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European Journal of Psychotraumatology 2021: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all... (Meta-Analysis)
Meta-Analysis
: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. : A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. : Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.28, 95% CI -0.39 to -0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. : Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antipsychotic Agents; Drug Synergism; Drug Therapy, Combination; Humans; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic
PubMed: 34992738
DOI: 10.1080/20008198.2020.1802920 -
Scientific Reports Dec 2019A systematic review and network-meta analysis (NMA) were performed to estimate significance of the anxiolytic effect of lavender essential oil taken as silexan capsules... (Comparative Study)
Comparative Study
A systematic review and network-meta analysis (NMA) were performed to estimate significance of the anxiolytic effect of lavender essential oil taken as silexan capsules versus other comparators (i.e., placebo/paroxetine/lorazepam). The outcome of interest was Hamilton Anxiety Scale (HAMA). Weighted mean differences (WMD) were calculated to estimate the treatment effect at the confidence interval of 95%. League tables were generated using treatment effect, for all pairwise comparisons, where WMD < 0 favors the column-defining treatment. Five studies were identified with a total of 524 participants receiving treatment with silexan 80 mg and 121 participants taking silexan 160 mg. The NMA results indicated that consumption of silexan 160 mg resulted in higher decline of HAMA score [WMD -1.14 (-1.10, 3.39)] in comparison to silexan 80 mg, placebo [-2.20 (-4.64, 0.24)] and paroxetine [-1.24 (-5.34, 2.85)]. The effect of silexan 80 mg was observed to be same as that of paroxetine. Overall, silexan 160 mg was noticed to be a more efficient treatment giving significant decline in HAMA score across other comparators. However, no improvements in HAMA score was observed for the group receiving lorazepam 0.5 mg when compared to silexan 160 mg, silexan 80 mg, paroxetine 20 mg, and placebo.
Topics: Anti-Anxiety Agents; Anxiety Disorders; Capsules; Humans; Lavandula; Lorazepam; Network Meta-Analysis; Oils, Volatile; Paroxetine; Personality Assessment; Plant Oils; Treatment Outcome
PubMed: 31792285
DOI: 10.1038/s41598-019-54529-9 -
Frontiers in Psychiatry 2020Antidepressants are prescribed for the treatment of a number of psychiatric disorders in children and adolescents, however there is still controversy about whether they...
Antidepressants are prescribed for the treatment of a number of psychiatric disorders in children and adolescents, however there is still controversy about whether they should be used in this population. This meta-review aimed to assess the effects of antidepressants for the acute treatment of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ADs), autistic spectrum disorder (ASD), enuresis, major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) in children and adolescents. Efficacy was measured as response to treatment (either as mean overall change in symptoms or as a dichotomous outcome) and tolerability was measured as the proportion of patients discontinuing treatment due to adverse events. Suicidality was measured as suicidal ideation, behavior (including suicide attempts) and completed suicide. PubMed, EMBASE, and Web of Science were systematically searched (until 31 October 2019) for existing systematic reviews and/or meta-analyses of double-blind randomized controlled trials. The quality of the included reviews was appraised using AMSTAR-2. Our meta-review included nine systematic reviews/meta-analyses (2 on ADHD; 1 on AD; 2 on ASD; 1 on enuresis; 1 on MDD, 1 on OCD and 1 on PTSD). In terms of efficacy this review found that, compared to placebo: fluoxetine was more efficacious in the treatment of MDD, fluvoxamine and paroxetine were better in the treatment of AD; fluoxetine and sertraline were more efficacious in the treatment of OCD; bupropion and desipramine improved clinician and teacher-rated ADHD symptoms; clomipramine and tianeptine were superior on some of the core symptoms of ASD; and no antidepressant was more efficacious for PTSD and enuresis. With regard to tolerability: imipramine, venlafaxine, and duloxetine were less well tolerated in MDD; no differences were found for any of the antidepressants in the treatment of anxiety disorders (ADs), ADHD, and PTSD; tianeptine and citalopram, but not clomipramine, were less well tolerated in children and adolescents with ASD. For suicidal behavior/ideation, venlafaxine (in MDD) and paroxetine (in AD) were associated with a significantly increased risk; by contrast, sertraline (in AD) was associated with a reduced risk. The majority of included systematic reviews/meta-analyses were rated as being of high or moderate in quality by the AMSTAR-2 critical appraisal tool (one and five, respectively). One included study was of low quality and two were of critically low quality. Compared to placebo, selected antidepressants can be efficacious in the acute treatment of some common psychiatric disorders, although statistically significant differences do not always translate into clinically significant results. Little information was available about tolerability of antidepressants in RCTs of OCD and in the treatment of ADHD, ASD, MDD, and PTSD. There is a paucity of data on suicidal ideation/behavior, but paroxetine may increase the risk of suicidality in the treatment of AD and venlafaxine for MDD. Findings from this review must be considered in light of potential limitations, such as the lack of comparative information about many antidepressants, the short-term outcomes and the quality of the available evidence.
PubMed: 32982805
DOI: 10.3389/fpsyt.2020.00717 -
BMC Medicine Nov 2018In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of... (Meta-Analysis)
Meta-Analysis
Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: a systematic review and meta-analysis of cohort studies of more than 9 million births.
BACKGROUND
In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication.
METHODS
The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs).
RESULTS
Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32).
CONCLUSIONS
The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.
Topics: Abnormalities, Drug-Induced; Cohort Studies; Female; Humans; Infant; Pregnancy; Pregnancy Trimester, First; Risk; Selective Serotonin Reuptake Inhibitors
PubMed: 30415641
DOI: 10.1186/s12916-018-1193-5 -
Health Technology Assessment... Mar 2015Premature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE... (Review)
Review
BACKGROUND
Premature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE can be either lifelong and present since first sexual experiences (primary), or acquired (secondary), beginning later (Godpodinoff ML. Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther 1989;15:130-4). Treatments include behavioural and pharmacological interventions.
OBJECTIVE
To systematically review evidence for clinical effectiveness of behavioural, topical and systemic treatments for PE.
DATA SOURCES
The following databases were searched from inception to 6 August 2013 for published and unpublished research evidence: MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects and the Health Technology Assessment database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science. The US Food and Drug Administration website and the European Medicines Agency (EMA) website were also searched.
METHODS
Randomised controlled trials (RCTs) in adult men with PE were eligible (or non-RCTs in the absence of RCTs). RCT data were extrapolated from review articles when available. The primary outcome was intravaginal ejaculatory latency time (IELT). Data were meta-analysed when possible. Other outcomes included sexual satisfaction, control over ejaculation, relationship satisfaction, self-esteem, quality of life, treatment acceptability and adverse events (AEs).
RESULTS
A total of 103 studies (102 RCTs, 65 from reviews) were included. RCTs were available for all interventions except yoga. The following interventions demonstrated significant improvements (p < 0.05) in arithmetic mean difference in IELT compared with placebo: topical anaesthetics - eutectic mixture of local anaesthetics (EMLA(®), AstraZeneca), topical eutectic mixture for PE (Plethora Solutions Ltd) spray; selective serotonin reuptake inhibitors (SSRIs) - citalopram (Cipramil(®), Lundbeck), escitalopram (Cipralex(®), Lundbeck), fluoxetine, paroxetine, sertraline, dapoxetine (Priligy(®), Menarini), 30 mg or 60 mg; serotonin-noradrenaline reuptake inhibitors - duloxetine (Cymbalta(®), Eli Lilly & Co Ltd); tricyclic antidepressants - inhaled clomipramine 4 mg; phosphodiesterase-5 (PDE5) inhibitors - vardenafil (Levitra(®), Bayer), tadalafil (Cialis(®), Eli Lilly & Co Ltd); opioid analgesics - tramadol (Zydol SR(®), Grünenthal). Improvements in sexual satisfaction and other outcomes compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol. Outcomes for interventions not compared with placebo were as follows: behavioural therapies - improvements over wait list control in IELT and other outcomes, behavioural therapy plus pharmacotherapy better than either therapy alone; alpha blockers - terazosin (Hytrin(®), AMCO) not significantly different to antidepressants in ejaculation control; acupuncture - improvements over sham acupuncture in IELT, conflicting results for comparisons with SSRIs; Chinese medicine - improvements over treatment as usual; delay device - improvements in IELT when added to stop-start technique; yoga - improved IELT over baseline, fluoxetine better than yoga. Treatment-related AEs were evident with most pharmacological interventions.
LIMITATIONS
Although data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within these reviews cannot be guaranteed by this assessment report.
CONCLUSIONS
Several interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how soon treatment effects end following treatment cessation and whether or not treatments can be stopped and resumed at a later time. In addition, assessment of the AEs associated with long-term treatment and whether or not different doses have differing AE profiles is required.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013005289.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Anesthetics, Local; Behavior Therapy; Humans; Male; Phosphodiesterase 5 Inhibitors; Premature Ejaculation; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 25768099
DOI: 10.3310/hta19210 -
Menopause (New York, N.Y.) Jan 2024The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared... (Meta-Analysis)
Meta-Analysis
Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause.
IMPORTANCE
The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared with placebo in two phase 3 randomized controlled trials. Its efficacy relative to available therapies is unknown.
OBJECTIVE
We conducted a systematic review and Bayesian network meta-analysis to compare efficacy with fezolinetant 45 mg and hormone therapy (HT) and non-HT for VMS in postmenopausal women.
EVIDENCE REVIEW
Using OvidSP, we systematically searched multiple databases for phase 3 or 4 randomized controlled trials in postmenopausal women with ≥7 moderate to severe VMS per day or ≥50 VMS per week published/presented in English through June 25, 2021. Mean change in frequency and severity of moderate to severe VMS from baseline to week 12 and proportion of women with ≥75% reduction in VMS frequency at week 12 were assessed using fixed-effect models.
FINDINGS
The network meta-analysis included data from the pooled phase 3 fezolinetant trials plus 23 comparator publications across the outcomes analyzed (frequency, 19 [34 regimens]; severity, 6 [7 regimens]; ≥75% response, 9 [15 regimens]). Changes in VMS frequency did not differ significantly between fezolinetant 45 mg and any of the 27 HT regimens studied. Fezolinetant 45 mg reduced the frequency of moderate to severe VMS events per day significantly more than all non-HTs evaluated: paroxetine 7.5 mg (mean difference [95% credible interval {CrI}], 1.66 [0.63-2.71]), desvenlafaxine 50 to 200 mg (mean differences [95% CrI], 1.12 [0.10-2.13] to 2.16 [0.90-3.40]), and gabapentin ER 1800 mg (mean difference [95% CrI], 1.63 [0.48-2.81]), and significantly more than placebo (mean difference, 2.78 [95% CrI], 1.93-3.62]). Tibolone 2.5 mg (the only HT regimen evaluable for severity) significantly reduced VMS severity compared with fezolinetant 45 mg. Fezolinetant 45 mg significantly reduced VMS severity compared with desvenlafaxine 50 mg and placebo and did not differ significantly from higher desvenlafaxine doses or gabapentin ER 1800 mg. For ≥75% responder rates, fezolinetant 45 mg was less effective than tibolone 2.5 mg (not available in the United States) and conjugated estrogens 0.625 mg/bazedoxifene 20 mg (available only as 0.45 mg/20 mg in the United States), did not differ significantly from other non-HT regimens studied and was superior to desvenlafaxine 50 mg and placebo.
CONCLUSIONS
The only HT regimens that showed significantly greater efficacy than fezolinetant 45 mg on any of the outcomes analyzed are not available in the United States. Fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency of moderate to severe VMS.
RELEVANCE
These findings may inform decision making with regard to the individualized management of bothersome VMS due to menopause.
Topics: Female; Humans; Hot Flashes; Desvenlafaxine Succinate; Network Meta-Analysis; Gabapentin; Bayes Theorem; Menopause; Estrogens, Conjugated (USP)
PubMed: 38016166
DOI: 10.1097/GME.0000000000002281 -
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 -
The Cochrane Database of Systematic... Apr 2023This is the second update of the original Cochrane review published in 2013 (issue 6), which was updated in 2016 (issue 11). Pruritus occurs in patients with disparate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is the second update of the original Cochrane review published in 2013 (issue 6), which was updated in 2016 (issue 11). Pruritus occurs in patients with disparate underlying diseases and is caused by different pathologic mechanisms. In palliative care patients, pruritus is not the most prevalent but is a burdening symptom. It can cause considerable discomfort and negatively affect patients' quality of life.
OBJECTIVES
To assess the effects of different pharmacological treatments compared with active control or placebo for preventing or treating pruritus in adult palliative care patients.
SEARCH METHODS
For this update, we searched CENTRAL (the Cochrane Library), MEDLINE (OVID) and Embase (OVID) up to 6 July 2022. In addition, we searched trial registries and checked the reference lists of all relevant studies, key textbooks, reviews and websites, and we contacted investigators and specialists in pruritus and palliative care regarding unpublished data.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) assessing the effects of different pharmacological treatments, compared with a placebo, no treatment, or an alternative treatment, for preventing or treating pruritus in palliative care patients.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the identified titles and abstracts, performed data extraction and assessed the risk of bias and methodological quality. We summarised the results descriptively and quantitatively (meta-analyses) according to the different pharmacological interventions and the diseases associated with pruritus. We assessed the evidence using GRADE and created 13 summary of findings tables.
MAIN RESULTS
In total, we included 91 studies and 4652 participants in the review. We added 42 studies with 2839 participants for this update. Altogether, we included 51 different treatments for pruritus in four different patient groups. The overall risk of bias profile was heterogeneous and ranged from high to low risk. The main reason for giving a high risk of bias rating was a small sample size (fewer than 50 participants per treatment arm). Seventy-nine of 91 studies (87%) had fewer than 50 participants per treatment arm. Eight (9%) studies had low risk of bias in the specified key domains; the remaining studies had an unclear risk of bias (70 studies, 77%) or a high risk of bias (13 studies, 14%). Using GRADE criteria, we judged that the certainty of evidence for the primary outcome (i.e. pruritus) was high for kappa-opioid agonists compared to placebo and moderate for GABA-analogues compared to placebo. Certainty of evidence was low for naltrexone, fish-oil/omega-3 fatty acids, topical capsaicin, ondansetron and zinc sulphate compared to placebo and gabapentin compared to pregabalin, and very low for cromolyn sodium, paroxetine, montelukast, flumecinol, and rifampicin compared to placebo. We downgraded the certainty of the evidence mainly due to serious study limitations regarding risk of bias, imprecision, and inconsistency. For participants suffering from uraemic pruritus (UP; also known as chronic kidney disease (CKD)-associated pruritus (CKD-aP)), treatment with GABA-analogues compared to placebo likely resulted in a large reduction of pruritus (visual analogue scale (VAS) 0 to 10 cm): mean difference (MD) -5.10, 95% confidence interval (CI) -5.56 to -4.55; five RCTs, N = 297, certainty of evidence: moderate. Treatment with kappa-opioid receptor agonists (difelikefalin, nalbuphine, nalfurafine) compared to placebo reduced pruritus slightly (VAS 0 to 10 cm, MD -0.96, 95% CI -1.22 to -0.71; six RCTs, N = 1292, certainty of evidence: high); thus, this treatment was less effective than GABA-analogues. Treatment with montelukast compared to placebo may result in a reduction of pruritus, but the evidence is very uncertain (two studies, 87 participants): SMD -1.40, 95% CI -1.87 to -0.92; certainty of evidence: very low. Treatment with fish-oil/omega-3 fatty acids compared to placebo may result in a large reduction of pruritus (four studies, 160 observations): SMD -1.60, 95% CI -1.97 to -1.22; certainty of evidence: low. Treatment with cromolyn sodium compared to placebo may result in a reduction of pruritus, but the evidence is very uncertain (VAS 0 to 10 cm, MD -3.27, 95% CI -5.91 to -0.63; two RCTs, N = 100, certainty of evidence: very low). Treatment with topical capsaicin compared with placebo may result in a large reduction of pruritus (two studies; 112 participants): SMD -1.06, 95% CI -1.55 to -0.57; certainty of evidence: low. Ondansetron, zinc sulphate and several other treatments may not reduce pruritus in participants suffering from UP. In participants with cholestatic pruritus (CP), treatment with rifampicin compared to placebo may reduce pruritus, but the evidence is very uncertain (VAS: 0 to 100, MD -42.00, 95% CI -87.31 to 3.31; two RCTs, N = 42, certainty of evidence: very low). Treatment with flumecinol compared to placebo may reduce pruritus, but the evidence is very uncertain (RR > 1 favours treatment group; RR 2.32, 95% CI 0.54 to 10.1; two RCTs, N = 69, certainty of evidence: very low). Treatment with the opioid antagonist naltrexone compared to placebo may reduce pruritus (VAS: 0 to 10 cm, MD -2.42, 95% CI -3.90 to -0.94; two RCTs, N = 52, certainty of evidence: low). However, effects in participants with UP were inconclusive (percentage of difference -12.30%, 95% CI -25.82% to 1.22%, one RCT, N = 32). In palliative care participants with pruritus of a different nature, the treatment with the drug paroxetine (one study), a selective serotonin reuptake inhibitor, compared to placebo may reduce pruritus slightly by 0.78 (numerical analogue scale from 0 to 10 points; 95% CI -1.19 to -0.37; one RCT, N = 48, certainty of evidence: low). Most adverse events were mild or moderate. Two interventions showed multiple major adverse events (naltrexone and nalfurafine).
AUTHORS CONCLUSIONS
Different interventions (GABA-analogues, kappa-opioid receptor agonists, cromolyn sodium, montelukast, fish-oil/omega-3 fatty acids and topical capsaicin compared to placebo) were effective for uraemic pruritus. GABA-analogues had the largest effect on pruritus. Rifampin, naltrexone and flumecinol tended to be effective for cholestatic pruritus. However, therapies for patients with malignancies are still lacking. Due to the small sample sizes in most meta-analyses and the heterogeneous methodological quality of the included trials, the results should be interpreted cautiously in terms of generalisability.
Topics: Animals; Humans; Capsaicin; Cromolyn Sodium; gamma-Aminobutyric Acid; Naltrexone; Ondansetron; Palliative Care; Paroxetine; Receptors, Opioid; Rifampin; Zinc Sulfate
PubMed: 37314034
DOI: 10.1002/14651858.CD008320.pub4 -
The Cochrane Database of Systematic... Aug 2018Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterised by inattention, hyperactivity, and impulsivity. ADHD can persist into... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterised by inattention, hyperactivity, and impulsivity. ADHD can persist into adulthood and can affects individuals' social and occupational functioning, as well as their quality of life and health. ADHD is frequently associated with other mental disorders such as substance use disorders and anxiety and affective disorders. Amphetamines are used to treat adults with ADHD, but uncertainties about their efficacy and safety remain.
OBJECTIVES
To examine the efficacy and safety of amphetamines for adults with ADHD.
SEARCH METHODS
In August 2017, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and two trials registers, and we ran citation searches for included studies. We also contacted the corresponding authors of all included studies, other experts in the field, and the pharmaceutical company, Shire, and we searched the reference lists of retrieved studies and reviews for other published, unpublished, or ongoing studies. For each included study, we performed a citation search in Web of Science to identify any later studies that may have cited it.
SELECTION CRITERIA
We searched for randomised controlled trials comparing the efficacy of amphetamines (at any dose) for ADHD in adults aged 18 years and over against placebo or an active intervention.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data from each included study. We used the standardised mean difference (SMD) and the risk ratio (RR) to assess continuous and dichotomous outcomes, respectively. We conducted a stratified analysis to determine the influence of moderating variables. We assessed trials for risk of bias and drew a funnel plot to investigate the possibility of publication bias. We rated the quality of the evidence using the GRADE approach, which yielded high, moderate, low, or very low quality ratings based on evaluation of within-trial risk of bias, directness of evidence, heterogeneity of data; precision of effect estimates, and risk of publication bias.
MAIN RESULTS
We included 19 studies that investigated three types of amphetamines: dexamphetamine (10.2 mg/d to 21.8 mg/d), lisdexamfetamine (30 mg/d to 70 mg/d), and mixed amphetamine salts (MAS; 12.5 mg/d to 80 mg/d). These studies enrolled 2521 participants; most were middle-aged (35.3 years), Caucasian males (57.2%), with a combined type of ADHD (78.8%). Eighteen studies were conducted in the USA, and one study was conducted in both Canada and the USA. Ten were multi-site studies. All studies were placebo-controlled, and three also included an active comparator: guanfacine, modafinil, or paroxetine. Most studies had short-term follow-up and a mean study length of 5.3 weeks.We found no studies that had low risk of bias in all domains of the Cochrane 'Risk of bias' tool, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment, but also because we noted attrition bias, and because we could not rule out the possibility of a carry-over effect in studies that used a cross-over design.Sixteen studies were funded by the pharmaceutical industry, one study was publicly funded, and two studies did not report their funding sources.Amphetamines versus placeboSeverity of ADHD symptoms: we found low- to very low-quality evidence suggesting that amphetamines reduced the severity of ADHD symptoms as rated by clinicians (SMD -0.90, 95% confidence interval (CI) -1.04 to -0.75; 13 studies, 2028 participants) and patients (SMD -0.51, 95% CI -0.75 to -0.28; six studies, 120 participants).Retention: overall, we found low-quality evidence suggesting that amphetamines did not improve retention in treatment (risk ratio (RR) 1.06, 95% CI 0.99 to 1.13; 17 studies, 2323 participants).Adverse events: we found that amphetamines were associated with an increased proportion of patients who withdrew because of adverse events (RR 2.69, 95% CI 1.63 to 4.45; 17 studies, 2409 participants).Type of amphetamine: we found differences between amphetamines for the severity of ADHD symptoms as rated by clinicians. Both lisdexamfetamine (SMD -1.06, 95% CI -1.26 to -0.85; seven studies, 896 participants; low-quality evidence) and MAS (SMD -0.80, 95% CI -0.93 to -0.66; five studies, 1083 participants; low-quality evidence) reduced the severity of ADHD symptoms. In contrast, we found no evidence to suggest that dexamphetamine reduced the severity of ADHD symptoms (SMD -0.24, 95% CI -0.80 to 0.32; one study, 49 participants; very low-quality evidence). In addition, all amphetamines were efficacious in reducing the severity of ADHD symptoms as rated by patients (dexamphetamine: SMD -0.77, 95% CI -1.14 to -0.40; two studies, 35 participants; low-quality evidence; lisdexamfetamine: SMD -0.33, 95% CI -0.65 to -0.01; three studies, 67 participants; low-quality evidence; MAS: SMD -0.45, 95% CI -1.02 to 0.12; one study, 18 participants; very low-quality evidence).Dose at study completion: different doses of amphetamines did not appear to be associated with differences in efficacy.Type of drug-release formulation: we investigated immediate- and sustained-release formulations but found no differences between them for any outcome.Amphetamines versus other drugsWe found no evidence that amphetamines improved ADHD symptom severity compared to other drug interventions.
AUTHORS' CONCLUSIONS
Amphetamines improved the severity of ADHD symptoms, as assessed by clinicians or patients, in the short term but did not improve retention to treatment. Amphetamines were associated with higher attrition due to adverse events. The short duration of studies coupled with their restrictive inclusion criteria limits the external validity of these findings. Furthermore, none of the included studies had an overall low risk of bias. Overall, the evidence generated by this review is of low or very low quality.
Topics: Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic
PubMed: 30091808
DOI: 10.1002/14651858.CD007813.pub3 -
Psychotherapy and Psychosomatics 2015Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical...
Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. Methods: The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: 'withdrawal symptoms' OR 'withdrawal syndrome' OR 'discontinuation syndrome' OR 'discontinuation symptoms', AND 'SSRI' OR 'serotonin' OR 'antidepressant' OR 'paroxetine' OR 'fluoxetine' OR 'sertraline' OR 'fluvoxamine' OR 'citalopram' OR 'escitalopram'. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. Results: There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. Conclusions: Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term 'discontinuation syndrome' that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by 'withdrawal syndrome'. © 2015 S. Karger AG, Basel.
PubMed: 25721705
DOI: 10.1159/000370338