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Drugs & Aging Nov 2022Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people's cognitive...
A Systematic Review of the Current Evidence from Randomised Controlled Trials on the Impact of Medication Optimisation or Pharmacological Interventions on Quantitative Measures of Cognitive Function in Geriatric Patients.
BACKGROUND
Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people's cognitive function. Here we aim to systematically review evidence on the impact of medication optimisation and drug interventions on cognitive function in older adults.
METHODS
A systematic review was performed using MEDLINE and Web of Science on May 2021. Only randomised controlled trials (RCTs) addressing the impact of medication optimisation or pharmacological interventions on quantitative measures of cognitive function in older adults (aged > 65 years) were included. Single-drug interventions (e.g., on drugs for dementia) were excluded. The quality of the studies was assessed by using the Jadad score.
RESULTS
Thirteen studies met the inclusion criteria. In five studies a positive impact of the intervention on metric measures of cognitive function was observed. Only one study showed a significant improvement of cognitive function by medication optimisation. The remaining four positive studies tested methylphenidate, selective oestrogen receptor modulators, folic acid and antipsychotics. The mean Jadad score was low (2.7).
CONCLUSION
This systematic review identified a small number of heterogenous RCTs investigating the impact of medication optimisation or pharmacological interventions on cognitive function. Five trials showed a positive impact on at least one aspect of cognitive function, with comprehensive medication optimisation not being more successful than focused drug interventions. More prospective trials are needed to specifically assess ways of limiting the negative impact of certain medication in particular and polypharmacy in general on cognitive function in older patients.
Topics: Aged; Humans; Cognition; Polypharmacy; Cognitive Dysfunction; Antipsychotic Agents; Randomized Controlled Trials as Topic
PubMed: 36284081
DOI: 10.1007/s40266-022-00980-9 -
Psychopharmacology Dec 2022Despite the reported efficacy of methylphenidate (MET) against Alzheimer's disease (AD)-associated apathy, a recent larger clinical trial was not included in pooled... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Despite the reported efficacy of methylphenidate (MET) against Alzheimer's disease (AD)-associated apathy, a recent larger clinical trial was not included in pooled analysis.
OBJECTIVES
This study aimed at investigating the efficacy of MET for attenuating apathy in patients diagnosed with AD.
METHODS
The PubMed, Cochrane Library, and EMBASE databases were searched from inception until March, 2022 to identify randomized controlled trials (RCTs). The primary outcome was apathy improvement assessed with the Neuropsychiatric Inventory (NPI) apathy subscale, Apathy Evaluation Scale (AES), or Clinical Global Impressions of Change scale (CGI-C apathy).
RESULTS
Meta-analysis of four RCTs revealed an improvement in apathy among patients receiving MET compared to placebo (MD = - 5.12, p = 0.04, three trials, 144 participants) at follow-ups of 1-3 months assessed with AES score. Despite the absence of improvement on NPI-apathy subscale at follow-ups of 1-2 months (MD = - 0.74, p = 0.37, three trials, 265 participants), significant improvement was noted at follow-ups of 6 months (MD = - 1.4, p = 0.02, one trial, 180 participants). Assessment with CGI-C apathy revealed no significant association between improvement in apathy with MET use (RR = 1.38, p = 0.05, three trials, 265 participants). No significant differences in global cognitive function (using the Mini Mental State Exam) or adverse events were noted between the two groups.
CONCLUSION
While AES score suggested an early attenuation effect of MET on apathy in different domains, the NPI-apathy subscale did not show early improvement in apathy until the 6-month follow-up. Further studies with longer follow-ups are needed to elucidate the efficacy of MET for relieving caregiver burden and improving global functional performance.
Topics: Humans; Methylphenidate; Apathy; Alzheimer Disease; Cognition
PubMed: 36243827
DOI: 10.1007/s00213-022-06261-y -
Neuropsychiatric Disease and Treatment 2022The pharmacological management of Autism Spectrum Disorder (ASD) in children remains a challenge due to limited effective management options and the absence of approved... (Review)
Review
PURPOSE
The pharmacological management of Autism Spectrum Disorder (ASD) in children remains a challenge due to limited effective management options and the absence of approved drugs to manage the core symptoms. This review aims to describe and highlight effective pharmacological management options employed in managing the core symptoms and comorbidities of ASD from eligible studies over the past decade.
METHODS
A search of databases; PubMed, Scopus, Science Direct, and PsychInfo for pharmacotherapeutic options for ASD was conducted in this systematic review. Duplicate studies were removed by utilizing the EndNote citation manager. The studies were subsequently screened independently by two authors. Eligible studies from 01 January 2012 to 01 January 2022 were included based on established eligibility criteria. A narrative synthesis was used for data analysis.
RESULTS
The systematic review provides a comprehensive list of effective management options for ASD comorbidities and core symptoms from 33 included studies. The management options for ASD comorbidities; insomnia, hyperactivity, irritability and aggression, gastrointestinal disturbances, and subclinical epileptiform discharges, were reviewed. Risperidone, aripiprazole, methylphenidate, guanfacine, levetiracetam, and atomoxetine are examples of effective pharmacological drugs against ASD comorbidities. Additionally, this review identified various drugs that improve the core symptoms of ASD and include but are not limited to, bumetanide, buspirone, intranasal oxytocin, intranasal vasopressin, and prednisolone.
CONCLUSION
This review has successfully summarized the pharmacological advancements made in the past decade to manage ASD. Although there is still no pharmacological cure for ASD core symptoms or additional drugs that have obtained regulatory approval for use in ASD, the availability of promising pharmacological agents are under evaluation and study.
PubMed: 35968512
DOI: 10.2147/NDT.S371013 -
The Cochrane Database of Systematic... Jul 2022Attention Deficit Hyperactivity Disorder (ADHD) can co-occur in up to 40% of people with epilepsy. There is debate about the efficacy and tolerability of stimulant and... (Review)
Review
BACKGROUND
Attention Deficit Hyperactivity Disorder (ADHD) can co-occur in up to 40% of people with epilepsy. There is debate about the efficacy and tolerability of stimulant and non-stimulant drugs used to treat people with ADHD and co-occurring epilepsy.
OBJECTIVES
To assess the effect of stimulant and non-stimulant drugs on children and adults with ADHD and co-occurring epilepsy in terms of seizure frequency and drug withdrawal rates (primary objectives), as well as seizure severity, ADHD symptoms, cognitive state, general behaviour, quality of life, and adverse effects profile (secondary objectives).
SEARCH METHODS
We searched the following databases on 12 October 2020: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 9 October 2020), CINAHL Plus (EBSCOhost, 1937 onwards). There were no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. SELECTION CRITERIA: We included randomised controlled trials of stimulant and non-stimulant drugs for people of any age, gender or ethnicity with ADHD and co-occurring epilepsy.
DATA COLLECTION AND ANALYSIS
We selected articles and extracted data according to predefined criteria. We conducted primary analysis on an intention-to-treat basis. We presented outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), except for individual adverse effects where we quoted 99% CIs. We conducted best- and worst-case sensitivity analyses to deal with missing data. We carried out a risk of bias assessment for each included study using the Cochrane risk of bias tool and assessed the overall certainty of evidence using the GRADE approach.
MAIN RESULTS
We identified two studies that matched our inclusion criteria: a USA study compared different doses of the stimulant drug osmotic-release oral system methylphenidate (OROS-MPH) with a placebo in 33 children (mean age 10.5 ± 3.0 years), and an Iranian study compared the non-stimulant drug omega-3 taken in conjunction with risperidone and usual anti-seizure medication (ASM) with risperidone and ASM only in 61 children (mean age 9.24 ± 0.15 years). All children were diagnosed with epilepsy and ADHD according to International League Against Epilepsy and Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria, respectively. We assessed both studies to be at low risk of detection and reporting biases, but assessments varied from low to high risk of bias for all other domains. OROS-MPH No participant taking OROS-MPH experienced significant worsening of epilepsy, defined as: 1. a doubling of the highest 14-day or highest two-day seizure rate observed during the 12 months before the trial; 2. a generalised tonic-clonic seizure if none had been experienced in the previous two years; or 3. a clinically meaningful intensification in seizure duration or severity (33 participants, 1 study; low-certainty evidence). However, higher doses of OROS-MPH predicted an increased daily risk of a seizure (P < 0.001; 33 participants, 1 study; low-certainty evidence). OROS-MPH had a larger proportion of participants receiving 'much improved' or 'very much improved' scores for ADHD symptoms on the Clinical Global Impressions for ADHD-Improvement tool (33 participants, 1 study; low-certainty evidence). OROS-MPH also had a larger proportion of people withdrawing from treatment (RR 2.80; 95% CI 1.14 to 6.89; 33 participants, 1 study; moderate-certainty evidence). Omega-3 Omega-3 with risperidone and ASM were associated with a reduction in mean seizure frequency by 6.6 seizures per month (95% CI 4.24 to 8.96; 56 participants, 1 study; low-certainty evidence) and an increase in the proportion of people achieving 50% or greater reduction in monthly seizure frequency (RR 2.79, 95% CI 0.84 to 9.24; 56 participants, 1 study; low-certainty evidence) compared to people on risperidone and ASM alone. Omega-3 with risperidone and ASM also had a smaller proportion of people withdrawing from treatment (RR 0.65, 95% CI 0.12 to 3.59; 61 participants, 1 study; low-certainty evidence) but a larger proportion of people experiencing adverse drug events (RR 1.40, 95% CI 0.44 to 4.42; 56 participants, 1 study; low-certainty evidence) compared to people on risperidone and ASM alone.
AUTHORS' CONCLUSIONS
In children with a dual-diagnosis of epilepsy and ADHD, there is some evidence that use of the stimulant drug OROS-MPH is not associated with significant worsening of epilepsy, but higher doses of it may be associated with increased daily risk of seizures; the evidence is of low-certainty. OROS-MPH is also associated with improvement in ADHD symptoms. However, this treatment was also associated with a large proportion of treatment withdrawal compared to placebo. In relation to the non-stimulant drug omega-3, there is some evidence for reduction in seizure frequency in children who are also on risperidone and ASM, compared to children who are on risperidone and ASM alone. Evidence is inconclusive whether omega-3 increases or decreases the risk of adverse drug events. We identified only two studies - one each for OROS-MPH and omega-3 - with low to high risk of bias. We assessed the overall certainty of evidence for the outcomes of both OROS-MPH and omega-3 as low to moderate. More studies are needed. Future studies should include: 1. adult participants; 2. a wider variety of stimulant and non-stimulant drugs, such as amphetamines and atomoxetine, respectively; and 3. additional important outcomes, such as seizure-related hospitalisations and quality of life. Clusters of studies which assess the same drug - and those that build upon the evidence base presented in this review on OROS-MPH and omega-3 - are needed to allow for meta-analysis of outcomes.
Topics: Adolescent; Adult; Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Drug Resistant Epilepsy; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Iran; Quality of Life; Risperidone
PubMed: 35844168
DOI: 10.1002/14651858.CD013136.pub2 -
Journal of Attention Disorders Dec 2022Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research.
OBJECTIVE
Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research.
METHOD
Controlled trials of adult ADHD measuring emotional behavior were included if another study offered a comparable analysis of the same treatment method. Standardized Mean Difference (SMD) of effects were calculated, and the size of effects for emotional and non-emotional ADHD behavior were compared.
RESULTS
13 out of 14 studies of methylphenidate, atomoxetine, and lisdexamfetamine demonstrated significant improvement in emotional behavior measures, with small to high SMDs. The proportional effect on emotional versus non-emotional behavior ranged from 46% to 110% for methylphenidate, 56% to 129% for atomoxetine, and 36% to 96% for lisdexamfetamine.
CONCLUSION
Psychopharmacological treatments for ADHD are likely to improve emotional behavior, and available scales are sensitive to these effects. Studies dedicated to treatment of this domain of function can further refine clinical approaches.
Topics: Adult; Humans; Atomoxetine Hydrochloride; Lisdexamfetamine Dimesylate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Treatment Outcome
PubMed: 35822610
DOI: 10.1177/10870547221110926 -
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 -
Naunyn-Schmiedeberg's Archives of... Jul 2022Curcumin has protective actions in neuropsychiatric disorders, acting as a neuroprotective agent. As a first approach, the study aimed at a systematic review of the...
Curcumin has protective actions in neuropsychiatric disorders, acting as a neuroprotective agent. As a first approach, the study aimed at a systematic review of the potential effects of curcumin on cognitive performance for attention-deficit-hyperactivity disorder (ADHD). This research was carried out in the databases of PubMed, Embase, SciELO, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and the Grey literature. Upon discovering the scarcity of relevant studies, and knowing that curcumin might have an ADHD hyperactive and anxious behavior, the study proposed to evaluate the effects of curcumin in an ADHD phenotype of spontaneously hypertensive Wistar rats (SHR). No studies were found that related to curcumin and ADHD. Fifteen SHRs were then divided into separate groups that received water (1 mg/kg/day), curcumin (50 mg/kg/day), or methylphenidate (1 mg/kg/day) for 42 days. Behavioral tests to assess activity (Open Field Test), anxiety and impulsivity (Elevated Plus-Maze, and Social Interaction), and memory (Y-Maze, and the Object Recognition Test) were all performed. The animals that were treated with curcumin showed less anxious and hyperactive behavior, as seen in the Open Field Test and the Social Interaction Test. Anxious behavior was measured by the EPM and was not modulated by any treatment. The results of the Y-Maze Test demonstrated that curcumin improved spatial memory. In the Object Recognition Test, neither the short nor the long-term memory was improved. The treatments that were used in this study beneficially modulated the anxious and hyperactive behavior of the SHR.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Behavior Rating Scale; Central Nervous System Stimulants; Curcumin; Disease Models, Animal; Motor Activity; Rats; Rats, Inbred SHR; Rats, Wistar
PubMed: 35394134
DOI: 10.1007/s00210-022-02236-0 -
Journal of Psychiatric Research May 2022Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of deficits in cognitive functions which has significant implications for quality of... (Review)
Review
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of deficits in cognitive functions which has significant implications for quality of life. Psychostimulants are demonstrated to improve symptoms of inattention and hyperactivity/impulsivity, however, their impact on cognition remains incompletely characterized. Herein, the aim of this systematic review is to synthesize the extant literature reporting on the effects of psychostimulants on cognitive function in individuals with ADHD.
METHOD
A systematic search of PubMed, Scopus, and Web of Science from inception to July 2021 was conducted. Additional studies were identified through Google Scholar and a manual search of the reference lists of relevant articles. Inclusion criteria were original studies that evaluated the cognitive function of individuals with ADHD taking psychostimulants drugs. We assessed the quality of the included papers using the Newcastle-Ottawa scale (NOS).
RESULTS
A total of 10 studies involving 753 subjects with ADHD and 194 healthy controls were identified and eligible for inclusion. Nine studies evaluated the impact of methylphenidate on cognitive function and one study investigated the use of lisdexamfetamine. Results indicated that attentional deficits such as memory, vigilance, divided attention, phasic and tonic alertness, and focused attention were improved in ADHD patients treated with psychostimulants. The efficacy of psychostimulants in improving other domains of cognition remains inconclusive due to conflicting evidence or insignificant findings (ie. academic performance and executive function). Overall, results indicate that psychostimulants may improve only select domains of cognition (ie. memory and attention).
CONCLUSION
Psychostimulants are reported to improve several disparate aspects of cognition among individuals with ADHD. Further research is needed to better understand the complex relationships between cognition and behavior in ADHD, as well as the impact of medication on these distinct aspects of functioning. Further research is also needed to determine whether the pro-cognitive effect of stimulants would be transferable to other mental disorders.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cognition; Humans; Methylphenidate; Quality of Life
PubMed: 35303614
DOI: 10.1016/j.jpsychires.2022.03.018 -
Addiction Biology Mar 2022Evidence for acute amphetamine effects on behavioural impulsivity in healthy populations remains elusive and, at times, mixed. This review collates and reviews the...
Evidence for acute amphetamine effects on behavioural impulsivity in healthy populations remains elusive and, at times, mixed. This review collates and reviews the clinical literature on the acute effects of amphetamines on measures of behavioural impulsivity in healthy adults. Randomised and placebo-controlled clinical trials that assessed behavioural impulsivity following the administration of an acute dose of amphetamine or a related psychostimulant (including amphetamine analogues and methylphenidate) were eligible for inclusion. The EBSCOHost, SCOPUS, PsychNet, Web of Science and ProQuest databases were searched from inception to 26 April 2021. Study selection, data extraction and the Cochrane risk of bias assessments were conducted by two independent reviewers. Reporting follows PRISMA guidelines, and the review was registered a priori on the PROSPERO database (Registration No: CRD42021249861). A total of 20 studies were included, comprising a total of 737 participants. Overall, results indicate that low-moderate doses of amphetamine and related psychostimulants may improve (i.e., reduce) impulsive responding without compromising performance, reflecting enhanced inhibitory control of behaviour. These effects are mild and appear most pronounced in individuals with high baseline impulsivity. This review highlights the need for greater consistency in behavioural task selection and future high-quality and well-designed studies to address current concerns around growing prescription psychostimulant use and misuse.
Topics: Adult; Amphetamine; Central Nervous System Stimulants; Humans; Impulsive Behavior; Methylphenidate
PubMed: 35229937
DOI: 10.1111/adb.13128 -
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