To investigate the efficacy of melatonin compared to placebo in improving sleep parameters in patients with primary sleep disorders.
PubMed was searched for randomized, placebo-controlled trials ...examining the effects of melatonin for the treatment of primary sleep disorders. Primary outcomes examined were improvement in sleep latency, sleep quality and total sleep time. Meta-regression was performed to examine the influence of dose and duration of melatonin on reported efficacy.
Adults and children diagnosed with primary sleep disorders.
Melatonin compared to placebo.
Nineteen studies involving 1683 subjects were included in this meta-analysis. Melatonin demonstrated significant efficacy in reducing sleep latency (weighted mean difference (WMD) = 7.06 minutes 95% CI 4.37 to 9.75, Z = 5.15, p<0.001) and increasing total sleep time (WMD = 8.25 minutes 95% CI 1.74 to 14.75, Z = 2.48, p = 0.013). Trials with longer duration and using higher doses of melatonin demonstrated greater effects on decreasing sleep latency and increasing total sleep time. Overall sleep quality was significantly improved in subjects taking melatonin (standardized mean difference = 0.22 95% CI: 0.12 to 0.32, Z = 4.52, p<0.001) compared to placebo. No significant effects of trial duration and melatonin dose were observed on sleep quality.
This meta-analysis demonstrates that melatonin decreases sleep onset latency, increases total sleep time and improves overall sleep quality. The effects of melatonin on sleep are modest but do not appear to dissipate with continued melatonin use. Although the absolute benefit of melatonin compared to placebo is smaller than other pharmacological treatments for insomnia, melatonin may have a role in the treatment of insomnia given its relatively benign side-effect profile compared to these agents.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: Several studies have demonstrated differences in omega-3 fatty acid composition in plasma and in erythrocyte membranes in patients with attention-deficit/hyperactivity disorder (ADHD) ...compared with unaffected controls. Omega-3 fatty acids have anti-inflammatory properties and can alter central nervous system cell membrane fluidity and phospholipid composition. Cell membrane fluidity can alter serotonin and dopamine neurotransmission. The goal of this meta-analysis was to examine the efficacy of omega-3 fatty acid supplementation in children with ADHD. Method: PubMed was searched for randomized placebo-controlled trials examining omega-3 fatty acid supplementation in children with ADHD symptomatology. The primary outcome measurement was standardized mean difference in rating scales of ADHD severity. Secondary analyses were conducted to determine the effects of dosing of different omega-3 fatty acids in supplements. Results: Ten trials involving 699 children were included in this meta-analysis. Omega-3 fatty acid supplementation demonstrated a small but significant effect in improving ADHD symptoms. Eicosapentaenoic acid dose within supplements was significantly correlated with supplement efficacy. No evidence of publication bias or heterogeneity between trials was found. Conclusion: Omega-3 fatty acid supplementation, particularly with higher doses of eicosapentaenoic acid, was modestly effective in the treatment of ADHD. The relative efficacy of omega-3 fatty acid supplementation was modest compared with currently available pharmacotherapies for ADHD such as psychostimulants, atomoxetine, or alphasubscript 2 agonists. However, given its relatively benign side-effect profile and evidence of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacologic interventions or for families who decline other psychopharmacologic options. (Contains 1 table and 3 figures.)
IMPORTANCE: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder associated with significant impairment and a lifetime prevalence of 1% to 3%; however, it is often missed in primary ...care settings and frequently undertreated. OBJECTIVE: To review the most current data regarding screening, diagnosis, and treatment options for OCD. EVIDENCE REVIEW: We searched PubMed, EMBASE, and PsycINFO to identify randomized controlled trials (RCTs), meta-analyses, and systematic reviews that addressed screening and diagnostic and treatment approaches for OCD among adults (≥18 years), published between January 1, 2011, and September 30, 2016. We subsequently searched references of retrieved articles for additional reports. Meta-analyses and systematic reviews were prioritized; case series and reports were included only for interventions for which RCTs were not available. FINDINGS: Among 792 unique articles identified, 27 (11 RCTs, 11 systematic reviews or meta-analyses, and 5 reviews/guidelines) were selected for this review. The diagnosis of OCD was revised for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, which addresses OCD separately from anxiety disorders and contains specifiers to delineate the presence of tics and degree of insight. Treatment advances include increasing evidence to support the efficacy of online-based dissemination of cognitive behavioral therapies, which have demonstrated clinically significant decreases in OCD symptoms when conducted by trained therapists. Current evidence continues to support the use of selective serotonin reuptake inhibitors as first-line pharmacologic interventions for OCD; however, more recent data support the adjunctive use of neuroleptics, deep-brain stimulation, and neurosurgical ablation for treatment-resistant OCD. Preliminary data suggest safety of other agents (eg, riluzole, ketamine, memantine, N-acetylcysteine, lamotrigine, celecoxib, ondansetron) either in combination with selective serotonin reuptake inhibitors or as monotherapy in the treatment of OCD, although their efficacy has not yet been established. CONCLUSIONS AND RELEVANCE: The dissemination of computer-based cognitive behavioral therapy and improved evidence supporting it represent a major advancement in treatment of OCD. Although cognitive behavioral therapy with or without selective serotonin reuptake inhibitors remains a preferred initial treatment strategy, increasing evidence that supports the safety and efficacy of neuroleptics and neuromodulatory approaches in treatment-resistant cases provides alternatives for patients whose condition does not respond to first-line interventions.
Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β), are elevated in subjects with major depressive disorder (MDD). ...The reason why this occurs is unclear. Elevated levels of inflammatory cytokines could be a result of brain dysfunction in MDD. It is also possible that inflammatory cytokines contribute to depressive symptoms in MDD. If the first assumption is correct, one would expect levels to normalize with resolution of the depressive episode after treatment. Several studies have measured changes in cytokine levels during antidepressant treatment; however, the results vary. The purpose of this study was to pool all available data on changes in serum levels of TNFα, IL-6, and IL-1β during antidepressant treatment to determine whether these levels change. Studies were included if they used an approved pharmacological treatment for depression, patients had a diagnosis of MDD, and serum levels of TNFα, IL-6, and/or IL-1β were measured before and after treatment. Twenty-two studies fulfilled these criteria. Meta-analysis of these studies showed that, overall, while pharmacological antidepressant treatment reduced depressive symptoms, it did not reduce serum levels of TNFα. On the other hand, antidepressant treatment did reduce levels of IL-1β and possibly those of IL-6. Stratified subgroup analysis by class of antidepressant indicated that serotonin reuptake inhibitors may reduce levels of IL-6 and TNFα. Other antidepressants, while efficacious for depressive symptoms, did not appear to reduce cytokine levels. These results argue against the notion that resolution of a depressive episode is associated with normalization of levels of circulating inflammatory cytokines; however, the results are consistent with the possibility that inflammatory cytokines contribute to depressive symptoms and that antidepressants block the effects of inflammatory cytokines on the brain.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Obsessive compulsive disorder is prevalent, disabling, incompletely understood, and often resistant to current therapies. Established treatments consist of specialized cognitive-behavioral ...psychotherapy and pharmacotherapy with medications targeting serotonergic and dopaminergic neurotransmission. However, remission is rare, and more than a quarter of OCD sufferers receive little or no benefit from these approaches, even when they are optimally delivered. New insights into the disorder, and new treatment strategies, are urgently needed. Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder. Here we review the current state of this evidence, including neuroimaging studies, genetics, neurochemical investigations, and insights from animal models. Finally, we review recent findings from small clinical trials of glutamate-modulating medications in treatment-refractory OCD. The precise role of glutamate dysregulation in OCD remains unclear, and we lack blinded, well-controlled studies demonstrating therapeutic benefit from glutamate-modulating agents. Nevertheless, the evidence supporting some important perturbation of glutamate in the disorder is increasingly strong. This new perspective on the pathophysiology of OCD, which complements the older focus on monoaminergic neurotransmission, constitutes an important focus of current research and a promising area for the ongoing development of new therapeutics.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We conducted a meta-analysis of randomized, placebo-controlled trials to determine the efficacy of antipsychotic and alpha-2 agonists in the treatment of chronic tic disorders and examine moderators ...of treatment effect. Meta-analysis demonstrated a significant benefit of antipsychotics compared to placebo (standardized mean difference (SMD)=0.58 (95% confidence interval (CI): 0.36-0.80). Stratified subgroup analysis found no significant difference in the efficacy of the 4 antipsychotic agents tested (risperidone, pimozide, haloperidol and ziprasidone). Meta-analysis also demonstrated a benefit of alpha-2 agonists compared to placebo (SMD=0.31 (95% confidence interval CI: 0.15-0.48). Stratified subgroup analysis and meta-regression demonstrated a significant moderating effect of co-occurring ADHD. Trials which enrolled subjects with tics and ADHD demonstrated a medium-to-large effect (SMD=0.68 (95%CI: 0.36-1.01) whereas trials that excluded subjects with ADHD demonstrated a small, non-significant benefit (SMD=0.15 (95%CI: -0.06 to 0.36). Our findings demonstrated significant benefit of both antipsychotics and alpha-2 agonists in treating tics but suggest alpha-2 agonists may have minimal benefit in tic patients without ADHD.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective:Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single ...dose of ketamine on suicidal ideation.Method:Individual participant data were obtained from 10 of 11 identified comparison intervention studies that used either saline or midazolam as a control treatment. The analysis included only participants who had suicidal ideation at baseline (N=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (the Montgomery-Åsberg Depression Rating Scale MADRS or the Hamilton Depression Rating Scale HAM-D) and self-report scales (the Quick Inventory of Depressive Symptomatology–Self Report QIDS-SR or the Beck Depression Inventory BDI), obtained for up to 1 week after ketamine administration.Results:Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen’s d=0.48–0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. Ketamine’s effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms.Conclusions:Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation. Ketamine’s effects on suicidal ideation were partially independent of its effects on mood, although subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine’s long-term safety and its efficacy in reducing suicide risk is needed before clinical implementation.
Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ...ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications.
RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, sham-controlled trial done at 21 centres in the USA and 18 in Europe. Patients with combined systolic–diastolic hypertension aged 18–75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, CA, USA) or a sham procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with ClinicalTrials.gov, number NCT02649426.
Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a sham procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (−8·5 mm Hg, SD 9·3) than with the sham procedure (−2·2 mm Hg, SD 10·0; baseline-adjusted difference between groups: −6·3 mm Hg, 95% CI −9·4 to −3·1, p=0·0001). No major adverse events were reported in either group.
Compared with a sham procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic–diastolic hypertension in the absence of medications.
ReCor Medical.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to ...assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications.
In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18–75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426.
Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 82% of 51 in the renal denervation group vs 47 82% of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (−8·0 mm Hg IQR –16·4 to 0·0 vs –3·0 mm Hg –10·3 to 1·8; median between-group difference –4·5 mm Hg 95% CI –8·5 to –0·3; adjusted p=0·022); the median between-group difference was –5·8 mm Hg (95% CI –9·7 to –1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups.
Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension.
ReCor Medical.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
PDF
