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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 -
Acta Neuropsychiatrica Aug 2023Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect... (Review)
Review
OBJECTIVES
Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect treatment outcomes adversely. We aimed to review all relevant previous reports.
METHODS
We performed a PUBMED search of English-language studies, combining terms concerning psychopathology (e.g. apathy) and classes of antidepressants (e.g. SSRI).
RESULTS
According to certain inclusion (e.g. use of DSM/ICD diagnostic criteria) and exclusion (e.g. presence of a clinical condition that may induce apathy) criteria, 50 articles were eligible for review. Together, they suggest that administration of antidepressants - usually SSRIs - can induce an apathy syndrome or emotional blunting, i.e. a decrease in emotional responsiveness, to circumstances which would have triggered intense mood reactions prior to pharmacotherapy. The reported prevalence of antidepressant-induced apathy ranges between 5.8 and 50%, and for SSRIs ranges between 20 and 92%. Antidepressant-induced apathy emerges independently of diagnosis, age, and treatment outcome and appears dose-dependent and reversible. The main treatment strategy is dose reduction, though some data suggest the usefulness of treatment with olanzapine, bupropion, agomelatine or amisulpride, or the methylphenidate-modafinil-olanzapine combination.
CONCLUSION
Antidepressant-induced apathy needs careful clinical attention. Further systematic research is needed to investigate the prevalence, course, aetiology, and treatment of this important clinical condition.
Topics: Selective Serotonin Reuptake Inhibitors; Apathy; Olanzapine; Antidepressive Agents; Bupropion
PubMed: 36644883
DOI: 10.1017/neu.2023.6 -
The Cochrane Database of Systematic... Feb 2022Attention deficit hyperactivity disorder (ADHD) is a psychiatric diagnosis increasingly used in adults. The recommended first-line pharmacological treatment is central... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a psychiatric diagnosis increasingly used in adults. The recommended first-line pharmacological treatment is central nervous system (CNS) stimulants, such as methylphenidate, but uncertainty remains about its benefits and harms.
OBJECTIVES
To assess the beneficial and harmful effects of extended-release formulations of methylphenidate in adults diagnosed with ADHD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, nine other databases and four clinical trial registries up to February 2021. We searched 12 drug regulatory databases for clinical trial data up to 13 May 2020. In addition, we cross-referenced all available trial identifiers, handsearched reference lists, searched pharmaceutical company databases, and contacted trial authors.
SELECTION CRITERIA
Randomised, double-blind, parallel-group trials comparing extended-release methylphenidate formulations at any dose versus placebo and other ADHD medications in adults diagnosed with ADHD.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. We assessed dichotomous outcomes as risk ratios (RRs), and rating scales and continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs). We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We meta-analysed the data using a random-effects model. We assessed three design characteristics that may impair the trial results' 'generalisability'; exclusion of participants with psychiatric comorbidity; responder selection based on previous experience with CNS stimulants; and risk of withdrawal effects. Our prespecified primary outcomes were functional outcomes, self-rated ADHD symptoms, and serious adverse events. Our secondary outcomes included quality of life, ADHD symptoms rated by investigators and by peers such as family members, cardiovascular variables, severe psychiatric adverse events, and other adverse events.
MAIN RESULTS
We included 24 trials (5066 participants), of which 21 reported outcome data for this review. We also identified one ongoing study. We included documents from six drug regulatory agencies covering eight trials. Twenty-one trials had an outpatient setting and three were conducted in prisons. They were primarily conducted in North America and Europe. The median participant age was 36 years. Twelve trials (76% of participants) were industry-sponsored, four (14% of participants) were publicly funded with industry involvement, seven (10% of participants) were publicly funded, and one had unclear funding. The median trial duration was eight weeks. One trial was rated at overall unclear risk of bias and 20 trials were rated at overall high risk of bias, primarily due to unclear blinding of participants and investigators, attrition bias, and selective outcome reporting. All trials were impaired in at least one of the three design characteristics related to 'generalisability'; for example, they excluded participants with psychiatric comorbidity such as depression or anxiety, or included participants only with a previous positive response to methylphenidate, or similar drugs. This may limit the trials' usefulness for clinical practice, as they may overestimate the benefits and underestimate the harms. Extended-release methylphenidate versus placebo (up to 26 weeks) For the primary outcomes, we found very low-certainty evidence that methylphenidate had no effect on 'days missed at work' at 13-week follow-up (mean difference (MD) -0.15 days, 95% confidence interval (CI) -2.11 to 1.81; 1 trial, 409 participants) or serious adverse events (risk ratio (RR) 1.43, CI 95% CI 0.85 to 2.43; 14 trials, 4078 participants), whereas methylphenidate improved self-rated ADHD symptoms (small-to-moderate effect; SMD -0.37, 95% CI -0.43 to -0.30; 16 trials, 3799 participants). For secondary outcomes, we found very low-certainty evidence that methylphenidate improved self-rated quality of life (small effect; SMD -0.15, 95% CI -0.25 to -0.05; 6 trials, 1888 participants), investigator-rated ADHD symptoms (small-to-moderate effect; SMD -0.42, 95% CI -0.49 to -0.36; 18 trials, 4183 participants), ADHD symptoms rated by peers such as family members (small-to-moderate effect; SMD -0.31, 95% CI -0.48 to -0.14; 3 trials, 1005 participants), and increased the risk of experiencing any adverse event (RR 1.27, 95% CI 1.19 to 1.37; 14 trials, 4214 participants). We rated the certainty of the evidence as 'very low' for all outcomes, primarily due to high risk of bias and 'indirectness of the evidence'. One trial (419 participants) had follow-up at 52 weeks and two trials (314 participants) included active comparators, hence long-term and comparative evidence is limited.
AUTHORS' CONCLUSIONS
We found very low-certainty evidence that extended-release methylphenidate compared to placebo improved ADHD symptoms (small-to-moderate effects) measured on rating scales reported by participants, investigators, and peers such as family members. Methylphenidate had no effect on 'days missed at work' or serious adverse events, the effect on quality of life was small, and it increased the risk of several adverse effects. We rated the certainty of the evidence as 'very low' for all outcomes, due to high risk of bias, short trial durations, and limitations to the generalisability of the results. The benefits and harms of extended-release methylphenidate therefore remain uncertain.
Topics: Adult; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 35201607
DOI: 10.1002/14651858.CD012857.pub2 -
International Journal of Geriatric... Sep 2021Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually... (Review)
Review
OBJECTIVES
Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually required, and many patients may not respond to initial therapy. Thus, there is a need for adjunctive treatment options. The objective of this systematic review is to assess the efficacy and safety of methylphenidate (MPH) in the treatment of geriatric depression.
METHODS
PubMed (1946-December 2020) and Embase (1947-December 2020) were queried using the following search terms: geriatrics, aged, geriatric patient, or elderly and depressive disorder, depression, major depression or late-life depression, and MPH. Studies were included if they were a randomized-controlled trial or open-label trial that investigated use of MPH for treatment of depression in adults aged 60 years and older.
RESULTS
After screening per the inclusion criteria, five prospective trials were included. All studies found improvement in depressive symptoms with use of MPH or MPH combined with citalopram. Study durations ranged from 8 to 16 weeks and MPH dosing ranged from 5 to 90 mg per day.
CONCLUSIONS
Based on the reviewed literature, MPH appears to be most effective when combined with citalopram and used short-term. MPH should be initiated at a low dose and titrated up to 10 or 20 mg per day based on response. Larger, long-term trials are needed to further define the role of MPH in this population.
Topics: Aged; Citalopram; Depression; Depressive Disorder, Major; Humans; Methylphenidate; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33829530
DOI: 10.1002/gps.5536 -
Cureus Sep 2023Attention deficit hyperactivity disorder (ADHD) is a fairly common psychiatric disorder among children. It has substantial consequences in terms of quality of life for... (Review)
Review
Attention deficit hyperactivity disorder (ADHD) is a fairly common psychiatric disorder among children. It has substantial consequences in terms of quality of life for those experiencing it and their families. In managing ADHD symptoms medication plays an essential role, including stimulants such as methylphenidate being a key component. Nevertheless, concerns have been raised about possible adverse reactions connected to these drugs. Thus, in this systematic review, an extensive analysis was conducted aiming at understanding any negative repercussions specifically from prolonged exposure to these medications among patients diagnosed with ADHD. The methodology entailed adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. While capturing relevant data through a meticulous search in various databases, filtered according to preset inclusion and exclusion criteria, 13 studies were considered for analysis. Conclusions indicate that the administration of stimulant medications can potentially translate into a small rise in blood pressure along with increased heart rate particularly when amphetamines are taken. However, no reports of notable serious cardiovascular events have emerged. In the domain of neuropsychiatry, it appears that long-term usage of methylphenidate generally bears no serious consequences, even though a hike in risk levels related to the occurrence of psychotic episodes was detected among those treated with amphetamines. Several gastrointestinal side effects including decreased appetite and stomach pain were reported, however, findings regarding ocular abnormalities or growth-related effects stood inconclusive. Therefore, based on this data the consensus is that stimulant medications do generate manageable and mild negative outcomes within the ADHD population. It is vital however to highlight the need for careful observation and further scientific inquiry to achieve a better grasp on both immediate as well as long-term implications involved.
PubMed: 37900465
DOI: 10.7759/cureus.45995 -
Cureus Dec 2022The treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents can be challenging and involve a combination of pharmacologic and... (Review)
Review
Efficacy of Cognitive Behavioral Therapy and Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder in Children and Adolescents: A Systematic Review.
The treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents can be challenging and involve a combination of pharmacologic and non-pharmacological approaches. Using recent literature, we aim to identify the effectiveness of cognitive behavioral therapy (CBT) and methylphenidate (MPH) in reducing the symptoms and improving the quality of life. The investigators conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Investigators independently conducted a routine search on PubMed and Google Scholar for articles published within the last five years through July 30, 2022. Fourteen studies were identified as generally good quality but with some limitations. The final analysis included 2098 patients with an age range of three to eighteen. Nine studies reporting the efficacy of MPH in children, adolescents, or both had different formulations and doses. Six studies documenting the effectiveness of CBT had varying sessions, duration per therapy, modality of administration, and participants. The diagnostic assessment measures showed that the parent symptom rating was the highest and appeared in 11 studies, reflecting the burden on the family. In addition, a structured-self-rated questionnaire rating appeared in eight studies, and two diagnostic assessment measures, teacher symptom rating and investigators, appeared in six. The studies demonstrated significant reductions in the primary symptoms of ADHD at assessment, which led to improved behavioral and functional status with a reduced impact on family and society. Further trials are needed to understand the benefits of CBT and MPH when combined to reduce psychiatry co-morbidities and improve learning and overall quality of life in the long term.
PubMed: 36660538
DOI: 10.7759/cureus.32647 -
JCPP Advances Sep 2023Robust synthesis of evidence to support treatment recommendations for preschoolers with attention-deficit/hyperactivity disorder (ADHD) is lacking. The aim of this...
BACKGROUND
Robust synthesis of evidence to support treatment recommendations for preschoolers with attention-deficit/hyperactivity disorder (ADHD) is lacking. The aim of this systematic review and meta-analysis was to review currently available evidence to evaluate the efficacy and acceptability of stimulants for preschool children with ADHD.
METHODS
We searched electronic databases (CENTRAL, Embase, PubMed) from the database inception to March, 2022; and clinical trial registries through WHO ICTRP from the database inception to July, 2022, and selected double-blinded randomized controlled trials (RCTs) that compared stimulants against placebo for the treatment of preschoolers (age ≤ 7 years) with ADHD. Change in ADHD symptom severity was the primary outcome (efficacy) and all-cause dropout rates (acceptability) was the secondary outcome. Data were pooled with random-effects models weighted by the inverse of the variance. Risk of bias of individual studies were assessed with the Cochrane Risk of Bias tool version 2. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of evidence. This study is registered with PROSPERO (CRD42022348597).
RESULTS
Five RCTs (three methylphenidate immediate-release, one methylphenidate extended-release, and one lisdexamfetamine) were included. The analysis of efficacy was based on 489 participants. Meta-analysis of change in ADHD symptom severity demonstrated a significant effect in favor of stimulants over placebo (standardized mean difference = -0.59; 95% CI -0.77, -0.41; < 0.0001). There was no evidence of heterogeneity but some concerns about publication bias. Regardless, the confidence of evidence was considered moderate. For acceptability, stimulants did not lead to an increased rate of all-cause discontinuation rates in comparison to placebo (OR = 0.59; 95% CI 0.15, 2.37; = 0.45) but the confidence of estimate was very low.
CONCLUSIONS
Our findings demonstrated that stimulants are efficacious in reducing ADHD symptoms among preschool children. Clinicians should consider the use of stimulants when making treatment recommendations for preschoolers with ADHD.
PubMed: 37720577
DOI: 10.1002/jcv2.12146 -
The Journal of Head Trauma...To provide a systematic review of published interventions for posttraumatic brain injury fatigue (PTBIF).
OBJECTIVE
To provide a systematic review of published interventions for posttraumatic brain injury fatigue (PTBIF).
METHODS
PubMed and OneSearch were systematically searched for PTBIF interventions published between January 1, 1989, and March 31, 2019. Search results were evaluated for inclusion based on an abstract and full-text review. Inclusion criteria were (1) an investigation of an intervention, (2) participant sample including individuals with traumatic brain injury (TBI), (3) report of fatigue outcome data among individuals with TBI, and (4) articles available in English, Spanish, French, German, Afrikaans, or Dutch. A risk of bias assessment was conducted on all included publications.
RESULTS
The search resulted in 2343 publications, with 37 meeting inclusion criteria for this review. Categories of PTBIF interventions were pharmacological ( n = 13), psychological ( n = 9), exercise-based ( n = 4), complementary alternative medicine ( n = 5), electrotherapeutic ( n = 3), and multimodal ( n = 3). Only methylphenidate, modafinil, and cognitive behavioral therapy interventions included multiple cohorts. Pharmacological and psychological interventions represented the groups with the lowest risk of bias.
CONCLUSIONS
This review includes 37 studies, with 21 studies published after 2014. Methylphenidate and melatonin were the only pharmacological agents found to reduce fatigue in randomized controlled trials. Creatine given to children prospectively at onset of injury reduced fatigue at follow-up. Walking and water aerobics were effective exercise interventions in isolated randomized controlled studies. One multimodal study of children after concussion was more effective at reducing fatigue and postconcussion symptoms than community standard of care. Other interventions had equivocal results. Overall, more work remains to understand and develop treatments for PTBIF.
Topics: Brain Concussion; Brain Injuries, Traumatic; Creatine; Fatigue; Humans; Melatonin; Methylphenidate
PubMed: 34354018
DOI: 10.1097/HTR.0000000000000710 -
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 American Academy of... Feb 2021Resting-state functional magnetic resonance imaging (R-fMRI) studies of the neural correlates of medication treatment in attention-deficit/hyperactivity disorder (ADHD)... (Review)
Review
OBJECTIVE
Resting-state functional magnetic resonance imaging (R-fMRI) studies of the neural correlates of medication treatment in attention-deficit/hyperactivity disorder (ADHD) have not been systematically reviewed. Our objective was to systematically identify, assess and summarize within-subject R-fMRI studies of pharmacological-induced changes in patients with ADHD. We critically appraised strengths and limitations, and provide recommendations for future research.
METHOD
Systematic review of published original reports in English meeting criteria in pediatric and adult patients with ADHD up to July 1, 2020. A thorough search preceded selection of studies matching prespecified criteria. Strengths and limitations of selected studies, regarding design and reporting, were identified based on current best practices.
RESULTS
We identified and reviewed 9 studies (5 pediatric and 4 adult studies). Sample sizes were small-medium (16-38 patients), and included few female participants. Medications were methylphenidate, amphetamines, and atomoxetine. Wide heterogeneity was observed in designs, analyses and results, which could not be combined quantitatively. Qualitatively, the multiplicity of brain regions and networks identified, some of which correlated with clinical improvements, do not support a coherent mechanistic hypothesis of medication effects. Overall, reports did not meet current standards to ensure reproducibility.
CONCLUSION
In this emerging field, the few studies using R-fMRI to analyze the neural correlates of medications in patients with ADHD suggest a potential modulatory effect of stimulants and atomoxetine on several intrinsic brain activity metrics. However, methodological heterogeneity and reporting issues need to be addressed in future research to validate findings which may contribute to clinical care. Such a goal is not yet at hand.
Topics: Adult; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Child; Female; Humans; Magnetic Resonance Imaging; Methylphenidate; Reproducibility of Results
PubMed: 33137412
DOI: 10.1016/j.jaac.2020.10.013