Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions

Elsayed, Omar H; Ercis, Mete; Pahwa, Mehak; Singh, Balwinder

doi:10.2147/ndt.s273503

Cited by 20 publications

(9 citation statements)

References 93 publications

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“…Bipolar disorder (BD) is a chronic illness with recurrent mood episodes/symptoms that can lead to significant functional impairment. 1,2 Best practices for the management of BD often focus on mood stabilizers for long-term stabilization. 3,4 The bipolar pharmacopoeia has evolved gradually over the last 25 years.…”

Section: Introductionmentioning

confidence: 99%

Patterns of pharmacotherapy for bipolar disorder: A GBC survey

et al. 2023

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ObjectivesTo understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized individuals with BD in North America, Europe, and Australia.MethodsData on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns.ResultsThis study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60%; vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort.ConclusionsMood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD.

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Section: Introductionmentioning

confidence: 99%

Patterns of pharmacotherapy for bipolar disorder: A GBC survey

et al. 2023

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“…Depression has also been associated with low levels of catalase, an enzyme responsible for the degradation of hydrogen peroxide into water and oxygen. In depressive situations, this enzyme is in deficit and, therefore, there is an accumulation of reactive oxygen species and consequently oxidative stress [ 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, although currently a lot of different treatment strategies exist, including pharmacological treatments, psychotherapies, and brain stimulation techniques, less than half of patients achieve a complete remission with the first treatment [ 17 , 26 , 27 ]. For these reasons, several solutions have been studied to fight depression and anxiety in a more effective and safe way.…”

Section: Introductionmentioning

confidence: 99%

Nanosystems, Drug Molecule Functionalization and Intranasal Delivery: An Update on the Most Promising Strategies for Increasing the Therapeutic Efficacy of Antidepressant and Anxiolytic Drugs

et al. 2023

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Depression and anxiety are high incidence and debilitating psychiatric disorders, usually treated by antidepressant or anxiolytic drug administration, respectively. Nevertheless, treatment is usually given through the oral route, but the low permeability of the blood–brain barrier reduces the amount of drug that will be able to reach it, thus consequently reducing the therapeutic efficacy. Which is why it is imperative to find new solutions to make these treatments more effective, safer, and faster. To overcome this obstacle, three main strategies have been used to improve brain drug targeting: the intranasal route of administration, which allows the drug to be directly transported to the brain by neuronal pathways, bypassing the blood–brain barrier and avoiding the hepatic and gastrointestinal metabolism; the use of nanosystems for drug encapsulation, including polymeric and lipidic nanoparticles, nanometric emulsions, and nanogels; and drug molecule functionalization by ligand attachment, such as peptides and polymers. Pharmacokinetic and pharmacodynamic in vivo studies’ results have shown that intranasal administration can be more efficient in brain targeting than other administration routes, and that the use of nanoformulations and drug functionalization can be quite advantageous in increasing brain–drug bioavailability. These strategies could be the key to future improved therapies for depressive and anxiety disorders.

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“…Schizophrenia is a chronic disorder, most commonly beginning in late adolescence and early adulthood, characterized by the presence of positive symptoms, such as hallucinations, delusions and significant and intense changes in thought and behavior (such as self or hetero-aggressiveness, agitation and bizarre attitudes), negative symptoms, such as dementia, impairment of interpersonal relationships, social isolation, apathy, alogia, anhedonia and lack of motivation and initiative to perform ordinary everyday activities, and cognitive symptoms, such as marked deficits in verbal and working memory, vigilance and attention [ 6 , 7 , 8 , 9 , 10 ]. In turn, bipolar disorder is also a chronic mental illness, typically characterized by either recurrent depressive episodes, including feelings of deep sadness and energy loss, or episodes of mania/hypomania, including periods during which people feel overly exhilarated, happy, irritable and/or energetic, with a reduced need to sleep [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Nanosystems for Brain Targeting of Antipsychotic Drugs: An Update on the Most Promising Nanocarriers for Increased Bioavailability and Therapeutic Efficacy

et al. 2023

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Orally administered antipsychotic drugs are the first-line treatment for psychotic disorders, such as schizophrenia and bipolar disorder. Nevertheless, adverse drug reactions jeopardize clinical outcomes, resulting in patient non-compliance. The design formulation strategies for enhancing brain drug delivery has been a major challenge, mainly due to the restrictive properties of the blood–brain barrier. However, recent pharmacokinetic and pharmacodynamic in vivo assays confirmed the advantage of the intranasal route when compared to oral and intravenous administration, as it allows direct nose-to-brain drug transport via neuronal pathways, reducing systemic side effects and maximizing therapeutic outcomes. In addition, the incorporation of antipsychotic drugs into nanosystems such as polymeric nanoparticles, polymeric mixed micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanoemulgels, nanosuspensions, niosomes and spanlastics, has proven to be quite promising. The developed nanosystems, having a small and homogeneous particle size (ideal for nose-to-brain delivery), high encapsulation efficiency and good stability, resulted in improved brain bioavailability and therapeutic-like effects in animal models. Hence, although it is essential to continue research in this field, the intranasal delivery of nanosystems for the treatment of schizophrenia, bipolar disorder and other related disorders has proven to be quite promising, opening a path for future therapies with higher efficacy.

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Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions

Cited by 20 publications

References 93 publications

Patterns of pharmacotherapy for bipolar disorder: A GBC survey

Patterns of pharmacotherapy for bipolar disorder: A GBC survey

Nanosystems, Drug Molecule Functionalization and Intranasal Delivery: An Update on the Most Promising Strategies for Increasing the Therapeutic Efficacy of Antidepressant and Anxiolytic Drugs

Nanosystems for Brain Targeting of Antipsychotic Drugs: An Update on the Most Promising Nanocarriers for Increased Bioavailability and Therapeutic Efficacy

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