Pharmacological Treatment Of Bipolar Disorder Research Articles

Pharmacologic treatment of bipolar disorder and comorbid adult attention-deficit/hyperactivity disorder.

Pharmacologic treatment of bipolar disorder and comorbid adult attention-deficit/hyperactivity disorder.

Real-world effectiveness of pharmacological treatments for bipolar disorder: register-based national cohort study.

Pharmacological treatment patterns for bipolar disorder have changed during recent years, but for better or worse? To investigate the comparative real-world effectiveness of antipsychotics and mood stabilisers in bipolar disorder. Register-based cohort study including all Finnish residents aged 16-65 with a diagnosis of bipolar disorder from in-patient care, specialised out-patient care, sickness absence and disability pensions registers between 1996 and 2018, with a mean follow-up of 9.3 years (s.d. = 6.4). Antipsychotic and mood stabiliser use was modelled using the PRE2DUP method and risk for hospital admission for psychiatric and non-psychiatric reasons when using versus not using medications was estimated using within-individual Cox models. Among 60 045 individuals (56.4% female; mean age 41.7 years, s.d. = 15.8), the five medications associated with lowest risk of psychiatric admissions were olanzapine long-acting injection (LAI) (aHR = 0.54, 95% CI 0.37-0.80), haloperidol LAI (aHR = 0.62, 0.47-0.81), zuclopenthixol LAI (aHR = 0.66, 95% CI 0.52-0.85), lithium (aHR = 0.74, 95% CI 0.71-0.76) and clozapine (aHR = 0.75, 95% CI 0.64-0.87). Only ziprasidone (aHR = 1.26, 95% CI 1.07-1.49) was associated with a statistically higher risk. For non-psychiatric (somatic) admissions, only lithium (aHR = 0.77, 95% CI 0.74-0.81) and carbamazepine (aHR = 0.91, 95% CI 0.85-0.97) were associated with significantly reduced risk, whereas pregabalin, gabapentin and several oral antipsychotics, including quetiapine, were associated with an increased risk. Results for a subcohort of first-episode patients (26 395 individuals, 54.9% female; mean age 38.2 years, s.d. = 13.0) were in line with those of the total cohort. Lithium and certain LAI antipsychotics were associated with lowest risks of psychiatric admission. Lithium was the only treatment associated with decreased risk of both psychiatric and somatic admissions.

Taiwan consensus on biological treatment of bipolar disorder during the acute, maintenance, and mixed phases: The 2022 update.

Bipolar disorder is a mood dysregulation characterized by recurrent symptoms and episodes of mania, hypomania, depression, and mixed mood. The complexity of treating patients with bipolar disorder prompted the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) to publish the first Taiwan consensus on pharmacological treatment of bipolar disorders in 2012. This paper presents the updated consensus, with changes in diagnostic criteria (i.e., mixed features) and emerging pharmacological evidence published up to April 2022. Our working group systemically reviewed the clinical research evidence and international guidelines and determined the levels of evidence for each pharmacological treatment on the basis of the most recent World Federation of Societies of Biological Psychiatry grading system. Four clinical-specific issues were proposed. The current TSBPN Bipolar Taskforce then discussed research evidence and clinical experience related to each treatment option in terms of efficacy and acceptability and then appraised final recommendation grades through anonymous voting. In the updated consensus, we include the pharmacological recommendations for bipolar disorder with mixed features considering its high prevalence, the severe clinical prognosis, and the absence of approved medications. Cariprazine, lurasidone, repetitive transcranial magnetic stimulation, and ketamine are incorporated as treatment options. In the maintenance phase, the application of long-acting injectable antipsychotics is emphasized, and the hazards of using antidepressants and conventional antipsychotics are proposed. This updated Taiwan consensus on pharmacological treatment for bipolar disorder provides concise evidence-based and empirical recommendations for clinical psychiatric practice. It may facilitate treatment outcome improvement in patients with bipolar disorder.

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients.

While treatment with antipsychotics and antiepileptics have been associated with an increased risk of diabetes mellitus (DM), lithium may have the opposite effect via inhibition of glycogen synthase kinase-3. The aim of this study was to investigate whether treatment of bipolar disorder with lithium, antipsychotics, or antiepileptics is associated with the risk of DM in a real-world clinical setting. Using nationwide registers, we identified all patients diagnosed with bipolar disorder in Danish Psychiatric Services from January 1, 1996, to January 1, 2019 (N= 30,451). The risk of developing DM was operationalized via hospital diagnoses and redeemed prescriptions for glucose-lowering drugs. For lithium, antipsychotics, valproate, and lamotrigine, we calculated hazard rate ratios (HRR) for developing DM via adjusted Cox proportional hazards models. Potential cumulative dose-response-like associations were examined using the log-rank test. During follow-up (245,181 person-years), 2107 (6.9%) patients developed DM. Compared with non-users of the respective drugs, we found no clinically or statistically significant difference in the risk of developing DM among patients receiving lithium (n= 11,690; incidence rate of DM/1000 person-years (IR)=8.87, 95% CI: 8.02-9.90; HRR=0.94, 95% CI: 0.84-1.06) or lamotrigine (n= 11,785; IR=7.58, 95% CI: 6.69-8.59; HRR=0.89, 95% CI: 0.77-1.02), respectively. Conversely, for patients receiving valproate (n= 5171; IR=12.68, 95% CI: 10.87-14.80; HRR=1.34, 95% CI: 1.14-1.58) and antipsychotics (n= 22,719; IR=12.00, 95% CI: 11.14-12.94; HRR=1.65, 95% CI: 1.45-1.88), respectively, there was increased risk of developing DM. For antipsychotics, we observed a clear cumulative dose-response-like association with the risk of DM. Treatment with valproate and antipsychotics-but not with lithium and lamotrigine-was associated with increased risk of DM in a real-world cohort of patients with bipolar disorder.

Clinical perspectives on the management of common psychiatric disorders in India

Psychiatric disorders are common health problems in patients of all age groups, under-diagnosis and under-treatment of these disorders can result in disability and serious complications. With an objective of creating a comprehensive evidence-based consensus on common mental health disorders and their management in the Indian setting, 10 expert groups meetings involving 98 psychiatrists across India were conducted in the month of May 2020. Clinical insights related to burden, signs and symptoms, diagnosis and management were summarized based on the discussions during these meetings. Experts agreed that depressive disorders and anxiety disorders represent two important psychiatric disorders in India. Selective serotonin reuptake inhibitors (SSRIs) are commonly used for the treatment of depression. Benzodiazepines are effective for the treatment of comorbid anxiety in patients with depression, but their long-term use causes adverse events such as dependence and withdrawal reaction. Obsessive compulsive disorder (OCD), bipolar disorder, substance use especially alcohol withdrawal syndrome, and sleep disorders are other common psychiatric disorders found among Indian patients. Lithium and valproate represent the commonly used and effective pharmacological treatments for bipolar disorder. SSRIs are preferred drugs in the treatment of OCD, whereas benzodiazepines such as chlordiazepoxide and diazepam represent important pharmacological treatment options for alcohol withdrawal. Early identification and timely and effective treatment of psychiatric disorders is important for prevention of complications. Treatment should be individualized based on efficacy, tolerability profile of the medicine, risk of drug interactions, and cost. This consensus may be useful to psychiatrists and general practitioners treating common psychiatric conditions in Indian patients.

Association between the pharmacological treatment of bipolar disorder and risk of traumatic injuries: a self-controlled case series study.

Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries. Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001-2019). A self-controlled case series design was applied to control for time-invariant confounders. A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71-5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88-1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09-1.66), p = 0.006]. This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.

Pharmacological treatment of bipolar disorder in pregnancy: An update on safety considerations.

Pregnancy in women with bipolar disorder (BD) can be considered a high-risk pregnancy in view of several clinical and pharmacotherapeutic considerations. Pharmacological treatment during pregnancy requires a careful weighing of psychotropic drug exposure against the risk of BD relapse. An untreated bipolar illness can negatively affect the health of mother as well as unborn child in the event of a relapse. Availability of well balanced, latest information on safety of prophylactic drugs for BD is crucial for making informed decisions. The review provides an evidence-based update (2015-2021) on the drug safety considerations involved in providing care for women with BD who are either pregnant or planning to conceive in near future. Literature review based on systematic reviews, meta-analyses, and data available from studies based on large-scale cohorts and birth registries has been synthesized and presented along with clinically relevant recommendations.

Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials.

Bipolar disorder (BD) is chronic psychiatric disorder associated with significant impairment in psychosocial functioning and quality of life. Although current pharmacological treatments for BD have improved its clinical management, many patients do not achieve remission, particularly those suffering from bipolar depression. In addition, available treatments are associated with a myriad of potential adverse effects, which highlights the need for novel therapeutic agents that can be effective for both phases of the illness with a reduced side effect burden. Cariprazine is a novel antipsychotic that is a dopamine D2/D3 partial agonist with a preference for D3 receptors. In this review, we examine the pharmacological properties, clinical efficacy and tolerability profile of cariprazine in patients with BD, taking into account the latest clinical trials data. We also review post hoc analyses addressing clinically relevant subgroups and symptom domains in BD. Current evidence suggests efficacy for cariprazine 3–12 mg/day in the treatment of acute manic and mixed episodes; for bipolar depression, the efficacy of cariprazine appears to be dose-related, with doses of 1.5–3 mg/day beneficial as monotherapy. Cariprazine is overall well-tolerated by patients in both manic and depressive episodes. Its most common side effects relative to placebo include akathisia, extrapyramidal symptoms and nausea. There are no metabolic concerns reported with cariprazine use. In summary, the latest evidence suggests that cariprazine is an effective and safe treatment option for BD.

Novel experimental and early investigational drugs for the treatment of bipolar disorder

ABSTRACT Introduction The quest toward more effective treatments for bipolar disorder (BD) solicits novel drugs and further research on the underpinning neurobiology. The present review aims to critically appraise the existing evidence about the pharmacological treatment of BD toward the development of novel treatment avenues. Areas covered The present review appraises animal and human studies concerning both the currently available psychotropic drugs, and the general medicine drugs which may represent a path toward the development of novel drugs for BD. PubMed and Scopus were last accessed on February 20th, 2021 for records indexed upon inception relevant to the pharmacological treatment of BD. Immune-modulating agents, anti-inflammatory agents, and glutamate antagonists represent the most intriguing potential targets for the development of new drugs for BD, thus receiving critical appraisal in the present text. Expert Opinion Regardless of the neurobiological pathways worthy of investigation toward the development of experimental drugs for BD, several unmet needs need to be addressed first. In particular, several biomarkers are altered in BD. However, it is the opinion herein expressed by the authors that it remains uncertain what comes first, that is peripheral changes or the disease.

Commentary: 20-Year Trends in the Pharmacologic Treatment of Bipolar Disorder by Psychiatrists in Outpatient Care Settings.

Using data from the US care system over 20 years, Rhee and colleagues (1) reported in the American Journal of Psychiatry (July 2020) that, among outpatients with Bipolar Disorder (BD), the prescriptions of second-generation antipsychotics (SGAs) massively increased (from 12.4% of BD outpatient in the 1997–2000 period to 51.4% in the 2013–2016 period), while the prescriptions of lithium and anticonvulsants decreased (from 62.3% of BD patients in the 1997–2000 period to 26.4% in the 2013–2016 period). The use of antidepressants, whose efficacy in bipolar depression is limited (2), constantly rose during the same period, these being often prescribed without any mood stabilizer (40.9% in the 2013–2016 period) in about half of the visits.

Antipsychotics Increasingly Prescribed for Bipolar Disorder

Antipsychotics Increasingly Prescribed for Bipolar Disorder

Case study: organizing outpatient pharmacological treatment of bipolar disorder in autism, intellectual disability and Phelan-McDermid syndrome (22q13.3 deletion syndrome)

Phelan-McDermid syndrome (PHMDS)/22q13.3 deletion syndrome is a rare genetic disorder associated with autism spectrum disorder (ASD), intellectual disability (ID), and bipolar disorder. While numerous cases have been reported describing successful pharmacological treatment of bipolar disorder in PHMDS, there is currently little guidance available on how to organize and execute such treatment. The aim of the current case study was to explore how pharmacological treatment of bipolar disorder in PHMDS may be organized and evaluated in an outpatient setting. Through a complex process of try and fail, including systematic evaluation of any change to the intervention and never implementing more than one change at the time, the patient gradually improved, regaining his communicative and adaptive skills. Four years passed from referral to this result was achieved. Organizing assessment and treatment as a collaborative effort involving specialized mental health professionals, professional caregivers and the patient’s family proved feasible. Many of the challenges present in assessment of psychiatric disorder in individuals with ASD and ID are likely to be present also in evaluation of treatment effects, particularly in disorders where symptoms occur in phases. The approach described in the current paper may contribute to reducing the impact of these challenges.

20-Year Trends in the Pharmacologic Treatment of Bipolar Disorder by Psychiatrists in Outpatient Care Settings.

Pharmacological options for treating bipolar disorder have increased over the past 20 years, with several second-generation antipsychotics receiving regulatory approval in the 1990s. The authors describe trends in use of pharmacological agents in the outpatient management of bipolar disorder. Using nationally representative data from the 1997-2016 National Ambulatory Medical Care Surveys, the authors examined trends in the use of mood stabilizers, first- and second-generation antipsychotics, and antidepressants among psychiatrist visits for which bipolar disorder was listed among the primary diagnoses. A logistic regression model was used to identify statistically significant trends, with covariates including age, gender, race/ethnicity, and primary insurance. Antipsychotics were increasingly more commonly prescribed, increasing from 12.4% of outpatient visits for bipolar disorder in the 1997-2000 period to 51.4% in the 2013-2016 period (adjusted odds ratio=5.05, 95% CI=3.65-7.01). Use of mood stabilizers decreased from 62.3% of visits for bipolar disorder in the 1997-2000 period to 26.4% in the 2013-2016 period (adjusted odds ratio=0.18, 95% CI=0.13-0.27). Prescription of antidepressants occurred in 47.0% of visits for bipolar disorder in the 1997-2000 period and 57.5% in the 2013-2016 period. Prescription of an antidepressant without a mood stabilizer increased substantially, from 17.9% in the 1997-2000 period to 40.9% in the 2013-2016 period (adjusted odds ratio=2.88, 95% CI=2.06-4.03). Substantial changes have occurred in the treatment of bipolar disorder over the past 20 years, with second-generation antipsychotics in large measure supplanting traditional mood stabilizers. Antidepressant prescriptions persisted despite a lack of evidence for their efficacy in bipolar disorder and concerns about increasing the risk of mania. Research is needed to compare the real-world effectiveness and tolerability of newer antipsychotics with those of traditional mood stabilizers.

A Review for Lithium: Pharmacokinetics, Drug Design, and Toxicity.

Lithium as a mood stabilizer has been used as the standard pharmacological treatment for Bipolar Disorder (BD) for more than 60 years. Recent studies have also shown that it has the potential for the treatment of many other neurodegenerative disorders, including Alzheimer's, Parkinson's and Huntington's disease, through its neurotrophic, neuroprotective, antioxidant and anti-inflammatory actions. Therefore, exploring its pharmacokinetic features and designing better lithium preparations are becoming important research topics. We reviewed many studies on the pharmacokinetics, drug design and toxicity of lithium based on recent relevant research from PubMed, Web of Science, Elsevier and Springer databases. Keywords used for searching references were lithium, pharmacology, pharmacokinetics, drug design and toxicity. Lithium is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Its level is initially highest in serum and then is evidently redistributed to various tissue compartments. It is not metabolized and over 95% of lithium is excreted unchanged through the kidney, but different lithium preparations may have different pharmacokinetic features. Lithium has a narrow therapeutic window limited by various adverse effects, but some novel drugs of lithium may overcome these problems. Various formulations of lithium have the potential for treating neurodegenerative brain diseases but further study on their pharmacokinetics will be required in order to determine the optimal formulation, dosage and route of administration.

Genetic Predictors of Lithium Response

Lithium remains a first-line pharmacological treatment of bipolar disorder (BD). However, treatment response is heterogeneous, with several lines of evidence implicating genetic factors. Unfortunately, neither hypothesis-driven approaches nor initial genome-wide association studies (GWAS) were successful in identifying genetic drivers of response heterogeneity, probably due to low statistical power and different phenotype measurements. Recently, a GWAS of the Consortium of Lithium Genetics (ConLiGen) has identified four single nucleotide polymorphisms (SNPs) mediating response to lithium, located in genes for two long non-coding RNAs. This success was only possible by international collaboration and the use of an established lithium response scale. The findings await further replication.

Nutraceuticals and nutritional supplements for the treatment of bipolar disorder: protocol for a systematic review

IntroductionFirst line pharmacological treatments for bipolar disorder (BD) can leave shortfalls in recovery leading to patients seeking alternative and adjunctive treatments such as nutraceuticals. This protocol for a systematic review...

A History of the Pharmacological Treatment of Bipolar Disorder.

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade’s experiments with lithium and the beginning of the so-called “Psychopharmacological Revolution” in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.

Novel Therapeutics in Bipolar Disorder

Existing pharmacological treatments for bipolar disorder have demonstrated insufficient efficacy, delayed onset of action, and significant side effects. Emerging evidence suggest that rapid antidepressant activity can be achieved in humans, and findings from the use of glutamatergic and anticholinergic drugs, for instance, reveal promising results. In the present article, we review evidence supporting the use of novel therapies in bipolar disorder, with focus on drugs acting in the glutamatergic system. In addition, anticholinergic drugs, melatonergic agonists, glucocorticoid modulators, and mechanistically diverse anti-inflammatory agents will be briefly discussed. While preliminary findings on novel therapies for bipolar disorder are encouraging, current evidence is still insufficient to support extensive use of these drugs routinely. Long-term safety, tolerability, and efficacy remain unclear; several clinical trials are underway and may add clarity to these questions. Early detection and prompt intervention have the potential to decelerate illness progression and lessen the burden associated with bipolar disorder; thus, novel therapies with rapid and sustained clinical benefits are urgent.

Pharmacological Treatment of Bipolar Disorder with Comorbid Alcohol Use Disorder.

Bipolar disorder (BD) spectrum and alcohol use disorders (AUDs) commonly occur together. Comorbidity between the two conditions predisposes patients to elevated risks of adverse outcomes, including hospitalization and suicide, compared with either condition alone. Despite the consistent relationship observed between BD and AUD, the underlying cause remains incompletely characterized. Few trials conducted have been able to identify promising interventions for patients with these disease states. The antipsychotic quetiapine has been evaluated most commonly as a therapeutic agent for patients with BD and AUD followed by naltrexone and acamprosate. Randomized controlled trials of quetiapine have consistently reported a lack of efficacy for the treatment of patients with BD and AUD. Trials of acamprosate have also been negative but small in size. Results of the sole randomized controlled trial of naltrexone have found large treatment effect sizes, but no statistically significant difference between treatment groups. Other agents including the antipsychotic aripiprazole, mood stabilizing agents including lamotrigine, lithium, and divalproex, and the antiepileptic agent topiramate have also been evaluated for the treatment of BD and AUD with mixed findings. The lone statistically significant treatment effect was observed in a randomized, placebo-controlled trial of divalproex added on to lithium which demonstrated a reduction in alcohol use. This review summarizes the available clinical evidence and current guideline recommendations for the treatment of comorbid BD and AUD, and provides discussion and recommendations based on the current literature.

Pharmacological Treatment of Bipolar Disorder in the Elderly

Due to the early age of onset, bipolar disorder is most commonly studied in younger adults, among whom the prevalence is 3.9% in adults aged 18–30 years. Unfortunately, relatively less attention has been paid to the unique needs of older adults with bipolar disorder (OABD), despite clinical complexities that include medical comorbidity, polypharmacy, cognitive decline, and phase of life losses of occupation and social identity. Furthermore, impaired cognitive performance in some older adults may limit the ability to stabilize mood episodes and interfere with the individual’s engagement in multi-modal treatment. Many OABD may also struggle with impairments in their independent activities of daily living (IADLs) which can lead to greater psychiatric, medical, psychological, financial, or social sequelae of mood episodes. Further complicating this picture is the fact that most OABD are treated by general psychiatrists or family practitioners due to a worldwide shortage of geriatric psychiatrists. This will become increasingly common as the mean life expectancy continues to increase. It is therefore incumbent on all general practitioners to understand the phases of bipolar disorder and the associated treatment options throughout the lifespan. Treatment of manic or depressive episodes focuses on symptomatic remission primarily through pharmacotherapy and neurotherapeutics. Management of the maintenance phase focuses on optimizing pharmacotherapy while reducing subclinical symptoms, treating comorbid illness, preventing relapse, and restoring psychosocial functioning and intacts identity through multimodal approaches including psychopharmacology, psychotherapy, diet, and lifestyle modifications. Comprehensive care for OABD is best achieved through close collaboration with the affected individual, the family physician, pharmacist, family members, and social supports.