Adult ADHD
Visual Abstract
Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis
Reviewed by Charles Li, MD
July 25, 2022
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Key Question
Which medications work best for ADHD?
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It depends on your age
Amphetamines are a good first-line medication for adults. Methylphenidate may be an excellent first-line treatment in children.
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How they answered it
Researchers combined data from 133 trials to see which medications were the safest and most effective.
Background
There are many treatment options for ADHD and even more studies behind them. Experts disagree at times on which treatments to recommend.
This study aimed to determine which treatments work best and which cause the mildest side effects.
Since ADHD can be different in adults and children, researchers also looked to see whether treatments work differently in adults and children.
Study Quote
The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medicati...
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Methods
The authors combined data from 133 clinical trials covering 18,199 children and adults. These studies were randomized and double-blinded, the gold standard of medical research.
They analyzed how well each drug worked in reducing ADHD symptoms within the first year.
They calculated differences in effectiveness between different drugs and the odds of patients having intolerable side effects from the drugs.
Study Quote
We did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted st...
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Effectiveness in Children
In children and teenagers, Adderall and Ritalin tended to work the best, though Strattera worked quite nicely as well.
These data were obtained from third-party observations and notes from the patients' doctors.
Of note, when teachers were surveyed, only studies with Ritalin and Provigil showed statistically significant improvements over the control group.
Ritalin and Adderall were the most effective in reducing ADHD symptoms in children, according to a large meta-analysis of ADHD clinical trials.
Study Quote
For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD -1·02, 95% CI -1·19 to -0·85 for amphetamines, -0·78, -0·93 to -0·62 for methylphenidate, -0·56, -0·66 to -0·45 for atomoxetine)...
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Effectiveness in Adults
In adults, Adderall, Ritalin, Wellbutrin, and Strattera proved to be highly effective in reducing ADHD symptoms across different clinical trials. Adderall was consistently better than the rest of the medications.
Provigil, in adults, did not show significant improvement in all studies. It doesn't necessarily mean that the drug doesn't work, but it does suggest that the data so far is inconsistent for Provigil in adults.
The medications above were the most effective in reducing ADHD symptoms in Adults, as found in a meta-analysis of adult ADHD clinical trials.
Study Quote
In adults (clinicians’ ratings), amphetamines (SMD –0·79, 95% CI –0·99 to –0·58), methylphenidate (–0·49, –0·64 to –0·35), bupropion (–0·46, –0·85 to –0·07), and atomoxetine (–0·45, –0·58 to –0·32), but not modafinil (0·16, –0·28 to 0·59), were better than placebo.
Side Effects: Children
In terms of side effects, there was precise data showing that children had significantly more intolerable side effects on Adderall (amphetamines) and Intuniv (guanfacine).
The other medications here, including Ritalin, also cause side effects, but the data across the different studies were less consistent.
Amphetamines and guanfacine were found to be less tolerable in ADHD clinical trials.
Study Quote
With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36–3·89) and adults (3·26, 1·54–6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20–5·81); and atomoxetine (2·33, 1·28–4...
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Side Effects: Adults
Provigil, Adderall, Ritalin, and Strattera all caused significant side effects in adults.
Adults given these medications were significantly more likely to drop out of the study due to side effects than the control group.
The margins of error in this analysis are too large to draw definite conclusions about which one is better.
Patients on modafenil, amphetamines, methylphenidate, and atomoxetine were significantly more likely to drop out of ADHD clinical trials than those in the control group.
Conclusions
The data in this study suggest that doctors may want to try Ritalin first in children and Adderall first in adults.
This is based on a comprehensive analysis of the best data available as of 2018.
But, as you can tell from the charts, there's still a lot of ambiguity about which medication works better. Different people may also experience each drug differently.
If you have ADHD or suspect that you may have ADHD, talk to your doctor about which medication may work best.
Study Quote
Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis suppo...
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A meta-analysis found that Adderall was highly effective in reducing ADHD symptoms in adults. However, it also carried a higher risk of intolerable side effects.
A large meta-analysis supports the initial use of methylphenidate in children for treatment of ADHD.