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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 -
Revue Neurologique May 2020Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques...
Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques and interventional management, but no comprehensive guideline encompassing all these treatments has yet been issued. We performed a systematic review of pharmacotherapy, neurostimulation, surgery, psychotherapies and other types of therapy for peripheral or central neuropathic pain, based on studies published in peer-reviewed journals before January 2018. The main inclusion criteria were chronic neuropathic pain for at least three months, a randomized controlled methodology, at least three weeks of follow-up, at least 10 patients per group, and a double-blind design for drug therapy. Based on the GRADE system, we provide weak-to-strong recommendations for use and proposal as a first-line treatment for SNRIs (duloxetine and venlafaxine), gabapentin and tricyclic antidepressants and, for topical lidocaine and transcutaneous electrical nerve stimulation specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a second-line treatment for pregabalin, tramadol, combination therapy (antidepressant combined with gabapentinoids), and for high-concentration capsaicin patches and botulinum toxin A specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a third-line treatment for high-frequency rTMS of the motor cortex, spinal cord stimulation (failed back surgery syndrome and painful diabetic polyneuropathy) and strong opioids (in the absence of an alternative). Psychotherapy (cognitive behavioral therapy and mindfulness) is recommended as a second-line therapy, as an add-on to other therapies. An algorithm encompassing all the recommended treatments is proposed.
Topics: Analgesics; Analgesics, Opioid; Antidepressive Agents; Cognitive Behavioral Therapy; Complementary Therapies; France; Humans; Mindfulness; Neuralgia; Pain Management; Practice Guidelines as Topic; Transcranial Magnetic Stimulation
PubMed: 32276788
DOI: 10.1016/j.neurol.2020.01.361 -
Expert Opinion on Drug Metabolism &... May 2020: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A... (Meta-Analysis)
Meta-Analysis
: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A clearer understanding of pregnancy-related effects on antidepressant disposition may facilitate the development of guidelines for appropriate dose adjustments during the course of pregnancy based on therapeutic drug monitoring.: We systematically reviewed studies comparing antidepressant levels in the same individuals during pregnant and non-pregnant states. Using dose-adjusted plasma concentration measurements, we estimated alteration ratios between the 3rd trimester and baseline (before or after pregnancy). Additionally, we performed a meta-analysis for changes in dose-adjusted concentrations to estimate mean differences.: Data for several antidepressants display clear alteration patterns during pregnancy. On the basis of the alteration ratios trimipramine, fluvoxamine, and nortriptyline show a prominent decrease in dose-adjusted levels, especially in the 3rd trimester. Clomipramine, imipramine, citalopram, and paroxetine show smaller decreases in dose-adjusted concentrations in the third trimester. For escitalopram, venlafaxine and fluoxetine, changes are considered negligible. For sertraline, there was a tendency toward increased dose-adjusted concentrations in pregnancy. Available evidence suffers from major limitations and factors affecting pharmacokinetics have been insufficiently addressed. Further research is required to promote knowledge on pregnancy effects on antidepressant pharmacokinetics.
Topics: Antidepressive Agents; Depression; Dose-Response Relationship, Drug; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third
PubMed: 32238008
DOI: 10.1080/17425255.2020.1750598 -
Regional Anesthesia and Pain Medicine May 2020The role of serotonin-norepinephrine reuptake inhibitors (SNRIs) in migraine prophylaxis has not been completely established. Current treatments for vestibular migraine... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
The role of serotonin-norepinephrine reuptake inhibitors (SNRIs) in migraine prophylaxis has not been completely established. Current treatments for vestibular migraine (VM) are based on scarce evidence. We aimed to perform an updated review focusing on the efficacy and tolerability of SNRIs for migraine and VM prevention.
METHODS
We searched the PubMed, Web of Science, and Cochrane Library databases for relevant studies. The primary outcome was migraine frequency. In the case of VM, the Dizziness Handicap Inventory (DHI) scores and Vertigo Severity Scores (VSSs) were extracted.
RESULTS
Six randomized controlled trials involving 418 patients were analyzed. Patients receiving SNRIs had fewer migraine days than those receiving a placebo (standardized mean difference -0.38, 95% CI -0.76 to -0.01, p=0.04). The effects of SNRIs and other active drugs were comparable. In patients with VM, venlafaxine had a significant advantage over other active drugs in decreasing the VSS (weighted mean difference (MD) -1.45, 95% CI -2.11 to -0.78, p<0.0001) and the emotional domain score of the DHI (MD -2.64, 95% CI -4.97 to -0.31, p=0.03). We found no significant difference in the rate of withdrawals due to any reason or withdrawals due to side effects between SNRIs and active drugs and between SNRIs and a placebo.
CONCLUSIONS
SNRIs were clinically safe and effective for migraine and VM prophylaxis, were better than a placebo, and not inferior to other active drugs. SNRIs may be a preferable choice for patients with VM with psychiatric disorders.
Topics: Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Serotonin and Noradrenaline Reuptake Inhibitors; Vertigo
PubMed: 32205412
DOI: 10.1136/rapm-2019-101207 -
Journal of Affective Disorders Apr 2020The efficacy ranking of antidepressants for post-stroke depression (PSD) has not been assessed thoroughly yet due to the lack of network meta-analyses with sufficiently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy ranking of antidepressants for post-stroke depression (PSD) has not been assessed thoroughly yet due to the lack of network meta-analyses with sufficiently large sample size.
METHODS
Seven databases including PubMed, Embase, CENTRAL, CBM, CNKI, WanFang and VIP were systematically searched for eligible randomized controlled trials (RCTs) regarding nine antidepressants (citalopram, escitalopram, venlafaxine, paroxetine, duloxetine, amitriptyline, doxepin, sertraline and mirtazapine) treating PSD patients. Stata 15 software and R software were utilized for statistical analyses.
RESULTS
51 RCTs were included in this NMA. For the key efficacy outcomes, escitalopram, mirtazapine, sertraline, citalopram, venlafaxine and paroxetine were associated with larger reduction of the Hamilton Depression Scale (HAMD) total score compared with placebo at 2 weeks. Among the nine antidepressants, escitalopram ranked the best while amitriptyline was the least helpful. At 4 weeks, citalopram ranked higher than placebo and the other eight antidepressants. In contrast, amitriptyline and doxepin were associated with minimal reduction of HAMD score. At 8 weeks, changes in HAMD score were significantly greater in nine antidepressants groups compared to placebo group. Besides, mirtazapine ranked higher than citalopram and escitalopram. At endpoint, mirtazapine was related to the highest response rate, followed by venlafaxine and escitalopram, respectively.
LIMITATIONS
No restriction was imposed on doses of every antidepressant.
CONCLUSIONS
Escitalopram was associated with a quicker relief of depression, but mirtazapine was probably the best option when it comes to the efficacy of 8-week treatment duration. Amitriptyline and doxepin were nearly the worst choice regardless of the duration (2, 4 or 8 weeks).
Topics: Antidepressive Agents; China; Citalopram; Depression; Depressive Disorder, Major; Humans; Network Meta-Analysis; Selective Serotonin Reuptake Inhibitors; Stroke; Treatment Outcome
PubMed: 32056924
DOI: 10.1016/j.jad.2020.02.005 -
Acta Neuropsychiatrica Aug 2020The aim of this paper was to provide a systematic review and update on the pharmacotherapy of social anxiety disorder (SAD), including the efficacy and tolerability of... (Comparative Study)
Comparative Study
OBJECTIVE
The aim of this paper was to provide a systematic review and update on the pharmacotherapy of social anxiety disorder (SAD), including the efficacy and tolerability of these agents, the ranking of interventions, and the grading of results by quality of evidence.
METHODS
The Common Mental Disorder Controlled Trial Register and two trial registries were searched for randomised controlled trials (RCTs) comparing any pharmacological intervention or placebo in the treatment of SAD. We performed a standard pairwise meta-analysis using a random effects model and carried out a network meta-analysis (NMA) using the statistical package, R. Quality of evidence was also assessed.
RESULTS
We included 67 RCTs in the review and 21 to 45 interventions in the NMA. Paroxetine was most effective in the reduction of symptom severity as compared to placebo. Superior response to treatment was also observed for paroxetine, brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline. Higher dropout rates were found for fluvoxamine. Brofaromine, escitalopram, fluvoxamine, paroxetine, pregabalin, sertraline, and venlafaxine performed worse in comparison to placebo for the outcome of dropouts due to adverse events. Olanzapine yielded a relatively high rank for treatment efficacy and buspirone the worse rank for dropouts due to any cause.
CONCLUSION
The differences between drugs and placebo were small, apart from a significant reduction in symptom severity and response for paroxetine. We suggest paroxetine as a first-line treatment of SAD, with the consideration of future research on the drug olanzapine as well as brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline because we observed a response to treatment.
Topics: Adult; Anti-Anxiety Agents; Humans; Network Meta-Analysis; Phobia, Social; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32039743
DOI: 10.1017/neu.2020.6 -
Therapeutic Drug Monitoring Apr 2020The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among...
BACKGROUND
The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among high-risk substance users. Various phenethylamines and NPS are also highly used in populations with mental disorders, depression, or attention deficit hyperactivity disorder (ADHD). Moreover, NPS use is highly prevalent among men and women with risky sexual behavior. Considering these specific populations and their frequent concurrent use of drugs, such as antidepressants, ADHD medication, and antiretrovirals, reports on potential interactions between these drugs, and phenethylamines 4-FA and 2C-B, were reviewed.
METHODS
The authors performed a systematic literature review on 4-FA and 2C-B interactions with antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, bupropion, venlafaxine, phenelzine, moclobemide, and tranylcypromine), ADHD medications (atomoxetine, dexamphetamine, methylphenidate, and modafinil), and antiretrovirals.
RESULTS
Limited literature exists on the pharmacokinetics and drug-drug interactions of 2C-B and 4-FA. Only one case report indicated a possible interaction between 4-FA and ADHD medication. Although pharmacokinetic interactions between 4-FA and prescription drugs remain speculative, their pharmacodynamic points toward interactions between 4-FA and ADHD medication and antidepressants. The pharmacokinetic and pharmacodynamic profile of 2C-B also points toward such interactions, between 2C-B and prescription drugs such as antidepressants and ADHD medication.
CONCLUSIONS
A drug-drug (phenethylamine-prescription drug) interaction potential is anticipated, mainly involving monoamine oxidases for 2C-B and 4-FA, with monoamine transporters being more specific to 4-FA.
Topics: Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Depressive Disorder; Dimethoxyphenylethylamine; Drug Interactions; Humans; Phenethylamines; Prescription Drugs
PubMed: 32022784
DOI: 10.1097/FTD.0000000000000725 -
Acta Psychiatrica Scandinavica May 2020In fixed-dose antidepressant trials, the lower range of the licensed dose achieves the optimal balance between efficacy and tolerability. Whether flexible upward...
BACKGROUND
In fixed-dose antidepressant trials, the lower range of the licensed dose achieves the optimal balance between efficacy and tolerability. Whether flexible upward titration while side-effects permit provides additional benefits is unknown.
METHODS
We did a systematic review of placebo-controlled randomized trials that examined selective serotonin reuptake inhibitors (SSRIs), venlafaxine or mirtazapine in the acute treatment of major depression. Our primary outcome was response, defined as 50% or greater reduction in depression severity. Secondary outcomes included drop-outs due to adverse effects and drop-outs for any reason. We conducted random-effects meta-analyses to calculate the ratios of odds ratios (RORs) between trials comparing the flexible dose titrating above the minimum licensed dose against placebo and those comparing the fixed minimum licensed dose against placebo.
RESULTS
We included 123 published and unpublished randomized controlled trials (29 420 participants). There was no evidence supporting efficacy of the flexible dosing over the fixed low dose of SSRIs (ROR 0.96, 95% CI: 0.73 to 1.25), venlafaxine (1.24, 0.96 to 1.60) or mirtazapine (0.77, 0.33 to 1.78). No important differences were noted for tolerability or for any subgroup analyses except the superior efficacy of venlafaxine flexible dosing between 75 and 150 mg over the fixed 75 mg (1.30, 1.02 to 1.65).
CONCLUSION
There was no evidence to support added value in terms of efficacy, tolerability or acceptability of flexibly titrating up the dosage over the minimum licensed dose of SSRIs or mirtazapine. For venlafaxine, increased efficacy can be expected by flexibly titrating up to 150 mg.
Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Mirtazapine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 31891415
DOI: 10.1111/acps.13145 -
Psychiatry Research Nov 2019Depression has brought huge disease burden to the world. This systematic review aimed to compare the efficacy and safety of pharmacological and non-pharmacological...
Depression has brought huge disease burden to the world. This systematic review aimed to compare the efficacy and safety of pharmacological and non-pharmacological treatments for major depressive disorder (MDD). We searched electronic databases with time range from 1990.1.1 to 2018.9.5. Randomized controlled trials (RCTs) including adult patients with MDD were eligible for inclusion. We conducted network meta-analyses using multivariate meta-analyses models under the frequency framework. Primary outcomes were efficacy (response rate) and safety (overall risk of adverse events). We estimated summary odds ratios (ORs) based on group-level data. 20,937 citations were identified, 91 trials comprising 10,991 participants were included in efficacy study, and 32 trials comprising 5245 participants were included in safety study. In terms of efficacy, all treatments studied (acupuncture, mirtazapine, herbal medicine, venlafaxine, physical exercise, cognitive-behavioral therapy (CBT), bupropion, fluoxetine, and vortioxetine) except for probiotics were significantly more effective than placebo. In terms of safety, bupropion, fluoxetine, venlafaxine, and vortioxetine were significantly less safe than placebo. Herbal medicine and mirtazapine had no significant difference in overall risk of adverse events compared with placebo. Acupuncture, CBT, physical exercise and probiotics were lack of eligible safety data.
Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Bupropion; Cognitive Behavioral Therapy; Depressive Disorder, Major; Fluoxetine; Humans; Mirtazapine; Network Meta-Analysis; Treatment Outcome; Venlafaxine Hydrochloride; Vortioxetine
PubMed: 31627074
DOI: 10.1016/j.psychres.2019.112595 -
Asia-Pacific Journal of Oncology Nursing 2019The recent American Society of Clinical Oncology (ASCO) Clinical Guidelines for chemotherapy-induced peripheral neuropathy (CIPN) management (48 Phase III trials... (Review)
Review
OBJECTIVE
The recent American Society of Clinical Oncology (ASCO) Clinical Guidelines for chemotherapy-induced peripheral neuropathy (CIPN) management (48 Phase III trials reviewed) only recommend duloxetine. However, before concluding that a CIPN intervention is ineffective, scientists and clinicians should consider the risk of Type II error in Phase III studies. The purpose of this systematic review was to characterize internal threats to validity in Phase III CIPN management trials.
METHODS
The PubMed, CINAHL, EMBASE, and Scopus databases were searched for Phase III clinical trials testing interventions for CIPN management between 1990 and 2018. The key search terms were neoplasms, cancer, neuropathy, and CIPN. Two independent researchers evaluated 24 studies, using a modified Joanna Briggs Institute Checklist for Randomized Control Trials developed by the authors specific for CIPN intervention trials.
RESULTS
Two studies exhibited minimal or no design flaws. 22/24 Phase III clinical trials for CIPN have two or greater design flaws due to sample heterogeneity, malapropos mechanism of action, malapropos intervention dose, malapropos timing of the outcome measurement, confounding variables, lack of a valid and reliable measurement, and suboptimal statistical validity.
CONCLUSIONS
Numerous CIPN interventions have been declared ineffective based on the results of Phase III trials. However, internal validity threats to numerous studies may have resulted in Type II error and subsequent dismissal of a potentially effective intervention. Patients may benefit from rigorous retesting of several agents (e.g., alpha-lipoic acid, duloxetine, gabapentin, glutathione, goshajinkigan, lamotrigine, nortriptyline, venlafaxine, and Vitamin E) to expand and validate the evidence regarding ASCO's recommendations for CIPN management.
PubMed: 31572750
DOI: 10.4103/apjon.apjon_14_19