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Expert Opinion on Pharmacotherapy Aug 2019: Bipolar I disorder (BDI) is amongst the most debilitating psychiatric conditions with a great impact on both patients and their families. A class of drugs commonly... (Review)
Review
: Bipolar I disorder (BDI) is amongst the most debilitating psychiatric conditions with a great impact on both patients and their families. A class of drugs commonly used in this condition is second-generation antipsychotics (SGAs) including asenapine, one of the latest to be introduced into the clinical practice worldwide to treat manic episodes in BDI. : The aim of this paper is to critically review the literature on the pharmacological characteristics, tolerability, and safety data of asenapine, as well as on its short- and long-term clinical trials in manic episodes as both a monotherapy and as an add-on treatment. : The available data indicate that asenapine is an effective antimanic agent in both adult and pediatric patients and that it might also improve depressive symptoms and recurrences in BDI patients. Its tolerability profile is good, and its most common side effects are somnolence, light extrapyramidal symptoms, dizziness, weight gain, and oral (but reversible) hypoesthesia. Taken together, the published studies indicate that asenapine might be an effective therapeutic agent in BDI with a broad spectrum of clinical activities. Further double-blind, short- and long-term studies are, however, necessary to clarify its precise role in the treatment of BD.
Topics: Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Dibenzocycloheptenes; Dizziness; Half-Life; Heterocyclic Compounds, 4 or More Rings; Humans
PubMed: 31132287
DOI: 10.1080/14656566.2019.1617849 -
The Journal of Nervous and Mental... Jul 2022This study aimed to explore the role of C-reactive protein (CRP) in the pathological mechanism and differential diagnoses of bipolar disorder (BD) and unipolar...
This study aimed to explore the role of C-reactive protein (CRP) in the pathological mechanism and differential diagnoses of bipolar disorder (BD) and unipolar depression (UD). We tested serum CRP levels of 176 BD and 86 UD patients, and 82 healthy controls (HCs), at acute and remission phases. In the acute phase, CRP levels were higher in BD than in UD patients and HC, and lower in UD patients than in HC. The CRP levels of BD patients in a manic episode were higher than those of HC; in a depressive or mixed episode, they were comparable to those of HC. The CRP levels of BD and UD patients during an acute depressive episode yielded an area under the curve of 0.676. CRP may be a state marker of acute manic episodes in BD and acute depressive episodes in UD, and a biomarker for distinguishing BD and UD.
Topics: Biomarkers; Bipolar Disorder; C-Reactive Protein; Depression; Depressive Disorder; Humans
PubMed: 35766544
DOI: 10.1097/NMD.0000000000001487 -
Dialogues in Clinical Neuroscience 2021This narrative review of systematic reviews and meta-analyses aims at compiling available evidence in various aspects of neurocognitive functioning in Bipolar Disorder... (Review)
Review
This narrative review of systematic reviews and meta-analyses aims at compiling available evidence in various aspects of neurocognitive functioning in Bipolar Disorder (BD). We conducted a MEDLINE literature search and identified 38 relevant systematic reviews and metaanalyses. Current evidence suggests that BD is associated with cognitive impairment across multiple domains and during all clinical states. However, there is a considerable cognitive heterogeneity within BD, which cannot be explained by clinical subtypes, and the pattern of neurocognitive impairment in BD overlaps with other psychiatric conditions such as major depression and schizophrenia. Residual depressive symptoms, poor clinical course and higher number of manic episodes may negatively impact cognitive performance, which is a major predictor of general functioning in BD. Evidence from available prospective studies does not support the notion of progressive cognitive decline in BD while some evidence exists to suggest patients may show some improvements in cognitive functioning following the first manic episode. Furthermore, a subset of patients may show premorbid cognitive abnormalities that could signal an early neurodevelopmental aetiology. Preliminary findings from small studies identify potential pro-cognitive effects of Cognitive Remediation, erythropoietin, intranasal insulin, lurasidone, mifepristone, repetitive Transcranial Magnetic Stimulation and transcranial Direct Current Stimulation in BD. Longitudinal studies in high-risk individuals can provide a better understanding of the development and progression of neurocognitive impairment in BD. Largescale randomised control trials are needed to compare the pro-cognitive efficacy of various pharmacological and non-pharmacological interventions in different cognitive subgroups of patients at different stages of BD.
Topics: Bipolar Disorder; Humans; Meta-Analysis as Topic; Neuropsychological Tests; Prospective Studies; Systematic Reviews as Topic; Transcranial Direct Current Stimulation
PubMed: 35860174
DOI: 10.1080/19585969.2022.2042164 -
Bipolar Disorders Sep 2019It has been suggested that agitated depression (AD) is a common, severe feature in bipolar disorder. We aimed to estimate the prevalence of AD and investigate whether...
OBJECTIVES
It has been suggested that agitated depression (AD) is a common, severe feature in bipolar disorder. We aimed to estimate the prevalence of AD and investigate whether presence of AD was associated with episodic and lifetime clinical features in a large well-characterized bipolar disorder sample.
METHOD
The prevalence of agitation, based on semi-structured interview and medical case-notes, in the most severe depressive episode was estimated in 2925 individuals with DSM-IV bipolar disorder recruited into the UK Bipolar Disorder Research Network. Predictors of agitation were ascertained using symptoms within the same episode and lifetime clinical features using multivariate models.
RESULTS
32.3% (n = 946) experienced agitation during the worst depressive episode. Within the same episode, significant predictors of presence of agitation were: insomnia (OR 2.119, P < 0.001), poor concentration (OR 1.966, P = 0.027), decreased libido (OR 1.960, P < 0.001), suicidal ideation (OR 1.861, P < 0.001), slowed activity (OR 1.504, P = 0.001), and poor appetite (OR 1.297, P = 0.029). Over the lifetime illness course, co-morbid panic disorder (OR 2.000, P < 0.001), suicide attempt (OR 1.399, P = 0.007), and dysphoric mania (OR 1.354, P = 0.017) were significantly associated with AD.
CONCLUSIONS
Agitation accompanied bipolar depression in at least one-third of cases in our sample and was associated with concurrent somatic depressive symptoms, which are also common features of mixed manic states. Furthermore, AD in our sample was associated with lifetime experience of mixed mania, in addition to severe lifetime illness course including comorbid panic disorder and suicidal behavior. Our results have implications for the diagnosis and treatment of agitated features in bipolar depression.
Topics: Adult; Anxiety; Bipolar Disorder; Comorbidity; Depression; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Prevalence; Psychomotor Agitation; Suicide, Attempted
PubMed: 31004555
DOI: 10.1111/bdi.12778 -
Journal of Psychiatric Research Jun 2020To assess the clinical efficacy of clozapine in bipolar disorder and its adverse effect profile. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the clinical efficacy of clozapine in bipolar disorder and its adverse effect profile.
METHODS
A literature search with no year and no language restriction was conducted. The search yielded 3858 articles, with 2453 remaining after duplicate removal; 9 were suitable for the systematic review. From the 9 included studies, 3 (100 patients treated with clozapine and 102 patients treated with other antipsychotics) could be included in a meta-analysis to test clozapine efficacy in the treatment of manic episodes.
RESULTS
Clozapine's efficacy was similar to other antipsychotics (Mean difference (MD): 0.03 [95%CI: 0.86-0.92], p = 0.59) in manic episodes. The systematic review also suggested that clozapine is faster at improving symptoms in manic episodes. In addition, two studies included patients with treatment resistant bipolar disorder (TRBD) and showed that clozapine is superior to other treatments for this specific population. Sedation was the most frequent side effect (49.6%), followed by constipation (31.8%) and tachycardia (23.2%).
CONCLUSION
Clozapine's efficacy was similar to other antipsychotics in manic episodes and is superior to other antipsychotics among TRBD patients.
Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Treatment Outcome
PubMed: 32182485
DOI: 10.1016/j.jpsychires.2020.02.026 -
Der Nervenarzt Mar 2020Bipolar disorder (BD) is a relevant psychiatric disorder, which requires early identification and treatment. (Review)
Review
BACKGROUND
Bipolar disorder (BD) is a relevant psychiatric disorder, which requires early identification and treatment.
OBJECTIVE
What are the guideline-concordant diagnostic and early recognition procedures regarding BD?
RESULTS
The current German S3 guidelines on BD are based on the ICD-10. The multiaxial and dimensional description should include disorder-relevant somatic, psychological and social factors as well as the level of functional impairment. A BD can be diagnosed when at least two affective episodes have occurred, of which at least one must have been hypomanic, manic or mixed. In people considered at increased risk for BD, (subsyndromal) symptoms should be identified via the patient history and screening tools, e.g. the hypomania checklist 32 (HCL-32) and the mood disorder questionnaire (MDQ). The differential diagnosis of BD should exclude unipolar depression, dysthymia, cyclothymia, schizophrenia, schizoaffective disorders and substance-induced or organically related BD. The risk of comorbid psychiatric disorders is increased 8-13-fold in BD. The most common somatic disorders include obesity, cardiovascular diseases, metabolic syndrome, diabetes, musculoskeletal disorders and migraine. Observation of the course by the clinician and the patient (e.g. mood charting) as well as examinations before and during pharmacological treatment should be part of the treatment plan. Early recognition of BD during a so-called prodromal stage is currently not reliably possible. In the case of a clinical suspicion, e.g. due to subsyndromal (hypo)manic symptoms, comorbid conditions should be addressed and symptom-based psychotherapeutic interventions should be considered.
CONCLUSION
Early recognition and accurate diagnosis of BD, which enables adequate and timely treatment, can improve outcomes.
Topics: Bipolar Disorder; Diagnosis, Differential; Early Diagnosis; Germany; Humans; Surveys and Questionnaires
PubMed: 32125440
DOI: 10.1007/s00115-020-00881-5 -
Journal of Psychiatric Research Aug 2023There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this... (Clinical Trial)
Clinical Trial
There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this pilot study, we treated six subjects with bipolar disorder types I and II (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria) who had been in a current depressive episode for at least four weeks. Four subjects were female (66.66%), and the mean age was 45.33 (±12.32). Subjects received adjunct treatment with two arketamine intravenous infusions one week apart-0.5 mg/kg first and then 1 mg/kg. The mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score was 36.66, which decreased to 27.83 24h after the first infusion of 0.5 mg/kg of arketamine (p = 0.036). In respect of the 1 mg/kg dose, the mean MADRS total score before the second infusion was 32.0, which dropped to 17.66 after 24h (p < 0.001). Arketamine appears to have rapid-acting antidepressant properties, consistent with previous animal studies on major depression. All individuals tolerated both doses, exhibiting nearly absent dissociation, and no manic symptoms. To the best of our knowledge, this pilot trial is the first to test the feasibility and safety of the (R)-enantiomer of ketamine (arketamine) for bipolar depression.
Topics: Female; Humans; Male; Antidepressive Agents; Bipolar Disorder; Depression; Depressive Disorder, Major; Double-Blind Method; Ketamine; Pilot Projects; Treatment Outcome
PubMed: 37385001
DOI: 10.1016/j.jpsychires.2023.06.028 -
Current Neuropharmacology 2023Bipolar Disorder (BD) is a highly comorbid condition, and rates of cooccurring disorders are even higher in youth. Comorbid disorders strongly affect clinical... (Review)
Review
BACKGROUND
Bipolar Disorder (BD) is a highly comorbid condition, and rates of cooccurring disorders are even higher in youth. Comorbid disorders strongly affect clinical presentation, natural course, prognosis, and treatment.
METHODS
This review focuses on the clinical and treatment implications of the comorbidity between BD and Attention-Deficit/Hyperactivity Disorder, disruptive behavior disorders (Oppositional Defiant Disorder and/or Conduct Disorder), alcohol and substance use disorders, Autism Spectrum Disorder, anxiety disorders, Obsessive-Compulsive Disorder, and eating disorders.
RESULTS
These associations define specific conditions which are not simply a sum of different clinical pictures, but occur as distinct and complex combinations with specific developmental pathways over time and selective therapeutic requirements. Pharmacological treatments can improve these clinical pictures by addressing the comorbid conditions, though the same treatments may also worsen BD by inducing manic or depressive switches.
CONCLUSION
The timely identification of BD comorbidities may have relevant clinical implications in terms of symptomatology, course, treatment and outcome. Specific studies addressing the pharmacological management of BD and comorbidities are still scarce, and information is particularly lacking in children and adolescents; for this reason, the present review also included studies conducted on adult samples. Developmentally-sensitive controlled clinical trials are thus warranted to improve the prognosis of these highly complex patients, requiring timely and finely personalized therapies.
Topics: Adult; Child; Humans; Adolescent; Bipolar Disorder; Autism Spectrum Disorder; Comorbidity; Anxiety Disorders; Obsessive-Compulsive Disorder; Attention Deficit Disorder with Hyperactivity
PubMed: 35794777
DOI: 10.2174/1570159X20666220706104117 -
Frontiers in Bioscience (Scholar... Jan 2022Recent studies provide evidence that similar to early-stage Parkinson's disease, depression is a neurodegenerative disease characterized by the degeneration of monoamine... (Review)
Review
Recent studies provide evidence that similar to early-stage Parkinson's disease, depression is a neurodegenerative disease characterized by the degeneration of monoamine axons. The major difference between the two disorders is that the symptoms of depression become evident without loss of monoamine neurons, while the motor symptoms of Parkinson's disease appear after loss of the cell body. Given that the axonal degeneration of monoamine neurons underlies the pathophysiology of neurological (Parkinson's disease) and neuropsychiatric (depression) diseases, axonal impairment of monoamine neurons is thought to also occur in schizophrenia and bipolar disorder and play a significant role in the pathophysiology of these mental illnesses. The positive symptoms of schizophrenia and manic symptoms of bipolar disorder are known to occur in hyper-monoaminergic states, opposite to depressive symptoms, negative/cognitive symptoms of schizophrenia, and motor disorders of Parkinson's disease, all occurring in hypo-monoaminergic states. Since monoamine axons have the capacity to spontaneously regenerate or sprout in response to damage in the adult brain and sometimes show hyperinnervation due to excessive regeneration/sprouting beyond normal levels, it is possible that schizophrenia and bipolar disorder are disorders that include excessive regeneration/sprouting of monoamine axons leading to hyper-monoaminergic states. Together, based on accumulating data from animal and human studies, the pathophysiology of schizophrenia, major depression, and bipolar disorder is summarized as follows: The degeneration of monoamine axons is associated with the negative and cognitive symptoms of schizophrenia, major and bipolar depression, while hyper-regeneration/sprouting of monoamine axons underlies the positive symptoms of schizophrenia and bipolar mania. The integrated understanding of schizophrenia, major depression, and bipolar disorder as monoamine axon disorder will open the door to the development of new diagnosis and treatment methods for major mental illnesses as well as early-stage Parkinson's disease.
Topics: Axons; Bipolar Disorder; Depression; Depressive Disorder, Major; Humans; Neurodegenerative Diseases; Parkinson Disease; Schizophrenia
PubMed: 35320915
DOI: 10.31083/j.fbs1401004 -
Psychiatry Research Jun 2022The current bipolar disorder treatment guidelines focus mainly on the prevention of recurrence and stabilization of acute mood episodes while neglecting outcomes related... (Review)
Review
The current bipolar disorder treatment guidelines focus mainly on the prevention of recurrence and stabilization of acute mood episodes while neglecting outcomes related to the longitudinal course of illness. We systematically reviewed studies that assess the impact of disease progression in the treatment of patients with bipolar disorder. We searched PubMed, Embase, and Web of Science for clinical trials that moderated treatment effects by number of previous episodes, disease length, or a clinical staging model. We retrieved 6,156 potential abstracts. After deduplication, 5,376 were screened and eight studies met inclusion criteria. Seven trials moderated results by number of prior episodes, and one of those also used a measure of disease length. One trial used a clinical staging model and yielded informing results. Only three studies evaluated pharmacological interventions, the other five assessing psychotherapeutic modalities. Most of the studies were post-hoc analysis of clinical trials not primarily aimed at studying variables associated with illness trajectory. Overall, a loss of efficacy was found according to clinical progression, which supports early intervention. Tailored recommendations according to disease stages cannot be made. Furthermore, we identified methodological weaknesses and strengths in this subfield of research, suggesting the use of clinical staging models for future studies.
Topics: Affect; Bipolar Disorder; Humans
PubMed: 35490572
DOI: 10.1016/j.psychres.2022.114572