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Medicine Sep 2023Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis.
BACKGROUND
Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD.
METHODS
We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model.
RESULTS
56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low.
CONCLUSION
Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.
Topics: Adult; Humans; Depressive Disorder, Major; Antipsychotic Agents; Network Meta-Analysis; Quetiapine Fumarate; Aripiprazole; Olanzapine; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 37746943
DOI: 10.1097/MD.0000000000034670 -
Oman Medical Journal Sep 2023In clinical experience, selecting atypical antipsychotics optimally balancing their benefits and potential side effects is seen to improve treatment adherence in...
OBJECTIVES
In clinical experience, selecting atypical antipsychotics optimally balancing their benefits and potential side effects is seen to improve treatment adherence in patients. This study aimed to compare the effectiveness and side effect profiles of aripiprazole and olanzapine in patients with psychotic disorders.
METHODS
In this double-blind clinical trial, the subjects were patients with psychotic disorders treated with aripiprazole and olanzapine. The subjects were randomly divided into two equally sized groups. One group was treated with olanzapine and the other group with aripiprazole. All participants were assessed using the positive and negative syndrome scale and side effects were monitored over a two-month follow-up period.
RESULTS
The participants comprised N = 76 patients (65 male; 11 female). Treatments with both aripiprazole (n = 38) and olanzapine (n = 38) were associated with a significant decrease in the severity of psychotic symptoms over the two-month treatment period. This decrease was achieved faster in the olanzapine group. There were no significant differences in the changes in body mass index, waist circumference, blood sugar, triglyceride, or cholesterol between the two groups. A qualitative difference between the groups was found in their total sleep duration.
CONCLUSIONS
Olanzapine was more effective than aripiprazole in reducing psychotic symptoms. There were no significant differences between the overall side effect profiles of the two drugs.
PubMed: 38249132
DOI: 10.5001/omj.2023.109 -
The Journal of Clinical Psychiatry Sep 2023Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for administration every 2 months. A randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and Efficacy of Aripiprazole 2-Month Ready-to-Use 960 mg: Secondary Analysis of Outcomes in Adult Patients With Schizophrenia in a Randomized, Open-label, Parallel-Arm, Pivotal Study.
Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for administration every 2 months. A randomized, open-label, 32-week trial evaluated the safety, tolerability, and pharmacokinetics of Ari 2MRTU 960 in clinically stable adults with schizophrenia or bipolar I disorder (per criteria). This secondary analysis evaluated the safety and efficacy of Ari 2MRTU 960 in the subpopulation of patients with schizophrenia. Patients were randomized to receive Ari 2MRTU 960 every 56 ± 2 days (4 injections scheduled) or aripiprazole once-monthly 400 mg (AOM 400) every 28 ± 2 days (8 injections scheduled). Data were collected during August 2019-July 2020 across 16 US sites. Primary endpoints included safety and tolerability, evaluated throughout. Secondary endpoints for efficacy in patients with schizophrenia included change from baseline at week 32 in Positive and Negative Syndrome Scale, Clinical Global Impression - Severity, and Subjective Well-being under Neuroleptic Treatment - Short Form scores, along with Clinical Global Impression - Improvement at week 32. Patients with schizophrenia were randomized to Ari 2MRTU 960 (n = 92) or AOM 400 (n = 93). The incidence of treatment-emergent adverse events (TEAEs) was similar between Ari 2MRTU 960 (66.3%) and AOM 400 (63.4%). The most frequently reported TEAE was increased weight (Ari 2MRTU 960: 21.7%; AOM 400: 18.3%). Patients in both treatment groups remained clinically stable throughout, with minimal change from baseline observed in efficacy parameters at week 32. Ari 2MRTU 960 was well tolerated in clinically stable patients with schizophrenia, with efficacy similar to AOM 400. ClinicalTrials.gov identifier: NCT04030143.
Topics: Humans; Adult; Aripiprazole; Schizophrenia; Antipsychotic Agents; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders
PubMed: 37672016
DOI: 10.4088/JCP.23m14873 -
Journal of Affective Disorders Mar 2024The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy, acceptability, tolerability, and safety for acute mania in children and adolescents.
METHOD
We systematically reviewed the double-blinded, randomized controlled trials (RCTs) comparing drugs or placebo for acute manic episodes of bipolar disorder in children and adolescents using PRISMA guidelines. We searched PubMed/MEDLINE, EMBASE, Web of Science, EBSCO, Scopus, the Cochrane Central Register of Controlled Trials, and https://clinicaltrials.gov from inception until November 20, 2022. Response to treatment was the primary outcome, and random-effects network meta-analyses were conducted (PROSPERO 2022: CRD42022367455).
RESULTS
Of 10,134 citations, we included 15 RCTs, including 2372 patients (47 % female), 15 psychotropic drugs, and the placebo. Risperidone 0.5-2.5 mg/day, aripiprazole 30 mg/day olanzapine, quetiapine 400 mg/day, quetiapine 600 mg/day, asenapine 5 mg/day, asenapine 10 mg, ziprasidone, and aripiprazole 10 mg were found to be effective (in comparison with placebo) in children and adolescents, respectively (τ = 0.0072, I = 10.2 %). The tolerability of aripiprazole 30 mg/day was lower than risperidone 0.5-2.5 mg/day and olanzapine. Oxcarbazepine had the highest discontinuation due to the adverse effects risk ratio.
LIMITATIONS
Efficacy ranking of the treatments could be performed by evaluating relatively few RCT results, and only monotherapies were considered.
CONCLUSIONS
Efficacy, acceptability, tolerability, and safety are changing with the doses of antipsychotics for children and adolescents with acute bipolar manic episodes. Drug selection and optimum dosage should be carefully adjusted in children and adolescents.
Topics: Humans; Adolescent; Adult; Child; Risperidone; Olanzapine; Aripiprazole; Bipolar Disorder; Quetiapine Fumarate; Mania; Network Meta-Analysis; Antipsychotic Agents; Dibenzocycloheptenes
PubMed: 38211745
DOI: 10.1016/j.jad.2024.01.067 -
Expert Review of Neurotherapeutics 2023Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder that affects a significant number of individuals worldwide. Major depressive disorder (MDD) is... (Review)
Review
INTRODUCTION
Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder that affects a significant number of individuals worldwide. Major depressive disorder (MDD) is among the most common comorbidities reported in people with OCD. The emergence of MDD in individuals with OCD can be attributed to the increased severity of OCD symptoms and their profound impact on daily functioning. Depressive symptoms can also modify the course of OCD.
AREAS COVERED
In this review, the authors explore potential shared neurobiological mechanisms that may underlie both OCD and MDD, such as disturbed sleep patterns, immunological dysregulations, and neuroendocrine changes. Furthermore, they address the challenges clinicians face when managing comorbid OCD and MDD. The authors also discuss a range of treatment options for OCD associated with MDD, including augmentation strategies for serotonin reuptake inhibitors (e.g. aripiprazole), psychotherapy (especially CBT/EPR), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and deep brain stimulation (DBS).
EXPERT OPINION
Although there is no 'rule of thumb' or universally acceptable strategy in the treatment of OCD comorbid with MDD, many clinicians, including the authors, tend to adopt a unique transdiagnostic approach to the treatment of OCD and related disorders, focusing on strategies known to be effective across diagnoses. Nevertheless, the existing 'cisdiagnostic approaches' still retain importance, i.e. specific therapeutic strategies tailored for more severe forms of individual disorders.
Topics: Humans; Depressive Disorder, Major; Depression; Obsessive-Compulsive Disorder; Transcranial Magnetic Stimulation; Deep Brain Stimulation; Treatment Outcome
PubMed: 37811649
DOI: 10.1080/14737175.2023.2265066 -
International Journal of Psychiatry in... Nov 2023The aim of this review is to analyse the literature regarding studies centred on the clinical outcome of individuals affected by schizophrenia and treated with various... (Review)
Review
OBJECTIVE
The aim of this review is to analyse the literature regarding studies centred on the clinical outcome of individuals affected by schizophrenia and treated with various antipsychotics, and then switched to orally administered partial D2-dopamine agonists (PD2A): Aripiprazole (ARI), brexpiprazole (BREX) or cariprazine (CARI).
METHOD
A PubMed literature search was performed on 16 February 2021, and updated on Jan 26, 2022 for literature on antipsychotic switching in individuals affected by schizophrenia. Literature was included from 2002 onward. Six strategies were defined: Abrupt, gradual and cross-taper switch, and 3 hybrid strategies. The primary outcome was all-cause discontinuation rate per switch strategy per goal medication.
RESULTS
In 10 reports on switching to ARI, 21 studies with different strategies were described, but there were only 4 reports and 5 strategies on switching to BREX. Only one study about CARI was included, but it was not designed as a switch study. The studies are difficult to compare due to differences in methodology, previous antipsychotic medication, doses of the introduced P2DA and study duration.
CONCLUSION
This analysis did not reveal evidence for a preferable switching strategy. A protocol should be developed which defines optimal duration, instruments to be used, and the timing of the exams.KEY MESSAGESMost switch studies on partial D2-agonists focus on ARI, with only a few on BREX, while little is known about the clinical outcome of switching individuals to CARIThere is a wide variation of possible switch methods: Abrupt switch - gradual switch - cross-tapering switch - hybrid strategies including plateau switchThe protocols used differ considerably between the studies. A strict comparison between the studies is difficult, for which reason the present evidence does not support an unambiguous preference for a particular switch strategy.From a methodological point of view, a standardised clinical protocol should be developed to allow comparisons between studies regarding the clinical outcome of individuals switched from one antipsychotic drug to another.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Dopamine Agonists; Dopamine; Aripiprazole
PubMed: 37428441
DOI: 10.1080/13651501.2023.2231047 -
Cureus Jan 2024Antipsychotics are considered a gold standard treatment for schizophrenia. However, there is considerable variation in antipsychotic medication choice. Factors...
Antipsychotics are considered a gold standard treatment for schizophrenia. However, there is considerable variation in antipsychotic medication choice. Factors considered involved include symptomatology, prior response, and adverse reactions. This case report presents a 38-year-old male patient with schizophrenia in acute psychosis refractory to several antipsychotics. Hypotheses for the mechanism of action of antipsychotics and psychopharmacology are discussed, and treatment resistance is defined. The patient's psychiatric, medical, and social history and past antipsychotic medications are reviewed. Afterward, the rationale for initiating perphenazine is discussed, and the patient's improvement with this medication is examined. Current literature on perphenazine's efficacy is also reviewed and discussed alongside its limitations.
PubMed: 38313962
DOI: 10.7759/cureus.51593 -
Indian Journal of Psychiatry Oct 2023Schizophrenia causes significant neurocognitive impairment. Treatment with antipsychotics leads to improvement in psychopathology and neurocognitive functions.
BACKGROUND
Schizophrenia causes significant neurocognitive impairment. Treatment with antipsychotics leads to improvement in psychopathology and neurocognitive functions.
AIM
To see comparative effectiveness of aripiprazole and olanzapine on neurocognitive profile of patients with schizophrenia.
MATERIALS AND METHODS
This was a comparative, prospective, and interventional study. Patients with schizophrenia as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), were assessed on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests at baseline. Patients were randomly assigned to aripiprazole (10-30 mg per day, orally) and olanzapine (5-20 mg per day, orally) groups on the basis of computer-generated random table number. Patients were reassessed at 10 weeks.
RESULTS
A total of 40 patients completed the study duration of 10 weeks. At baseline, the majority of patients showed significant impairment in one or more domains of neurocognition. Both aripiprazole and olanzapine led to improvement in psychiatric symptoms as well as neurocognitive profile. Aripiprazole treatment leads to significant improvement in mental speed as compared to olanzapine. A highly significant decrease in the value of the Stroop effect indicates improvement ( = 0.000**) with aripiprazole and visual-spatial constructive ability ( < 0.001). The olanzapine group showed highly significant improvement in performance of category fluency ( < 0.01) and verbal fluency ( < 0.01).
CONCLUSION
The study concludes that aripiprazole and olanzapine have strong potential to improve specific domains of neurocognitive profile.
PubMed: 38108052
DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_303_23 -
Life (Basel, Switzerland) Jun 2024Microglia are the primary innate immune cells of the central nervous system and extensively contribute to brain homeostasis. Dysfunctional or excessive activity of...
Prenatal Immune Challenge Differentiates the Effect of Aripiprazole and Risperidone on CD200-CD200R and CX3CL1-CX3CR1 Dyads and Microglial Polarization: A Study in Organotypic Cortical Cultures.
Microglia are the primary innate immune cells of the central nervous system and extensively contribute to brain homeostasis. Dysfunctional or excessive activity of microglia may be associated with several neuropsychiatric disorders, including schizophrenia. Therefore, we examined whether aripiprazole and risperidone could influence the expression of the and axes, which are crucial for the regulation of microglial activity and interactions of these cells with neurons. Additionally, we evaluated the impact of these drugs on microglial pro- and anti-inflammatory markers (, , , , , , and ) and cytokine release (IL-6, IL-10). The research was executed in organotypic cortical cultures (OCCs) prepared from the offspring of control rats (control OCCs) or those exposed to maternal immune activation (MIA OCCs), which allows for the exploration of schizophrenia-like disturbances in animals. All experiments were performed under basal conditions and after additional stimulation with lipopolysaccharide (LPS), following the "two-hit" hypothesis of schizophrenia. We found that MIA diminished the mRNA level of and affected the OCCs' response to additional LPS exposure in terms of this parameter. LPS downregulated the expression and profoundly changed the mRNA levels of pro- and anti-inflammatory microglial markers in both types of OCCs. Risperidone increased expression in MIA OCCs, while aripiprazole treatment elevated the gene levels of the dyad in control OCCs. The antipsychotics limited the LPS-generated increase in the expression of proinflammatory factors ( and ) and enhanced the mRNA levels of anti-inflammatory components ( and ) of microglial polarization, mostly in the absence of the MIA procedure. Finally, we observed a more pronounced modulating impact of aripiprazole on the expression of pro- and anti-inflammatory cytokines when compared to risperidone in MIA OCCs. In conclusion, our data suggest that MIA might influence microglial activation and crosstalk of microglial cells with neurons, whereas aripiprazole and risperidone could beneficially affect these changes in OCCs.
PubMed: 38929704
DOI: 10.3390/life14060721 -
International Review of Neurobiology 2024Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in... (Review)
Review
Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.
Topics: Humans; Alcoholism; Acamprosate; Naltrexone; Disulfiram; Sodium Oxybate; Baclofen; Drug Repositioning; Substance Withdrawal Syndrome; Alcohol Drinking
PubMed: 38555115
DOI: 10.1016/bs.irn.2024.02.002