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Clinical Psychology Review Feb 2018Prominent cognitive deficits have been documented in bipolar disorder, and multiple studies suggest that these deficits can be observed among non-affected first-degree... (Review)
Review
Prominent cognitive deficits have been documented in bipolar disorder, and multiple studies suggest that these deficits can be observed among non-affected first-degree relatives of those with bipolar disorder. Although there is variability in the degree of cognitive deficits, these deficits are robustly relevant for functional outcomes. A separate literature documents clear difficulties in emotionality, emotion regulation, and emotion-relevant impulsivity within bipolar disorder, and demonstrates that these emotion-relevant variables are also central to outcome. Although cognitive and emotion domains are typically studied independently, basic research and emergent findings in bipolar disorder suggest that there are important ties between cognitive deficits and the emotion disturbances observed in bipolar disorder. Understanding these relationships has relevance for fostering more integrative research, for clarifying relevant aspects related to functionality and vulnerability within bipolar disorder, and for the development of novel treatment interventions. Bipolar disorder (BD) is a severe psychiatric illness that has been ranked as one of the 20 leading medical causes of disability (WHO, 2011). BD has been shown to be the psychiatric disorder with the highest rates of completed suicide across two major cohort studies (Ilgen et al., 2010; Nordentoft, Mortensen, & Pedersen, 2011). In a cross-national representative sample, one in four persons diagnosed with bipolar I disorder reported a suicide attempt (Merikangas et al., 2011). Rates of relapse remain high despite available treatments (Gitlin, Swendsen, Heller, & Hammen, 1995), and in the year after hospitalization for manic episode, two-thirds of patients do not return to work (Strakowski et al., 1998). Poverty, homelessness, and incarceration are all too common (Copeland et al., 2009). Despite the often poor outcomes, there is also evidence for outstanding accomplishments and creativity among those with milder forms of the disorder and their family members (Coryell et al., 1989; Jamison, 1993; Murray & Johnson, 2010). Some individuals appear to achieve more than the general population, suggesting the importance of understanding the variables that predict differential outcome within bipolar disorder. Within this paper, we focus on two key predictors of outcomes within bipolar disorder: cognition and emotionality. We review evidence that problems in cognition and emotionality are prominent among those diagnosed with the disorder, are not artifacts of symptom state, and relate substantively to poorer outcomes. Although traditionally studied separately, new work points toward the idea that cognition and emotionality are intricately linked within bipolar disorder. Drawing from research within bipolar disorder as well as outside of bipolar disorder, we build a model of how cognition and emotionality might be tied within bipolar disorder. We then provide suggestions for future research. Before considering findings, it is worth noting that there are several forms of the disorder, defined by varying degrees and duration of manic symptoms (APA, 2013; WHO, 1993). Manic episodes are defined by abnormally elevated or irritable mood, accompanied by increased activity and at least three symptoms (four if mood is only irritable) such as decreased need for sleep, increased self-confidence, racing thoughts or flight of ideas, rapid speech, distractibility, goal-directed activity, and engagement in pleasurable activities without regard to potential negative consequences. To meet criteria for mania, these symptoms must persist for at least one week or require hospitalization, and must lead to difficulties with functioning. If functional impairment is not more than mild and duration is between 4 and 6 days, the episode is considered a hypomanic episode. Bipolar I disorder (BD I) is diagnosed on the basis of at least one lifetime manic episode within the DSM-5 and by at least two episodes within the ICD, whereas bipolar II disorder is diagnosed on the basis of at least one hypomanic episode (and no manic episodes) as well as major depressive episodes. Cyclothymic disorder is defined by chronic but milder fluctuations between manic and depressive symptoms. Most research focuses on BD I. In addition to diagnosed samples, research has focused on those at high risk for bipolar disorder, including first-degree relatives of those with BD. This work draws on the evidence for extremely high heritability of BD I, with estimates from community-based twin studies of 0.85 (Kieseppä, Partonen, Haukka, Kaprio, & Lönnqvist, 2014). Other research has considered high risk for BD by virtue of lifetime subsyndromal symptoms, as measured by scales such as the Hypomanic Personality Scale (Eckblad & Chapman, 1986) or the General Behavior Inventory (Depue, Krauss, Spoont, & Arbisi, 1989). The study of high-risk individuals provides a way to decipher whether deficits are present before the onset of the disorder, of importance given models suggesting that episodes of the disorder may change brain function (Chang, Steiner, & Ketter, 2000; Strakowski, 2012) as well as individuals' perceptions of their emotion regulation. Beyond defining BD, it is worth defining some of the many different neuropsychological tasks that have been widely studied in BD. Perhaps no area has received more attention than executive function. Executive function is related to three core functions: 1) inhibition, the ability to suppress irrelevant information in working memory in order to accomplish an established goal; 2) working memory, the ability to hold and manipulate information in mind; and 3) cognitive flexibility, the ability to shift strategies in response to feedback (Diamond, 2013; Miyake et al., 2000). Attention (defined as the process of selecting information reception from internal or external cues) is implicated in all three of these aspects of executive function. Much of the literature we will discuss focuses on response inhibition, or the ability to suppress a prepotent response, which is considered a subtype of inhibition. Some tests measure multiple facets of executive function; for example the Trails B test likely requires working memory and cognitive flexibility (Sánchez-Cubillo et al., 2009). Aside from executive function, multiple other facets of cognition have been widely studied in bipolar disorder. Verbal and non-verbal memory are related to the ability to register, store and retrieve verbal or visual information (Lezak, 1995). Verbal fluency is measured as the number of verbal responses a person can generate to a given target, such as a specific semantic category (e.g., animals, furniture) or phonetic category (e.g., words that begin with letter F) (Diamond, 2013). Although cognitive tasks have been designed to evaluate these specific functions, it is important to note that most measures are highly inter-correlated and may assess multiple overlapping functions to some extent (for example, the Trails B test is often described as an "executive function" task, although this task likely involves both working memory and cognitive flexibility. Not surprisingly, then, some authors label the function of certain tests differently, and this is particularly evident in meta-analyses of cognition. As we describe findings in this paper, we will use the terms proposed by the authors but will also identify key tests used to define a cognitive construct. With this background in mind, we turn to a discussion of cognitive deficits, then of emotion-related traits. Our hope is that those concise summaries provide evidence for the importance of both domains, but also specificity regarding the facets of emotion and cognition that are most impaired in BD. This specificity then guides our consideration of models that integrate cognition and emotion.
Topics: Bipolar Disorder; Cognition Disorders; Emotions; Humans; Neuropsychological Tests
PubMed: 29195773
DOI: 10.1016/j.cpr.2017.11.006 -
CNS Drugs Sep 2015Approximately 40% of patients with bipolar disorder experience mixed episodes, defined as a manic state with depressive features, or manic symptoms in a patient with... (Review)
Review
Approximately 40% of patients with bipolar disorder experience mixed episodes, defined as a manic state with depressive features, or manic symptoms in a patient with bipolar depression. Compared with bipolar patients without mixed features, patients with bipolar mixed states generally have more severe symptomatology, more lifetime episodes of illness, worse clinical outcomes and higher rates of comorbidities, and thus present a significant clinical challenge. Most clinical trials have investigated second-generation neuroleptic monotherapy, monotherapy with anticonvulsants or lithium, combination therapy, and electroconvulsive therapy (ECT). Neuroleptic drugs are often used alone or in combination with anticonvulsants or lithium for preventive treatment, and ECT is an effective treatment for mixed manic episodes in situations where medication fails or cannot be used. Common antidepressants have been shown to worsen mania symptoms during mixed episodes without necessarily improving depressive symptoms; thus, they are not recommended during mixed episodes. A greater understanding of pathophysiological processes in bipolar disorder is now required to provide a more accurate diagnosis and new personalised treatment approaches. Targeted, specific treatments developed through a greater understanding of bipolar disorder pathophysiology, capable of affecting the underlying disease processes, could well prove to be more effective, faster acting, and better tolerated than existing therapies, therefore providing better outcomes for individuals affected by bipolar disorder. Until such time as targeted agents are available, second-generation neuroleptics are emerging as the treatment of choice in the management of mixed states in bipolar disorder.
Topics: Antidepressive Agents; Bipolar Disorder; Clinical Trials as Topic; Databases, Bibliographic; Disease Management; Electroconvulsive Therapy; Humans
PubMed: 26369921
DOI: 10.1007/s40263-015-0275-6 -
Journal of Affective Disorders Jan 2015Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. This review aimed to examine the impact of cannabis use on the incidence of manic symptoms and on their occurrence in those with pre-existing bipolar disorder.
METHODS
A systematic review of the scientific literature using the PRISMA guidelines. PsychINFO, Cochrane, Scopus, Embase and MEDLINE databases were searched for prospective studies.
RESULTS
Six articles met inclusion criteria. These sampled 2391 individuals who had experienced mania symptoms. The mean length of follow up was 3.9 years. Studies support an association between cannabis use and the exacerbation of manic symptoms in those with previously diagnosed bipolar disorder. Furthermore, a meta-analysis of two studies suggests that cannabis use is associated with an approximately 3-fold (Odds Ratio: 2.97; 95% CI: 1.80-4.90) increased risk for the new onset of manic symptoms.
LIMITATIONS
We were only able to identify a small number of studies of variable quality, thus our conclusions remain preliminary.
CONCLUSIONS
Our findings whilst tentative, suggest that cannabis use may worsen the occurrence of manic symptoms in those diagnosed with bipolar disorder, and may also act as a causal risk factor in the incidence of manic symptoms. This underscores the importance of discouraging cannabis use among youth and those with bipolar disorder to help prevent chronic psychiatric morbidity. More high quality prospective studies are required to fully elucidate how cannabis use may contribute to the development of mania over time.
Topics: Adolescent; Adult; Aged; Bipolar Disorder; Cannabis; Humans; Marijuana Smoking; Middle Aged; Risk Factors; Young Adult
PubMed: 25285897
DOI: 10.1016/j.jad.2014.09.016 -
Australian Family Physician Sep 2013Bipolar disorder affects about 1% of Australians and impacts severely on relationships, careers and general functional capacity. General practitioners are central in the...
BACKGROUND
Bipolar disorder affects about 1% of Australians and impacts severely on relationships, careers and general functional capacity. General practitioners are central in the management of patients with bipolar disorder.
OBJECTIVE
To update clinicians on the recognition, diagnosis and management of bipolar disorder in light of recent research.
DISCUSSION
There is growing concern about the over-diagnosis of bipolar disorder, and increasing evidence that bipolar depression may present differently to unipolar depression. Antipsychotics are the initial agents of choice for the acute treatment of mania. For preventive treatment, lithium and atypical antipsychotics have the strongest evidence base. Lithium has been shown to be more effective than valproate. The main effect of lithium and most of the atypical antipsychotics is on prevention of manic relapse; only olanzapine and quetiapine also protect against depression. Lamotrigine is an agent with evidence for prevention of depressive relapse, but have minimal activity against mania. The role of antidepressants remains contentious, while there is strong support for quetiapine. Finally, there is growing evidence from randomised controlled trials of the benefit of psychological therapies in conjunction with medications.
Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Secondary Prevention
PubMed: 24024220
DOI: No ID Found -
Psychiatria Polska Dec 2022Bipolar affective disorder (BPAD) is a chronic mental disorder, characterised by mood swings, alternating between depression and manic or hypomanic episodes.... (Review)
Review
Bipolar affective disorder (BPAD) is a chronic mental disorder, characterised by mood swings, alternating between depression and manic or hypomanic episodes. Unfortunately, in some patients pharmacological treatment does not bring satisfactory results, and a certain group of patients shows resistance to treatment. Therefore, other treatment methods are sought after, including a change in diet. The most promising nutrition model is the ketogenic diet. In the presented case study of a male patient, thanks to the introduction of the ketogenic diet, full remission of the disease was achieved, doses of lamotrigine were reduced and quetiapine was completely discontinued. Previously, neither lamotrigine monotherapy nor combined treatment with quetiapine achieved euthymia. The effects of the diet may be related to, among others, the influence on ionic channels and increase in blood acidity (similarly to mood stabilisers), increase in gamma-aminobutyric acid (GABA) concentration, modulation of GABAA receptors and blocking of AMPA receptors by medium-chain fatty acids. The ketogenic diet influences glutamate metabolism and nerve cell metabolism, which uses ketone bodies as energy sources. Ketosis can also stimulate the biogenesis of mitochondria, improve brain metabolism, act as a neuroprotective factor, as well as increase glutathione synthesis and reduce oxidative stress. However, there is a need for carefully planned studies, with an appropriate representative group, to verify the potential benefits and risks of introducing the ketogenic diet in patients with BPAD.
Topics: Humans; Male; Bipolar Disorder; Lamotrigine; Diet, Ketogenic; Quetiapine Fumarate; Mood Disorders; Anticonvulsants
PubMed: 37098202
DOI: 10.12740/PP/OnlineFirst/136356 -
PloS One 2017Although cognitive behavioral therapy (CBT) is considered a promising adjuvant to pharmacotherapy for treating bipolar disorder (BD), its efficacy is unproven. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although cognitive behavioral therapy (CBT) is considered a promising adjuvant to pharmacotherapy for treating bipolar disorder (BD), its efficacy is unproven. The present review and meta-analysis evaluated the treatment outcomes of patients with BD treated with CBT plus medication and compared these data with the outcomes of those who received standard care alone.
METHODS
Electronic searches from inception to July 31, 2016, were performed using PubMed, Medline OVID, Cochrane Library, EMBASE, CINAHL plus, and PsycINFO. In the extensive electronic literature search, keywords such as "bipolar disorder," "manic-depressive psychosis," "bipolar affective disorder," "bipolar depression," "cognitive therapy," "cognitive-behavioral therapy," and "psychotherapy" were transformed into MeSH terms, and only randomized controlled trials (RCTs) were included. The pooled odds ratios (ORs) of relapse rates and Hedges's g, along with 95% confidence intervals (CIs), for the mean differences in the levels of depression, mania, and psychosocial functioning were calculated. Further subgroup analyses were conducted according to the characteristics of the CBT approaches, patients, and therapists, if the data were available.
RESULT
A total of 19 RCTs comprising 1384 patients with type I or II BD were enrolled in our systematic review and meta-analysis. The main analysis revealed that CBT could lower the relapse rate (pooled OR = 0.506; 95% CI = 0.278 -0.921) and improve depressive symptoms (g = -0.494; 95% CI = -0.963 to -0.026), mania severity (g = -0.581; 95% CI = -1.127 to -0.035), and psychosocial functioning (g = 0.457; 95% CI = 0.106-0.809).
CONCLUSIONS
CBT is effective in decreasing the relapse rate and improving depressive symptoms, mania severity, and psychosocial functioning, with a mild-to-moderate effect size. Subgroup analyses indicated that improvements in depression or mania are more potent with a CBT treatment duration of ≥90 min per session, and the relapse rate is much lower among patients with type I BD.
Topics: Bipolar Disorder; Cognitive Behavioral Therapy; Humans; Publication Bias; Randomized Controlled Trials as Topic; Social Behavior; Treatment Outcome
PubMed: 28472082
DOI: 10.1371/journal.pone.0176849 -
JAMA Psychiatry May 2020Behavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Behavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early intervention delays new mood episodes in high-risk youths.
OBJECTIVE
To determine whether family-focused therapy (FFT) for high-risk youths is more effective than standard psychoeducation in hastening recovery and delaying emergence of mood episodes during the 1 to 4 years after an active period of mood symptoms.
DESIGN, SETTINGS, AND PARTICIPANTS
This multisite randomized clinical trial included referred youths (aged 9-17 years) with major depressive disorder or unspecified (subthreshold) bipolar disorder, active mood symptoms, and at least 1 first- or second-degree relative with bipolar disorder I or II. Recruitment started from October 6, 2011, and ended on September 15, 2016. Independent evaluators interviewed participants every 4 to 6 months to measure symptoms for up to 4 years. Data analysis was performed from March 13 to November 3, 2019.
INTERVENTIONS
High-risk youths and parents were randomly allocated to FFT (12 sessions in 4 months of psychoeducation, communication training, and problem-solving skills training; n = 61) or enhanced care (6 sessions in 4 months of family and individual psychoeducation; n = 66). Youths could receive medication management in either condition.
MAIN OUTCOMES AND MEASURES
The coprimary outcomes, derived using weekly psychiatric status ratings, were time to recovery from prerandomization symptoms and time to a prospectively observed mood (depressive, manic, or hypomanic) episode after recovery. Secondary outcomes were time to conversion to bipolar disorder I or II and longitudinal symptom trajectories.
RESULTS
All 127 participants (82 [64.6%] female; mean [SD] age, 13.2 [2.6] years) were followed up for a median of 98 weeks (range, 0-255 weeks). No differences were detected between treatments in time to recovery from pretreatment symptoms. High-risk youths in the FFT group had longer intervals from recovery to the emergence of the next mood episode (χ2 = 5.44; P = .02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (χ2 = 4.44; P = .03; hazard ratio, 0.59; 95% CI, 0.35-0.97) than youths in enhanced care. Specifically, FFT was associated with longer intervals to depressive episodes (log-rank χ2 = 6.24; P = .01; hazard ratio, 0.53; 95% CI, 0.31-0.88) but did not differ from enhanced care in time to manic or hypomanic episodes, conversions to bipolar disorder, or symptom trajectories.
CONCLUSIONS AND RELEVANCE
Family skills-training for youths at high risk for bipolar disorder is associated with longer times between mood episodes. Clarifying the relationship between changes in family functioning and changes in the course of high-risk syndromes merits future investigation.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01483391.
Topics: Adolescent; Bipolar Disorder; Child; Disease Progression; Family Therapy; Female; Humans; Male; Mood Disorders; Psychotropic Drugs; Treatment Outcome
PubMed: 31940011
DOI: 10.1001/jamapsychiatry.2019.4520 -
Psychiatria Polska Oct 2023Bipolar affective illness (bipolar disorder - BD), also known as manic-depressive illness, is characterized by periodic opposite states of mood, activity, and motivation... (Review)
Review
Bipolar affective illness (bipolar disorder - BD), also known as manic-depressive illness, is characterized by periodic opposite states of mood, activity, and motivation (mania and depression) sometimes of extreme intensity. The development and maintenance of such states in evolution can betoken a possibility of their adaptive character, enabling adaptation to an unfavorable external situation (depression) and a mobilization to using resources when available (mania). In the article, the main focus is put on the evolutionary aspect of "bipolarity" and manic/hypomanic states. Molecular-genetic studies show that in evolution, the genes connected with a predisposition to BD have been conserved. In the paper, the evolutionary adaptive concepts connected with the functioning of Homo sapiens during the middle and late Pleistocene periods were discussed as well as the "mismatch" theories associated with not befitting brain functioning to contemporary conditions. The benefits of mania and hypomania, also in the context of their link to depression were delineated, indicating their relationship to the increase in reproductive success. They result from such features of mania/hypomania as increased exploratory, psychomotor and sexual activity, and prompt risk-taking. The reproductive success can be connected with hyperthymic and cyclothymic temperaments, most frequently occurring in subjects with BD. The hyperthymic temperament often leads to increased social status and a tendency to leadership, and the cyclothymic temperament can increase creativity. Examples of the relationship between manic/hypomanic states and the phenomenon of emigration as well as the advancement of American society are provided.
Topics: Humans; Bipolar Disorder; Mania; Temperament; Affect; Leadership
PubMed: 38345120
DOI: 10.12740/PP/159424 -
Danish Medical Journal Mar 2018Major reasons for the insufficient effects of current treatment options in bipolar disorder include delayed intervention for prodromal depressive and manic symptoms and... (Review)
Review
Major reasons for the insufficient effects of current treatment options in bipolar disorder include delayed intervention for prodromal depressive and manic symptoms and decreased adherence to psychopharmacological treatment. The reliance on subjective information and clinical evaluations when diagnosing and assessing the severity of depressive and manic symptoms calls for less biased and more objective markers. By using electronic devices, fine-grained data on complex psychopathological aspects of bipolar disorder can be evaluated unobtrusively over the long term. Moreover, electronic data could possibly represent candidate markers of diagnosis and illness activity in bipolar disorder and allow for early and individualized intervention for prodromal symptoms outside clinical settings. The present dissertation concerns the use of electronic monitoring as a marker and treatment intervention in bipolar disorder and investigated the scientific literature and body of evidence within the area, which includes ten original study reports and two systematic reviews, one of which included a meta-analysis, conducted by the author of the dissertation. Taken together, the literature presented in this dissertation illustrates that 1) smartphone-based electronic self-monitoring of mood seems to reflect clinically assessed depressive and manic symptoms and enables the long-term characterization of mood instability in bipolar disorder; 2) preliminary results suggest that smartphone-based automatically generated data (e.g. the number of text messages sent/day; the number of incoming and outgoing calls/day; the number of changes in cell tower IDs/day; and voice features) seem to reflect clinically assessed depressive and manic symptoms in bipolar disorder; 3) smartphone-based electronic self-monitoring had no effects on the severity of depressive and manic symptoms in bipolar disorder, according to a randomized controlled trial; and 4) electronic monitoring of psychomotor activity and heart rate variability seems to reflect illness activity in bipolar disorder and differentiate between patients with bipolar disorder and healthy control individuals. These findings point toward the usefulness of electronic monitoring as a marker of illness in bipolar disorder. Using electronic monitoring as a treatment intervention could provide innovative and novel interventions on-demand with a potential global reach, filling the gap between availability and the need for treatment. However, future studies using rigorous methodology and more randomized controlled trials that carefully investigate the positive effects and possible harmful effects of electronic monitoring in bipolar disorder are needed. In addition, patient safety, privacy issues, data security and legal aspects are major concerns that must be considered and addressed when using electronic monitoring.
Topics: Affect; Bipolar Disorder; Humans; Monitoring, Physiologic; Randomized Controlled Trials as Topic; Severity of Illness Index; Smartphone
PubMed: 29510813
DOI: No ID Found -
Psychiatria Danubina Oct 2023Bipolar disorder and Parkinson's disease are two distinct neurological conditions that share common features related to dopaminergic dysfunction. This article presents a... (Review)
Review
Bipolar disorder and Parkinson's disease are two distinct neurological conditions that share common features related to dopaminergic dysfunction. This article presents a comprehensive review of the existing literature to investigate the association between bipolar disorder and Parkinson's disease, focusing on the dopaminergic hypothesis and potential therapeutic options. The dopaminergic hypothesis suggests that both bipolar disorder and Parkinson's disease involve impairments in the nigrostriatal or mesolimbic dopaminergic pathways. Studies have demonstrated alterations in dopamine regulation during manic and depressive phases of bipolar disorder. Similarly, Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms. Recent analyses have highlighted a predisposition to Parkinson's disease in individuals with bipolar disorder. Longitudinal studies and meta-analyses have demonstrated an increased risk of developing Parkinson's disease in patients with bipolar disorder. However, differentiating idiopathic Parkinson's disease from parkinsonism induced by medications used in bipolar disorder can be challenging. Dopamine transporter (DAT) scans can aid in making a differential diagnosis. Treatment options for patients with both bipolar disorder and Parkinson's disease are limited. Neuroleptics, commonly used to manage psychotic symptoms in Parkinson's disease, may worsen motor symptoms and have limitations in bipolar disorder patients. Clozapine has shown efficacy in treating psychosis without worsening motor symptoms. Pimavanserin, an inverse agonist of the 5-HT2A receptor can offer new opportunities. However, its efficacy in bipolar disorder patients with Parkinson's disease remains unexplored. In conclusion, the association between bipolar disorder and Parkinson's disease is supported by the involvement of the dopaminergic system in both conditions. The identification of shared mechanisms opens new avenues for potential therapeutic interventions. Further research is needed to investigate the efficacy of pimavanserin and explore other treatment options for individuals with both bipolar disorder and Parkinson's disease.
Topics: Humans; Parkinson Disease; Bipolar Disorder; Drug Inverse Agonism; Piperidines; Dopamine
PubMed: 37800205
DOI: No ID Found