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International Journal of Psychiatry in... Sep 2023Worldwide, there are now three marketed dopamine D2 partial agonists: aripiprazole, brexpiprazole and cariprazine. These three drugs share a number of properties other... (Review)
Review
Worldwide, there are now three marketed dopamine D2 partial agonists: aripiprazole, brexpiprazole and cariprazine. These three drugs share a number of properties other than their action at D2 receptors. Pharmacologically, they are 5HT2 antagonists and D3 and 5HT1A partial agonists but with little or no alpha-adrenergic, anticholinergic or antihistaminic activity. They also share a long duration of action. Clinically, D2 partial agonists are effective antipsychotics and generally have useful antimanic and antidepressant activity. They are usually well tolerated, causing akathisia and insomnia only at the start of treatment, and are non-sedating. These drugs also share a very low risk of increased prolactin and of weight gain and accompanying metabolic effects. They may also have a relatively low risk of tardive dyskinesia. There is some evidence that they are preferred by patients to dopamine antagonists. Individual dopamineD2 partial agonists have much in common and as a group they differ importantly from dopamine D2 antagonists. Dopamine D2 partial agonists should be considered a distinct class of antipsychotics.Key pointsD2 partial agonists share many pharmacological and clinical propertiesD2 partial agonists differ in several important respects from D2 antagonistsD2 partial agonists should be considered a discrete class of antipsychotics.
Topics: Humans; Antipsychotic Agents; Dopamine Agonists; Dopamine; Aripiprazole; Receptors, Dopamine D2
PubMed: 36495086
DOI: 10.1080/13651501.2022.2151473 -
The Medical Letter on Drugs and... Apr 2024
Topics: Humans; Bipolar Disorder; Antipsychotic Agents; Benzodiazepines
PubMed: 38576143
DOI: 10.58347/tml.2024.1699a -
Therapeutic Advances in... 2023This review presents a comprehensive guide for optimizing medication management in older adults with depression within an outpatient setting. Medication optimization... (Review)
Review
This review presents a comprehensive guide for optimizing medication management in older adults with depression within an outpatient setting. Medication optimization involves tailoring the antidepressant strategy to the individual, ensuring the administration of appropriate medications at optimal dosages. In the case of older adults, this process necessitates not only adjusting or changing antidepressants but also addressing the concurrent use of inappropriate medications, many of which have cognitive side effects. This review outlines various strategies for medication optimization in late-life depression: (1) Utilizing the full dose range of a medication to maximize therapeutic benefits and strive for remission. (2) Transitioning to alternative classes (such as a serotonin and norepinephrine reuptake inhibitor [SNRI], bupropion, or mirtazapine) when first-line treatment with selective serotonin reuptake inhibitors [SSRIs] proves inadequate. (3) Exploring augmentation strategies like aripiprazole for treatment-resistant depression. (4) Implementing measurement-based care to help adjust treatment. (5) Sustaining an effective antidepressant strategy for at least 1 year following depression remission, with longer durations for recurrent episodes or severe presentations. (6) Safely discontinuing anticholinergic medications and benzodiazepines by employing a tapering method when necessary, coupled with counseling about the benefits of stopping them. Additionally, this article explores favorable medications for depression, as well as alternatives for managing anxiety, insomnia, allergy, overactive bladder, psychosis, and muscle spasm in order to avoid potent anticholinergics and benzodiazepines.
PubMed: 38022834
DOI: 10.1177/20451253231212327 -
Journal of Neurology Dec 2023Our systematic review examines the effectiveness and safety of non-pharmacologic and pharmacologic interventions in preventing or treating traumatic brain injury...
BACKGROUND
Our systematic review examines the effectiveness and safety of non-pharmacologic and pharmacologic interventions in preventing or treating traumatic brain injury (TBI)-related delirium in acute care.
METHODS
We searched four electronic databases (MEDLINE, EMBASE, CENTRAL/CDSR, and PsycINFO) to identify randomized controlled trials (RCTs), quasi-experimental, and observational studies. Eligible studies included adults with TBI, at least one comparator group, delirium as an outcome and took place in acute care. Two reviewers independently completed all study screening, data abstraction, and risk of bias assessment using the Cochrane risk of bias 2 tool for RCTs or risk of bias in non-randomized studies-of interventions tool for observational studies. We implemented the PROGRESS-Plus framework to describe social determinants of health (SDoH) reporting.
RESULTS
We identified 20,022 citations, reviewed 301 in full text, and included eight studies in the descriptive synthesis. The mean age of study participants ranged from 32 to 62 years. 12.5% of included studies reported SDoH. Included studies had moderate-to-high risk of bias. Studies compared reorientation programs and an intervention bundle to usual care, but these interventions were not better than usual care in treating TBI-related delirium. Individual studies found that rosuvastatin and aripiprazole were more efficacious than placebo, and dexmedetomidine was more efficacious than propofol and haloperidol for preventing TBI-related delirium. No studies reported safety as the primary outcome.
CONCLUSIONS
We identified efficacious pharmacologic interventions for preventing TBI-related delirium, but these studies were at moderate-to-high risk of bias, which limits our confidence in these findings. Future studies should incorporate safety outcomes, and a diverse study population, including older adults.
Topics: Humans; Aged; Adult; Middle Aged; Haloperidol; Brain Injuries, Traumatic; Propofol; Delirium
PubMed: 37634162
DOI: 10.1007/s00415-023-11889-7 -
Biomolecules Aug 2023The concurrent use of several medications is a common practice in the treatment of complex psychiatric conditions. One such commonly used combination is aripiprazole...
The concurrent use of several medications is a common practice in the treatment of complex psychiatric conditions. One such commonly used combination is aripiprazole (ARI), an antipsychotic, and trazodone (TRZ), an antidepressant. In addition to their effects on dopamine and serotonin systems, both of these compounds are inhibitors of the 7-dehydrocholesterol reductase (DHCR7) enzyme. To evaluate the systemic and nervous system distribution of ARI and TRZ and their effects on cholesterol biosynthesis, adult mice were treated with both ARI and TRZ for 21 days. The parent drugs, their metabolites, and sterols were analyzed in the brain and various organs of mice using LC-MS/MS. The analyses revealed that ARI, TRZ, and their metabolites were readily detectable in the brain and organs, leading to changes in the sterol profile. The levels of medications, their metabolites, and sterols differed across tissues with notable sex differences. Female mice showed higher turnover of ARI and more cholesterol clearance in the brain, with several post-lanosterol intermediates significantly altered. In addition to interfering with sterol biosynthesis, ARI and TRZ exposure led to decreased ionized calcium-binding adaptor molecule 1 (IBA1) and increased DHCR7 protein expression in the cortex. Changes in sterol profile have been also identified in the spleen, liver, and serum, underscoring the systemic effect of ARI and TRZ on sterol biosynthesis. Long-term use of concurrent ARI and TRZ warrants further studies to fully evaluate the lasting consequences of altered sterol biosynthesis on the whole body.
Topics: Humans; Female; Male; Mice; Animals; Aripiprazole; Trazodone; Chromatography, Liquid; Polypharmacy; Tandem Mass Spectrometry; Cholesterol; Sterols; Brain; Phytosterols
PubMed: 37759721
DOI: 10.3390/biom13091321 -
Vaccine Jun 2023The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines have been approved for children and adolescents for protecting against SARS-CoV-2 infection. This...
INTRODUCTION
The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines have been approved for children and adolescents for protecting against SARS-CoV-2 infection. This longitudinal study aimed to compare adverse outcomes after SARS-CoV-2 vaccination in children with neurodevelopmental disorders (ND) (e.g., attention-deficit/hyperactivity disorder [ADHD], autism spectrum disorder [ASD], communication disorders, intellectual disability, and tic disorders) and healthy control children.
METHODS
A total of 1335 children who received the SARS-CoV-2 vaccination (762 children with ND and 573 healthy controls) were recruited. All subjects were followed-up for 180 days, and outcome events were defined as outpatient department (OPD) or emergency department (ER) visits during follow-up. Multivariate Cox proportional hazards regression models were used to identify the potential differences in outcomes between the propensity score-matched ND group (n = 311) and the control group (n = 311), and to explore the factors associated with outcomes among all children with ND (n = 762).
RESULTS
Compared with the control group, children with ND exhibited a higher likelihood of subsequent OPD or ER visits and paediatric neurology OPD visits after the first dose of vaccination. However, we found that only a small proportion of the children visited the OPD or ER because of adverse vaccination-related effects. Among all children with ND, those with communication disorders showed a higher likelihood of any OPD or ER visit. Paediatric neurology OPD visits were associated with communication disorders, intellectual disability, and methylphenidate and aripiprazole prescriptions. ADHD and ASD were not associated with adverse outcomes.
CONCLUSIONS
No specific ND diagnosis or medication use clearly increased the risk of adverse effects of SARS-CoV-2 vaccination. Children with ND can be reassured that the SARS-CoV-2 vaccination is a safe regimen to protect themselves.
Topics: Adolescent; Child; Humans; Autism Spectrum Disorder; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Drug-Related Side Effects and Adverse Reactions; Follow-Up Studies; Intellectual Disability; Longitudinal Studies; Neurodevelopmental Disorders; SARS-CoV-2; Vaccination
PubMed: 37271705
DOI: 10.1016/j.vaccine.2023.05.067 -
Psychiatry Research Feb 2024Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient.
Topics: Humans; Antipsychotic Agents; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia
PubMed: 38150810
DOI: 10.1016/j.psychres.2023.115637 -
Psychiatry Research Jul 2023Combination therapy with antipsychotics has been investigated for treating schizophrenia, and has shown clear advantages among non-invasive therapies. Transcutaneous... (Randomized Controlled Trial)
Randomized Controlled Trial
Combination therapy with antipsychotics has been investigated for treating schizophrenia, and has shown clear advantages among non-invasive therapies. Transcutaneous electrical acupoint stimulation (TEAS) is a novel non-invasive treatment with definite efficacy in treating mental disorders. The current study aimed to investigate the efficacy of TEAS in further improving the psychotic symptoms in patients with first-episode schizophrenia (FES) being treated with pharmacological drugs. This 8-week, preliminary, sham-controlled, randomized clinical trial was conducted in patients with FES to compare the efficacy of TEAS and sham TEAS in combination with aripiprazole treatment. The primary outcome was a change in the Positive and Negative Syndrome Scale (PANSS) score after ending the intervention (Week 8). A total of 49 participants completed the whole treatment cycle. The linear mixed-effects regression for PANSS indicated a significant time × group interaction (F(2, 116)=9.79, p <0.001). The PANSS score differed by 8.77 points (95% CI, -2.07 to -15.47 points; p=.01) between the TEAS group and the sham TEAS group after 8 weeks of treatment; this difference was significant. This study indicates that 8 weeks of TEAS combined with aripiprazole treatment can effectively treat FES. Thus, TEAS is an effective combination therapy to improve the psychiatric symptoms of FES.
Topics: Humans; Transcutaneous Electric Nerve Stimulation; Schizophrenia; Aripiprazole; Acupuncture Points; Antipsychotic Agents
PubMed: 37245485
DOI: 10.1016/j.psychres.2023.115255 -
Neuropsychopharmacology Reports Mar 2024This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy,... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.
METHODS
Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.
RESULTS
A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.
CONCLUSIONS
Overall BRE showed similar utility to ARI and a good risk-benefit balance.
Topics: Humans; Aripiprazole; Depressive Disorder, Major; Japan; Psychomotor Agitation; Network Meta-Analysis; Weight Gain; Randomized Controlled Trials as Topic; Thiophenes; Quinolones
PubMed: 38219278
DOI: 10.1002/npr2.12414 -
Journal of Affective Disorders Feb 2024Intravenous racemic ketamine is a promising treatment for treatment-resistant depression. However, its clinical utility compared with intranasal esketamine and the other... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy, tolerability and acceptability of intravenous racemic ketamine with intranasal esketamine, aripiprazole and lithium as augmentative treatments for treatment-resistant unipolar depression: A systematic review and network meta-analysis.
BACKGROUND
Intravenous racemic ketamine is a promising treatment for treatment-resistant depression. However, its clinical utility compared with intranasal esketamine and the other well-studied conventional pharmacological interventions (i.e., aripiprazole and lithium) as augmentative treatments for treatment-resistant unipolar depression in adults remains unclear. Therefore, we aimed to compare the efficacy, tolerability and acceptability of intravenous racemic ketamine with intranasal esketamine, aripiprazole and lithium under such conditions.
METHODS
The Cochrane Library, PubMed, CINHAL and ClinicalTrials.gov databases were systematically searched from their inception to 10 May 2023. Randomised controlled trials evaluating these drugs were included. A random-effects network meta-analysis was also performed.
RESULTS
In the primary analysis, all four drugs were significantly more effective than placebo. In addition, intravenous racemic ketamine was significantly more effective and acceptable than intranasal esketamine and aripiprazole. Intravenous racemic ketamine was not significantly different from placebo in tolerability, whereas intranasal esketamine and aripiprazole were significantly less tolerable than placebo. Lithium did not differ significantly from intravenous racemic ketamine in efficacy, tolerability and acceptability.
LIMITATIONS
The sample size of patients treated with intravenous racemic ketamine was small.
CONCLUSIONS
Intravenous racemic ketamine may be a better augmentative treatment for treatment-resistant unipolar depression than intranasal esketamine and aripiprazole. Whether intravenous racemic ketamine or lithium is superior is unclear currently. A larger head-to-head trial of intravenous racemic ketamine versus conventional augmentative treatments for treatment-resistant unipolar depression is needed.
Topics: Adult; Humans; Ketamine; Aripiprazole; Antidepressive Agents; Lithium; Network Meta-Analysis; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Depression
PubMed: 37949235
DOI: 10.1016/j.jad.2023.11.023