Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: Adults with ADHD
Intervention: Lisdexamfetamine or methylphenidate ᵃ
Comparison: Placebo ᵃ
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Immediate-release methylphenidate versus placebo | ||
Treatment response (follow-up: 3-6 weeks) ᵇ | Favors intervention | Moderate |
ADHD symptoms (Conners’ Adult ADHD Rating Scales - inattention subscale [CAARS] or Barkley Adult ADHD Rating Scale - final values; follow-up: 3-4 weeks) | No statistically significant difference | Low |
ADHD symptoms (ADHD-Rating Scale [ADHD-RS] - change scores; follow-up: 7 weeks) | No statistically significant difference | Very Low |
Clinical Global Impression (CGI) score of 1 or 2 (follow-up: 7 weeks) | No statistically significant difference | Moderate |
Discontinued due to adverse events (follow-up: 3-7 weeks) | Occurs more commonly with immediate-release methylphenidate compared with placebo (favors comparison) | High |
Controlled-release methylphenidate versus placebo | ||
Quality of life (Quality-of-Life Enjoyment and Satisfaction Questionnaire) | No statistically significant difference | High |
Treatment response (follow-up: 6-8 weeks) ᶜ | Favors intervention | Moderate |
ADHD total symptoms (investigator or self-rated; multiple scales including CAARS and ADHD-RS total scores; up to 13 weeks' follow-up) | Favors intervention | Moderate to Low |
ADHD inattention symptoms (investigator or self-rated; CAARS; up to 8 weeks' follow-up) | Favors intervention | Moderate to Low |
ADHD inattention symptoms (investigator rated; CAARS; change scores; at 13 weeks' follow-up) | No statistically significant difference | Low |
ADHD hyperactivity symptoms (investigator or self-rated; CAARS or ADHD-RS hyperactivity subscale; up to 13 weeks' follow-up) | No statistically significant difference | Low |
ADHD hyperactivity symptoms (investigator rated; CAARS hyperactive subscale; change scores; at 5-8 weeks' follow-up) | Favors intervention | Low |
CGI score of 1 or 2 (follow-up: 8 weeks); 7-13 weeks | Favors intervention | High |
Discontinued due to adverse events (follow-up: 6-13 weeks) | Occurs more commonly with controlled-release methylphenidate compared with placebo (favors comparison) | High |
Lisdexamfetamine versus placebo | ||
Quality of life (Adult ADHD Quality-of-Life Questionnaire); 10 weeks | Favors intervention | Very Low |
ADHD total symptoms investigator rated (ADHD-RS total scores); change scores reported; 4-10 weeks | Favors intervention | Moderate |
ADHD inattention symptoms investigator rated (ADHD-RS inattention subscale); 10 weeks | Favors intervention | Low |
ADHD hyperactivity symptoms investigator rated (ADHD-RS hyperactivity subscale); 10 weeks | Favors intervention | Low |
CGI score of 1 or 2 (follow-up: 4 weeks) | Favors intervention | Moderate |
Discontinuation due to adverse events (follow-up: 4-6 weeks) | Occurs more commonly with lisdexamfetamine compared with placebo (favors comparison) | Low |
Recommendations as stated in the source guideline The National Institute for Health and Care Excellence (NICE) 2019 guideline update on Attention deficit hyperactivity disorder: diagnosis and management makes the following recommendation: Offer lisdexamfetamine or methylphenidate as first-line pharmacologic treatment for adults with ADHD. Note that this is an off-label use of lisdexamfetamine for some adults, and some preparations of methylphenidate.
Note The overall rating in this table is based on outcomes which have been deemed critical for decision-making by the guideline development group. Please see the full text guideline for additional information on outcomes classified as important. The guideline committee noted that the drugs that showed a most convincing clinically important benefit from the evidence were methylphenidate, lisdexamfetamine, dextroamphetamine, atomoxetine, and guanfacine. The committee discussed that stimulant medications (e.g., methylphenidate, lisdexamfetamine) generally have a faster onset compared to nonstimulant medications (e.g., atomoxetine, guanfacine). Therefore, they felt that it is better to use a stimulant medication as first-line treatment to allow more rapid assessment of whether a person is responsive. Lisdexamfetamine is a pro-drug of dextroamphetamine. The committee agreed, based on consensus, that dextroamphetamine should only be prescribed when someone has responded very well to lisdexamfetamine but is unable to tolerate its longer effect profile. ᵃ The guideline considered the evidence for other pharmacologic treatments for ADHD in adults including atomoxetine, guanfacine, venlafaxine, and modafinil. In addition to placebo, they also looked at active comparisons (different medications versus each other). See guideline for more information. ᵇ Two studies, defined at a 30% decrease in ADHD investigator symptom rating scale (AISRS) and Clinical Global Impression Scale-Improvement (CGI-I) of 1 or 2; or a decrease of at least 2 points on CGI-Severity scale and a 30% reduction on DSM-IV rating scale. ᶜ Three studies, defined as CGI-I of 1 or 2 and a 30% reduction on the AISRS (2 studies), or a 30% reduction on Wender-Reimherr Adult Attention Deficit Disorder Scale.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: Adults with ADHD
Intervention: Dextroamphetamine
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
ADHD symptoms (follow-up: 6-7 weeks) | Favors intervention | Moderate |
ADHD symptoms: inattentive subscale (follow-up: 6-7 weeks) | Favors intervention | Moderate |
ADHD symptoms: hyperactive subscale (follow-up: 6-7 weeks) | Favors intervention | Moderate |
Clinical Global Impression-Improvement score of 1 or 2 (follow-up: 6 weeks) | Favors intervention | Moderate |
Recommendations as stated in the source guideline The National Institute for Health and Care Excellence (NICE) 2019 guideline update on Attention deficit hyperactivity disorder: diagnosis and management makes the following recommendation: Consider dextroamphetamine for adults whose ADHD symptoms are responding to lisdexamfetamine but who cannot tolerate the longer effect profile. Note that this is an off-label use.
Note Lisdexamfetamine is a pro-drug of dextroamphetamine. The guideline committee agreed, based on consensus, that dextroamphetamine should only be prescribed when someone has responded very well to lisdexamfetamine but is unable to tolerate its longer effect profile.
This evidence table is related to the following section/s:
Cochrane Clinical Answers
Cochrane Clinical Answers (CCAs) provide a readable, digestible, clinically focused entry point to rigorous research from Cochrane systematic reviews. They are designed to be actionable and to inform decision making at the point of care and have been added to relevant sections of the main Best Practice text.
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