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Journal of Affective Disorders Oct 2023The concurrent assessment of weight and affective psychopathology outcomes relevant to the psychopharmacology of major eating disorders (EDs), namely anorexia nervosa... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The concurrent assessment of weight and affective psychopathology outcomes relevant to the psychopharmacology of major eating disorders (EDs), namely anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), warrants systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
PubMed, Scopus, and ClinicalTrials.gov were inquired from inception through August 31st, 2022, for RCTs documenting any psychopharmacological intervention for EDs diagnosed according to validated criteria and reporting weight and psychopathology changes. Adopted keywords were: "anorexia nervosa," "bulimia nervosa," "binge eating disorder," "antidepressant," "antipsychotic," and "mood stabilizer." No language restriction applied.
RESULTS
5122 records were identified, and 203 full-texts were reviewed. Sixty-two studies entered the qualitative synthesis (AN = 22, BN = 23, BED = 17), of which 22 entered the meta-analysis (AN = 9, BN = 10, BED = 3). Concerning BMI increase in AN, olanzapine outperformed placebo (Hedges'g = 0.283, 95%C·I. = 0.051-0.515, I = 0 %; p = .017), whereas fluoxetine failed (Hedges'g = 0.351, 95%C.I. = -0.248 to 0.95, I = 63.37 %; p = .251). Fluoxetine not significantly changed weight (Hedges'g = 0.147, 95%C.I. = -0.157-0.451, I = 0 %; p = .343), reducing binging (Hedges'g = 0.203, 95%C.I. = 0.007-0.399, I = 0 %; p = .042), and purging episodes (Hedges'g = 0.328, 95%C.I. = -0.061-0.717, I = 58.97 %; p = .099) in BN. Lisdexamfetamine reduced weight (Hedges'g = 0.259, 95%C.I. = 0.071-0.446, I = 0 %; p = .007) and binging (Hedges'g = 0.571, 95%C.I. = 0.282-0.860, I = 53.84 %; p < .001) in BED.
LIMITATIONS
Small sample size, short duration, and lack of reliable operational definitions affect most of the included sponsored RCTs.
CONCLUSIONS
The efficacy of different drugs varies across different EDs, warranting additional primary studies recording broad psychopathological and cardiometabolic outcomes besides weight, especially against established psychotherapy interventions.
Topics: Humans; Fluoxetine; Psychopharmacology; Randomized Controlled Trials as Topic; Feeding and Eating Disorders; Bulimia Nervosa; Binge-Eating Disorder; Anorexia Nervosa; Antipsychotic Agents
PubMed: 37393954
DOI: 10.1016/j.jad.2023.06.068 -
Journal of Orthopaedic Surgery and... Jul 2023The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy and safety of duloxetine was conducted. The outcomes of interests were to assess changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), and Clinical Global Impression (CGI). The rate of of adverse events and those leading to therapy discontinuation were also investigated.
MATERIAL AND METHODS
This study followed the 2020 PRISMA guidelines. The literature search started in December 2022 accessing PubMed, Google scholar, Embase, and Scopus databases. All the RCTs investigating the efficacy and safety of daily administration of duloxetine for fibromyalgia were accessed. Studies reporting quantitative data under the outcomes of interest, and including a minimum of 10 patients who completed a minimum of 4 weeks follow-up, were included. Studies on combined pharmacological and non-pharmacological managements for fibromyalgia were not considered.
RESULTS
Data from 3432 patients (11 RCTs) were included. The mean age of the patients was 46.4 ± 10.7 years old, and the mean BMI 25.3 ± 3.2 kg/m. 90% (3089 of 3432 patients) were women. The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30-60, 120 mg/daily, and placebo groups, while the 60-120 mg /daily group performed the worst results. Concerning the CGI severity scale, placebo resulted in the lowest improvement, and no differences were found in the other groups. Concerning the BPI interference and severity pain scores, the 30-60 mg/daily group reported the worst result, along with the placebo group. The rate of adverse events leading to study discontinuation were lower in the 60-120 group, followed by the 30-60 and 30 mag/daily groups. Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed.
CONCLUSIONS
Duloxetine could help in improving symptoms of fibromyalgia. The dose of duloxetine should be customised according to individual patients. Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia. The dose of duloxetine must be customised according to individual patients. Level of evidence I Meta-analysis of double-blind RCTs.
Topics: Humans; Female; Adult; Middle Aged; Male; Duloxetine Hydrochloride; Fibromyalgia; Thiophenes; Treatment Outcome; Pain; Randomized Controlled Trials as Topic
PubMed: 37461044
DOI: 10.1186/s13018-023-03995-z -
Pharmacology, Biochemistry, and Behavior Sep 2023Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications.... (Review)
Review
Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.
Topics: Humans; Cannabidiol; Cannabinoids; Cannabis; Hallucinogens; Attention Deficit Disorder with Hyperactivity; Dronabinol; Randomized Controlled Trials as Topic
PubMed: 37543051
DOI: 10.1016/j.pbb.2023.173607 -
JAMA Psychiatry Nov 2023In individuals with schizophrenia, antipsychotic-induced dysfunctions are frequent but often underexplored in clinical practice. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
In individuals with schizophrenia, antipsychotic-induced dysfunctions are frequent but often underexplored in clinical practice.
OBJECTIVE
To synthetize the data of observational studies exploring the prevalence of sexual dysfunction in individuals with schizophrenia-spectrum disorders as well as associated factors.
DATA SOURCES
A systematic literature search without language or time restrictions was conducted in Google, Google Scholar, PubMed/MEDLINE, Science Direct, and Université Sorbonne Paris Cité for studies published up to June 8, 2022.
STUDY SELECTION
All observational studies reporting a prevalence of sexual dysfunction in schizophrenia-spectrum disorder were included.
DATA EXTRACTION AND SYNTHESIS
The MOOSE guidelines with independent extraction by 2 observers and random-effects models were used.
MAIN OUTCOMES AND MEASURES
The prevalence of sexual dysfunction and each specific dysfunction.
RESULTS
A total of 72 of 1119 studies from 33 countries on 6 continents published from inception to June 2022 were included with a total of 21 076 participants with schizophrenia. The pooled global prevalence of sexual dysfunctions was 56.4% (95% CI, 50.5-62.2), with a prevalence of 55.7% (95% CI, 48.1-63.1) for men and 60.0% (95% CI, 48.0-70.8) for women. The most frequent sexual dysfunction was erectile dysfunction in men (44%; 95% CI, 33.5-55.2), followed by loss of libido in men (41%; 95% CI, 30.7-51.4), ejaculation dysfunction in men (39%; 95% CI, 26.8-51.8), orgasm dysfunction in women (28%; 95% CI, 18.4-40.2), and amenorrhea in women (25%; 95% CI, 17.3-35.0). Factors associated with heterogeneity were study design, time and location, sociodemographic data, alcohol use disorder, psychiatric diagnosis, illness severity, and the use of antidepressants and anxiolytics. Sexual dysfunctions were more frequent in schizophrenia vs schizoaffective disorders, and erectile disorders were less frequent in individuals with longer illness duration. Antidepressant and mood stabilizer prescriptions were associated with lower rates of erection disorders (β, -6.30; 95% CI, -10.82 to -1.78); P = .006 and -13.21; 95% CI, -17.59 to -8.83; P < .001, respectively) and ejaculation disorders (β, -6.10; 95% CI, -10.68 to -1.53; P = .009 and β, -11.57; 95% CI, -16.34 to -6.80; P < .001, respectively). No obvious improvements in the rates of sexual dysfunction at other times were found, and there were conflicting results regarding antipsychotic classes.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found a high prevalence of sexual dysfunction among individuals with schizophrenia, with considerable heterogeneity in associated factors. The findings also suggest that some dysfunctions may be explained by schizophrenia. The association between lower rates of dysfunction and antidepressant use suggests that treating comorbid depression could be an effective strategy to improve sexual health. A lack of data on metabolic parameters and physical health in general was also noted, while these issues are frequent in the care of schizophrenia.
Topics: Male; Humans; Female; Schizophrenia; Antipsychotic Agents; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Erectile Dysfunction; Antidepressive Agents
PubMed: 37703012
DOI: 10.1001/jamapsychiatry.2023.2696 -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
Journal of Affective Disorders Sep 2023Transcutaneous auricular vagus nerve stimulation (taVNS) is used for treating depression but the efficacy and safety have not been well assessed. This study was... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Transcutaneous auricular vagus nerve stimulation (taVNS) is used for treating depression but the efficacy and safety have not been well assessed. This study was conducted to evaluate the efficacy and safety of taVNS in depression.
METHODS
The retrieval databases included English databases of PubMed, Web of Science, Embase, the Cochrane Library and PsycINFO, and Chinese databases of CNKI, Wanfang, VIP and Sino Med, and the retrieval period was from their inception to November 10, 2022. The clinical trial registers (ClinicalTrials.gov and Chinese Clinical Trial Registry) were also searched. Standardized mean difference and the risk ratio were used as the effect indicator and the effect size was represented by the 95 % confidence interval. Revised Cochrane risk-of-bias tool for randomized trials and the Grades of Recommendation, Assessment, Development and Evaluation system were used to assess the risk of bias and quality of evidence respectively.
RESULTS
Totally, 12 studies of 838 participants were included. taVNS could significantly improve depression and reduce Hamilton Depression Scale scores. Low to very low evidence showed that taVNS had higher response rates than sham-taVMS and comparable response rates compared to antidepressants (ATD) and that taVNS combined with ATD had comparable efficacy to ATD with fewer side effects.
LIMITATIONS
The number of studies in subgroups was small and the evidence quality was low to very low.
CONCLUSIONS
taVNS is an effective and safe method for alleviating depression scores and had a comparable response rate to ATD.
Topics: Humans; Vagus Nerve Stimulation; Randomized Controlled Trials as Topic; Transcutaneous Electric Nerve Stimulation; Antidepressive Agents; Vagus Nerve; Depressive Disorder
PubMed: 37230264
DOI: 10.1016/j.jad.2023.05.048 -
The Cochrane Database of Systematic... Nov 2023A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines.
OBJECTIVES
To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses.
MAIN RESULTS
Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low.
AUTHORS' CONCLUSIONS
In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
Topics: Adult; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Fluoxetine; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Alprazolam; Clomipramine; Reboxetine; Clonazepam; Desipramine; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Tricyclic; Benzodiazepines; Diazepam
PubMed: 38014714
DOI: 10.1002/14651858.CD012729.pub3 -
Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y -
JAMA Psychiatry Dec 2023Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of antidepressants have shown small to medium effect sizes, but generalizability to clinical settings is unclear, where medical comorbidity is highly prevalent.
OBJECTIVE
To perform an umbrella systematic review of the meta-analytic evidence and meta-analysis of the efficacy and safety of antidepressant use in populations with medical diseases and comorbid depression.
DATA SOURCES
PubMed and EMBASE were searched from inception until March 31, 2023, for systematic reviews with or without meta-analyses of randomized clinical trials (RCTs) examining the efficacy and safety of antidepressants for treatment or prevention of comorbid depression in any medical disease.
STUDY SELECTION
Meta-analyses of placebo- or active-controlled RCTs studying antidepressants for depression in individuals with medical diseases.
DATA EXTRACTION AND SYNTHESIS
Data extraction and quality assessment using A Measurement Tool for the Assessment of Multiple Systematic Reviews (AMSTAR-2 and AMSTAR-Content) were performed by pairs of independent reviewers following PRISMA guidelines. When several meta-analyses studied the same medical disease, the largest meta-analysis was included. Random-effects meta-analyses pooled data on the primary outcome (efficacy), key secondary outcomes (acceptability and tolerability), and additional secondary outcomes (response and remission).
MAIN OUTCOMES AND MEASURES
Antidepressant efficacy presented as standardized mean differences (SMDs) and tolerability (discontinuation for adverse effects) and acceptability (all-cause discontinuation) presented as risk ratios (RRs).
RESULTS
Of 6587 references, 176 systematic reviews were identified in 43 medical diseases. Altogether, 52 meta-analyses in 27 medical diseases were included in the evidence synthesis (mean [SD] AMSTAR-2 quality score, 9.3 [3.1], with a maximum possible of 16; mean [SD] AMSTAR-Content score, 2.4 [1.9], with a maximum possible of 9). Across medical diseases (23 meta-analyses), antidepressants improved depression vs placebo (SMD, 0.42 [95% CI, 0.30-0.54]; I2 = 76.5%), with the largest SMDs for myocardial infarction (SMD, 1.38 [95% CI, 0.82-1.93]), functional chest pain (SMD, 0.87 [95% CI, 0.08-1.67]), and coronary artery disease (SMD, 0.83 [95% CI, 0.32-1.33]) and the smallest for low back pain (SMD, 0.06 [95% CI, 0.17-0.39]) and traumatic brain injury (SMD, 0.08 [95% CI, -0.28 to 0.45]). Antidepressants showed worse acceptability (24 meta-analyses; RR, 1.17 [95% CI, 1.02-1.32]) and tolerability (18 meta-analyses; RR, 1.39 [95% CI, 1.13-1.64]) compared with placebo. Antidepressants led to higher rates of response (8 meta-analyses; RR, 1.54 [95% CI, 1.14-1.94]) and remission (6 meta-analyses; RR, 1.43 [95% CI, 1.25-1.61]) than placebo. Antidepressants more likely prevented depression than placebo (7 meta-analyses; RR, 0.43 [95% CI, 0.33-0.53]).
CONCLUSIONS AND RELEVANCE
The results of this umbrella systematic review of meta-analyses found that antidepressants are effective and safe in treating and preventing depression in patients with comorbid medical disease. However, few large, high-quality RCTs exist in most medical diseases.
Topics: Humans; Antidepressive Agents; Comorbidity; Depression; Meta-Analysis as Topic; Systematic Reviews as Topic
PubMed: 37672261
DOI: 10.1001/jamapsychiatry.2023.2983 -
Journal of Neurology Oct 2023To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.
METHODS
Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).
RESULTS
Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).
CONCLUSIONS
All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.
Topics: Humans; Child; Valproic Acid; Topiramate; Network Meta-Analysis; Levetiracetam; Ethosuximide; Anticonvulsants; Epilepsy, Generalized; Seizures; Randomized Controlled Trials as Topic
PubMed: 37378757
DOI: 10.1007/s00415-023-11834-8