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Bipolar Disorders May 2024Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder... (Review)
Review
Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.
BACKGROUND
Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD.
METHODS
We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials.
RESULTS
Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias.
CONCLUSIONS
Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Cognitive Dysfunction; Central Nervous System Stimulants; Off-Label Use; Methylphenidate
PubMed: 38433530
DOI: 10.1111/bdi.13414 -
Journal of the American Academy of... Jan 2008Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed and prescribed stimulant medications in... (Review)
Review
OBJECTIVE
Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed and prescribed stimulant medications in adolescent and young adult populations. The purpose of this systematic review of the literature is to evaluate the extent and characteristics of stimulant misuse and diversion in attention-deficit/hyperactivity disorder (ADHD) and non-ADHD individuals.
METHOD
We conducted a systematic review of the literature of available studies looking at misuse and diversion of prescription ADHD medications using misuse, diversion, stimulants, illicit use, and ADHD medications as key words for the search.
RESULTS
We identified 21 studies representing 113,104 subjects. The studies reported rates of past year nonprescribed stimulant use to range from 5% to 9% in grade school- and high school-age children and 5% to 35% in college-age individuals. Lifetime rates of diversion ranged from 16% to 29% of students with stimulant prescriptions asked to give, sell, or trade their medications. Recent work suggests that whites, members of fraternities and sororities, individuals with lower grade point averages, use of immediate-release compared to extended-release preparations, and individuals who report ADHD symptoms are at highest risk for misusing and diverting stimulants. Reported reasons for use, misuse, and diversion of stimulants include to concentrate, improve alertness, "get high," or to experiment.
CONCLUSIONS
The literature suggests that individuals both with and without ADHD misuse stimulant medications. Recent work has begun to document the context, motivation, and demographic profile of those most at risk for using, misusing, and diverting stimulants. The literature highlights the need to carefully monitor high-risk individuals for the use of nonprescribed stimulants and educate individuals with ADHD as to the pitfalls of the misuse and diversion of the stimulants.
Topics: Adolescent; Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Sectional Studies; Drug Prescriptions; Female; Health Surveys; Humans; Illicit Drugs; Male; Methylphenidate; Self Administration; Substance-Related Disorders; United States
PubMed: 18174822
DOI: 10.1097/chi.0b013e31815a56f1 -
Minerva Anestesiologica Oct 2023Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering.
EVIDENCE ACQUSITION
Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery.
EVIDENCE SYNTHESIS
Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks.
CONCLUSIONS
Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.
Topics: Humans; Adult; Shivering; Nefopam; Clonidine; Tramadol; Network Meta-Analysis; Doxapram; Meperidine; Methylphenidate
PubMed: 37458681
DOI: 10.23736/S0375-9393.23.17410-4 -
Neuroscience and Biobehavioral Reviews Jul 2024Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant... (Meta-Analysis)
Meta-Analysis Review
Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant effects on cognition have mostly tested single-dose effects, and there is no meta-analysis of non-stimulant effects. This systematic review and meta-analysis tested the clinically more relevant longer-term effects of Methylphenidate (20 studies; minimum 1 week) and Atomoxetine (8 studies; minimum 3 weeks) on reaction time, attention, inhibition, and working memory, searching papers on PubMed, Embase, Ovid MEDLINE, and PsycINFO. The meta-analysis of 18 studies in 1667 subjects showed that methylphenidate was superior to placebo in all cognitive domains with small to medium effect sizes (Hedges g of 0.34-0.59). The meta-analysis of atomoxetine included 7 studies in 829 subjects and showed no effects in working memory, but superior effects in the other domains with medium to large effect sizes (Hedge's g of 0.36-0.64). Meta-regression analysis showed no drug differences on cognitive effects. The meta-analyses show for the first time that chronic Methylphenidate and Atomoxetine have comparable effects of improving executive functions in people with ADHD.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Executive Function; Central Nervous System Stimulants; Methylphenidate; Atomoxetine Hydrochloride; Memory, Short-Term
PubMed: 38718988
DOI: 10.1016/j.neubiorev.2024.105703 -
Child: Care, Health and Development Jan 2024The efficacy of structured physical exercise (SPE) has been examined in empirical studies to treat attention deficit hyperactivity disorder (ADHD). This review aimed (i)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The efficacy of structured physical exercise (SPE) has been examined in empirical studies to treat attention deficit hyperactivity disorder (ADHD). This review aimed (i) to systematically review and quantify the effects of SPE on ADHD symptomology and executive function (primary outcomes) and on physical health, physical fitness and mental health issues (secondary outcomes) in children/adolescents with ADHD; (ii) to evaluate the study quality and explore moderation of the effects of SPE; and (iii) to summarize the design of SPE interventions.
METHODS
An extensive literature search in the databases of PubMed, Web of Science and EBSCOhost was conducted to identify eligible intervention studies for meta-analysis. A descriptive account of the features of the studies is provided, including assessment of risk/quality (ROB-2/ROBINS-I). Standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated with random effects models to compare post-intervention effects.
RESULTS
A total of 18 studies were included in the review. The majority of the studies examined the effects of SPE lasting for 3-12 weeks. Assessment of bias/quality indicated half of the included studies as high quality. The meta-analysis (pooled n = 627) revealed that SPE had a positive effect on primary and secondary outcomes, that is, inattention (SMD = -1.79), executive function (SMD = 2.19), physical fitness (SMD = 1.39) and mental health issues (SMD = -0.89). Subgroup analysis showed that long-term practice of SPE, featured/tailored SPE, non-Chinese participants, taking methylphenidate and study with low quality had larger effects.
CONCLUSIONS
There is emerging evidence that SPE is a promising option to enhance symptom management and physical/mental health in children/adolescents with ADHD.
Topics: Child; Adolescent; Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Exercise; Exercise Therapy
PubMed: 37433667
DOI: 10.1111/cch.13150 -
Journal of the National Cancer Institute Aug 2008Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related fatigue, but no consensus has been reached on which drugs are useful. This systematic review and meta-analysis aims to review the available evidence and make recommendations for practice and research.
METHODS
We searched the Cochrane register of controlled trials (through the second quarter 2007), Medline (January 1, 1966, through August 1, 2007), and EMBASE (January 1, 1980, through August 1, 2007) by use of a predetermined list of search terms. Cochrane Collaboration meta-analysis review methodology was used for this study. The change in fatigue score on the instrument used in each study and other outcomes of interest (adverse events and withdrawal rates) were compared between treatment and control arms by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided.
RESULTS
We identified 27 eligible trials of drug treatments for cancer-related fatigue (with a total of 6746 participants). The overall effect size for all drug classes was small. A meta-analysis of two studies (n = 264 patients) indicated that methylphenidate (a psychostimulant) was superior to placebo (standardized mean difference [SMD] in change in fatigue score = -0.30, 95% confidence interval [CI] = -0.54 to -0.05; P = .02) for treating cancer-related fatigue. A meta-analysis of 10 studies (n = 2226 patients) evaluating erythropoietin in anemic cancer patients who were undergoing chemotherapy indicated that erythropoietin was superior to placebo (SMD = -0.30, 95% CI = -0.46 to -0.29; P = .008). Among anemic patients (four studies with n = 964 patients), improvement in fatigue was associated with darbepoetin treatment compared with placebo treatment (SMD = -0.13, 95% CI = -0.27 to 0.00; P = .05). Progestational steroids and paroxetine were no better than placebo in the treatment of cancer-related fatigue.
CONCLUSIONS
There is some evidence that treatment of cancer-related fatigue with methylphenidate appears to be effective. More robust evidence indicates that treatment with hematopoietic agents appears to relieve cancer-related fatigue caused by chemotherapy-induced anemia. Further confirmatory trials are required for both observations.
Topics: Anemia; Antidepressive Agents, Second-Generation; Antineoplastic Agents; Central Nervous System Stimulants; Darbepoetin alfa; Dopamine Uptake Inhibitors; Erythropoietin; Fatigue; Hematinics; Humans; Methylphenidate; Neoplasms; Odds Ratio; Paroxetine; Progestins; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 18695134
DOI: 10.1093/jnci/djn250 -
Journal of Clinical PsychopharmacologyStimulants can cause psychotic symptoms at high doses and with parenteral use, but it remains uncertain whether the clinical use of prescription stimulants (PS) at...
PURPOSE/BACKGROUND
Stimulants can cause psychotic symptoms at high doses and with parenteral use, but it remains uncertain whether the clinical use of prescription stimulants (PS) at therapeutic doses precipitates psychosis or influences long-term psychosis risk. Although serious, psychosis is a relatively uncommon event that is difficult to detect in brief randomized controlled trials. There have been several large-scale observational studies of PS and psychosis risk, which have not been reviewed; therefore, we conducted a systematic review of observational studies of PS and psychosis risk in adults and children.
METHODS/PROCEDURE
We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered with International Prospective Register of Systematic Reviews (CRD42021243484). Eligible studies were longitudinal observational studies, either cohort or case-control, published in English that reported on PS exposure and risk of psychotic events or disorders. Risk of bias assessments were performed with the ROBINS-I instrument.
FINDINGS/RESULTS
There were 10,736 reports screened, and 8 were ultimately included (n = 232,567 patients): 4 retrospective cohort studies, 1 nested case-control study, 2 self-controlled case series, and 1 prospective cohort study. Exposure to methylphenidate (MPH) was more commonly studied than amphetamine (AMPH). In the 3 studies with lowest risk of bias, there was no effect of MPH exposure on psychosis risk, but there was evidence for increased risk with AMPH in 1 study.
IMPLICATIONS/CONCLUSIONS
We conclude that observational studies do not support a clear-cut effect of prescribed MPH on psychosis risk but that AMPH has been less well studied and may increase psychosis risk.
Topics: Adult; Amphetamine; Case-Control Studies; Central Nervous System Stimulants; Child; Humans; Methylphenidate; Prescriptions; Prospective Studies; Psychotic Disorders; Retrospective Studies
PubMed: 35489031
DOI: 10.1097/JCP.0000000000001552 -
Korean Journal of Anesthesiology Dec 2023Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery.
METHODS
CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis.
RESULTS
We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs.
CONCLUSIONS
Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.
Topics: Humans; Pregnancy; Female; Diclofenac; Ketorolac; Celecoxib; Cesarean Section; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Pain
PubMed: 37066603
DOI: 10.4097/kja.23014 -
Journal of Affective Disorders Sep 2021Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation strategies are often helpful at reducing the severity of depression. While there are many potential adjunctive medication choices, psychostimulants are among the more controversial options.
OBJECTIVES
The present review sought to clarify the comparative efficacy and safety of different stimulant-like medications to treat depression.
METHODS
We conducted a systematic review and network meta-analysis of randomized, controlled trials (RCTs) using psychostimulant medications to treat adults with depression. Outcomes were pooled using rate ratios (RRs) for dichotomous outcomes (e.g., response, adverse events) and standardized mean differences (SMDs) for continuous outcomes (e.g., change in depression scores).
RESULTS
We identified 37 eligible studies (ranging from 1958 to 2016). We assessed nine psychostimulants: methylphenidate (n=14), dextroamphetamine (n=9), modafinil (n=6), lisdexamphetamine (n=3), methylamphetamine (n=3), pemoline (n=2), atomoxetine (n=1), desipramine (n=1), and imipramine (n=1). Overall, psychostimulants demonstrated efficacy for depression, reduced fatigue and sleepiness, and appeared well-tolerated. However, there was inconsistent evidence across particular psychostimulants. For example, the only psychostimulant which demonstrated efficacy for depression-in terms of both symptom severity and response rates-was methylphenidate.
CONCLUSIONS
While our review suggests that some psychostimulants-particularly methylphenidate-appear well-tolerated and demonstrate some efficacy for depression, as well as fatigue and sleepiness, the strength of evidence in our estimates was low to very low for most agents given the small sample sizes, few RCTs, and imprecision in most estimates. A lack of consistent evidence precludes a definitive hierarchy of treatments and points to a need for additional, high-quality RCTs.
Topics: Adult; Central Nervous System Stimulants; Depression; Fatigue; Humans; Methylphenidate; Network Meta-Analysis
PubMed: 34144366
DOI: 10.1016/j.jad.2021.05.119 -
BMJ Supportive & Palliative Care Sep 2023Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed.
METHODS
Medline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model.
RESULTS
This review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil.
CONCLUSION
Paroxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.
Topics: Humans; Modafinil; Central Nervous System Stimulants; Paroxetine; Network Meta-Analysis; Methylphenidate; Fatigue; Neoplasms
PubMed: 34593386
DOI: 10.1136/bmjspcare-2021-003244