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JAMA Oct 2023Bipolar disorder affects approximately 8 million adults in the US and approximately 40 million individuals worldwide. (Review)
Review
IMPORTANCE
Bipolar disorder affects approximately 8 million adults in the US and approximately 40 million individuals worldwide.
OBSERVATIONS
Bipolar disorder is characterized by recurrent episodes of depression and mania or hypomania. Bipolar depressive episodes are similar to major depressive episodes. Manic and hypomanic episodes are characterized by a distinct change in mood and behavior during discrete time periods. The age of onset is usually between 15 and 25 years, and depression is the most frequent initial presentation. Approximately 75% of symptomatic time consists of depressive episodes or symptoms. Early diagnosis and treatment are associated with a more favorable prognosis. Diagnosis and optimal treatment are often delayed by a mean of approximately 9 years following an initial depressive episode. Long-term treatment consists of mood stabilizers, such as lithium, valproate, and lamotrigine. Antipsychotic agents, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine, are recommended, but some are associated with weight gain. Antidepressants are not recommended as monotherapy. More than 50% of patients with bipolar disorder are not adherent to treatment. Life expectancy is reduced by approximately 12 to 14 years in people with bipolar disorder, with a 1.6-fold to 2-fold increase in cardiovascular mortality occurring a mean of 17 years earlier compared with the general population. Prevalence rates of metabolic syndrome (37%), obesity (21%), cigarette smoking (45%), and type 2 diabetes (14%) are higher among people with bipolar disorder, contributing to the risk of early mortality. The annual suicide rate is approximately 0.9% among individuals with bipolar disorder, compared with 0.014% in the general population. Approximately 15% to 20% of people with bipolar disorder die by suicide.
CONCLUSIONS AND RELEVANCE
Bipolar disorder affects approximately 8 million adults in the US. First-line therapy includes mood stabilizers, such as lithium, anticonvulsants, such as valproate and lamotrigine, and atypical antipsychotic drugs, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine.
Topics: Humans; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Psychotropic Drugs
PubMed: 37815563
DOI: 10.1001/jama.2023.18588 -
World Psychiatry : Official Journal of... Oct 2023Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated...
Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.
PubMed: 37713549
DOI: 10.1002/wps.21120 -
Expert Opinion on Emerging Drugs Mar 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 3% of school-age children. The core symptoms are deficits in social communication... (Review)
Review
INTRODUCTION
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 3% of school-age children. The core symptoms are deficits in social communication and restricted and repetitive patterns of behavior. Associated problems in cognition, language, behavior, sleep and mood are prevalent. Currently, no established pharmacological treatment exists for core ASD symptoms. Risperidone and aripiprazole are used to manage associated irritability, but their effectiveness is limited and adverse events are common.
AREAS COVERED
This mini-review summarizes existing scientific literature and ongoing clinical trials concerning cannabinoid treatment for ASD. Uncontrolled case series have documented improvements in both core ASD symptoms and related behavioral challenges in children treated with cannabis extracts rich in cannabidiol (CBD). Placebo-controlled studies involving CBD-rich cannabis extracts and/or pure CBD in children with ASD have demonstrated mixed efficacy results. A similar outcome was observed in a placebo-controlled study of pure CBD addressing social avoidance in Fragile X syndrome. Importantly, these studies have shown relatively high safety and tolerability.
EXPERT OPINION
While current clinical data suggest the potential of CBD and CBD-rich cannabis extract in managing core and behavioral deficits in ASD, it is prudent to await the results of ongoing placebo-controlled trials before considering CBD treatment for ASD.
Topics: Child; Humans; Aripiprazole; Autism Spectrum Disorder; Cannabidiol; Cannabinoids; Irritable Mood; Randomized Controlled Trials as Topic
PubMed: 38226593
DOI: 10.1080/14728214.2024.2306290 -
Expert Opinion on Pharmacotherapy 2023Long-acting injectable antipsychotics (LAIs) are an effective, but potentially underutilized treatment option in schizophrenia and other severe mental illnesses.... (Review)
Review
INTRODUCTION
Long-acting injectable antipsychotics (LAIs) are an effective, but potentially underutilized treatment option in schizophrenia and other severe mental illnesses. Prescribing information typically focuses on how to initiate treatment from the corresponding oral formulations. However, in clinical practice other scenarios, such as switching from other oral antipsychotics or other LAIs, occur frequently, requiring guidance.
AREAS COVERED
Pharmacodynamic properties of antipsychotics and their relation to rebound symptoms. Pharmacokinetic properties of LAIs and their implications for switching approaches. Specific approaches to switching to LAIs.
EXPERT OPINION
The LAI landscape has evolved significantly in the last decade with more formulations available, longer dosing intervals, and extended indications. However, currently available LAIs have various shortcomings, e.g. short dosing intervals, need for oral supplementation, loading regimens, deep intramuscular injection and/or restricted indications. Recent improvements include a one-day initiation option for aripiprazole lauroxil, aripiprazole monohydrate once-monthly, risperidone in situ microparticles and subcutaneous risperidone. Future LAI developments should focus on longer dosing intervals, subcutaneous administration, expansion of LAIs beyond currently available antipsychotic agents and indications beyond schizophrenia and bipolar disorder. In the future, LAIs might become a first-line treatment after initial oral stabilization for chronic mental disorders with need for maintenance treatment and presence of significant non-adherence.
Topics: Humans; Antipsychotic Agents; Risperidone; Schizophrenia; Bipolar Disorder; Injections, Intramuscular; Delayed-Action Preparations
PubMed: 37345508
DOI: 10.1080/14656566.2023.2228686 -
The Medical Letter on Drugs and... Dec 2023
Topics: Humans; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors
PubMed: 38133585
DOI: 10.58347/tml.2023.1691a -
BMJ (Clinical Research Ed.) Aug 2023To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational... (Review)
Review
OBJECTIVE
To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs).
DESIGN
Umbrella review.
DATA SOURCES
PubMed, PsychInfo, Embase, up to 9 February 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted.
RESULTS
101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive).
CONCLUSIONS
Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events.
STUDY REGISTRATION
PROSPERO CRD42018093045.
FUNDING
None.
Topics: Adolescent; Adult; Female; Humans; Infant, Newborn; Pregnancy; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Hallucinogens; Randomized Controlled Trials as Topic; Risk Assessment; Sleepiness; Systematic Reviews as Topic; Meta-Analysis as Topic; Observational Studies as Topic
PubMed: 37648266
DOI: 10.1136/bmj-2022-072348 -
Acta Psychiatrica Scandinavica Jul 2023The augmentation of serotonin reuptake inhibitors (SRIs) can be achieved by add-on therapy with different pharmacological agents in obsessive-compulsive disorder (OCD)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The augmentation of serotonin reuptake inhibitors (SRIs) can be achieved by add-on therapy with different pharmacological agents in obsessive-compulsive disorder (OCD) for a better clinical outcome. This network meta-analysis (NMA) was conducted to evaluate and compare the effects of available augmentation agents for SRIs in OCD.
METHOD
The data was extracted from 59 relevant clinical trials after a literature search on MEDLINE/PubMed, Scopus, Cochrane databases and clinical trial registries. PRISMA guidelines were followed in data extraction, analysis and reporting. Random effects Bayesian NMA was done to pool the effects across the interventions for the change in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scoring from baseline to the end of the study. Network graph was built, consistency model was run, node splitting analysis was performed, treatments were ranked as per SUCRA score and meta-regression was done for refractoriness to SRIs and duration of augmentation therapy as the predictor variables.
RESULTS
The drugs showing significant reduction in YBOCS scoring were pregabalin (MD:-8.1;95% CrI: -16, -0.43), memantine (MD:-6.2;95% CrI: -9.9, -2.3), lamotrigine (MD:-6;95% CrI: -12, -0.47), ondansetron (MD:-5.7;95% CrI: -11, -0.67), granisetron (MD:-5.6;95% CrI: -11, -0.44), aripiprazole (MD:-5.4;95% CrI:-9.1, -1.6), risperidone (MD:-3.3;95% CrI: -6.4, -0.20) and topiramate (MD:-5.3;95% CrI: -9.6, -0.97). The node-split analysis showed that direct and indirect pooled effect sizes for all comparisons were comparable. Meta-regression showed a statistically non-significant association between YBOCS score reduction with the duration of augmentation therapy, but significant with SRI-refractory status. Finally, the results were sorted based on certainty of evidence.
CONCLUSION
Memantine was found to be most effective augmentation agent for SRIs in OCD, followed by lamotrigine, ondansetron and granisetron with moderate certainty of evidence. The augmentation agents showed better symptom reduction in patients with SRI-refractory OCD in comparison to non-refractory OCD.
PROSPERO REGISTRATION
CRD42022360110.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Ondansetron; Drug Therapy, Combination; Lamotrigine; Network Meta-Analysis; Bayes Theorem; Granisetron; Memantine; Obsessive-Compulsive Disorder; Treatment Outcome
PubMed: 37177823
DOI: 10.1111/acps.13568 -
The Medical Letter on Drugs and... Jun 2023
Topics: Humans; Alzheimer Disease; Quinolones; Thiophenes; Psychomotor Agitation; Antipsychotic Agents
PubMed: 37339089
DOI: 10.58347/tml.2023.1679b