Therefore, restoring the oxidative imbalance could be beneficial in the treatment of bipolar disorder. The firstline pharmacotherapy for bipolar disorder is lithium, anticonvulsants (particularly sodium valproate), and atypical antipsychotics. In the present review, we sought to describe the effects of these first-line medications on oxidative stress in bipolar patients. Methods: We systematically searched databases through January 2022, including the Web of Science, PubMed, Scopus, and Embase, with no language or time restrictions. Eligible articles that assessed oxidative markers in bipolar patients following standard pharmacotherapy were included. Result: According to Newcastle Ottawa and NIH scales, the overall quality of the included articles was low, and their heterogeneity prevented us from performing a meta-analysis. Conclusion: We found that standard medications, especially lithium, can potentially alleviate oxidative imbalance based on a reduction in oxidative markers, such as TBARs and MDA, although randomized clinical trials are needed to unequivocally confirm these results.

Patterns of pharmacotherapy for bipolar disorder: A GBC survey.

To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia. Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns. This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD-I (60%; vs. BD-II = 33%). Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First-generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD-II (47%) compared to BD-I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. Mood-stabilizing anticonvulsants, second-generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first-generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence-based guidelines to help improve treatment practices in BD.

Beyond pharmacotherapy for bipolar disorder– a group psychotherapeutic intervention for bipolar affective disorder patients: a treatment protocol and research proposal

Beyond pharmacotherapy for bipolar disorder– a group psychotherapeutic intervention for bipolar affective disorder patients: a treatment protocol and research proposal

Korean Medication Algorithm Project for Bipolar Disorder 2022, Fifth Revision: An Executive Summary

We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder. The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts. For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state. The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

Pharmacotherapy for bipolar disorder in adults with high-functioning autism

ABSTRACT Introduction The association between high-functioning autism (HFA) and bipolar disorder (BD) in adult subjects has been confirmed by a growing number of studies. However, identifying and treating BD in this population is a clinical challenge and requires careful assessment and adequate knowledge of both disorders. Areas covered This review aims to provide a clinical presentation of mood episodes in HFA individuals, and an update on the pharmacotherapy of BD in these individuals, sharing with the reader expert opinion on the current state of the art and future perspectives. Expert opinion BD has an atypical clinical presentation in HFA subjects with the possibility of diagnostic and therapeutic mistakes. Despite the absence of controlled studies, the available evidence indicates mood stabilizers, especially lithium, as the first treatment option. HFA subjects are particularly vulnerable to pharmacological side effects, such as extrapyramidal and catatonic symptoms with antipsychotics, or activation syndrome with antidepressants. Accordingly, initial titration of these drugs should be slow and their use should be limited in time. Among antipsychotics, dopamine receptor antagonists with combined serotonergic activity are preferable. Further research is needed to improve the diagnostic process and to delineate the effectiveness of different drugs for BD in HFA subjects.

Differential expression profile between amygdala and blood during chronic lithium treatment in a rat model of depression – a pilot study

Lithium is a mood stabilizer widely used in the pharmacotherapy of bipolar disorder and treatment‑resistant depression. Taking into account dysregulated inflammatory activity in depression and the immunomodulatory role of lithium, we hypothesized that genes associated with inflammatory responses may be potential biomarkers of lithium action. We aimed to compare gene expression changes between the brain and the periphery after chronic lithium administration in an animal model of depression. Depressive behavior was induced by chronic mild stress protocol for 4 weeks. After 2 weeks, rats started to receive lithium (study group) or water (reference group). The control group were rats not exposed to stress. Amygdala, hippocampus, frontal cortex and peripheral blood were analyzed using whole transcriptome expression microarrays. Changes were confirmed with qPCR and ELISA assay. After 2 weeks of lithium administration, we observed significant changes in gene expression between amygdala and peripheral blood. Logistic regression analysis determined Alox15 expression as a predictor of lithium status, as its expression was tissue‑specific and increased in amygdala and decreased in blood. Analysis of serum ALOX15 protein revealed its upregulation after two‑week lithium administration. Our study suggests that lithium may have therapeutic potential in depressive behaviors. These results indicate immunomodulatory effect of lithium and that Alox15 may be a new potential marker of chronic lithium treatment.

Differential expression profile between amygdala and blood during chronic lithium treatment in a rat model of depression - a pilot study.

Lithium is a mood stabilizer widely used in the pharmacotherapy of bipolar disorder and treatment‑resistant depression. Taking into account dysregulated inflammatory activity in depression and the immunomodulatory role of lithium, we hypothesized that genes associated with inflammatory responses may be potential biomarkers of lithium action. We aimed to compare gene expression changes between the brain and the periphery after chronic lithium administration in an animal model of depression. Depressive behavior was induced by chronic mild stress protocol for 4 weeks. After 2 weeks, rats started to receive lithium (study group) or water (reference group). The control group were rats not exposed to stress. Amygdala, hippocampus, frontal cortex and peripheral blood were analyzed using whole transcriptome expression microarrays. Changes were confirmed with qPCR and ELISA assay. After 2 weeks of lithium administration, we observed significant changes in gene expression between amygdala and peripheral blood. Logistic regression analysis determined Alox15 expression as a predictor of lithium status, as its expression was tissue‑specific and increased in amygdala and decreased in blood. Analysis of serum ALOX15 protein revealed its upregulation after two‑week lithium administration. Our study suggests that lithium may have therapeutic potential in depressive behaviors. These results indicate immunomodulatory effect of lithium and that Alox15 may be a new potential marker of chronic lithium treatment.

A Systematic Review of the Clinical Use of Gabapentin and Pregabalin in Bipolar Disorder

Despite its prevalence and disease burden, several chasms still exist with regard to the pharmacotherapy of bipolar disorder (BD). Polypharmacy is commonly encountered as a significant proportion of patients remain symptomatic, and the management of the depressive phase of the illness is a particular challenge. Gabapentin and pregabalin have often been prescribed off-label in spite of a paucity of evidence and clinical practice guidelines to support its use. This systematic review aimed to synthesize the available human clinical trials and inform evidence-based pharmacological approaches to BD management. A total of six randomized, controlled trials (RCTs) and 13 open-label trials involving the use of gabapentin and pregabalin in BD patients were reviewed. Overall, the studies show that gabapentin and its related drug pregabalin do not have significant clinical efficacy as either monotherapy or adjunctive therapy for BD. Gabapentin and pregabalin are probably ineffective for acute mania based on the findings of RCT, with only small open-label trials to support its potential adjunctive role. However, its effects on the long-term outcomes of BD remain to be elucidated. The evidence base was significantly limited by the generally small sample sizes and the trials also had heterogeneous designs and generally high risk of bias.

Effects of non-peptide nociceptin/orphanin FQ receptor ligands on methylphenidate-induced hyperactivity in mice: Implications for bipolar disorders

Bipolar disorder is a psychiatric pathology characterized by biphasic mood episodes of mania or hypomania and depression. The pharmacotherapy of bipolar disorder has significant adverse effects impairing treatment adherence and patient quality of life. The N/OFQ-NOP receptor system has been widely implicated with mood disorders. Clinical and preclinical findings suggest antidepressants actions for NOP antagonists. More recently, the administration of NOP agonists has shown to promote depressant states. The present study aimed to investigate the effects of non-peptide NOP ligands in methylphenidate-induced manic-like behavior in mice. The NOP agonist Ro 65–6570 (0.01–1 mg/kg, ip), at the higher dose, did not affect spontaneous locomotion per se, but prevented the methylphenidate (10 mg/kg, sc)-induced hyperlocomotion. The NOP partial agonist AT-090 (0.001–0.03 mg/kg, ip) and the NOP antagonist SB-612111 (1–10 mg/kg, ip) did not significantly affect the psychostimulant-induced hyperactivity. Experiments performed with mice lacking the NOP receptor (NOP(−/−)) demonstrated that the treatment with methylphenidate induced similar hyperlocomotion in NOP(−/−) and NOP(+/+) mice. In conclusion, these findings suggest a potential role for NOP agonists in the prevention of manic states, especially by counteracting the hyperactivity symptom of bipolar patients. However, more studies are necessary in order to evaluate these compounds in other features of bipolar disorder.

Clinical picture and treatment of bipolar affective disorder in children and adolescents.

Bipolar disorder (BD) is characterized by pathological changes in mood as well as recurring episodes of mania, hypomania, depression and mixed symptoms. In recent years, the number of BD diagnoses has risen considerably in children and adolescents. Itis believed that anaverage rate of prevalence of bipolar spectrum disorder in the pediatric population is 1.8%, and BD type I - 1.2%, and the prevalence of the disorder increases with the age of patients. Despite the same diagnostic criteria, there are premises that suggest thatthe symptoms of the disorder are present with a different frequency among children and adolescents than in adults. The most frequent manic symptom in persons with childhood-onset of the illness is thought to be irritability, and in adolescence -hyperactivity. BD in children and adolescent population is accompanied by a high rate of comorbid psychiatric conditions. Attention deficit hyperactivity disorder and borderline personality disorder constitute particular diagnostic challenges. Early onset of BP is linked with a more severe course of the illness, worse prognosis, and a higher suicidal rate. Pharmacotherapy of BD in the pediatric population includes 1st and 2nd generation mood stabilizers, while their efficacy and safety profiles are different than in adults. The American Food and Drug Administration recommends treating manic episodes in young persons with lithium, aripiprazole, quetiapine, risperidone, olanzapine and depressive episodes with a combination therapy of olanzapine and fluoxetine.

Acceptability of Acute and Maintenance Pharmacotherapy of Bipolar Disorder: A Systematic Review of Randomized, Double-Blind, Placebo-Controlled Clinical Trials.

The aim of the study was to estimate and rank the risk for the discontinuation due to adverse events (DAEs), 7% or more weight gain (WG), and somnolence during the acute and maintenance treatment of bipolar disorder with a mood stabilizer or an antipsychotic monotherapy. The search of MEDLINE, EMBASE, PsycINFO, and clinicaltrials.gov from the inception to December 31, 2018, provided 32 studies in mania, 16 in bipolar depression, and 13 in maintenance. Data of DAEs, WG, and somnolence from each study were extracted. The risk for these variables of an active treatment relative to placebo was estimated with a number needed to harm (NNH) as a single study and pooled sample. For DAEs, pooled NNH ranged from 19 with carbamazepine to -21 with quetiapine-XR in mania, 11 with quetiapine-IR 600 mg/d to -37 with olanzapine/fluoxetine combination in bipolar depression, and 5 with lithium to -8 with asenapine in maintenance. For WG, pooled NNH ranged from 9 with olanzapine to -78 with aripiprazole in mania, 5 with olanzapine to -112 with lithium in bipolar depression, and 4 with olanzapine to 126 with asenapine in maintenance. For somnolence, pooled NNH was from 5 with carbamazepine to 23 with cariprazine in mania, 3 with quetiapine-XR 300 mg/d to 79 with lurasidone in bipolar depression, and 11 with olanzapine to -49 with aripiprazole in maintenance. All medications studied in bipolar disorder were relatively well tolerated during different phases of treatment; however, the risk for short- and long-term WG and somnolence varied widely among included psychotropics.

Diagnosis and Pharmacotherapy of Bipolar Disorder

Diagnosis and Pharmacotherapy of Bipolar Disorder

Obesity and the pharmacotherapy of bipolar disorder

Obesity, as an important risk factor for the development of diabetes, cancer or cardiovascular diseases, is one of the most important problems of modern medicine. Studies show that obesity often coexists with psychiatric disorders, including the bipolar disorder (BD) – the prevalence of obesity can be 1.5 times higher in BD patients when compared with the general population. Additionally, the risk of mood disorders in obese patients is also increased. The probable aetiology of the bidirectional relation between BD and overweight and obesity is likely complex – genetic factors, abnormalities in the immune system or an increased frequency of eating disorders are all present. Obesity in BD patients may be associated with an impairment of the mental and physical well-being, poorer co-operation in the treatment and lower quality of life. Drugs used in BD therapy have different predilections for inducing significant weight gain. The highest metabolic risk is associated with olanzapine and clozapine (among antipsychotics), amitriptyline, mirtazapine and paroxetine in the antidepressant group, and among the mood stabilizers (excluding antipsychotics) lithium and valproate. Amongst the possible therapeutic measures in patients with overweight or obesity, nonpharmacological as well as pharmacological procedures are mentioned. The newly registered antipsychotics with a possibly favourable metabolic profile (lurasidon, Cariprazine, and brexpiprazole) as well as the combination of bupropion/naltrexone or bariatric surgery carry interesting prospects for the future.

E.04.02 Sex differences in the pharmacotherapy of bipolar disorder

E.04.02 Sex differences in the pharmacotherapy of bipolar disorder

69.4 MANAGEMENT OF PEDIATRIC BIPOLAR DISORDER

Pediatric bipolar disorder (BD) often manifests in adolescence. The management of BD requires a multidimensional approach and involves psychological and psychosocial interventions, in addition to medication management. The purpose of this presentation is to define what is known about the pharmacotherapy of BD in pediatric patients.

Beyond Pharmacotherapy for Bipolar Disorder: The Role of Adjunctive Psychological Treatments

Recent years have seen increased research attention to psychological interventions as adjuncts to medication treatment of bipolar disorder (BD). Adjunctive psychological treatments are recommended in all major clinical guidelines for BD, and we now know that evidence-based treatment involves both pharmacotherapy and psychological therapy. We provide an overview of what is known about psychological interventions for BD, including the existing evidence base, core content elements of therapy, and emerging innovations. An overarching theme is the patient as a motivated agent in his or her own well-being; we emphasize recovery-oriented treatment goals, self-management approaches, and digital platforms to improve access to these empowering activities. Mental health professionals are encouraged to support their patients' participation in evidence-based psychological therapies as part of a holistic approach to managing BD. [ Psychiatr Ann. 2019;49(9):399–404.]

Complex Combination Pharmacotherapy for Bipolar Disorder: Knowing When Less Is More or More Is Better.

Combination pharmacotherapy for bipolar disorder is commonplace and often reflects the severity and complexity of the illness and the comorbid conditions frequently associated with it. Across treatment settings, about one-fifth of patients with bipolar disorder appear to receive four or more psychotropic medications. Practice patterns often outpace the evidence-based literature, insofar as few systematic studies have examined the efficacy and safety of two or more medications for any given phase of illness. Most randomized trials of combination pharmacotherapy focus on the utility of pairing a mood stabilizer with a second-generation antipsychotic for prevention of either acute mania or relapse. In real-world practice, patients with bipolar disorder often take more elaborate combinations of mood stabilizers, antipsychotics, antidepressants, anxiolytics, stimulants, and other psychotropics for indefinite periods that do not necessarily arise purposefully and logically. In this article, I identify clinical factors associated with complex combination pharmacotherapy for patients with bipolar disorder; describe approaches to ensuring that each component of a treatment regimen has a defined role; discuss the elimination of unnecessary, ineffective, or redundant drugs in a regimen; and address complementary, safe, rationale-based drug combinations that target specific domains of psychopathology for which monotherapies often provide inadequate benefit.

Psychopharmacological Decision Making in Bipolar Disorder During Pregnancy and Lactation: A Case-by-Case Approach to Using Current Evidence.

The safety of pharmacotherapy for bipolar disorder during pregnancy and lactation remains a subject of debate and uncertainty. Clinicians must balance concerns about anatomical and behavioral teratogenicity, maternal mental health, exposure to multiple drugs, and heightened risks for peripartum mood episodes. Risk-benefit analyses must consider factors such as illness severity, past pregnancy treatment outcomes, known drug responsivity, psychosocial supports, and key windows during fetal development. Pharmacological decision making usually changes over the course of pregnancy, given developments in maternal physiology and critical relapse risk periods. Among mood stabilizers, given current research, many experts eschew divalproex and carbamazepine, consider lamotrigine relatively benign, and voice strong opinions for or against lithium. Most second-generation antipsychotics are considered relatively safe, apart from possible extrapyramidal and other motor signs of withdrawal after delivery. In this review, the authors analyze the practical questions, current controversies, and available evidence regarding psychotropic drug therapy during pregnancy and lactation in bipolar disorder.

Personalized Pharmacotherapy for Bipolar Disorder: How to Tailor Findings From Randomized Trials to Individual Patient-Level Outcomes.

The quest for "personalized medicine" in psychiatry has focused mainly on pursuing potential biomarkers such as pharmacogenetic predictors of drug response. However, the collective randomized trial database across phases of bipolar disorder allows one to identify clinical characteristics that inform the likelihood of desired treatment outcomes. In turn, those characteristics, termed moderators and mediators of drug response, enable those who administer treatment to construct clinical profiles that can help them tailor pharmacotherapies to the features of a given patient rather than simply to an overall diagnosis. Bipolar disorder typically involves more heterogeneous than uniform clinical presentations, partly because of its highly prevalent psychiatric and medical comorbid conditions. Further clinical diversity arises from characteristics such as bipolar I versus II disorder subtype, rapid cycling, mixed versus pure affective episodes, psychosis, anxiety, chronicity, cognitive dysfunction, and suicidality, among other distinguishing features. By coupling such profiles with an awareness of the psychotropic breadth of spectrum held by particular medications, clinicians can devise strategic combination therapy regimens, capitalizing on synergies and using drugs that exert multiple relevant effects, addressing comorbid conditions, incorporating medications that could offset adverse effects of other agents, and avoiding or deprescribing medication options that lack known evidence to target symptoms within the clinical profile of a given patient.