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General Psychiatry 2022Bipolar depression (BD-D) is both common and incredibly challenging to treat. Even treated individuals with BD-D experience depression approximately 19% of the time, and... (Review)
Review
Bipolar depression (BD-D) is both common and incredibly challenging to treat. Even treated individuals with BD-D experience depression approximately 19% of the time, and subsyndromal depression an additional 18%. This stands in clear contrast to the approximately 10% of time spent in hypomania and 1% of time spent in mania. Despite this high illness burden, there remain relatively few treatment options approved by the US Food and Drug Administration for BD-D. Of the approved medications, four are second-generation antipsychotics (SGAs) and one is an SGA combined with an antidepressant. However, particularly when used long-term, antipsychotics can pose a significant risk of adverse effects, raising the clinical conundrum of weighing the risks associated with long-term antipsychotic use versus the risk of relapse when patients are off medications. Here, we review commonly used treatments for BD-D, including antipsychotics, classic mood stabilisers, electroconvulsive therapy and psychotherapy. We then address the somewhat controversial topic of antidepressant use in BD-D. Finally, we summarise emerging treatment options and highlight ongoing clinical trials. We hope this review will help compare the risks and benefits of several common and novel options for the treatment of patients with BD-D. In doing so, we also hope this review will aid the individualised selection of treatments based on each patient's history and treatment goals.
PubMed: 36035376
DOI: 10.1136/gpsych-2022-100760 -
Noro Psikiyatri Arsivi 2021Bipolar disorder is a disabling psychiatric disorder which causes premature death and loss of quality of life. Despite the developments, novel treatments are partially... (Review)
Review
Bipolar disorder is a disabling psychiatric disorder which causes premature death and loss of quality of life. Despite the developments, novel treatments are partially effective and insufficient responses to treatment may cause loss of quality of life. Contemporary approaches to treatment planning involve taking the current symptoms and the personal treatment history of the patient into account and tailoring them for the treatment of each patient, i.e. individualized treatment. In this article, effects and side effects of antipsychotics, mood stabilizers and sedative hypnotic medications are reviewed and presented briefly for clinicians. Although novel developments have been observed in the literature about mixed states and psychotic symptoms, evidence-based options are still limited. Efficacy of mood stabilizers may be prolonged and additional medications may also be needed frequently in patients treated with mood stabilizers. Antipsychotics may cause several side effects and cannot be maintained for a long time in some of those patients. These factors may limit the use of mood stabilizers or antipsychotics. Therefore, the experience of the clinician and personal history of the patient still have importance in the procedure.
PubMed: 34658632
DOI: 10.29399/npa.27411 -
BMC Psychiatry Jun 2023Bipolar disorder (BD) is characterized by intensive mood fluctuations. While hormones imbalance plays important role in the mood swings, it is unknown whether peripheral...
BACKGROUND
Bipolar disorder (BD) is characterized by intensive mood fluctuations. While hormones imbalance plays important role in the mood swings, it is unknown whether peripheral hormones profiles could differentiate the manic and depressive mood episodes in BD. In this study, we investigated the changes of various hormones and inflammatory markers across distinct mood episodes of BD in a large clinical study to provide mood episode-specific peripheral biomarkers for BD.
METHODS
A total of 8332 BD patients (n = 2679 depressive episode; n = 5653 manic episode) were included. All patients were in acute state of mood episodes and need hospitalization. A panel of blood tests were performed for levels of sex hormones (serum levels of testosterone, estradiol, and progesterone), stress hormones (adrenocorticotropic hormone and cortisol), and an inflammation marker (C-reactive protein, CRP). A receiver operating characteristic (ROC) curve was used to analyze the discriminatory potential of the biomarkers for mood episodes.
RESULTS
In overall comparison between mood episodes, the BD patients expressed higher levels of testosterone, estradiol, progesterone, and CRP (P < 0.001) and lower adrenocorticotropic hormone (ACTH) level (P < 0.001) during manic episode. The episode-specific changes of testosterone, ACTH, and CRP levels remained between the two groups (P < 0.001) after correction for the confounding factors including age, sex, BMI, occupation, marital status, tobacco use, alcohol consumption, psychotic symptoms, and age at onset. Furthermore, we found a sex- and age-specific impact of combined biomarkers in mood episodes in male BD patients aged ≥ 45 years (AUC = 0.70, 95% CI, 0.634-0.747), not in females.
CONCLUSIONS
While both hormone and inflammatory change is independently associated with mood episodes, we found that the combination of sex hormones, stress hormones and CRP could be more effective to differentiate the manic and depressive episode. The biological signatures of mood episodes in BD patients may be sex- and age-specific. Our findings not only provide mood episode-related biological markers, but also better support for targeted intervention in BD treatments.
Topics: Female; Humans; Male; Bipolar Disorder; Mania; Progesterone; Hydrocortisone; Biomarkers; Adrenocorticotropic Hormone; Testosterone; Estradiol
PubMed: 37340368
DOI: 10.1186/s12888-023-04846-1 -
Neuroscience Letters Apr 2022This mini-review aims to show a discrepancy between favorable data of lithium's therapeutic activity and the decreased use of the drug worldwide. The data point to... (Review)
Review
This mini-review aims to show a discrepancy between favorable data of lithium's therapeutic activity and the decreased use of the drug worldwide. The data point to lithium as the best mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most encouraging psychiatric use of lithium is the augmentation of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium is the most efficacious antisuicidal drug among all mood stabilizers. The drug also exerts antiviral, immunomodulatory, and neuroprotective effects which may be of major clinical value. On the other hand, the data of lithium use show that its therapeutic application in many countries has declined. A reason for this can be the introduction and heavy promotion of other mood-stabilizers, while lithium is an "orphan" drug with the minimal interest of any drug company. Probably, very important is also a perception of lithium as a "toxic drug", pointing to its side effects, mainly thyroid, renal and cognitive ones. In recent years, several proposals to turn back this anomalous association appeared, challenging a negative perception of lithium and optimizing its long-term administration. They show the data on lithium superiority over other mood stabilizers and point to the proper management of the lithium-induced side effects. This endeavor aims to allow a larger number of mood disorder patients to become beneficiaries of lithium use.
Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds
PubMed: 35346779
DOI: 10.1016/j.neulet.2022.136590 -
Cureus Aug 2022Bipolar disorder (BD) is a mood disorder characterized by severe mood swings and or periods of depression. This study examined the role that practicing yoga has on the... (Review)
Review
Bipolar disorder (BD) is a mood disorder characterized by severe mood swings and or periods of depression. This study examined the role that practicing yoga has on the symptoms of BD. One of the main goals was to identify if patients with BD believe that yoga is a viable treatment option. Six research databases were searched using the keywords "yoga" AND "therapy" AND "BD" AND "bipolar depression." Articles published in 2005 and later were included in the search. After duplicates were removed, and inclusion and exclusion criteria were applied, five articles were analyzed and included in this literature review. Results of this review indicate that yoga has been shown to be associated with both benefits and risks for the treatment of BD. Studies have shown that yoga might relieve some symptoms of BD and depression. However, due to the lack of research on the impact of yoga on BD and the small number of studies included in this review, results should be approached with caution. Overall, yoga was well-tolerated in the studies reviewed in this article. Yoga may relieve the symptoms of depression. Future research should analyze the long-term impact of yoga on bipolar depression. Yoga instructional standards should also be considered.
PubMed: 36072189
DOI: 10.7759/cureus.27688 -
Current Neuropharmacology 2023An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different...
BACKGROUND
An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated.
OBJECTIVES
The main aim of this study is to systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer's disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated to negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline.
METHODS
A systematic review of the literature was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to February 2022. Sixty-one articles on patients with AD, VaD, or FTD and BD or (hypo) mania have been included.
RESULTS
Manic symptoms seem to be associated to disease progression in AD, have a greatly variable temporal relationship with cognitive decline in VaD, and frequently coincide with or precede cognitive impairment in FTD. Overall, mood stabilizers, and electroconvulsive therapy may be the most effective treatments, while the benefits of short-term treatment with antipsychotic agents must be balanced with the associated risks. Importantly, low-dose lithium salts may exert neuroprotective activity in patients with AD.
CONCLUSION
Prevalence, course, and characteristics of manic syndromes in patients with dementia may be differentially affected by the nature of the underlying neurodegenerative conditions.
Topics: Humans; Bipolar Disorder; Frontotemporal Dementia; Alzheimer Disease; Mania; Antipsychotic Agents; Antimanic Agents
PubMed: 35794767
DOI: 10.2174/1570159X20666220706110157 -
Neuropsychiatric Disease and Treatment 2020Bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) are two cyclic mood illnesses, sometimes presenting together. Their comorbidity appears to be linked to... (Review)
Review
Bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) are two cyclic mood illnesses, sometimes presenting together. Their comorbidity appears to be linked to common biological mechanisms and usually results in more severity of mood symptoms and a poorer long-term outcome. Nevertheless, the management of comorbid PMDD/BD has been scarcely studied. Therefore, the aim of the present paper was to review the published literature on the treatment of comorbid PMDD/BD and to provide point-by-point hypotheses to address these complex clinical cases. We searched PubMed to identify the studies focused on the treatment and management of comorbid PMDD/BD using the following search words, alone and in combination: premenstrual dysphoric disorder, bipolar disorder, comorbid, treatment, management, pharmacotherapy, psychotherapy. The search was conducted on the 1st of June 2019 and yielded 55 records. Four papers met our inclusion/exclusion criteria and were therefore included in our qualitative synthesis. Integrating the few data pertaining to the treatment of comorbid PMDD/BD with the large amount of published data on the two conditions separately, we can suggest that the management of comorbid PMDD/BD needs as a first step to stabilize the bipolar symptoms by means of optimal dosages of mood stabilizers. Then, in euthymic BD patients, the PMDD symptoms could be treated with estroprogestins (first-line treatment). On the contrary, during acute phases of BD, antidepressants (for major depressive episodes) and atypical antipsychotics/hormonal modulators (for manic episodes) could be considered as promising add-on treatments to mood stabilizers. In case of resistant PMDD/BD symptoms, combined strategies should be taken into account, as well as alternative treatments, such as lifestyle changes. In conclusion, RCTs on comorbid PMDD/BD are still lacking. The management of this complex condition is therefore challenging and it requires a tailored treatment.
PubMed: 32103961
DOI: 10.2147/NDT.S202881 -
Frontiers in Psychiatry 2020This paper focuses on depression that precedes an onset of manifest bipolar disorder as early stage bipolar disorder. First, we review how to pragmatically identify the... (Review)
Review
This paper focuses on depression that precedes an onset of manifest bipolar disorder as early stage bipolar disorder. First, we review how to pragmatically identify the clinical characteristics of patients presenting with an episode of depression who subsequently go on to develop episodes of mania or hypomania. The existing literature shows a strong consensus: accurate identification of depression with early onset and recurrent course with multiple episodes, subthreshold hypomanic and/or mixed symptoms, and family history of bipolar disorder or completed suicide have been shown by multiple authors as signs pointing to bipolar diagnosis. This contrasts with relatively limited information available to guide management of such "pre-bipolar" (pre-declared bipolar) patients, especially those in the adult age range. Default assumption of unipolar depression at this stage carries significant risk. Antidepressants are still the most common pharmacological treatment used, but clinicians need to be aware of their potential harm. In some patients with unrecognized bipolar depression, antidepressants can not only produce switch to (hypo)mania, but also mixed symptoms, or worsening of depression with an increased risk of suicide. We review pragmatic management strategies in the literature beyond clinical guidelines that can be considered for this at-risk group encompassing the more recent child and adolescent literature. In the future, genetic research could make the early identification of bipolar depression easier by generating informative markers and polygenic risk scores.
PubMed: 32595530
DOI: 10.3389/fpsyt.2020.00500 -
Journal of the American Academy of... Oct 2022Mood instability is associated with the onset of bipolar disorder (BD) in youth with a family history of the illness. In a clinical trial with youth at high risk for BD,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Mood instability is associated with the onset of bipolar disorder (BD) in youth with a family history of the illness. In a clinical trial with youth at high risk for BD, we examined the association between mood instability and symptomatic, psychosocial, and familial functioning over an average of 2 years.
METHOD
Youth (aged 9-17 years) with major depressive disorder or other specified BD, current mood symptoms, and a family history of BD were rated by parents on a mood instability scale. Participants were randomly assigned to 4 months of family-focused therapy or enhanced care psychoeducation, both with medication management as needed. Independent evaluators rated youth every 4-6 months for up to 4 years on symptom severity and psychosocial functioning, whereas parents rated mood instability of the youth and levels of family conflict.
RESULTS
High-risk youth (N = 114; mean age 13.3 ± 2.6 years; 72 female) were followed for an average of 104.3 ± 65.8 weeks (range, 0-255 weeks) after randomization. Youth with other specified BD (vs major depressive disorder), younger age, earlier symptom onset, more severe mood symptoms, lower psychosocial functioning, and more familial conflict over time had higher mood instability ratings throughout the study period. Mood instability mediated the association between baseline diagnosis and mother/offspring conflict at follow-up (Z = 2.88, p = .004, αβ = 0.19, 95% CI = 0.06-0.32). Psychosocial interventions did not moderate these associations.
CONCLUSION
A questionnaire measure of mood instability tracked closely with symptomatic, psychosocial, and family functioning in youth at high risk for BD. Interventions that are successful in reducing mood instability may enhance long-term outcomes among high-risk youth.
CLINICAL TRIAL REGISTRATION INFORMATION
Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.
Topics: Adolescent; Affect; Bipolar Disorder; Child; Depressive Disorder, Major; Family Conflict; Family Therapy; Female; Humans
PubMed: 35307538
DOI: 10.1016/j.jaac.2022.03.009 -
Journal of Affective Disorders Feb 2022Mood and anxiety are widely associated with physical conditions, but research and treatment are complicated by their overlap, clinical heterogeneity, and manifestation...
BACKGROUND
Mood and anxiety are widely associated with physical conditions, but research and treatment are complicated by their overlap, clinical heterogeneity, and manifestation on a spectrum rather than as discrete disorders. In contrast to previous work relying on threshold-level disorders, we examined the association between empirically-derived profiles of mood and anxiety syndromes with physical conditions in a nationally-representative sample of US adolescents.
METHODS
Participants were 2,911 adolescents (aged 13-18) from the National Comorbidity Survey-Adolescent Supplement who provided information on physical conditions and reported at least one lifetime mood-anxiety 'syndrome' based on direct interviews with the Composite International Diagnostic Interview Version 3.0. Mood-anxiety syndromes reflected 3-level ratings from subthreshold to severe distress/impairment, and subtyped mood episodes. Stepwise latent profile analysis identified mood-anxiety profiles and tested associations with physical conditions.
RESULTS
Three mood-anxiety profiles were identified: "Mood-GAD" (25.6%)-non-atypical depression, mania, generalized anxiety; "Atypical-Panic" (11.3%)-atypical depression, panic; and "Reference" (63.1%)-lower mood and anxiety except specific phobia. Headaches were more prevalent in Mood-GAD and Atypical-Panic than Reference (47.9%, 50.1%, and 37.7%, respectively; p=0.011). Heart problems were more common in Mood-GAD than Atypical-Panic (7.4% v 2.2%, p=0.004) and Reference, with back/neck pain more prevalent in Mood-GAD than Reference (22.5% v 15.3%, p=0.016).
LIMITATIONS
Broad categories of physical conditions without information on specific diagnoses; replication regarding specificity is recommended.
CONCLUSIONS
Heart problems and pain-related conditions were differentially associated with specific mood-anxiety profiles. Subtyping depression and anxiety-inclusive of subthreshold syndromes-and their patterns of clustering may facilitate etiologic and intervention work in multimorbidity.
Topics: Adolescent; Anxiety; Anxiety Disorders; Comorbidity; Humans; Panic; Phobic Disorders; Prevalence
PubMed: 34838604
DOI: 10.1016/j.jad.2021.11.056