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Progress in Neuro-psychopharmacology &... Jun 2024The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic... (Review)
Review
BACKGROUND
The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.
METHODS
PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.
RESULTS
Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.
CONCLUSION
Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
PubMed: 38879067
DOI: 10.1016/j.pnpbp.2024.111056 -
Cureus May 2024Affective disorders impose a significant burden on public health due to their high prevalence and associated suffering. This study addresses gaps in current literature...
INTRODUCTION
Affective disorders impose a significant burden on public health due to their high prevalence and associated suffering. This study addresses gaps in current literature and clinical practice by providing insights into medication usage trends, which can inform treatment strategies and optimize patient care. The study aims to investigate drug utilization patterns, particularly focusing on defined daily dose/1000/day, among individuals attending a psychiatric outpatient department of a tertiary care hospital.
METHODS
This cross-sectional, prospective drug utilization study included 600 affective disorder patients aged 18 years and above. The study period spanned 12 months, from March 2021 to February 2022. Data on demographics, diagnosis, treatment, and counseling were collected and analyzed using descriptive statistics.
RESULTS
Among the 600 patients analyzed, bipolar mood disorder was the most prevalent (239 patients, 39.83%), followed by depressive disorder (208 patients, 34.67%). Triple therapy was the most common prescription regimen, accounting for 308 encounters (51.33%). The average number of drugs per encounter was 3.75 ± 1.01. A combination of psychotherapy and medication counseling sessions was provided to 594 patients or their relatives, representing 99% of the total encounters.
CONCLUSION
The study highlights the prevalent use of triple therapy in managing affective disorders, especially bipolar mood disorder and mania disorder. Effective utilization of essential drug lists and comprehensive patient counseling underscores the importance of holistic care in psychiatric outpatient settings.
RECOMMENDATION
Given the high prevalence of triple therapy, further research into the efficacy and safety of this treatment approach is warranted. Additionally, continued emphasis on patient education and counseling can enhance treatment adherence and overall outcomes in individuals with affective disorders.
PubMed: 38872682
DOI: 10.7759/cureus.60290 -
Expert Opinion on Therapeutic Targets May 2024Inflammasome complexes, especially NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release... (Review)
Review
INTRODUCTION
Inflammasome complexes, especially NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release of the inflammatory cytokines IL-1β and IL-18, and seems to interact with purinergic and kynurenine pathways, all of which are implicated in mood disorders development and progression.
AREAS COVERED
Emerging evidence supports NLRP3 inflammasome as a promising pharmacological target for mood disorders. We discussed the available evidence from animal models and human studies and provided a reflection on drawbacks and perspectives for this novel target.
EXPERT OPINION
Several studies have supported the involvement of NLRP3 inflammasome in MDD. However, most of the evidence comes from animal models. The role of NLRP3 inflammasome in BD as well as its anti-manic properties is not very clear and requires further exploration. There is evidence of anti-manic effects of P2×R7 antagonists associated with reduction in the brain levels of IL-1β and TNF-α in a murine model of mania. The involvement of other NLRP3 inflammasome expressing cells besides microglia, like astrocytes, and of other inflammasome complexes in mood disorders also deserves further investigation. Preclinical and clinical characterization of NLRP3 and other inflammasomes in mood disorders is needed before considering translational approaches, including clinical trials.
Topics: Animals; Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Mood Disorders; Disease Models, Animal; Mice; Molecular Targeted Therapy; Bipolar Disorder; Purinergic P2X Receptor Antagonists; Depressive Disorder, Major
PubMed: 38871633
DOI: 10.1080/14728222.2024.2366872 -
International Journal of Bipolar... Jun 2024Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide...
BACKGROUND
Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.
RESULTS
We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.
CONCLUSIONS
Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
PubMed: 38865039
DOI: 10.1186/s40345-024-00341-y -
Industrial Psychiatry Journal 2024Gender confusion in the context of mania is very less frequently described in the literature. The actuality of a primary psychiatric condition in gender identity...
Gender confusion in the context of mania is very less frequently described in the literature. The actuality of a primary psychiatric condition in gender identity complaint has significant bearing on the applicable operation and prognostic. This case series describes cases of bipolar affective complaint presenting in a manic occasion whose mania was marked by hypersexuality and the desire to be of opposite gender. Both of these symptoms resolved with treatment of the manic occasion. Case 1 describes a 17-year-old male presenting with an episodic illness, with current manic episode. He is currently interested in boys and has started enjoying feminine activities. Upon treatment, his symptoms showed improvement. Case 2 describes a 22-year-old gay male, with a total duration of 7 years, current episode mania. Now, he is considering himself a lesbian and feels he is mentally a modern female. After 4 months of treatment, there was significant improvement in his complaints and he stopped cross-dressing as a female. Case 3 shows a 21-year-old female, with manic episode. After 1 month, the patient began acting and speaking more like a boy. The patient has shown improvement while taking lithium 900 mg, divalproex sodium 1000 mg, risperidone 6 mg, and chlorpromazine 150 mg. Gender dysphoria occurring along with a psychotic episode and resolving with management of the primary psychiatric disorder are rarely recorded. The central issue in similar cases is a proper workup and diagnosis. Psychiatrists should be aware of this scenario so that proper treatment strategies for gender incongruence can be planned and not be brushed aside as "just another symptom."
PubMed: 38853792
DOI: 10.4103/ipj.ipj_156_23 -
JAMA Network Open Jun 2024Alcohol use disorder (AUD) is present in nearly half of individuals with bipolar disorder (BD) and is associated with markedly worsening outcomes. Yet, the concurrent...
IMPORTANCE
Alcohol use disorder (AUD) is present in nearly half of individuals with bipolar disorder (BD) and is associated with markedly worsening outcomes. Yet, the concurrent treatment of BD and AUD remains neglected in both research and clinical care; characterizing their dynamic interplay is crucial in improving outcomes.
OBJECTIVE
To characterize the longitudinal alcohol use patterns in BD and examine the temporal associations among alcohol use, mood, anxiety, and functioning over time.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study selected participants and analyzed data from the Prechter Longitudinal Study of Bipolar Disorder (PLS-BD), an ongoing cohort study that recruits through psychiatric clinics, mental health centers, and community outreach events across Michigan and collects repeated phenotypic data. Participants selected for the present study were those with a diagnosis of BD type I (BDI) or type II (BDII) who had been in the study for at least 5 years. Data used were extracted from February 2006 to April 2022, and follow-up ranged from 5 to 16 years.
MAIN OUTCOMES AND MEASURES
Alcohol use was measured using the Alcohol Use Disorders Identification Test. Depression, mania or hypomania, anxiety, and functioning were measured using the 9-Item Patient Health Questionnaire, the Altman Self-Rating Mania Scale, the 7-item Generalized Anxiety Disorder assessment scale, and the Life Functioning Questionnaire, respectively.
RESULTS
A total of 584 individuals (386 females (66.1%); mean [SD] age, 40 [13.6] years) were included. These participants had a BDI (445 [76.2%]) or BDII (139 [23.8%]) diagnosis, with or without a lifetime diagnosis of AUD, and a median (IQR) follow-up of 9 (0-16) years. More problematic alcohol use was associated with worse depressive (β = 0.04; 95% credibility interval [CrI], 0.01-0.07) and manic or hypomanic symptoms (β = 0.04; 95% CrI, 0.01-0.07) as well as lower workplace functioning (β = 0.03; 95% CrI, 0.00-0.06) over the next 6 months, but increased depressive and manic or hypomanic symptoms were not associated with greater subsequent alcohol use. These latter 2 associations were more pronounced in BDII than BDI (mania or hypomania: β = 0.16 [95% CrI, 0.02-0.30]; workplace functioning: β = 0.26 [95% CrI, 0.06-0.45]). Alcohol use was not associated with anxiety over time.
CONCLUSIONS AND RELEVANCE
This study found that alcohol use, regardless of diagnostic status, was associated with mood instability and poorer work functioning in BD, but increased mood symptoms were not associated with subsequent alcohol use. Given its prevalence and repercussions, dimensional and longitudinal assessment and management of alcohol use are necessary and should be integrated into research and standard treatment of BD.
Topics: Humans; Bipolar Disorder; Female; Male; Adult; Longitudinal Studies; Middle Aged; Alcohol Drinking; Alcoholism; Affect; Michigan; Anxiety
PubMed: 38848066
DOI: 10.1001/jamanetworkopen.2024.15295 -
Current Pharmaceutical Design Jun 2024Bipolar disorder is a neuropsychiatric disease characterized by an abundance of undesired ideas and thoughts associated with recurrent episodes of mania or hypomania and...
Bipolar disorder is a neuropsychiatric disease characterized by an abundance of undesired ideas and thoughts associated with recurrent episodes of mania or hypomania and depression. Alterations in the circuits, including the prefrontal cortex, striatum, and limbic system, regulate mood and cause variation in several crucial neurotransmitters, including serotonin, dopamine, GABA, and glutamate. Imbalances in dopamine levels have been implicated in the manic phase, while variance in serotonin is linked to depressive episodes. The precise pathophysiology of bipolar disorder is still unknown. Though different treatments are available, like lithium, risperidone, valproic acid, etc., which are widely used, they come with certain limitations, including narrow therapeutic index, hypothyroidism, weight gain, extrapyramidal symptoms, etc. The interest in herbal- based treatments for bipolar disorder arises from the desire for alternative, potentially more natural, and holistic approaches with fewer side effects. The current review focuses on the potential effects of herbal drugs and their derivatives to alleviate the symptoms of bipolar disorder.
PubMed: 38847247
DOI: 10.2174/0113816128312442240519184440 -
The Cochrane Database of Systematic... Jun 2024Mental health problems contribute significantly to the overall disease burden worldwide and are major causes of disability, suicide, and ischaemic heart disease. People... (Review)
Review
BACKGROUND
Mental health problems contribute significantly to the overall disease burden worldwide and are major causes of disability, suicide, and ischaemic heart disease. People with bipolar disorder report lower levels of physical activity than the general population, and are at greater risk of chronic health conditions including cardiovascular disease and obesity. These contribute to poor health outcomes. Physical activity has the potential to improve quality of life and physical and mental well-being.
OBJECTIVES
To identify the factors that influence participation in physical activity for people diagnosed with bipolar disorder from the perspectives of service users, carers, service providers, and practitioners to help inform the design and implementation of interventions that promote physical activity.
SEARCH METHODS
We searched MEDLINE, PsycINFO, and eight other databases to March 2021. We also contacted experts in the field, searched the grey literature, and carried out reference checking and citation searching to identify additional studies. There were no language restrictions.
SELECTION CRITERIA
We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that focused on the experiences and attitudes of service users, carers, service providers, and healthcare professionals towards physical activity for bipolar disorder.
DATA COLLECTION AND ANALYSIS
We extracted data using a data extraction form designed for this review. We assessed methodological limitations using a list of predefined questions. We used the "best fit" framework synthesis based on a revised version of the Health Belief Model to analyse and present the evidence. We assessed methodological limitations using the CASP Qualitative Checklist. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) guidance to assess our confidence in each finding. We examined each finding to identify factors to inform the practice of health and care professionals and the design and development of physical activity interventions for people with bipolar disorder.
MAIN RESULTS
We included 12 studies involving a total of 592 participants (422 participants who contributed qualitative data to an online survey, 170 participants in qualitative research studies). Most studies explored the views and experiences of physical activity of people with experience of bipolar disorder. A number of studies also reported on personal experiences of physical activity components of lifestyle interventions. One study included views from family carers and clinicians. The majority of studies were from high-income countries, with only one study conducted in a middle-income country. Most participants were described as stable and had been living with a diagnosis of bipolar disorder for a number of years. We downgraded our confidence in several of the findings from high confidence to moderate or low confidence, as some findings were based on only small amounts of data, and the findings were based on studies from only a few countries, questioning the relevance of these findings to other settings. We also had very few perspectives of family members, other carers, or health professionals supporting people with bipolar disorder. The studies did not include any findings from service providers about their perspectives on supporting this aspect of care. There were a number of factors that limited people's ability to undertake physical activity. Shame and stigma about one's physical appearance and mental health diagnosis were discussed. Some people felt their sporting skills/competencies had been lost when they left school. Those who had been able to maintain exercise through the transition into adulthood appeared to be more likely to include physical activity in their regular routine. Physical health limits and comorbid health conditions limited activity. This included bipolar medication, being overweight, smoking, alcohol use, poor diet and sleep, and these barriers were linked to negative coping skills. Practical problems included affordability, accessibility, transport links, and the weather. Workplace or health schemes that offered discounts were viewed positively. The lack of opportunity for exercise within inpatient mental health settings was a problem. Facilitating factors included being psychologically stable and ready to adopt new lifestyle behaviours. There were positive benefits of being active outdoors and connecting with nature. Achieving balance, rhythm, and routine helped to support mood management. Fitting physical activity into a regular routine despite fluctuating mood or motivation appeared to be beneficial if practised at the right intensity and pace. Over- or under-exercising could be counterproductive and accelerate depressive or manic moods. Physical activity also helped to provide a structure to people's daily routines and could lead to other positive lifestyle benefits. Monitoring physical or other activities could be an effective way to identify potential triggers or early warning signs. Technology was helpful for some. People who had researched bipolar disorder and had developed a better understanding of the condition showed greater confidence in managing their care or providing care to others. Social support from friends/family or health professionals was an enabling factor, as was finding the right type of exercise, which for many people was walking. Other benefits included making social connections, weight loss, improved quality of life, and better mood regulation. Few people had been told of the benefits of physical activity. Better education and training of health professionals could support a more holistic approach to physical and mental well-being. Involving mental health professionals in the multidisciplinary delivery of physical activity interventions could be beneficial and improve care. Clear guidelines could help people to initiate and incorporate lifestyle changes.
AUTHORS' CONCLUSIONS
There is very little research focusing on factors that influence participation in physical activity in bipolar disorder. The studies we identified suggest that men and women with bipolar disorder face a range of obstacles and challenges to being active. The evidence also suggests that there are effective ways to promote managed physical activity. The research highlighted the important role that health and care settings, and professionals, can play in assessing individuals' physical health needs and how healthy lifestyles may be promoted. Based on these findings, we have provided a summary of key elements to consider for developing physical activity interventions for bipolar disorder.
Topics: Humans; Bias; Bipolar Disorder; Caregivers; Exercise; Health Personnel; Qualitative Research; Quality of Life; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 38837220
DOI: 10.1002/14651858.CD013557.pub2 -
JAMA Psychiatry Jun 2024Several psychotherapy protocols have been evaluated as adjuncts to pharmacotherapy for patients with bipolar disorder (BD). Little is known about their comparative...
IMPORTANCE
Several psychotherapy protocols have been evaluated as adjuncts to pharmacotherapy for patients with bipolar disorder (BD). Little is known about their comparative effectiveness.
OBJECTIVE
To compare the effectiveness of 2 types of group psychotherapy, skill-oriented, material-based cognitive behavioral therapy (SEKT) and supportive, patient-centered, emotion-focused therapy (FEST), to prevent relapse in patients with euthymic BD.
DESIGN, SETTING, AND PARTICIPANTS
This was a large, observer-blind, randomized clinical trial conducted over 18 months (posttreatment after 6 months; follow-up at 12 and 18 months). In addition to psychiatric care as usual (including mood-stabilizing medication), each participant at 9 clinical outpatient units in Germany received 24 hours of group psychotherapy over 4, full-day sessions spread over 5 months. Patients with euthymic BD type 1 (BD 1) or BD type 2 (BD 2) between the ages of 18 and 50 years were randomly assigned to 1 of 2 forms of psychotherapy, SEKT or FEST. Independent clinicians blinded to patient grouping performed assessments using structured interviews (Structured Clinical Interview for DSM Disorders and Longitudinal Interval Follow-Up Evaluation) and self-rating and clinician rating for inclusion criteria and outcome. Kaplan-Meier survival curves were calculated for time to relapse. Cox proportional hazards statistics and propensity score matching were calculated for the multivariate analysis. Study data were analyzed from March 2020 to September 2022.
INTERVENTIONS
SEKT intervention is a structured cognitive behavioral therapy integrating elements of interpersonal social rhythm therapy, and of mindfulness-based cognitive therapy. FEST psychotherapy has its roots in emotion-focused, supportive, and nondirective therapy.
MAIN OUTCOMES AND MEASURES
Recurrence of a new affective episode assessed by blinded interviewer with the LIFE interview. In addition, self-rating and clinician rating of depressive and mania symptoms as well as level of social functioning were assessed.
RESULTS
Of 348 screened referrals, 305 patients (median [IQR] age, 34 [18-50] years; 162 male [53%]) with euthymic BD 1 or BD 2 were included in the study. A total of 207 patients (68%) had BD 1, 98 (32%) had BD 2, and 278 (91%) received psychiatric care. Both therapies were equally effective in preventing recurrence of a new episode. Outcome (higher rate of new episodes) was not predicted by kind of treatment (SEKT: 69 [49%] relapse; FEST: 63 [46%] relapse) but was predicted by BD 2, comorbidity, attending all sessions, and the interaction of type of treatment by BD 1 or 2. Patients with BD 2 had the highest rate of relapse (60 [61%] relapse), in particular, when treated by SEKT (39 [70%] relapse).
CONCLUSIONS AND RELEVANCE
Results of this randomized clinical trial revealed that a structured, skill-oriented, material-based cognitive behavioral therapy (SEKT) and a supportive, patient-centered, emotion-focused therapy (FEST) were equally effective in preventing relapse of affective episodes when delivered in a new, intensive group format. Additionally, there were baseline factors, in particular BD 2, that influenced outcomes.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02506322.
PubMed: 38837133
DOI: 10.1001/jamapsychiatry.2024.1310 -
Journal of Psychopathology and Clinical... Jun 2024Bipolar disorder (BD) is a chronic psychiatric condition characterized by large episodic changes in mood and energy. Recently, BD has been proposed to be conceptualized...
Evidence for mood instability in patients with bipolar disorder: Applying multilevel hidden Markov modeling to intensive longitudinal ecological momentary assessment data.
Bipolar disorder (BD) is a chronic psychiatric condition characterized by large episodic changes in mood and energy. Recently, BD has been proposed to be conceptualized as chronic cyclical mood instability, as opposed to the traditional view of alternating discrete episodes with stable periods in-between. Recognizing this mood instability may improve care and call for high-frequency measures coupled with advanced statistical models. To uncover empirically derived mood states, a multilevel hidden Markov model (HMM) was applied to 4-month ecological momentary assessment data in 20 patients with BD, yielding ∼9,820 assessments in total. Ecological momentary assessment data comprised self-report questionnaires (5 × daily) measuring manic and depressive constructs. Manic and depressive symptoms were also assessed weekly using the Altman Self-Rating Mania Scale and the Quick Inventory for Depressive Symptomatology Self-Report. Alignment between HMM-uncovered momentary mood states and weekly questionnaires was assessed with a multilevel linear model. HMM uncovered four mood states: neutral, elevated, mixed, and lowered, which aligned with weekly symptom scores. On average, patients remained < 25 hr in one state. In almost half of the patients, mood instability was observed. Switching between mood states, three patterns were identified: patients switching predominantly between (a) neutral and lowered states, (b) neutral and elevated states, and (c) mixed, elevated, and lowered states. In all, elevated and lowered mood states were interspersed by mixed states. The results indicate that chronic mood instability is a key feature of BD, even in "relatively" euthymic periods. This should be considered in theoretical and clinical conceptualizations of the disorder. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38829323
DOI: 10.1037/abn0000915