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Journal of Affective Disorders Apr 2022To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of augmentation agents.
METHODS
We included randomized controlled trials comparing one active drug with another or with placebo following a treatment course up to 24 weeks. Nineteen agents were included: stimulants, atypical antipsychotics, thyroid hormones, antidepressants, and mood stabilizers. Data for response/remission and all-cause discontinuation rates were analyzed. We estimated effect-size by relative risk using pairwise and NMA with random-effects model.
RESULTS
A total of 65 studies (N = 12,415) with 19 augmentation agents were included in the NMA. Our findings from the NMA for response rates, compared to placebo, were significant for: liothyronine, nortriptyline, aripiprazole, brexpiprazole, quetiapine, lithium, modafinil, olanzapine (fluoxetine), cariprazine, and lisdexamfetamine. For remission rates, compared to placebo, were significant for: thyroid hormone(T4), aripiprazole, brexpiprazole, risperidone, quetiapine, and olanzapine (fluoxetine). Compared to placebo, ziprasidone, mirtazapine, and cariprazine had statistically significant higher discontinuation rates. Overall, 24% studies were rated as having low risk of bias (RoB), 63% had moderate RoB and 13% had high RoB.
LIMITATIONS
Heterogeneity in TRD definitions, variable trial duration and methodological clinical design of older studies and small number of trials per comparisons.
CONCLUSIONS
This NMA suggests a superiority of the regulatory approved adjunctive atypical antipsychotics, thyroid hormones, dopamine compounds (modafinil and lisdexamfetamine) and lithium. Acceptability was lower with ziprasidone, mirtazapine, and cariprazine. Further research and head-to-head studies should be considered to strengthen the best available options for TRD.
Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Humans; Network Meta-Analysis
PubMed: 34986373
DOI: 10.1016/j.jad.2021.12.134 -
European Neuropsychopharmacology : the... Jan 2022The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder... (Review)
Review
The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder (BD). The PRISMA method was followed to search the MEDLINE for Randomized Controlled trials, Post-hoc analyses and Meta-analyses and review papers up to August 1st 2020, with the combination of the words 'bipolar', 'manic', 'mania', 'manic depression' and 'manic depressive' and 'randomized'. Trials and meta-analyses concerning the use of lithium either as monotherapy or in combination with other agents in adults were identified concerning acute mania (Ν=64), acute bipolar depression (Ν=78), the maintenance treatment (Ν=73) and the treatment of other issues (N = 93). Treatment guidelines were also identified. Lithium is efficacious for the treatment of acute mania including concomitant psychotic symptoms. In acute bipolar depression it is efficacious only in combination with specific agents. For the maintenance phase, it is efficacious as monotherapy mainly in the prevention of manic while its efficacy for the prevention of depressive episodes is unclear. Its combinations increase its therapeutic value. It is equaly efficacious in rapid and non-rapid cycling patients, in concomitant obsessive-compulsive symptoms, alcohol and substance abuse, the neurocognitive deficit, suicidal ideation and fatigue The current systematic review provided support for the usefulness of lithium against a broad spectrum of clinical issues in Bipolar disorder. Its efficacy is comparable to that of more recently developed agents.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds; Mania; Randomized Controlled Trials as Topic
PubMed: 34980362
DOI: 10.1016/j.euroneuro.2021.10.003 -
Molecular Psychiatry Feb 2022A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Female; Haloperidol; Humans; Lithium; Male; Mania; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Tamoxifen; Valproic Acid
PubMed: 34642461
DOI: 10.1038/s41380-021-01334-4 -
Clinical Journal of the American... May 2015The Extracorporeal Treatments in Poisoning Workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments in poisoning. Here,... (Review)
Review
The Extracorporeal Treatments in Poisoning Workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments in poisoning. Here, the EXTRIP workgroup presents its recommendations for lithium poisoning. After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations. In total, 166 articles met inclusion criteria, which were mostly case reports, yielding a very low quality of evidence for all recommendations. A total of 418 patients were reviewed, 228 of which allowed extraction of patient-level data. The workgroup concluded that lithium is dialyzable (Level of evidence=A) and made the following recommendations: Extracorporeal treatment is recommended in severe lithium poisoning (1D). Extracorporeal treatment is recommended if kidney function is impaired and the [Li(+)] is >4.0 mEq/L, or in the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of the [Li(+)] (1D). Extracorporeal treatment is suggested if the [Li(+)] is >5.0 mEq/L, significant confusion is present, or the expected time to reduce the [Li(+)] to <1.0 mEq/L is >36 hours (2D). Extracorporeal treatment should be continued until clinical improvement is apparent or [Li(+)] is <1.0 mEq/L (1D). Extracorporeal treatments should be continued for a minimum of 6 hours if the [Li(+)] is not readily measurable (1D). Hemodialysis is the preferred extracorporeal treatment (1D), but continuous RRT is an acceptable alternative (1D). The workgroup supported the use of extracorporeal treatment in severe lithium poisoning. Clinical decisions on when to use extracorporeal treatment should take into account the [Li(+)], kidney function, pattern of lithium toxicity, patient's clinical status, and availability of extracorporeal treatments.
Topics: Antimanic Agents; Consensus; Delphi Technique; Drug Overdose; Evidence-Based Medicine; Humans; Lithium; Lithium Compounds; Renal Dialysis
PubMed: 25583292
DOI: 10.2215/CJN.10021014 -
Annals of Internal Medicine Sep 2019Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016.
BACKGROUND
Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016.
PURPOSE
To assess the benefits and harms of nonpharmacologic and pharmacologic interventions to prevent suicide and reduce suicide behaviors in at-risk adults.
DATA SOURCES
MEDLINE, EMBASE, PsycINFO, and other databases from November 2011 through May 2018.
STUDY SELECTION
Systematic reviews (SRs) and randomized controlled trials (RCTs) that assessed nonpharmacologic or pharmacologic therapies for adults at risk for suicide.
DATA EXTRACTION
One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy.
DATA SYNTHESIS
Eight SRs and 15 RCTs were included. The evidence for psychological interventions suggests that cognitive behavioral therapy (CBT) reduces suicide attempts, suicidal ideation, and hopelessness compared with treatment as usual (TAU). Limited evidence suggests that dialectical behavior therapy (DBT) reduces suicidal ideation compared with wait-list control or crisis planning. The evidence for pharmacologic treatments suggests that ketamine reduces suicidal ideation with minimal adverse events compared with placebo or midazolam. Lithium reduces rates of suicide among patients with unipolar or bipolar mood disorders compared with placebo. However, no differences were observed between lithium and other medications in reducing suicide.
LIMITATION
Qualitative synthesis of new evidence with existing meta-analyses, methodological shortcomings of studies, heterogeneity of nonpharmacologic interventions, and limited evidence for pharmacologic treatments and harms.
CONCLUSION
Both CBT and DBT showed modest benefit in reducing suicidal ideation compared with TAU or wait-list control, and CBT also reduced suicide attempts compared with TAU. Ketamine and lithium reduced the rate of suicide compared with placebo, but there was limited information on harms. Limited data are available to support the efficacy of other nonpharmacologic or pharmacologic interventions.
PRIMARY FUNDING SOURCE
U.S. Department of Veterans Affairs Veterans Health Administration. (PROSPERO: CRD42018104978).
Topics: Antidepressive Agents; Cognitive Behavioral Therapy; Crisis Intervention; Dialectical Behavior Therapy; Humans; Ketamine; Lithium Compounds; Patient Education as Topic; Risk Factors; Suicidal Ideation; Suicide; United States; Suicide Prevention
PubMed: 31450239
DOI: 10.7326/M19-0869 -
BMC Oral Health Sep 2017The continuous development in dental processing ensures new opportunities in the field of fixed prosthodontics in a complete virtual environment without any physical... (Review)
Review
BACKGROUND
The continuous development in dental processing ensures new opportunities in the field of fixed prosthodontics in a complete virtual environment without any physical model situations. The aim was to compare fully digitalized workflows to conventional and/or mixed analog-digital workflows for the treatment with tooth-borne or implant-supported fixed reconstructions.
METHODS
A PICO strategy was executed using an electronic (MEDLINE, EMBASE, Google Scholar) plus manual search up to 2016-09-16 focusing on RCTs investigating complete digital workflows in fixed prosthodontics with regard to economics or esthetics or patient-centered outcomes with or without follow-up or survival/success rate analysis as well as complication assessment of at least 1 year under function. The search strategy was assembled from MeSH-Terms and unspecific free-text words: {(("Dental Prosthesis" [MeSH]) OR ("Crowns" [MeSH]) OR ("Dental Prosthesis, Implant-Supported" [MeSH])) OR ((crown) OR (fixed dental prosthesis) OR (fixed reconstruction) OR (dental bridge) OR (implant crown) OR (implant prosthesis) OR (implant restoration) OR (implant reconstruction))} AND {("Computer-Aided Design" [MeSH]) OR ((digital workflow) OR (digital technology) OR (computerized dentistry) OR (intraoral scan) OR (digital impression) OR (scanbody) OR (virtual design) OR (digital design) OR (cad/cam) OR (rapid prototyping) OR (monolithic) OR (full-contour))} AND {("Dental Technology" [MeSH) OR ((conventional workflow) OR (lost-wax-technique) OR (porcelain-fused-to-metal) OR (PFM) OR (implant impression) OR (hand-layering) OR (veneering) OR (framework))} AND {(("Study, Feasibility" [MeSH]) OR ("Survival" [MeSH]) OR ("Success" [MeSH]) OR ("Economics" [MeSH]) OR ("Costs, Cost Analysis" [MeSH]) OR ("Esthetics, Dental" [MeSH]) OR ("Patient Satisfaction" [MeSH])) OR ((feasibility) OR (efficiency) OR (patient-centered outcome))}. Assessment of risk of bias in selected studies was done at a 'trial level' including random sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting, and other bias using the Cochrane Collaboration tool. A judgment of risk of bias was assigned if one or more key domains had a high or unclear risk of bias. An official registration of the systematic review was not performed.
RESULTS
The systematic search identified 67 titles, 32 abstracts thereof were screened, and subsequently, three full-texts included for data extraction. Analysed RCTs were heterogeneous without follow-up. One study demonstrated that fully digitally produced dental crowns revealed the feasibility of the process itself; however, the marginal precision was lower for lithium disilicate (LS2) restorations (113.8 μm) compared to conventional metal-ceramic (92.4 μm) and zirconium dioxide (ZrO2) crowns (68.5 μm) (p < 0.05). Another study showed that leucite-reinforced glass ceramic crowns were esthetically favoured by the patients (8/2 crowns) and clinicians (7/3 crowns) (p < 0.05). The third study investigated implant crowns. The complete digital workflow was more than twofold faster (75.3 min) in comparison to the mixed analog-digital workflow (156.6 min) (p < 0.05). No RCTs could be found investigating multi-unit fixed dental prostheses (FDP).
CONCLUSIONS
The number of RCTs testing complete digital workflows in fixed prosthodontics is low. Scientifically proven recommendations for clinical routine cannot be given at this time. Research with high-quality trials seems to be slower than the industrial progress of available digital applications. Future research with well-designed RCTs including follow-up observation is compellingly necessary in the field of complete digital processing.
Topics: Computer-Aided Design; Dental Prosthesis Design; Dental Prosthesis, Implant-Supported; Humans; Workflow
PubMed: 28927393
DOI: 10.1186/s12903-017-0415-0 -
Bioengineering (Basel, Switzerland) Jul 2022Tooth wear is considered a well-developed issue in daily clinical practice; however, there is no standard protocol for treatment. The aim of this manuscript was to... (Review)
Review
Tooth wear is considered a well-developed issue in daily clinical practice; however, there is no standard protocol for treatment. The aim of this manuscript was to systematically review the literature to evaluate the clinical outcomes of direct or indirect restorations for treating tooth wear. A literature search was conducted through the PubMed MedLine, Scopus, ISI Web of Science, Scielo, and EMBASE databases up to 29 April 2022. Clinical studies evaluating the clinical performance of direct or indirect restorations for treating tooth wear for a minimum follow-up of 6 months were included in the review. A total of 2776 records were obtained from the search databases. After full-text reading, 16 studies were included in the qualitative analysis. Considering the high heterogenicity of the studies included, a meta-analysis could not be performed. All studies included the rehabilitation of anterior and posterior teeth with extensive wear, using both indirect and direct restorations for a maximum follow-up of 10 years. Restoration materials included ceramo-metal crowns, full gold crowns, lithium disilicate ceramic, zirconia, polymer infiltrated ceramic networks, and resin composites. Most of the reports assessed the survival rate of the restorations and the clinical features using the United States Public Health Service (USPHS) Evaluation System criteria. Contradictory discoveries were perceived concerning the type of restoration with better clinical performance. Considering the current literature available, there is no evidence in the superiority of any restoration technique to ensure the highest clinical performance for treating tooth wear.
PubMed: 36004871
DOI: 10.3390/bioengineering9080346 -
The Cochrane Database of Systematic... Sep 2021Bipolar disorder is a chronic mental disorder with repetitive mania/hypomania as well as depressive episodes, which eventually results in marked impairment in overall... (Review)
Review
BACKGROUND
Bipolar disorder is a chronic mental disorder with repetitive mania/hypomania as well as depressive episodes, which eventually results in marked impairment in overall functioning and health-related quality of life. A worldwide prevalence rate of 2.4% has been reported. The risk of suicide is higher in people with bipolar disorder than those with other mental disorders. Therefore, effective management of bipolar disorder in the maintenance period is warranted to minimize the risk of relapse or recurrence. Although lithium has been the standard treatment of bipolar disorder for many years, it is associated with adverse effects and teratogenicity. Lamotrigine is approved to be expected for prevention of recurrence for the maintenance treatment of bipolar disorder. In addition, lamotrigine is as effective as lithium. Therefore, we performed a systematic review to confirm the efficacy and safety of lamotrigine in the maintenance treatment of bipolar disorder.
OBJECTIVES
To assess the efficacy and tolerability of lamotrigine in the maintenance treatment of bipolar disorder.
SEARCH METHODS
We searched Ovid MEDLINE, Embase, PsycINFO, the Cochrane Common Mental Disorders Group's Specialized Register (CCMDCTR) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 21 May 2021. We also searched international trial registries and contacted experts in the field.
SELECTION CRITERIA
We included randomized controlled trials enrolling adults with bipolar disorder who were treated with lamotrigine, placebo or lithium.
DATA COLLECTION AND ANALYSIS
Two reviews authors independently checked the eligibility of studies and extracted data using a standardized form. Data extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in the term of efficacy and tolerability. Study information were then entered into RevMan web.
MAIN RESULTS
We included 11 studies with a total of 2314 participants in this review; 1146 were randomized to lamotrigine, 869 were randomized to placebo and, 299 to lithium. We rated all studies as having an unclear risk of bias in at least one domain of Cochrane's tool for assessing risk of bias, with the most commonly observed weakness being selection bias (random sequence generation and allocation concealment). We judged five studies to be at a high risk of detection bias (blinding of outcome assessment). These potential biases pose as major threat to the validity of the included studies in this review. Outcomes of efficacy showed a possible advantage of lamotrigine over placebo. The estimated risk ratio (RR) for recurrence of manic symptom at one year as measured by the Young Mania Rating Scale (YMRS) was 0.67, (95% confidence interval (CI) 0.51 to 0.87; 3 studies, 663 participants; low-certainty evidence) in favor of lamotrigine. The RR of clinical worsening with the need for additional psychotropic treatment (RR 0.82, 95% CI 0.70 to 0.98; 4 studies, 756 participants) based on moderate-certainty evidence. The possible benefits of lamotrigine were also seen for the outcome of treatment withdrawal due to any reason at 6-12 months after treatment (RR 0.88, 95% CI 0.78 to 0.99; 4 studies, 700 participants; moderate-certainty evidence). Regarding tolerability, our analyses showed that the incidence rates of adverse effects were similar between the lamotrigine group and the placebo group (short-term effect: RR 1.07, 95% CI 0.81 to 1.42; 5 studies, 1138 participants; very low-certainty evidence; long-term effect: RR 0.97, 95% CI 0.77 to 1.23; 4 studies, 756 participants; moderate-certainty evidence). In the comparison between lamotrigine and lithium, efficacy was similar between groups except for recurrence of mania episode at one year. Recurrence of manic symptoms was higher in the lamotrigine group than that of the lithium group (RR 2.13, 95% CI 1.32 to 3.44; 3 studies, 602 participants; moderate-certainty evidence). Analysis of adverse effects at 6-12 months showed that a lower proportion of participants experienced at least one adverse effect when treated with lamotrigine compared to lithium (RR 0.70, 95% CI 0.51 to 0.96; 4 studies, 691 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Low- to moderate-certainty evidence collectively suggests that lamotrigine may be superior to placebo as a treatment modality for bipolar disorder. In comparison to lithium, people with bipolar disorder seem to tolerate lamotrigine better in the long run; however, the demonstrated efficacy in the maintenance of bipolar disorder was similar between the two groups.
Topics: Adult; Anticonvulsants; Bipolar Disorder; Humans; Lamotrigine; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 34523118
DOI: 10.1002/14651858.CD013575.pub2 -
Molecular Psychiatry Aug 2021We searched Embase, PubMed, and CENTRAL from inception until 22 May 2020 to investigate which antipsychotics and/or mood stabilizers are better for patients with bipolar...
We searched Embase, PubMed, and CENTRAL from inception until 22 May 2020 to investigate which antipsychotics and/or mood stabilizers are better for patients with bipolar disorder in the maintenance phase. We performed two categorical network meta-analyses. The first included monotherapy studies and studies in which the two drugs used were specified (i.e., aripiprazole, aripiprazole once monthly, aripiprazole+lamotrigine, aripiprazole+valproate, asenapine, carbamazepine, lamotrigine, lamotrigine+valproate, lithium, lithium+oxcarbazepine, lithium+valproate, olanzapine, paliperidone, quetiapine, risperidone long-acting injection, valproate, and placebo). The second included studies on second-generation antipsychotic combination therapies (SGAs) (i.e., aripiprazole, lurasidone, olanzapine, quetiapine, and ziprasidone) with lithium or valproate (LIT/VAL) compared with placebo with LIT/VAL. Outcomes were recurrence/relapse rate of any mood episode (RR-any, primary), depressive episode (RR-dep) and manic/hypomanic/mixed episode (RR-mania), discontinuation, mortality, and individual adverse events. Risk ratios and 95% credible interval were calculated. Forty-one randomized controlled trials were identified (n = 9821; mean study duration, 70.5 ± 36.6 weeks; percent female, 54.1%; mean age, 40.7 years). All active treatments other than carbamazepine, lamotrigine+valproate (no data) and paliperidone outperformed the placebo for RR-any. Aripiprazole+valproate, lamotrigine, lamotrigine+valproate, lithium, olanzapine, and quetiapine outperformed placebo for RR-dep. All active treatments, other than aripiprazole+valproate, carbamazepine, lamotrigine, and lamotrigine+valproate, outperformed placebo for RR-mania. Asenapine, lithium, olanzapine, quetiapine, and valproate outperformed placebo for all-cause discontinuation. All SGAs+LIT/VALs other than olanzapine+LIT/VAL outperformed placebo+LIT/VAL for RR-any. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-dep. Aripiprazole+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-mania. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for all-cause discontinuation. Treatment efficacy, tolerability, and safety profiles differed among treatments.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 33177610
DOI: 10.1038/s41380-020-00946-6 -
World Psychiatry : Official Journal of... Jun 2020Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis-orders in this age...
Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects.
Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis-orders in this age group and are used not infrequently off-label. However, the adverse effects of these medications require special attention during developmentally sensitive periods of life. For this meta-review, we systematically searched network meta-analyses and meta-analyses of randomized controlled trials (RCTs), individual RCTs, and cohort studies reporting on 78 a priori selected adverse events across 19 categories of 80 psychotropic medications - including antidepressants, antipsychotics, anti-attention-deficit/hyperactivity disorder (ADHD) medications and mood stabilizers - in children and adolescents with mental disorders. We included data from nine network meta-analyses, 39 meta-analyses, 90 individual RCTs, and eight cohort studies, including 337,686 children and adolescents. Data on ≥20% of the 78 adverse events were available for six antidepressants (sertraline, escitalopram, paroxetine, fluoxetine, venlafaxine and vilazodone), eight antipsychotics (risperidone, quetiapine, aripiprazole, lurasidone, paliperidone, ziprasidone, olanzapine and asenapine), three anti-ADHD medications (methylphenidate, atomoxetine and guanfacine), and two mood stabilizers (valproate and lithium). Among these medications with data on ≥20% of the 78 adverse events, a safer profile emerged for escitalopram and fluoxetine among antidepressants, lurasidone for antipsychotics, methylphenidate among anti-ADHD medications, and lithium among mood stabilizers. The available literature raised most concerns about the safety of venlafaxine, olanzapine, atomoxetine, guanfacine and valproate. Nausea/vomiting and discontinuation due to adverse event were most frequently associated with antidepressants; sedation, extrapyramidal side effects, and weight gain with antipsychotics; anorexia and insomnia with anti-ADHD medications; sedation and weight gain with mood stabilizers. The results of this comprehensive and updated quantitative systematic meta-review of top-tier evidence regarding the safety of antidepressants, antipsychotics, anti-ADHD medications and mood stabilizers in children and adolescents can inform clinical practice, research and treatment guidelines.
PubMed: 32394557
DOI: 10.1002/wps.20765