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Journal of Affective Disorders Jul 2024Intravenous (IV) racemic ketamine and intranasal (IN) esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). This systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Intravenous (IV) racemic ketamine and intranasal (IN) esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). This systematic review aims to evaluate the efficacy and safety of ketamine and esketamine at various dosages for depression.
METHODS
We included randomized controlled trials (RCTs) with parallel group dose comparison of ketamine and esketamine for depression/TRD. Ovid Medline, Embase, PsycINFO, Scopus and Cochrane databases were searched. Standardized mean differences were calculated using Hedges'-g to complete random effects meta-analysis. The efficacy outcomes were changes in depression outcomes for IV ketamine and IN esketamine respectively. Safety was assessed by reported adverse effects.
RESULTS
A random effects meta-analysis of studies (n = 12) showed efficacy in reducing depression symptoms with IV ketamine (Hedges'g = 1.52 [0.98-2.22], Z = 4.23, p < 0.001) and IN esketamine (Hedges' g = 0.31 [0.18-0.44], Z = 4.53, P < 0.001) compared to control/placebo. Treatment response was observed at IV ketamine doses ≤0.2 mg/kg, >0.2-0.5 mg/kg and > 0.5 mg/kg. Higher IV ketamine doses (>0.5 mg/kg) did not lead to greater treatment response. Esketamine doses of 56-84 mg were superior to 28 mg dose.
LIMITATIONS
Overall quality of evidence was low and limited by small number of studies. Publication bias was high.
CONCLUSIONS
This meta-analysis suggests that IV ketamine may be efficacious at doses as low as 0.2 mg/kg, with increasing dose response at 0.5 mg/kg, without demonstrable increased benefit at 1 mg/kg, based on a small number of studies. Efficacy for IN esketamine increases with doses above 28 mg with best response being found between 56 and 84 mg for reducing depressive symptoms.
Topics: Ketamine; Humans; Administration, Intranasal; Depressive Disorder, Major; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Administration, Intravenous; Treatment Outcome; Dose-Response Relationship, Drug; Randomized Controlled Trials as Topic
PubMed: 38537759
DOI: 10.1016/j.jad.2024.03.137 -
Neurology Apr 2024To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal...
BACKGROUND AND OBJECTIVES
To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal neurodevelopmental outcomes, focusing on social, emotional, behavioral, and adaptive domains of human function, and the frequency of neurodevelopmental and psychiatric disorders in ASM-exposed offspring.
METHODS
Electronic searches of MEDLINE, PsychINFO, and EMBASE were conducted and limited to studies published between 1990 and 2023 in English. Studies were eligible if they prospectively or retrospectively reported neurodevelopmental outcomes of ASM-exposed offspring. The Newcastle-Ottawa scale was used to conduct methodologic quality assessments of included studies, and a narrative synthesis integrated the review findings.
RESULTS
Forty-three studies were included. Valproate has been consistently associated with a 2- to 4-fold increased risk of autism spectrum disorder (ASD), 2- to 5-fold increased risk of intellectual disability (ID), and poor adaptive functioning. Growing evidence indicates that topiramate is associated with a 2-fold increased risk of ASD and 3- to 4-fold increased risk of ID. The risks of adverse neurodevelopmental outcomes for valproate and topiramate seem to be dose dependent. Phenobarbital has been suggested to be associated with deleterious neurodevelopmental effects, but data are limited. Levetiracetam has recently been linked with an increased risk of attention deficit hyperactivity disorder and anxiety disorders in a single study. Carbamazepine has been associated with variable neurodevelopmental outcomes. Lamotrigine seems to be "safe" in terms of postnatal neurodevelopment. Data for oxcarbazepine, phenytoin, and clonazepam are limited but seem to have little-to-no risk of adverse outcomes. Evidence for the remaining ASMs, including gabapentin, pregabalin, lacosamide, zonisamide, clobazam, perampanel, ethosuximide, or brivaracetam, is lacking. Several methodologic limitations impeded data synthesis, including heterogeneity in outcome measures and small samples of monotherapy exposures.
DISCUSSION
The findings of this review support the conclusion that valproate and topiramate use during pregnancy is associated with a significantly increased risk of neurodevelopmental effects on the fetus. Apart from lamotrigine, which seems to be free of adverse neurodevelopmental effects, data for the other ASMs are mixed or inadequate to draw definite conclusions. Further research into the neurodevelopmental effects of prenatal exposure to ASMs, including most newer agents, is much needed.
Topics: Pregnancy; Female; Humans; Valproic Acid; Lamotrigine; Topiramate; Autism Spectrum Disorder; Retrospective Studies; Anticonvulsants
PubMed: 38531021
DOI: 10.1212/WNL.0000000000209175 -
Pharmacogenetics and Genomics Jul 2024This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal... (Review)
Review
PURPOSE
This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
METHODS
Pubmed, Scopus and EMBASE were searched for eligible reviews in May 2023. Two authors independently screened titles and abstracts and assessed full-text reviews for eligibility. The quality of meta-analyses and case-control studies was appraised with Assessing the Methodological Quality of Systematic Reviews 2 and Newcastle-Ottawa Scale, respectively. Narrative summaries of each antiepileptic drug were analyzed. Preestablished protocol was registered on the International Prospective Register of Systematic Reviews Registry(ID: CRD42023403957).
RESULTS
Included studies are systematic reviews, meta-analyses and case-control studies evaluating the association of HLA-B*1502 allele with the following antiepileptics. Seven meta-analyses for carbamazepine, three meta-analyses for lamotrigine (LTG), three case-control studies for oxcarbazepine, nine case-control studies for phenytoin and four case-control studies for phenobarbitone were included. The findings of this umbrella review suggest that there is a strong association between HLA-B-1502 with SJS/TEN for carbamazepine and oxcarbazepine and a milder association for lamotrigine and phenytoin.
CONCLUSION
In summary, although HLA-B*1502 is less likely to be associated with phenytoin or lamotrigine-induced SJS/TEN compared to carbamazepine-induced SJS/TEN, it is a significant risk factor that if carefully screened, could potentially reduce the development of SJS/TEN. In view of potential morbidity and mortality, HLA-B*1502 testing may be beneficial in patients who are initiating lamotrigine/phenytoin therapy. However, further studies are required to examine the association of other alleles with the development of SJS/TEN and to explore the possibility of genome-wide association studies before initiation of treatment.
Topics: Stevens-Johnson Syndrome; Humans; Anticonvulsants; HLA-B15 Antigen; Carbamazepine; Lamotrigine; Genetic Predisposition to Disease; Alleles
PubMed: 38527170
DOI: 10.1097/FPC.0000000000000531 -
Schizophrenia Bulletin Apr 2024People with first-episode psychosis (FEP) in low- and lower-middle-income countries (LMIC) experience delays in receiving treatment, resulting in poorer outcomes and...
BACKGROUND AND HYPOTHESIS
People with first-episode psychosis (FEP) in low- and lower-middle-income countries (LMIC) experience delays in receiving treatment, resulting in poorer outcomes and higher mortality. There is robust evidence for effective and cost-effective early intervention in psychosis (EIP) services for FEP, but the evidence for EIP in LMIC has not been reviewed. We aim to review the evidence on early intervention for the management of FEP in LMIC.
STUDY DESIGN
We searched 4 electronic databases (Medline, Embase, PsycINFO, and CINAHL) to identify studies describing EIP services and interventions to treat FEP in LMIC published from 1980 onward. The bibliography of relevant articles was hand-searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.
STUDY RESULTS
The search strategy produced 5074 records; we included 18 studies with 2294 participants from 6 LMIC countries. Thirteen studies (1553 participants) described different approaches for EIP. Pharmacological intervention studies (n = 4; 433 participants) found a high prevalence of metabolic syndrome among FEP receiving antipsychotics (P ≤ .005). One study found a better quality of life in patients using injectables compared to oral antipsychotics (P = .023). Among the non-pharmacological interventions (n = 3; 308 participants), SMS reminders improved treatment engagement (OR = 1.80, CI = 1.02-3.19). The methodological quality of studies evidence was relatively low.
CONCLUSIONS
The limited evidence showed that EIP can be provided in LMIC with adaptations for cultural factors and limited resources. Adaptations included collaboration with traditional healers, involving nonspecialist healthcare professionals, using mobile technology, considering the optimum use of long-acting antipsychotics, and monitoring antipsychotic side effects.
Topics: Humans; Psychotic Disorders; Developing Countries; Early Medical Intervention; Antipsychotic Agents
PubMed: 38525604
DOI: 10.1093/schbul/sbae025 -
Addiction (Abingdon, England) Jul 2024To conduct a systematic review and meta-analysis and pool the incremental net benefits (INBs) of varenicline compared with behaviour support with bupropion or nicotine... (Meta-Analysis)
Meta-Analysis Review
AIMS
To conduct a systematic review and meta-analysis and pool the incremental net benefits (INBs) of varenicline compared with behaviour support with bupropion or nicotine replacement therapy (NRT), behaviour support alone and unaided cessation in adult smokers making a first-time attempt to quit.
METHODS
A search for economic evaluation studies was conducted from inception to 30 September 2022, on PubMed, Embase, Cost-Effectiveness Analysis (CEA) Registry by Tufts Medical Centre, EconLit and the NHS Economic Evaluation Database (NHS EED). Eligible studies were included if they were (1) conducted among adults ages 18 years old and older who were smokers attempting to quit for the first time; (2) compared varenicline to behaviour support with bupropion or NRT, behaviour support alone and unaided cessation; and (3) performed a CEA or cost-utility analysis. The INBs were calculated and pooled across studies stratified by country income level and study perspective using the random-effects model. Statistical heterogeneity between studies was assessed using the I statistic and Cochrane Q statistic.
RESULTS
Of the 1433 identified studies, 18 studies were included in our review. Our findings from healthcare system/payer perspective suggested that the use of varenicline is statistically significantly cost-effective compared with bupropion (pooled INB, $830.75 [95% confidence interval, $208.23, $1453.28]), NRTs ($636.16 [$192.48, $1079.84]) and unaided cessation ($4212.35 [$1755.79, $6668.92]) in high-income countries. Similarly, varenicline is also found to be cost-effective compared to bupropion ($2706.27 [$1284.44, $4128.11]), NRTs ($3310.01 [$1781.53, $4838.50]) and behavioural support alone ($5438.22 [$4105.99, $6770.46]) in low- and middle-income countries.
CONCLUSION
Varenicline is cost-effective as a smoking cessation aid when compared with behavioural support with bupropion or nicotine replacement therapies and behavioural support alone in both high-income countries and low- and middle-income countries, from the healthcare system/payer perspective in adult smokers who attempt to quit for the first time.
Topics: Humans; Varenicline; Smoking Cessation; Cost-Benefit Analysis; Smoking Cessation Agents; Bupropion; Tobacco Use Cessation Devices; Behavior Therapy; Adult
PubMed: 38520121
DOI: 10.1111/add.16464 -
Expert Opinion on Pharmacotherapy Mar 2024We systematically reviewed extant studies evaluating the efficacy and tolerability of xanomeline and xanomeline-trospium (KarXT) for treatment of adults with...
INTRODUCTION
We systematically reviewed extant studies evaluating the efficacy and tolerability of xanomeline and xanomeline-trospium (KarXT) for treatment of adults with schizophrenia.
METHODS
In accordance with PRISMA guidelines, articles were systematically searched for in databases and clinical trial registries.
RESULTS
A total of 4 preclinical trials and 3 randomized controlled trials (RCTs) were included in this review. A 4-week RCT observed a difference of 24.0 points (SD 21.0) in the Positive and Negative Syndrome Scale (PANSS) total score between xanomeline and placebo groups ( = 0.039). A 5-week RCT observed PANSS total score changes from baseline to week 5, including -17.4 and -5.9 points in KarXT and placebo groups, respectively (LSMD -11.6 points; 95% CI -16.1 to -7.1; < 0.001; d = 0.75). Another 5-week RCT observed PANSS total score changes from baseline to week 5, including -21.2 (SE 1.7) and -11.6 (SE 1.6) points in KarXT and placebo groups, respectively (LSMD -9.6; 95% CI -13.9 to -5.2; < 0.0001; d = 0.61). Side effects include constipation, nausea, vomiting, dyspepsia, and dry mouth.
CONCLUSION
KarXT offers an innovative non-D2 blocking approach, representing a promising treatment avenue for schizophrenia.
Topics: Adult; Animals; Humans; Antipsychotic Agents; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 38515004
DOI: 10.1080/14656566.2024.2334424 -
Journal of Affective Disorders Jun 2024The impacts of antidepressant pharmacotherapies on cardiovascular risk are unclear. We completed a systematic review with meta-analysis to assess the effect of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The impacts of antidepressant pharmacotherapies on cardiovascular risk are unclear. We completed a systematic review with meta-analysis to assess the effect of paroxetine on heart rate variability (HRV) in patients with major depressive disorder (MDD).
METHODS
The searches were accomplished via EMBASE, MEDLINE/PubMed (using the National Library of Medicine), Cochrane Library, CINAHL, Scopus, and Web of Science databases. We included non-blind, single, or double-blind randomized control trials in patients older than 18 diagnosed with MDD. Paroxetine needs to be enforced as a chronic therapeutic medication. We included individual studies that investigated resting HRV.
RESULTS
We documented 402 studies, only following screening and eligibility phases; only six were included (five studies in the meta-analysis). No significant change was noticed for the SDNN index: subtotal = 8.23 [CI: -2.17, 18.63], p = 0.12, I2 = 54 % (very low quality of evidence). A significant change was distinguished for the LF index: subtotal = 0.74 [CI: 0.33, 1.15], p = 0.0004, I2 = 0 % (low quality of evidence). A significant alteration was perceived for the HF index: subtotal = 0.33 [CI: 0.06, 0.6], p = 0.02, I2 = 0 % (low quality of evidence).
CONCLUSION
Meta-analysis demonstrated that paroxetine could advance HRV in MDD patients. Nevertheless, our supposition is founded only on statistical analysis and the very low quality of evidence breakdown reinforces the necessity for further studies to confirm or reject this theory.
Topics: Humans; Paroxetine; Depressive Disorder, Major; Heart Rate; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 38513773
DOI: 10.1016/j.jad.2024.03.071 -
Asian Journal of Psychiatry May 2024Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD.... (Meta-Analysis)
Meta-Analysis Review
Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace.
METHODS
PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes.
RESULTS
A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo.
CONCLUSION
Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.
Topics: Humans; Randomized Controlled Trials as Topic; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Piperazines; Drug Therapy, Combination; Antidepressive Agents; Outcome Assessment, Health Care
PubMed: 38513509
DOI: 10.1016/j.ajp.2024.104005 -
Clinics (Sao Paulo, Brazil) 2024The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic review and meta-analysis, the authors evaluate the efficacy and side effects of olanzapine as a prophylactic antiemetic in adult patients who undergo general anesthesia and assess adverse effects.
METHODS
A systematic search was done on electronic bibliographic databases in July 2023. Randomized controlled trials of olanzapine as a prophylactic antiemetic for PONV in adults who underwent general anesthesia were included. The authors excluded non-RCTs and retracted studies. The authors set no date of publication or language limits. The outcomes were the incidence of PONV within 24 h postoperatively and the safety of olanzapine. The risk of bias was assessed according to the tool suggested by the National Heart, Lung, and Blood Institute.
RESULTS
Meta-analysis included 446 adult patients. Olanzapine reduced on average 38 % the incidence of PONV. The estimated risk ratio (95 % CI) of olanzapine versus control was 0.62 (0.42-0.90), p = 0.010, I = 67 %. In the subgroup meta-analysis, doses of olanzapine (10 mg) reduced on average 49 % of the incidence of PONV (RR = 0.51 [0.34-0.77], p = 0.001, I = 31 %).
CONCLUSIONS
This systematic review with meta-analysis indicated that olanzapine as a prophylactic antiemetic alone or combined with other antiemetic agents reduced the incidence of postoperative nausea and vomiting. However, this conclusion must be presented with some degree of uncertainty due to the small number of studies included. There was a lack of any evidence to draw conclusions on side effects.
Topics: Adult; Humans; Antiemetics; Postoperative Nausea and Vomiting; Olanzapine; Anesthesia, General
PubMed: 38513297
DOI: 10.1016/j.clinsp.2024.100345 -
Systematic Reviews Mar 2024Antidepressants, noninvasive brain stimulation (NIBS), and their combination are commonly used in routine clinical practice. Nevertheless, there is a continuous dispute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antidepressants, noninvasive brain stimulation (NIBS), and their combination are commonly used in routine clinical practice. Nevertheless, there is a continuous dispute regarding whether the effectiveness of NIBS in combination with antidepressants exceeds that of antidepressants alone. This meta-analysis aimed to evaluate the existing evidence and draw a definitive conclusion on this issue.
METHODS
We conducted a comprehensive search of five databases: Embase, PubMed, Web of Science, SinoMed, and the Cochrane Database of Randomized Controlled Trials. The search was conducted until October 6, 2023. The primary outcomes were the pre- and post-intervention depression and anxiety scores. Secondary outcomes included dropout rates, response rates, and certain levels of neurotransmitters [ 5-hydroxytryptamine (5-HT), dopamine (DA), and gamma-aminobutyric acid (GABA)] at the end of the intervention. Subgroup, meta-regression, and sensitivity analyses were performed to explore the sources of heterogeneity. The data were analysed using R 4.2.2.
RESULTS
We included 18 RCTs [1357 participants; 11 studies used repetitive transcranial magnetic stimulation (rTMS) and 7 studies used transcranial direct current stimulation (tDCS)]. The follow-up duration varied from two weeks to three months. Overall, whether in combination with rTMS or tDCS, antidepressants proved more effective in alleviating depressive symptoms compared to when used as monotherapy. However, this advantage was not evident during the follow-up period. (p > 0.05). And the combination's efficacy in improving anxiety was found to be lacking. Post-treatment serum levels of 5-HT, DA, and GABA were higher in the rTMS group were higher than antidepressant medication group (p < 0.05). Furthermore, subgroup analysis results indicated that only the rTMS + antidepressant medication treatment significantly improved remission and remission rates. The meta-regression results showed that the type of antidepressant and the sex of the participants had a significant association with the depression score.
CONCLUSION
Combination treatment with NIBS was significantly more effective in improving depression symptoms than medication alone. rTMS combined with antidepressants appears to be more effective in improving response and remission rates. However, efficacy may be influenced by the type of medicine used in combination, and long-term efficacy data is lacking.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023388259.
Topics: Humans; Transcranial Direct Current Stimulation; Depression; Serotonin; Randomized Controlled Trials as Topic; Antidepressive Agents; Transcranial Magnetic Stimulation; gamma-Aminobutyric Acid; Brain
PubMed: 38509623
DOI: 10.1186/s13643-024-02480-w