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Tijdschrift Voor Psychiatrie 2019Attention-deficit/hyperactivity disorder (ADHD) is a frequently occurring problem in child and adolescent psychiatry. Most prevalent comorbid disorders are oppositional...
Attention-deficit/hyperactivity disorder (ADHD) is a frequently occurring problem in child and adolescent psychiatry. Most prevalent comorbid disorders are oppositional defiant behavior, tics, autism spectrum disorder, anxiety and depression. Stimulants are the first pharmacological choice. Recently, long-acting guanfacin became available in Belgium and the Netherlands.
AIM: To investigate the efficacy of guanfacin on comorbid symptoms in ADHD.
METHOD: A systematic search in Medline and Cochrane databases for randomized controlled trials in which the effect of guanfacin on comorbid symptoms is evaluated.
RESULTS: Guanfacin had an effect on autism symptoms, oppositional defiant symptoms and possibly on tics in children and adolescents with adhd. On anxiety symptoms, no effect was reported. The effect on depression needs to be further investigated. The side effects of guanfacin are similar in comorbid disorders and pure ADHD.
CONCLUSION: Guanfacin is a treatment option for ADHD in children and adolescents with comorbid autism or behavioural symptoms and possibly also tics, as it has a demonstrated effect on these comorbid features. Further research is necessary in order to decide on the preference for a particular medication in ADHD with these various comorbid disorders.Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Comorbidity; Female; Guanfacine; Humans; Male; Tic Disorders; Treatment Outcome
PubMed: 31907899
DOI: No ID Found -
Scientific Reports Nov 2019Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a... (Meta-Analysis)
Meta-Analysis
Therapeutic effects of methylphenidate for attention-deficit/hyperactivity disorder in children with borderline intellectual functioning or intellectual disability: A systematic review and meta-analysis.
Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a first-line treatment for ADHD, however no previous meta-analysis has evaluated its overall efficacy for ADHD in children with comorbid intellectual disability (ID) or borderline intellectual functioning. The PubMed/MEDLINE, Cochrane CENTRAL and ScienceDirect databases were systematically searched from inception through 2018/7/15 for clinical studies that investigated the effects of methylphenidate in children with ADHD and ID. A random-effects model meta-analysis was used for data synthesis. Eight studies (average Jadad score = 2.5) enrolling 242 participants receiving methylphenidate and 181 participants receiving placebo were included. The meta-analysis showed that methylphenidate led to a significant improvement in ADHD symptoms relative to placebo (Hedges' g = 0.878, p < 0.001). Meta-regression analysis pointed to an association between the dose of methylphenidate and overall improvement in ADHD severity (slope = 1.334, p < 0.001). Finally, there was no significant difference in drop-out rate [odds ratio (OR) = 1.679, p = 0.260] or rate of treatment discontinuation due to adverse events (OR = 4.815, p = 0.053) between subjects receiving methylphenidate and those taking placebos. Our study suggests that methylphenidate retains its efficacy in children with ADHD and borderline intellectual functioning or ID.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Intellectual Disability; Methylphenidate; Odds Ratio; Placebo Effect; Severity of Illness Index; Treatment Outcome
PubMed: 31685858
DOI: 10.1038/s41598-019-52205-6 -
Current Neuropharmacology 2020To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.
OBJECTIVE
To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.
METHODS
We conducted two researches on the PubMed, Scopus and Embase using the keywords ("elderly") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine") and then ("Alzheimer" OR "dementia") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine").
RESULTS
Twenty-nine papers met all the eligibility criteria. The results are encouraging as 81.5% of the studies showed clinical improvement of the investigated condition.
CONCLUSION
Amphetamines and methylphenidate are probably effective strategies for different conditions in the elderly population. However, further studies are needed to provide more robust evidence on efficacy, dosage and safety for this population.
Topics: Aged; Amphetamine; Dementia; Depressive Disorder, Major; Humans; Lisdexamfetamine Dimesylate; Methylphenidate
PubMed: 31660835
DOI: 10.2174/1570159X17666191010093021 -
Pain Medicine (Malden, Mass.) Apr 2020Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, in a synergistic manner. The aim of this review was to determine the effects of diclofenac combined with TPC compared with diclofenac monotherapy for low back pain (LBP) management.
METHODS
We searched for randomized clinical trials on the MEDLINE, EMBASE, LILACS, and Cochrane databases of records of clinical trials, among other sources. We evaluated the risk of bias regarding randomization, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases. A random-effects meta-analysis to examine patients with acute LBP (N = 1,108 adults) was performed, along with a subsequent sensitivity analysis.
RESULTS
Five studies in patients with LBP were included in the qualitative synthesis. Four of these studies in acute LBP were included in the first meta-analysis. A sensitivity test based on risk of bias (three moderate- to high-quality studies) found that the combination therapy of diclofenac plus TPC was associated with a significant reduction in the duration of treatment (around 50%) compared with diclofenac monotherapy (odds ratio = 2.23, 95% confidence interval = 1.59 to 3.13, P < 0.00001). We found no differences in the safety profile and patient satisfaction.
CONCLUSIONS
This meta-analysis demonstrated that combination therapy of diclofenac with TPC might have an analgesic superiority compared with diclofenac monotherapy in acute LBP. However, there is not enough evidence to recommend this therapy in other types of pain due to the scarcity of high-quality studies.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Therapy, Combination; Humans; Low Back Pain; Pain Measurement; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex
PubMed: 31529101
DOI: 10.1093/pm/pnz216 -
Daru : Journal of Faculty of Pharmacy,... Dec 2019The study systematically reviewed the effectiveness of pharmacological treatments alone or combined with brief cognitive-behavioural therapy (BCBT) for treating Iranian... (Comparative Study)
Comparative Study
OBJECTIVES
The study systematically reviewed the effectiveness of pharmacological treatments alone or combined with brief cognitive-behavioural therapy (BCBT) for treating Iranian amphetamine abusers. The secondary aim was to review the efficacy of BCBT alone or combined with pharmacological treatments for treating amphetamine abusers in the world.
EVIDENCE ACQUISITION
Published trials were considered for inclusion. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Web of Science, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, Cochrane Drugs and Alcohol Group's Specialised Register of Trials, Embase, CINAHL, Scopus, PsychINFO, Iran Medex, Magiran and the Scientific Information Database were searched (January 2001 to March 2019). The reference lists of included studies were hand searched for more information. A systematic literature search in eight databases produced 10 trials.
RESULTS
Risperidone reduced positive psychotic symptoms while aripiprazole reduced negative psychotic symptoms. Methylphenidate reduced craving and depression compared with placebo. Topiramate reduced addiction severity and craving for methamphetamine abuse compared with placebo. Buprenorphine reduced methamphetamine craving more than methadone. Haloperidol and risperidone reduced psychosis. Riluzole reduced craving, withdrawal, and depression compared with placebo. Abstinence from amphetamine or reduction in amphetamine abuse was confirmed in four BCBT studies and one study which applied BCBT with a pharmacological treatment which were stable between two and 12-months. Other changes in BCBT studies were as follows: reduced polydrug use; drug injection, criminality and severity of amphetamine dependence at six-month follow-up; improved general functioning; mental health; stage of change as well as improved motivation to change in a pharmacological + BCBT study.
CONCLUSION
A review of trials indicates that pharmacological treatments and BCBT in a research setting outperform control conditions in treating amphetamines abuse and associated harms. Large-scale studies should determine if both treatments can be effective in clinical settings.
Topics: Amphetamine-Related Disorders; Aripiprazole; Clinical Trials as Topic; Cognitive Behavioral Therapy; Combined Modality Therapy; Humans; Iran; Methylphenidate; Risperidone
PubMed: 31228128
DOI: 10.1007/s40199-019-00282-3 -
Evidence-based Mental Health Aug 2019The comparative efficacy and tolerability of methylphenidate (MPH) and neurofeedback (NF) in individuals with attention-deficit/hyperactivity disorder (ADHD) remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The comparative efficacy and tolerability of methylphenidate (MPH) and neurofeedback (NF) in individuals with attention-deficit/hyperactivity disorder (ADHD) remains uncertain. This study aimed to fill this gap by means of a systematic review/meta-analysis.
METHODS
PubMed, OVID, ERIC, Web of Science, ClinialTrials.gov and a set of Chinese databases were searched until 22 August 2018. Standardised mean differences (SMD) were pooled using comprehensive meta-analysis software.
RESULTS
18 randomised controlled trials (RCTs) were included (778 individuals with ADHD in the NF arm and 757 in the MPH group, respectively; 13 studies in Chinese, five in English). At the study first endpoint, MPH was significantly more efficacious than NF on ADHD core symptoms (ADHD symptoms combined: SMD=-0.578, 95% CI (-1.063 to -0.092)) and on two neuropsychological parameters (inattention:-0.959 (-1.711 to -0.208); inhibition:-0.469 (-0.872 to -0.066)). Dropouts were significantly lower in NF versus MPH (OR=0.412, 0.186 to 0.913). Results were robust to sensitivity analyses, with two important exceptions: removing Chinese studies and non-funded studies, no differences emerged between MPH and NF, although the number of studies was small. At the study follow-up, MPH was superior to NF in some outcomes, but results were inconsistent across raters.
CONCLUSIONS
Due to the risk of bias of included studies, the results of the sensitivity analysis excluding Chinese and non-funded studies, and the mixed findings on at the follow-up endpoint, further high quality studies are needed to assess the comparative efficacy and acceptability of NF and MPH in individuals with ADHD.
TRIAL REGISTRATION NUMBER
CRD42018090256.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate; Neurofeedback; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic
PubMed: 31221690
DOI: 10.1136/ebmental-2019-300088 -
The Cochrane Database of Systematic... Jun 2019Hepatic encephalopathy is a common complication of cirrhosis, with high related morbidity and mortality. Its presence is associated with a wide spectrum of change... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatic encephalopathy is a common complication of cirrhosis, with high related morbidity and mortality. Its presence is associated with a wide spectrum of change ranging from clinically obvious neuropsychiatric features, known as 'overt' hepatic encephalopathy, to abnormalities manifest only on psychometric or electrophysiological testing, 'minimal' hepatic encephalopathy. The exact pathogenesis of the syndrome is unknown but ammonia plays a key role. Drugs that specifically target ammonia include sodium benzoate, glycerol phenylbutyrate, ornithine phenylacetate, AST-120 (spherical carbon adsorbent), and polyethylene glycol.
OBJECTIVES
To evaluate the beneficial and harmful effects of pharmacotherapies that specifically target ammonia versus placebo, no intervention, or other active interventions, for the prevention and treatment of hepatic encephalopathy in people with cirrhosis.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Controlled Trials Register, CENTRAL, MEDLINE, Embase, and three other databases to March 2019. We also searched online trials registries such as ClinicalTrials.gov, European Medicines Agency, WHO International Clinical Trial Registry Platform, and the Food and Drug Administration for ongoing or unpublished trials. In addition, we searched conference proceedings, checked bibliographies, and corresponded with investigators.
SELECTION CRITERIA
We included randomised clinical trials comparing sodium benzoate, glycerol phenylbutyrate, ornithine phenylacetate, AST-120, and polyethylene glycol versus placebo or non-absorbable disaccharides, irrespective of blinding, language, or publication status. We included participants with minimal or overt hepatic encephalopathy or participants who were at risk of developing hepatic encephalopathy.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the included reports. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RR) or mean differences (MD), both with 95% confidence intervals (CIs), and I statistic values as a marker of heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary domains and the certainty of the evidence using GRADE.
MAIN RESULTS
We identified 11 randomised clinical trials that fulfilled our inclusion criteria. Two trials evaluated the prevention of hepatic encephalopathy while nine evaluated the treatment of hepatic encephalopathy. The trials assessed sodium benzoate (three trials), glycerol phenylbutyrate (one trial), ornithine phenylacetate (two trials), AST-120 (two trials), and polyethylene glycol (three trials). Overall, 499 participants received these pharmacotherapies while 444 participants received a placebo preparation or a non-absorbable disaccharide. We classified eight of the 11 trials as at 'high risk of bias' and downgraded the certainty of the evidence to very low for all outcomes.Eleven trials, involving 943 participants, reported mortality data, although there were no events in five trials. Our analyses found no beneficial or harmful effects of sodium benzoate versus non-absorbable disaccharides (RR 1.26, 95% CI 0.49 to 3.28; 101 participants; 2 trials; I = 0%), glycerol phenylbutyrate versus placebo (RR 0.65, 95% CI 0.11 to 3.81; 178 participants; 1 trial), ornithine phenylacetate versus placebo (RR 0.73, 95% CI 0.35 to 1.51; 269 participants; 2 trials; I = 0%), AST-120 versus lactulose (RR 1.05, 95% CI 0.59 to 1.85; 41 participants; 1 trial), or polyethylene glycol versus lactulose (RR 0.50, 95% CI 0.09 to 2.64; 190 participants; 3 trials; I = 0%).Seven trials involving 521 participants reported data on hepatic encephalopathy. Our analyses showed a beneficial effect of glycerol phenylbutyrate versus placebo (RR 0.57, 95% CI 0.36 to 0.90; 178 participants; 1 trial; number needed to treat for an additional beneficial outcome (NNTB) 6), and of polyethylene glycol versus lactulose (RR 0.19, 95% CI 0.08 to 0.44; 190 participants; 3 trials; NNTB 4). We did not observe beneficial effects in the remaining three trials with extractable data: sodium benzoate versus non-absorbable disaccharides (RR 1.22, 95% CI 0.51 to 2.93; 74 participants; 1 trial); ornithine phenylacetate versus placebo (RR 2.71, 95% CI 0.12 to 62.70; 38 participants; 1 trial); or AST-120 versus lactulose (RR 1.05, 95% CI 0.59 to 1.85; 41 participants; 1 trial).Ten trials, involving 790 participants, reported a total of 130 serious adverse events. Our analyses found no evidence of beneficial or harmful effects of sodium benzoate versus non-absorbable disaccharides (RR 1.08, 95% CI 0.44 to 2.68; 101 participants; 2 trials), glycerol phenylbutyrate versus placebo (RR 1.63, 95% CI 0.85 to 3.13; 178 participants; 1 trial), ornithine phenylacetate versus placebo (RR 0.92, 95% CI 0.62 to 1.36; 264 participants; 2 trials; I = 0%), or polyethylene glycol versus lactulose (RR 0.57, 95% CI 0.18 to 1.82; 190 participants; 3 trials; I = 0%). Likewise, eight trials, involving 782 participants, reported a total of 374 non-serious adverse events and again our analyses found no beneficial or harmful effects of the pharmacotherapies under review when compared to placebo or to lactulose/lactitol.Nine trials, involving 733 participants, reported data on blood ammonia. We observed significant reductions in blood ammonia in placebo-controlled trials evaluating sodium benzoate (MD -32.00, 95% CI -46.85 to -17.15; 16 participants; 1 trial), glycerol phenylbutyrate (MD -12.00, 95% CI -23.37 to -0.63; 178 participants; 1 trial), ornithine phenylacetate (MD -27.10, 95% CI -48.55 to -5.65; 231 participants; 1 trial), and AST-120 (MD -22.00, 95% CI -26.75 to -17.25; 98 participants; 1 trial). However, there were no significant differences in blood ammonia concentrations in comparison with lactulose/lactitol with sodium benzoate (MD 9.00, 95% CI -1.10 to 19.11; 85 participants; 2 trials; I = 0%), AST-120 (MD 5.20, 95% CI -2.75 to 13.15; 35 participants; 1 trial), and polyethylene glycol (MD -29.28, 95% CI -95.96 to 37.39; 90 participants; 2 trials; I = 88%).
FUNDING
Five trials received support from pharmaceutical companies while four did not; two did not provide this information.
AUTHORS' CONCLUSIONS
There is insufficient evidence to determine the effects of these pharmacotherapies on the prevention and treatment of hepatic encephalopathy in adults with cirrhosis. They have the potential to reduce blood ammonia concentrations when compared to placebo, but their overall effects on clinical outcomes of interest and the potential harms associated with their use remain uncertain. Further evidence is needed to evaluate the potential beneficial and harmful effects of these pharmacotherapies in this clinical setting.
Topics: Adult; Ammonia; Carbon; Cause of Death; Female; Glycerol; Hepatic Encephalopathy; Humans; Lactulose; Liver Cirrhosis; Male; Middle Aged; Ornithine; Oxides; Phenylbutyrates; Placebos; Polyethylene Glycols; Randomized Controlled Trials as Topic; Sodium Benzoate
PubMed: 31204790
DOI: 10.1002/14651858.CD012334.pub2 -
Current Neuropharmacology 2019Advances in basic and molecular biology have promoted the use of cell cultures in a wide range of areas, including the evaluation of drug efficacy, safety and toxicity. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Advances in basic and molecular biology have promoted the use of cell cultures in a wide range of areas, including the evaluation of drug efficacy, safety and toxicity.
OBJECTIVE
This article aims to provide a general overview of the methodological parameters of cell cultures used to investigate therapeutic options for Attention Deficit Hyperactivity Disorder.
METHOD
A systematic search was performed in the electronic databases PubMed, Scopus, and DOAJ. In vitro experimental studies using cell cultures were included.
RESULTS
A total of 328 studies were initially identified, with 16 included for qualitative synthesis. Seven studies used neuronal cells (SH-SY5Y neuroblastoma and PC12 cell line) and nine used nonneuronal cells. All the studies described the culture conditions, but most studies were inconsistent with regard to reporting results and raw data. Only one-third of the studies performed cell viability assays, while a further 30% conducted gene expression analysis. Other additional tests included electrophysiological evaluation and transporter activity. More than 50% of the studies evaluated the effects of drugs such as methylphenidate and atomoxetine, while plant extracts were assessed in four studies and polyunsaturated fatty acids in one.
CONCLUSION
We suggested a flowchart to guide the planning and execution of studies, and a checklist to be completed by authors to allow the standardized reporting of results. This may guide the elaboration of laboratory protocols and further in vitro studies.
Topics: Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Cell Culture Techniques; Cells, Cultured; Central Nervous System Stimulants; Child; Humans; Methylphenidate; Neurons
PubMed: 31079591
DOI: 10.2174/1570159X17666190409143155 -
Drugs & Aging Apr 2019We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.
METHODS
A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue.
RESULTS
The search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.29; I = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15-1.92; I = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96-3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73-1.27).
CONCLUSIONS
Topical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug-Related Side Effects and Adverse Reactions; Humans; Osteoarthritis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31073923
DOI: 10.1007/s40266-019-00661-0 -
Revista de Neurologia May 2019Methylphenidate is a widely-used drug for the treatment of attention deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Sustained-attention...
INTRODUCTION
Methylphenidate is a widely-used drug for the treatment of attention deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Sustained-attention deficits and poorer task performance in these disorders have been associated with default mode network (DMN) dysfunction in fMRI studies. DMN is a set of brain areas more activated during the resting-state. Under the execution of external tasks, there is an attenuation of DMN activity. In healthy individuals, DMN and task-positive network are anticorrelated. It has been suggested that methylphenidate could normalize the attenuated task-related DMN deactivation in attention- and inhibitory control-related disorders and that such normalization could improve task performance.
PATIENTS AND METHODS
To explore the hypothesis of DMN deactivation after methylphenidate administration, we conducted a systematic review of the literature.
RESULTS
After a systematic search, 12 studies were included in this review. For eligibility, studies were required to measure the effects of methylphenidate administration on the DMN activity. Eleven studies showed evidence of MPH-induced improvements in brain areas related to DMN. The results suggest a normalization of brain circuits in individuals with DMN dysfunction.
CONCLUSIONS
Our preliminary findings strongly suggest methylphenidate improves DMN dysfunction presented in ADHD and other neuropsychiatric disorders. Further studies are needed to better understand this effect and expand comprehension of methylphenidate action mechanisms.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate; Nerve Net; Task Performance and Analysis
PubMed: 31070233
DOI: 10.33588/rn.6810.2018487