Effect size of various ADHD treatment modalities
To the best of our knowledge, this overview is the most comprehensive existing collection of data on the effect sizes of ADHD treatment methods.
Its purpose is to compare the effectiveness of the various forms of ADHD treatment so that—after also taking potential side effects into account—the most appropriate treatment for each individual case can be selected.
The effect size of a treatment is the degree to which symptoms improve.
The magnitude of the effect sizes found is described using standard criteria.1
One measure used to quantify effect size is SMD (standardized mean difference, Cohen’s d; sometimes also Hedges’ g, a slightly modified form of Cohen’s d):
- 0.20 to 0.49: A “small” effect (also called “purely statistical”).23 This is generally difficult to observe in an individual, but can be very important for public health when it involves a general exposure affecting many individuals.
- 0.50 to 0.79: A “moderate” effect (also called “subtle”).23 Should be noticeable to an attentive observer. Clinical benefit begins at 0.5.
- 0.80 and above: A “large” / “strong” effect (also called “obvious”)23 represents a clearly noticeable improvement.
The average effect size for psychotropic medications overall is 0.49 (SMD).4 The average effect size of antidepressants on depression is 0.30.5 Psychotherapy for depression: 0.6; sports: 0.8.
High potency levels (0.8 and above) are generally less common in medicine.6
Medications (especially stimulants) are the most effective treatment for ADHD.
ADHD medications also hold a special place among psychiatric medications. Compared to the typical effect size of psychiatric medications, the effect size of stimulants for ADHD is exceptionally high, ranging from 1.1 to 1.5 (AMP) and from 0.9 to 1.1 (MPH).78 These are the highest effect sizes ever found for psychiatric medications.9
Behavioral therapy alone is nowhere near as effective as medication alone, with an effect size of 0.5 (see below).
Non-stimulants are less effective:
0.8 Atomoxetine
0.6 Guanfacine
and take weeks to take full effect.
The effect size of stimulants thus far exceeds doctors’ typical expectations. Unlike with depression, medications are much more effective here than psychotherapy (which is less effective for ADHD—with an effect size of approximately 0.5—than for depression), though psychotherapy takes several years to take effect, if it works at all (see below), whereas stimulants
- only need to be administered once
- take effect as early as the first day (unlike antidepressants, which sometimes take weeks before you can tell if they’re helping)
- do not share the risk of the sometimes very severe side effects associated with tapering off antidepressants.
These benefits, combined with the high effect size, are the reason why experienced ADHD physicians primarily use medication—and stimulants in particular—while less experienced physicians, alternative practitioners and psychotherapists (the latter two of whom are not permitted to prescribe medication) are more easily cut off from this unusual experience. Without knowledge of the specific characteristics of stimulants in ADHD—relying solely on general medical and psychological experience—there is a higher likelihood of rejecting the use of stimulants.
In the MTA study involving N = 579 children aged 7 to 9, a combination of medication and intensive behavioral interventions did not perform significantly better than medication alone.1011 For impulsive-aggressive symptoms and emotional disorders, medication and behavioral therapy were equally effective.12 A recent comprehensive meta-analysis of k = 190 studies involving N = 26,114 participants reached similar conclusions.13
It has been reported that ADHD medications enhance the therapeutic effectiveness of psychotherapy when taken during psychotherapy.14 As we understand it, in many cases these medications are what make therapy possible in the first place, since stimulants correct the dopamine deficiency and thereby restore dopamine’s neurotrophic effect—which is necessary for learning ability—by supporting the brain’s plasticity. ⇒ Neurophysiological Correlates of Learning Problems in ADHD
Several experienced specialists report that 70% to 80% of people with ADHD no longer require psychotherapy after starting ADHD medication. This is consistent with our experience. However, this should not prevent us from treating milder cases of ADHD primarily with psychotherapy and, in particular, treating ADHD in young children through parent training.
Medications for ADHD are effective only as long as they are administered. Psychotherapy, environmental interventions, and psychoeducation, on the other hand, have long-term effects that extend beyond their immediate application.
The effect sizes mentioned in this article generally refer to SMD (standard mean difference) values.1516 17
SMD is a measure that allows different studies to be compared with one another. However, it always depends on what the comparison is made against, since SMD represents a comparative value; thus, a treatment method will have a very different SMD when compared to a placebo than when compared to a “standard treatment” or to another treatment method. Nevertheless, taken as a whole, the data provide an overview of the comparative effectiveness of different medications and treatment modalities.
When evaluating studies on effect sizes, a distinction must be made between blinded and unblinded assessments.18 Unblinded evaluators are biased and overestimate treatment effects.19 In the case of parent ratings, knowledge of the intervention increases parental tolerance toward ADHD and/or their ability to cope with the negative effects, rather than reducing the symptoms.20 Participation in the study itself is even more likely to lead to bias (“the effort must have been worth it”), which is why parent ratings in particular should be viewed with special caution. Clinician ratings (especially in industry-funded studies) also carry an increased risk of bias. By comparison, teacher ratings are significantly more neutral.
The effect sizes listed in the headings indicate the range of results from the studies and meta-analyses; the lowest and highest values have been omitted to limit bias caused by outliers. Furthermore, values are only listed in the headings if a sufficient number of studies or meta-analyses allow for a reliable conclusion.
1. Effectiveness of Treatment Methods
The various treatment options have varying degrees of effectiveness.
Depending on the problem at hand, a lower or higher SMD is “better.”
In this overview, we have standardized the SMD values from the studies so that a higher value always indicates greater efficacy in treating ADHD symptoms.
1.1. Comparison by Effect Size (SMD)
SMD (standardized mean difference, Cohen’s d) is one of the measures used to quantify effect size: small = 0.20, medium = 0.50, large = 0.80.
SMD 0.2: NNT = 8.9321
SMD 0.3: The mean score for the experimental group is higher than the score of 62% of the participants in the control group22
SMD 0.5: 69% higher than in the control group; NNT = 3.6221
SMD 0.6: 73% larger
SMD 0.75: 77% larger
SMD 0.8: NNT = 2.3421
SMD 1.0: approximately 70% probability of treatment benefit23
SMD 2.0: just under a 90% probability of treatment benefit23
SMD is calculated as the mean of the treatment group minus the mean of the comparison group, with the result divided by the pooled standard deviation of the groups. SMD is thus a measure of effect size that reflects differences in means between two groups with equal group sizes and equal group variances. The effect is measured in comparison to a control intervention (usually a placebo). Therefore, SMD does not measure the total improvement, but rather by how much the improvement was greater than that of the control (usually the placebo). Unless otherwise specified, the effect size based on SMD refers to the difference relative to the placebo,
Treatment based on the person with ADHD’s preference (0.18 to 0.31)
Treatment that was tailored to the preferences of people with ADHD generally showed (not specifically in relation to ADHD) a reduction of
greater effect size.
In addition, treatment discontinuations decreased overall (not specifically related to ADHD)
Both factors are significant enough that they should be taken into account when choosing among several possible treatment options.
1.1.1. Drug treatment by effect size (0.61 to 0.68)
Review Articles
A review found an effect size for
- Pharmacological treatment of ADHD by
- 0.67 (parent rating)
- 0.68 (teacher rating) and for
- psychological interventions by
- 0.42 (parent rating) and
- 0.25 (teacher rating).27
Meta-analyses
- Children and Adolescents
- 0.75 (teacher rating), meta-analysis (k = 63 RPCCT studies, N = 11,788 children and adolescents) (10 medications, most commonly MPH and ATX, average duration 7.9 weeks)28
- 0.74 (practitioner rating; evidence of bias, particularly in industry-funded studies), meta-analysis (k = 63 randomized controlled trials, N = 11,788 children and adolescents) (10 medications, most commonly MPH and ATX, mean duration 7.9 weeks)28
- 0.63 (parent rating), meta-analysis (k = 63 randomized controlled trials, N = 11,788 children and adolescents) (10 medications, most commonly MPH and ATX, average duration 7.9 weeks)28
- 0.61 meta-analysis (k = 49 studies, N = 7,685 children and adolescents) of all ADHD medications with regard to overall ADHD symptoms29
- Adults
1.1.1.1. Stimulants: 0.8 to 1.5
Regardless of age
- Stimulants are 0.44 better than non-stimulants (expert rating).30
- Stimulants are 0.25 times more effective than non-stimulants (meta-analysis of k = 15 RCTs involving N = 4,648 children and/or adolescents aged 6 to 17 with ADHD)32
- 0.83 for stimulants
- 0.58 for non-stimulants
In children and adolescents
- 0.88 for ADHD symptoms overall (meta-analysis, k = 12, N = 1,620)29
- Stimulants were more effective than non-stimulants and were associated with 32% fewer treatment discontinuations than placebo (OR = 0.68).28
For adults:
-
Overall Symptoms of ADHD
-
0.8 for ADHD symptoms overall33
-
0.61 after 12 weeks as assessed by experts (meta-analysis, double-blind RCT)34
-
0.43 in the patient rating when limited to low-bias studies (meta-analysis)34
-
0.39 after 12 weeks based on self-assessment (meta-analysis, double-blind RCT)34; no longer superior to placebo after 26 weeks based on self-assessment
-
0.31 after 26 weeks in the expert assessment (meta-analysis, double-blind RCT)34; no longer better than placebo after 26 weeks in the self-assessment
-
-
Emotional dysregulation
In adults, the effect size of methylphenidate appears to be smaller than in children and adolescents, whereas this is not the case with amphetamines.31
1.1.1.1.1. Amphetamine-based medications: 1.1 to 1.52
-
Amphetamine-based medications, regardless of age
- Total amphetamine medications:
- by symptoms:
- by active ingredient
- Lisdexamfetamine (Vyvanse)
- 1.6139
- Dextroamphetamine (immediate release)
- 1.2440 (e.g., Attentin)
- Sustained release dextroamphetamine (not LDX)
- 1.1340
- Mixed amphetamine salts, immediate release
- Sustained-release mixtures of amphetamine salts (e.g., Adderall XR; a mixture of dexamphetamine and levoamphetamine in a 3:1 ratio)
- Lisdexamfetamine (Vyvanse)
-
Children and adolescents:
- Total amphetamine medications:
- 1.16 (meta-analysis, k = 5, N = 757 children)29 Lisdexamfetamine performed significantly better, with scores of 1.34, 1.46, and 1.53 (3 studies), compared to mixed amphetamine salts, which scored 0.76 and 0.77.
- 1.0243
- 0.84 on Arztrating; k = 3, N = 81344
- 0.57 on the parent rating scale; k = 7, N = 1,24744
- 0.55 on the teacher rating scale; k = 5, N = 74544
- Lisdexamfetamine
- 1.6145
- 1.5240
- 1.44 (meta-analysis, 3 studies on children)29
- 1.2846
- In a randomized, double-blind study involving N = 200 participants who did not respond to MPH, lisdexamfetamine was compared with atomoxetine. Lisdexamfetamine performed significantly better than atomoxetine in 2 out of 6 categories and in the overall assessment. With regard to learning and school performance, lisdexamfetamine was 0.19 SMD better than atomoxetine.47
- Dextroamphetamine (immediate release and LDX)
- Mixed amphetamine salts (Adderall):
- Extended-release amphetamine suspension
- 0.8 / 0.5 to 0.8 for up to 13 hours50
- Total amphetamine medications:
-
Adults:
1.1.1.1.2. Methylphenidate: 0.9 to 1.1
-
Methylphenidate, regardless of age
- Total MPH:
- Total ADHD symptoms
- individual ADHD symptoms
- Immediate-release methylphenidate (immediate release)
- Sustained-release methylphenidate: 1.0862
- Total MPH:
-
MPH in children and adolescents:
- MPH in General
- Total ADHD symptoms
- 0.87 on the teacher rating scale (meta-analysis, k = 5, N = 668)63
- 0.84 in the parent rating48
- 0.82 in the teacher rating48
- 0.78 in the clinic rating (meta-analysis)4348
- 0.77 in teacher ratings (Cochrane meta-analysis, k = 19 studies, N = 1,698)63
- 0.74 (meta-analysis, k = 424, N = 32,718)64
- 0.73 (meta-analysis)35
- individual ADHD symptoms
- Inattention: 0.8 35
- Executive memory: 0.26 gg compared to placebo (meta-analysis of k = 36 studies)65
- non-executive memory: 0.60 higher than placebo (meta-analysis, k = 36)65
- Response time: 0.24 days compared to placebo (meta-analysis, k = 36)65
- Variability in reaction time: 0.62 gg compared to placebo (meta-analysis, k = 36)65
- Inhibition of reaction time: 0.41 gg compared to placebo (meta-analysis, k = 36)65
- Total ADHD symptoms
- Concerta:
- Children and adolescents: 1.049
- Equasym Retard:
- Children and adolescents: 0.6 to 1.849
- MPH, immediate release
- Sustained-release methylphenidate
- MPH in General
-
Adults:
- Total MPH (without distinguishing between immediate release and sustained release)
- 0.58 for immediate release MPH (meta-analysis, k = 18 RCTs with N = 2,045 adults)70
- Dose level
- 0.58 at an average dose of 57.4 mg/day
- + 0.12 for each 10 mg increase per dose
- Dosage regimen
- 0.53 variable dosage
- 0.40 solid cans
- Dose level
- OROS-MPH
- 0.5171
- Ritalin LA
- Sustained-release MPH compared to placebo72
- ADHD symptoms overall
- 0.42 Physician assessment; k = 18, N = 4,183
- 0.37 Self-assessment; k = 16, N = 3,799
- 0.31 Peers and family members; k = 3, N = 1,005
- Quality of Life
- 0.15 Self-assessment; k = 6, N = 1,888
- 0.15 reduction in days of work lost; k = 1, N = 409
- ADHD symptoms overall
- Emotional dysregulation:
Meta-analyses comparing MPH with atomoxetine:
Compared to atomoxetine, MPH showed barely any superiority across all of its dosage forms (0.0773 to 0.097475 ). With regard to inattention, MPH was marginally superior overall (0.1373).
However, OROS-MPH proved to be more effective than atomoxetine by 0.3175 to 0.3274.
The response rate for MPH was 14% higher.73
Meta-analyses comparing MPH with neurofeedback:
Methylphenidate was shown to be superior to neurofeedback with an effect size of (meta-analysis, k = 18 RCTs, N = 778 participants):76
- 0.59 for core ADHD symptoms
- 0.96 for inattention
- 0.47 for inhibition
with a 40% higher treatment discontinuation rate among MPH patients.
1.1.1.1.3. Mazindol
Mazindol, a wake-promoting substance with stimulant properties, showed a high effect size of 1.09 on core ADHD symptoms in adults with ADHD.9
Further studies on this topic should be awaited to confirm these findings.
1.1.1.2. Total non-stimulants: 0.52 to 0.71
Total non-stimulants
- Age-independent
- 0.7142
- in children and adolescents
- 0.52 for ADHD symptoms overall (meta-analysis, k = 37, N = 6,065)29
The effect size of stimulants was reported to be 0.44 greater than that of non-stimulants (expert rating).30
1.1.1.2.1. Guanfacine: 0.67 to 0.76 for children and adolescents
Guanfacine has an effect size of 0.57 to 0.76 when used as monotherapy.
- Children and adolescents:
α-2 Agonists (Guanfacine and Clonidine) in Children and Adolescents
- 0.59 for total ADHD symptoms (meta-analysis, k = 12, N = 2,276 children and adolescents) with α-2-agonist monotherapy (k = 9, N = 1,550):78
- 0.56 for hyperactivity/impulsivity (k = 9, N = 1,550)
- 0.57 for inattention (k = 9, N = 1,550)
- 0.44 for ODD symptoms (k = 9, N = 1,550)
- Fewer discontinuations of monotherapy due to lack of efficacy compared with placebo
- 0.52 (approx.) for total ADHD symptoms (meta-analysis, k = 11, N = 1,885 children and adolescents)29
1.1.1.2.2. Atomoxetine: 0.63 for children and adolescents, 0.45 for adults
-
Atomoxetine, regardless of age:
-
Children and adolescents:
-
Adults:
-
0.57 in a double-blind crossover RCT vs. placebo81
-
0.51 after 12 weeks in the expert assessment (meta-analysis, double-blind RCT)34; no longer superior to placebo after 26 weeks in the expert assessment
-
0.46 (meta-analysis)71
-
0.45 (meta-analysis)43
-
0.41 after 10 weeks (meta-analysis, k = 5)82
-
0.40 on the clinician rating scale (meta-analysis, k = 12, N = 3,375)83
-
0.39 after 12 weeks in the patent rating (meta-analysis, double-blind RCT)34
-
0.36 in the patient rating when limited to low-bias studies (meta-analysis)34
-
0.35 after 26 weeks in the patient rating (meta-analysis, k = 16 double-blind RCTs, N = 2,379)34, no better than placebo in the expert rating
-
0.33 on the patient rating scale after 12 weeks (meta-analysis, k = 12, N = 3,375)83
-
0.41 after 6 months (meta-analysis)82
-
0.2456
-
-
Individual symptoms:
Atomoxetine has an NNT of 5 for attention problems associated with ADHD36
2.57 times as many treatment discontinuations as with placebo (meta-analysis, k = 12, N = 3,375).83
1.1.1.2.3. Modafinil: 0.62 to 0.76 KiJu
- Modafinil is not age-dependent:
- Children and adolescents:
- 0.71 to 0.77 compared to placebo (meta-analysis, k = 5 RCTs)84
- 0.76 (meta-analysis, k = 4, N = 667)29, with 3 of the 4 studies reporting an effect size ranging from 0.42 to 0.54.
- 0.67 in the teacher rating48
- 0.62 in the clinic rating (meta-analysis)4348
- 0.52 (meta-analysis)40
- 0.46 in the parent rating48
- Adults:
- minus 0.16 (meta-analysis)43
1.1.1.2.4. Viloxazine: 0.45 to 0.63
1.1.1.2.5. Bupropion: 0.32 to 0.46
Meta-analyses:
- Bupropion, regardless of age:
- 0.33 (meta-analysis)85
- The medications that showed a significant reduction on the ADHD rating scale compared to placebo were
- Bupropion (SMD: 0.33)
- Dasotralin (SMD: 0.49)
- Venlafaxine (SMD: 0.71)
- Viloxazine (SMD: 0.45)
- Other medications (centanafadine, duloxetine, edivoxetine, reboxetine, tipepidine, vortioxetine) were no more effective than placebo in reducing the severity of ADHD symptoms
- None of the medications showed a significant difference in efficacy compared to methylphenidate
- Duloxetine (OR: 15) was associated with significantly more treatment-related adverse events than methylphenidate
- The medications that showed a significant reduction on the ADHD rating scale compared to placebo were
- 0.3246
- 0.2240
- 0.33 (meta-analysis)85
- Children and adolescents:
- Adults:
1.1.1.2.6. Clonidine: 0.38
- Age-independent:
- 0.03 (meta-analysis)40
- Children and adolescents:
- in children with ADHD and comorbid tics or Tourette syndrome
- 0.40 in the parent assessment (study with N = 68 participants)86
For studies on alpha-2 agonists in general (guanfacine and clonidine), see “Guanfacine Monotherapy” and “Guanfacine Combination Therapy with Stimulants.”
1.1.1.2.7. Centanafadin
Manufacturer’s specification: 0.656
No significant effect (meta-analysis)85
We will have to wait for further independent studies.
1.1.1.2.8. Dasotralin
-
0.49 (meta-analysis)85
-
0.48 (6-week RCT with N = 342 children aged 6–12 years) at 4 mg/day. 2 mg/day was virtually ineffective.87 56
-
0.35 for total ADHD symptoms (meta-analysis, k = 8, in children and adults)88
-
0.33 for inattention (meta-analysis, k = 8, in children and adults)88
-
0.27 for hyperactivity/impulsivity (meta-analysis, k = 8, in children and adults)88
1.1.1.2.9. Cannabinoids, Sativex
There is only one small RCT on THC with N = 30 participants. It found an effect size of 0.2 compared to placebo for cognitive performance.8990
1.1.1.2.10. SGA (second-generation antipsychotics) for hyperactivity in children with ASD
A meta-analysis (k = 13, N = 712) examined the effect size of second-generation antipsychotics on the ADHD symptom of hyperactivity in children with ASD:91
- 0.66 stimulants
- 0.59 SGA
1.1.1.2.11. Desipramine
Desipramine improved the core symptoms of ADHD in children and adolescents86
-
1.42 on the parent rating scale (k = 2, N = 99)
-
0.97 on the teacher rating scale (k = 2, N = 89)
-
Improvement in physician ratings (k = 2, N = 103, not specified in SMD)
-
0.90 on the parent rating scale for children with ADHD and comorbid tics or Tourette syndrome (study with N = 68 participants)
Due to its broad-spectrum effects and the resulting high incidence of side effects, desipramine is no longer available on the market in most countries.
1.1.1.2.12. Tipepidine
- 0.38 in children and adolescents, according to a single study (N = 51)29
- No significant effect compared to placebo (meta-analysis)85
1.1.1.2.13. Nortriptyline
Improvement in the core symptoms of ADHD in children and adolescents, as rated by physicians. No data provided in SMD.86
1.1.1.2.14. Venlafaxine
0.71 (meta-analysis)85
This figure does not in any way correspond to the experiences shared on the ADxS forum or those of the ADHD specialists known to us.
In our experience, venlafaxine has little or no effect on ADHD symptoms.
Given the sometimes serious side effects (we know of several people with ADHD who experienced severe side effects during tapering, ranging from the tapering process failing to requiring hospitalization), we view venlafaxine with great skepticism.
1.1.1.2.15. Selegiline
No improvement over placebo in terms of ADHD symptom relief (meta-analysis, k = 2).92
1.1.1.2.16. Edivoxetin
No significant effect compared to placebo (meta-analysis)85
1.1.1.2.17. Reboxetine
No significant effect compared to placebo (meta-analysis)85
1.1.1.2.18. Vortioxetine
No significant effect compared to placebo (meta-analysis)85
1.1.1.2.19. Duloxetine
No significant effect compared to placebo (meta-analysis)85
Significantly more treatment-related adverse events than with methylphenidate.85
1.1.1.3. Combination therapy
1.1.1.3.1. Combination therapy with guanfacine and stimulants: 0.36 gg more than stimulants alone
A combination of MPH and guanfacine is more effective than MPH alone.
For adjunctive treatment with α-2 agonists (k = 3, N = 726), the meta-analysis showed an additional effect of:78
- 0.36 for total ADHD symptoms
- 0.33 for hyperactivity/impulsivity
- 0.34 for inattention
A meta-analysis found that, when alpha-2 agonists (guanfacine, clonidine) were taken in addition to stimulants by children and adolescents, the overall effect size on ADHD symptoms was:29
- 0.36 as the additional effect of alpha-2 agonists compared to stimulants alone (k = 5, N = 724)
- The two studies found values of 0.64 and 0.34 for Guanfacin XR (both statistically significant)
- The three studies found values of 0.34, 0.30, and 0.16 for clonidine (only one of which was statistically significant).
A study found that guanfacine plus MPH was more effective than guanfacine or MPH alone:93
- Guanfacine alone: a reduction in symptoms of at least 50% in 68% of people with ADHD
- Methylphenidate alone: a reduction in symptoms of at least 50% in 81% of people with ADHD
- Combination therapy with MPH and guanfacine: a reduction in symptoms of at least 50% in 91% of people with ADHD)
1.1.1.4. Vitamins, Minerals, Natural Supplements
1.1.1.4.1. Probiotics: 0.25
Compared to a placebo, probiotics improved ADHD symptoms:94
- 0.25 Total ADHD Symptoms
- 0.14 Inattention
- 0.08 Hyperactivity/Impulsivity
One study found a strong effect (SMD 1.25; Cohen’s d) of Lactiplantibacillus plantarum and Levilactobacillus brevis at a dose of 109 CFU/day on hyperactivity and impulsivity only in younger children (ages 5 to 9) with ASD. We were unable to discern from the data the mild to moderate improvement in hyperactivity and impulsivity in young children with ADHD reported by the authors.95
1.1.1.4.2. Omega-3 / Omega-6 PUFA supplementation: 0.08 to 0.17
There is barely any evidence to support the effectiveness of PUFAs (omega-3 and omega-6 fatty acids) in treating ADHD.
Although the existing research suggests, at best, that omega-3 may have an advantage over omega-6 in ADHD, there are a surprising number of studies that tested omega-6. Furthermore, most studies lasted no longer than 16 weeks, even though the brain needs up to 3 months to recover from an omega-3 deficiency.96
Even in parent ratings—which are subject to bias due to parents’ knowledge of their child’s gift—the effects fell below the minimum threshold of 0.2 considered meaningful for a treatment.97
Meta-analyses:
-
0.38 for omega-3 (meta-analysis, k = 7, N = 534, Hedges’ g)98
-
0.35 for omega-3, when limited to studies lasting at least 4 months and comparing omega-3 to a placebo.99 Neither a high dose of EPA nor a high EPA/DHA ratio improved ADHD symptoms.
-
0.16 to 0.17 in parent and teacher ratings100
-
0.06 to 0.17 for ADHD symptoms, a meta-analysis of k = 31 studies with N = 1,755 patients:101
- 0.17 on the parent rating scale (k = 23)
- 0.06 in the teacher rating (k = 10)
-
0.16 for omega-3 on core ADHD symptoms (meta-analysis with k = 22 studies and N = 1,789 participants)99
-
0.11 for the effect of omega-3 on ADHD symptoms. Meta-analysis of k = 7 studies involving N = 719 children and adolescents29
-
0.08 on the parent rating scale (meta-analysis of k = 16 studies with N = 1,116 participants). The effect on hyperactivity/impulsivity (0.08) was slightly greater than that on inattention (0.01). Overall, we found evidence with high certainty that PUFAs had no effect on parent-rated ADHD symptoms, inattention, or hyperactivity/impulsivity, and only evidence with low certainty of an improvement.102
-
Overall, high certainty regarding evidence that PUFAs had no effect on parent-rated ADHD symptoms, inattention, or hyperactivity/impulsivity, and only low certainty regarding evidence of improvement (meta-analysis, k = 37)102
-
No significant improvement in ADHD symptoms as measured by the Conners Rating Scale following omega-3 supplementation in 6 out of 6 RCTs (N = 564), in 2 out of 2 augmentation studies and in 4 out of 4 monotherapy studies (meta-analysis, k = 12)103
With regard to individual symptoms:
- Cognitive attention: 1.09 (meta-analysis, k = 3, N = 214, Hedges’ g)98
- Quality of life: 0.01 (meta-analysis of k = 31 studies with N = 1,755 patients)101
- Behavioral difficulties
1.1.1.4.3. Zinc
A meta-analysis of k = 6 RCTs involving N = 489 children found an effect size for:104
- 0.62 core ADHD symptoms
- 0.93 Hyperactivity (not statistically significant)
- 0.21 Inattention (not statistically significant)
One study (Bilici, 2004) reports an effect size of 1.61 for children and adolescents.29
Unfortunately, these values do not correspond in any way to empirical evidence regarding the general population of people with ADHD. However, they may apply to people with ADHD who have an existing zinc deficiency.
1.1.1.4.4. Saffron
In this regard, a single study found an effect size of 0.97 for ADHD symptoms in children and adolescents.29
Another study (Baziar 2019) reported that saffron is as effective as methylphenidate.
1.1.1.4.5. Phosphatidylserine
There is only one study on the effect of phosphate dilyserin on ADHD, which found an effect size of 0.85 for ADHD symptoms in children and adolescents.29
1.1.1.4.6. Micronutrients
0.49 on overall functional ability (meta-analysis, k = 16, N = 1,719)105
1.1.1.4.7. St. John’s Wort
In this regard, a single study found a 0.22-point increase in ADHD symptoms among children and adolescents.29
1.1.1.4.8. Iron
A study found an effect size of 0.15 for ADHD symptoms in children and adolescents.29
1.1.1.4.9. Antioxidants
One study found a deterioration of 0.14, while another found an improvement of 0.38 in children and adolescents. Overall, no effect on ADHD symptoms was observed.29
1.1.1.4.10. Acetyl-L-carnitine
One study found a deterioration of 0.06, while another found an improvement of 0.21 in children and adolescents. Overall, no effect on ADHD symptoms was observed.29
1.1.2. Effectiveness of Non-Pharmacological Treatments for ADHD by Effect Size
Efficacy is reported as an effect size (SMD). Higher values are better.
A review study found an effect size of 0.67 (parent rating) and 0.68 (teacher rating) for pharmacological treatment of ADHD, and 0.42 (parent rating) and 0.25 (teacher rating) for psychological interventions.27
A review of inter- and intra-individual psychological treatment approaches for ADHD found that psychoeducation and parent training, school-based interventions, reinforcement strategies, and neurofeedback consistently showed small to moderate effect sizes in reducing hyperactivity/impulsivity in children. Emotional self-regulation, social skills training, and cognitive training, on the other hand, yielded unsatisfactory results. Combining these approaches with medication resulted in significantly greater improvements.106
A meta-analysis of k = 32 published RCTs on behavioral interventions (all interventions aimed at increasing desired behaviors and reducing undesired behaviors, i.e., classical contingency management, behavior therapy [primarily delivered by mediators such as parents or teachers], and cognitive-behavioral therapy [such as verbal self-instruction, problem-solving strategies, or social skills training] in children aged 3 to 18 years, found18
- unmasked
- 0.68 positive parenting behavior
- 0.57 negative parenting behavior
- 0.47 social skills
- 0.37 parental self-concept
- 0.35 ADHD in children
- 0.28 Academic Performance
- 0.26 Behavioral problems
- Even after blinding, only some of the results remained statistically significant:
- 0.63 positive parenting behavior
- 0.43 negative parenting behavior
- 0.31 Behavioral problems
According to a meta-analysis, various forms of therapy improved various symptoms in ADHD (SMD: standard mean difference; higher is better: up to 0.5 is low to moderate, up to 1 is moderate to high, and 1 or higher is high)107
- Depression
- Cognitive Behavioral Therapy (moderate to large effect size)
- 0.52 SMD in the follow-up in the group comparison
- 0.74 SMD in the follow-up, subjectively for people with ADHD
- Neurofeedback
- ineffective when compared across groups
- subjectively somewhat more effective than cognitive behavioral therapy
- DBT
- ineffective when compared across groups
- subjectively moderately effective, less effective than cognitive behavioral therapy
- MBSR
- ineffective when compared across groups
- subjectively moderately effective, even less effective than DBT
- Cognitive Behavioral Therapy (moderate to large effect size)
- Symptoms of anxiety
- Cognitive Behavioral Therapy (moderate to large effect size)
- 0.73 SMD in the follow-up in the between-group comparison
- 0.74 SMD in the follow-up, subjectively for the person with ADHD
- Neurofeedback
- ineffective when compared across groups
- subjectively more effective in the long term than cognitive behavioral therapy
- MBSR
- ineffective when compared across groups
- subjectively moderately effective, ineffective in the long term
- DBT
- completely ineffective
- Cognitive Behavioral Therapy (moderate to large effect size)
- Self-worth
- Cognitive Behavioral Therapy (moderate to large effect size)
- ineffective when compared across groups
- 1.40 SMD in the follow-up, subjectively for people with ADHD
- Neurofeedback
- ineffective when compared across groups
- subjectively more effective in the long term than cognitive behavioral therapy
- MBSR
- ineffective when compared across groups
- subjectively moderately effective, ineffective in the long term
- DBT
- completely ineffective
- Cognitive Behavioral Therapy (moderate to large effect size)
- Quality of Life
- Cognitive Behavioral Therapy (moderate to large effect size)
- ineffective to slightly effective in a group comparison
- 0.57 SMD in the follow-up, subjectively for people with ADHD
- MBSR
- Subjectively, very good in the short term
- DBT
- Very effective in the short term when compared to other groups, but ineffective in the long term
- Subjectively, moderately effective in the short term; weakly effective in the long term
- Cognitive Behavioral Therapy (moderate to large effect size)
- emotional dysregulation
- Cognitive Behavioral Therapy (moderate to large effect size)
- 0.64 SMD in the follow-up, in a group comparison
- 0.73 SMD in the follow-up, subjectively for people with ADHD
- MBSR
- Showed weak efficacy in the short term when compared to other groups; long-term effects are unknown
- Subjectively very effective in the short term; long-term effects are unknown
- Cognitive Behavioral Therapy (moderate to large effect size)
1.1.2.1. Sports (endurance training): approx. 0.8 (0.62 to 1.96)
In addition to the effect size of the treatment, adherence to the therapy should also be taken into account. Therefore, people with ADHD should engage in the sport they enjoy the most.108 Exercise is only beneficial if it is actually done. Furthermore, anything that brings you joy improves your quality of life.
1.1.2.1.1. Review Articles on the Effect Size of Sports on ADHD
A review analyzed 37 meta-analyses comprising 106 studies and found a Hedges’ g of:109
- Inattention: 0.92
- Impulse control: 0.82
- cognitive flexibility: 0.52
- Emotional symptoms: limited evidence
- Social symptoms: limited evidence
- Working memory: limited evidence
- Hyperactivity: not significant
- Behavioral functions: not significant
A review of 8 meta-analyses comprising k = 99 RCTs, N = 5,656, found a Hedges’ g of:110
- 0.67 for ADHD and schizophrenia
- General cognition: 0.92 for ADHD and schizophrenia (review of 2 METASTUDIES with k = 22 RCTs, N = 920)110
- The average session lasted 45 minutes, 3 times a week for 10 weeks
An even more comprehensive review, which analyzed 133 meta-analyses comprising 2,724 RCTs and N = 258,279 participants, found the following across the general population (i.e., not limited to people with ADHD):111
- general cognition: 0.42
- Memory: 0.26
- more pronounced in children and adolescents than in adults
- Executive functions: 0.24
- more pronounced in children and adolescents than in adults
- more pronounced in ADHD than in other conditions
The effects were generally greater for low- and moderate-intensity interventions. Shorter interventions (1–3 months) and exergames (video games that require physical activity) had the greatest impact on general cognition and memory.
1.1.2.1.2. Meta-analyses on the Effect Size of Sports on ADHD
-
Overall ADHD Symptoms
- 0.93 (meta-analysis of k = 5 studies with N = 144 participants)112 Unfortunately, no comparison was made with the effect size of medication
- 0.83 core ADHD symptoms reduced through closed-skill training (meta-analysis of k = 22 RCTs involving children and adolescents with ADHD)113
- 0.65 for endurance training in children with ADHD (meta-analysis, k = 8, N = 249)114
- 0.39 core ADHD symptoms reduced through regular sports (meta-analysis of k = 22 RCTs involving children and adolescents with ADHD)113
-
Individual ADHD symptoms
- Impulse control
- 1.98 through open-skills training (meta-analysis, k = 15, N = 578; recommended: 12 weeks, at least twice a week at moderate or high intensity)115
- 1.94 through activities involving open-ended skills (meta-analysis of k = 44 studies from 1983 to 2022 involving N = 1,757 children and adolescents, compared to controlled alternatives, e.g., waiting list, no intervention, watching a video, or a sedentary attention control))108
- 1.3 through regular sports (meta-analysis, k = 11, N = 346 children with ADHD/ASD)116
- 1.0 from ball games among children and adolescents (meta-analysis, k = 16, N = 668)117
- 1.0 through closed-skills training (meta-analysis, k = 15, N = 578; recommended: 12 weeks, at least twice a week at moderate or high intensity)115
- 0.83 inhibition through aerobic sports (meta-analysis of k = 9 RCTs (mean PEDro score: 7.78) in children with ADHD aged 6 to 12 years)118 Sessions lasting 60 to 90 minutes, moderate intensity, and a minimum duration of 6 to 12 sessions promoted inhibition and cognitive flexibility
- 0.78 (meta-analysis, k = 11 studies with N = 713 children)119 Two 60-minute or longer open training sessions per week showed the greatest effect on inhibition in children with ADHD
- 0.76 (meta-analysis of k = 15 studies involving N = 664 children and adolescents aged 6 to 18)120
- 0.69 (meta-analysis, k = 16, N = 668)117
- 0.676 (meta-analysis of k = 23 studies with N = 535)121
- 0.56 (meta-analysis, k = 8, N = 249)114
- 0.50 (meta-analysis of k = 24 studies with N = 914 children and adolescents with ADHD)122
- Hyperactivity
- 1.60 through activities involving closed-skill tasks, dominated by aerobic exercises (meta-analysis of k = 44 studies from 1983 to 2022 involving N = 1,757 children and adolescents, compared to controlled alternatives (e.g., waiting list, no intervention, watching a video, or sedentary attention control))108
- 0.676 (meta-analysis of k = 23 studies with N = 535)121
- 0.56 (meta-analysis, k = 8, N = 249)114
- 0.06 (meta-analysis of k = 15 RCTs with N = 734 participants)123
- Cognitive flexibility
- 1.44 through multi-component physical exercises (meta-analysis of k = 44 studies from 1983 to 2022 involving N = 1,757 children and adolescents, compared to controlled alternatives (e.g., waiting list, no intervention, watching a video, or sedentary attention control))108
- 1.33 through closed-skills training (meta-analysis, k = 15, N = 578; recommended: 12 weeks, at least twice a week at moderate or high intensity)115
- 0.97 through Open Skills Training (meta-analysis, k = 15, N = 578; recommended: 12 weeks, at least twice a week at moderate or high intensity)115
- 0.85 through regular sports (meta-analysis, k = 11, N = 346 children with ADHD/ASD)116
- 0.78 (meta-analysis of k = 15 studies involving N = 664 children and adolescents aged 6 to 18)120
- 0.70 for school-age children (meta-analysis, k = 19 RCTs)124
- 0.65 cognitive flexibility through aerobic sports (meta-analysis of k = 9 RCTs (mean PEDro score: 7.78) in children with ADHD aged 6 to 12)118 Sessions lasting 60 to 90 minutes, moderate intensity, and a minimum duration of 6 to 12 sessions promoted inhibition and cognitive flexibility
- 0.64 from aerobic sports (meta-analysis, k = 16, N = 668)117
- 0.64 improvement in cognitive functions through virtual reality exercises in children with mild ADHD (meta-analysis, n = 9)125
- 0.45 (meta-analysis of k = 24 studies involving N = 914 children and adolescents with ADHD)122
- executive functions
- 1.96 through activities involving open-ended skills that require participants to respond in a dynamically changing and externally controlled environment (Meta-analysis of k = 44 studies from 1983 to 2022 involving N = 1,757 children and adolescents, compared to controlled alternatives (e.g., waiting list, no intervention, watching a video, or a sedentary attention control))108
- 1.22 (meta-analysis of k = 15 RCTs with N = 734 participants)123
- 1.15 from all types of physical activity (meta-analysis of k = 44 studies from 1983 to 2022 involving N = 1,757 children and adolescents, compared to controlled alternatives (e.g., waiting list, no intervention, watching a video, or sedentary attention control))108
- 0.90 through regular sports (meta-analysis, k = 11, N = 346 children with ADHD/ASD)116
- 0.68 Executive functions through regular exercise (meta-analysis of k = 22 RCTs involving children and adolescents with ADHD)113
- 0.61 (meta-analysis of k = 15 studies involving N = 664 children and adolescents aged 6 to 18)120
- 0.58 (meta-analysis, k = 8, N = 249)114
- 0.45 from virtual reality MOVEMENT exercises in children with mild ADHD (meta-analysis, k = 10)125
- 0.38 from virtual reality MOTION exercises in children with mild ADHD (meta-analysis, k = 5)125
- Working memory
- 1.21 from activities involving closed-skill exercises, dominated by aerobic exercise (meta-analysis of k = 44 studies from 1983 to 2022 involving N = 1,757 children and adolescents, compared with controlled alternatives (e.g., waiting list, no intervention, watching a video, or sedentary attention control))108
- 0.85 through closed-skills training (meta-analysis, k = 15, N = 578; recommended: 12 weeks, at least twice a week at moderate or high intensity)115
- 0.74 among schoolchildren (meta-analysis, k = 19 RCTs)124
- 0.52 (meta-analysis, k = 16, N = 668)117
- 0.50 (meta-analysis of k = 24 studies with N = 914 children and adolescents with ADHD)122
- 0.48 from aerobic sports (meta-analysis of k = 9 RCTs (mean PEDro score: 7.78) in children with ADHD aged 6 to 12 years).118 Sessions lasting 60 to 90 minutes, moderate intensity, and a minimum duration of 6 to 12 sessions promoted inhibition and cognitive flexibility
- 0.28 on working memory (not statistically significant) due to regular sports (meta-analysis, k = 11, N = 346 children with ADHD/ASD)116
- Memory
- 0.45 from virtual reality exercises in children with mild ADHD (meta-analysis, k = 5)125
- Gross motor skills
- Fine motor skills
- 0.30 (not statistically significant) due to regular sports (meta-analysis, k = 11, N = 346 children with ADHD/ASD)116
- Inattention
- 1.51 from activities involving closed-skill tasks, which were dominated by aerobic exercises (meta-analysis of k = 44 studies from 1983 to 2022 involving N = 1,757 children and adolescents, compared to controlled alternatives (e.g., waiting list, no intervention, watching a video, or sedentary attention control))108
- 0.84 (meta-analysis, k = 8, N = 249)114
- 0.604 to 0.715 (meta-analysis of k = 23 studies with N = 535)121
- 0.60 (meta-analysis of k = 15 RCTs with N = 734 participants)123
- 0.5 through virtual reality exercises in children with mild ADHD (meta-analysis, k = 6)125
- 0.48 (meta-analysis of k = 10 RCTs with N = 474 children aged 6 to 12)126
- The effect size was moderated by the type, frequency, and duration of physical activity, not by the setting in which the physical activity took place or the timing of the individual interventions.
- 0.32 through regular sports (meta-analysis of k = 22 RCTs involving children and adolescents with ADHD)113
- 0.29 (not statistically significant) (meta-analysis of k = 32 RCTs (including 5 on ADHD) with N = 1,255 children and adolescents). In contrast, the meta-analysis found a significant effect for ASD (0.50), depression (0.68), and obesity (0.58)127
- Symptoms of anxiety (in cases of comorbid ADHD)
- Depression
- 0.57 (meta-analysis, k = 18 RCTs, N = 830)128
- Social disorders
- 0.59 (meta-analysis, k = 8, N = 249)114
- emotional problems
- Behavioral problems
- 0.347 (meta-analysis of k = 23 studies with N = 535)121
- social problems:
- 0.27 (not statistically significant) (meta-analysis of k = 15 RCTs with N = 734 participants)123
- Aggressive behavior:
- 0.24 (not statistically significant) (meta-analysis of k = 15 RCTs with N = 734 participants)123
- Task switching (set shifting, set switching, inhibition switching)
- 0.35 for school-age children (meta-analysis, k = 19 RCTs)124
- Sleep
- Subjective improvement, but no significant measurable improvement (meta-analysis, k = 8, N = 131)129
- Impulse control
1.1.2.1.3. Individual Studies on the Effect Size of Sports on ADHD
- A 0.77 reduction in global ADHD symptom severity among participants with various disorder profiles who participated in a group aerobic exercise program, compared to the passive control group130
- 0.66 for ADHD symptoms among N = 150 adolescents aged 12 to 15, as measured by the Strengths and Difficulties Questionnaire (SDQ) (RCT)131
1.1.2.1.4. The Effect Size of Sports on Other Disorders
- Depression:
- 0.72 (not statistically significant) (meta-analysis of k = 15 RCTs with N = 734 participants)123
- 0.68 (meta-analysis of k = 32 RCTs (including 5 related to ADHD) with N = 1,255 children and adolescents)127
- 0.66 Group Aerobics Program130
- 0.62 Cochrane meta-analysis (k = 35 studies with N = 1,356 participants)132
- Long-term effect: 0.33
- 0.18 when limited to studies with a high degree of blinding. The comparative studies on the effect size of psychotherapy (k = 7 studies, N = 189) or medication (k = 4 studies, N = 300) each found an identical SMD for endurance training
- Sleep quality:
- 0.88 Group Aerobics Program130
- Anxiety
- 0.87 Group Aerobics Program130
- Obesity
- 0.58 (meta-analysis of k = 32 RCTs involving N = 1,255 children and adolescents)127
1.1.2.2. Cognitive Behavioral Therapy: 0.5 (0.3 to 0.85)
Cognitive Behavioral Therapy (CBT)
- The effect largely persists after the end of treatment
- It takes a very long time for the effects to set in
- A good, trusting, and supportive patient-therapist relationship is essential for the treatment to be effective
Meta-analyses:133
-
1.09 for adults in the patient assessment after 52 weeks (meta-analysis)34; not significantly better than placebo in the expert assessment
-
1.03 compared to the waiting list (meta-analysis, k = 17)134
-
0.79 compared to waiting lists (meta-analysis, k = 4 studies, N = 160 participants)135
-
0.76 for adults in the expert assessment after 12 weeks (meta-analysis)34; not significantly better than placebo in the self-assessment
-
0.70 (meta-analysis, k = 3 studies with N = 107 participants)136
-
0.66 compared to standard treatment (meta-analysis, k = 17)134
-
0.43 compared to active control groups (e.g., psychoeducation, progressive muscle relaxation, encouragement) (meta-analysis, k = 3, N = 191)137
-
0.33 compared with active control treatment (meta-analysis, k = 17)134
A comprehensive meta-analysis of k = 190 studies involving N = 26,114 participants with ADHD-HI found that stimulants were more effective than behavioral therapy, cognitive training, or non-stimulants. Stimulants combined with behavioral therapy appeared to be the most effective.138 See below under “Efficacy by OR” for more on this.
Regarding individual symptoms
-
Inattention in Adults with ADHD Treated with Behavioral Therapy (meta-analysis)139
- 1.18 in the observer-rated outcome compared with the waiting list or usual care (0.44, 0.92, 0.95, 2.41; k = 4 studies with N = 124 adults)
- 0.93 in self-report ratings compared with a waiting list or usual care (0.18, 0.28, 0.68, 0.82, 0.92, 1.18, 1.22, 1.35, 1.71; k = 9 studies with N = 215 adults)
- compared to active interventions (psychoeducation, neurofeedback, clinical management, cognitive training)
- in the third-party observation rating
- below 0.0 = slightly negative SMD = slight deterioration (k = 4 studies with N = 229 adults, compared with psychoeducation, MPH, or placebo)
- 0.5 for k = 2 studies with a combined total of N = 49 adults, only one of which was statistically significant
- in the self-assessment rating
- below 0.0 = slightly negative SMD = slight deterioration (k = 8 studies with N = 298 adults)
- 0.4 for k = 3 studies with N = 91 adults, of which only 1 was statistically significant
- in the third-party observation rating
-
Attention symptoms
-
0.39 (meta-analysis of k = 17 RCTs with N = 1,075 participants) through cognitive interventions 140
- Working memory training: no significant effect on attention symptoms
- Multiple cognitive training: 0.51 for attention symptoms
-
executive functions
- 0.32 (meta-analysis of k = 17 RCTs with N = 1,075 participants) through cognitive interventions 140
- Working memory training: no significant effect on executive function
- Multiple cognitive training: 0.5 on executive function
- 0.32 (meta-analysis of k = 17 RCTs with N = 1,075 participants) through cognitive interventions 140
-
Hyperactivity/Impulsivity
- 0.31 (meta-analysis of k = 17 RCTs with N = 1,075 participants) through multiple cognitive training interventions140
Overall, only the frequency of treatment had a significant impact on ADHD symptoms and executive functioning.140
Individual studies:
-
Effect on observer-reported ADHD symptoms in adults
- CBT vs. supportive therapy
- 0.56141
- MBCT vs. the waiting list
- 0.85142
- CBT vs. educational support
- 0.53143
- CBT vs. the waiting list
- 1.68144
- CBT versus continued medication alone
- Internet-based CBT, in addition to medication, for adults with ADHD, compared to medication alone147
- 0.59 to 0.50 for ADHD symptoms
- 0.87 to 0.25 for executive functions
- 0.74 to 0.28 for quality of life
- 0.66 to 0.42 for global functionality
- 0.43 for anxiety
- CBT vs. supportive therapy
-
Effect on self-reported ADHD symptoms in adults
- 0.16 CBT compared to supportive therapy148, citing two studies. Only one of these focused on CBT141; the second study examined DBT/skill training and also reported a positive outcome149.
- 0.84 CBT compared to a waiting list148, citing 5 studies. However, the analysis included only studies on MBCT150142 151 , internet-based CBT152, and brief therapy153
- 1.0146
-
CBT without concurrent medication:
1.1.2.3. Mindfulness-Based Cognitive Therapy (MBCT)
Overall ADHD Symptoms
- 0.79 for “mindfulness” in adults after 12 weeks in the expert assessment (meta-analysis)34; however, it was not significantly better than placebo in the self-assessment. It remains unclear whether the assessment focused on mindfulness-based behavioral therapy or mindfulness training in general.
- 0.63 for “mindfulness” in adults after 26 weeks in the expert assessment (meta-analysis)34; however, it was not significantly better than placebo in the self-assessment. It remains unclear whether the assessment focused on mindfulness-based behavioral therapy or mindfulness training in general.
People with ADHD who received MBCT (mindfulness-based cognitive therapy) in addition to standard treatment showed a significantly greater reduction in ADHD symptoms [M-difference = -3.44 (-5.75, -1.11), p = 0.004, d = 0.41]. This effect was maintained through the 6-month follow-up. Among people who received additional MBCT treatment, 27% showed a 30% reduction in ADHD-HI symptoms (p = 0.001), compared to only 4% of people with ADHD who did not receive additional MBCT treatment.155
The effect largely persisted even after the end of treatment.
executive functions
- 0.45 for “mindfulness” in adults after 12 weeks (meta-analysis)34; however, self-assessments showed no significant improvement over placebo. It is unclear whether the analysis focused on mindfulness-based behavioral therapy or mindfulness training in general.
1.1.2.3. Psychoeducation
- 0.77 for adults in the expert assessment (meta-analysis)34; however, not significantly better than placebo in the self-assessment
1.1.2.4. Parent Training: 0.31 to 0.68
The results pertain to improvements in children’s problematic behavior through parent training.
Parenting classes include, for example,29
- Parenting and behavioral strategy programs for parents of preschoolers
- Psychoeducation for Families
- New Forest Parenting Package for Parents of Preschoolers
Meta-analyses:
- 0.86 for group parent training156
- 0.68 for ADHD (k = 11, N = 603 children aged 33 to 144 months)157
- 0.61 with regard to ADHD in preschoolers158
- 0.42 to 0.53159
- 0.40 for ADHD160
- 0.31 with respect to ADHD symptoms in children (k = 11 RCTs, N = 1,078)29
- 0.31, k = 4 studies161; however, antidepressants were assigned an effect size of 0.85, stimulants an effect size of 0.35, and multimodal treatment an effect size of 0.28—findings that deviate so significantly from other research that they raise questions about the reliability of the data.
Improvement in certain symptoms:
- Externalizing behavior in the child (e.g., rule-breaking, oppositional behavior, or aggression):
- the child’s internalizing behavior (e.g., withdrawal or anxiety):
- 0.48, statistically significant (k = 2, N = 142)162
- 0.59 for comorbid behavioral problems157
- 0.93 on parental self-esteem157
1.1.2.5. Cognitive Self-Regulation Training: 0.54
- Out-of-school: 0.58 (meta-analysis, k = 5 studies)163; however, antidepressants were attributed an effect size of 0.85, stimulants an effect size of 0.35, and multimodal treatment an effect size of 0.28. These figures do not correspond in any way with the clinical evidence, which raises questions regarding the reliability of the data.
- in school settings: 0.49 (meta-analysis, k = 2 studies)163; however, antidepressants were attributed an effect size of 0.85, stimulants an effect size of 0.35, and multimodal treatment an effect size of 0.28. These figures do not correspond in any way with the clinical evidence, which raises questions regarding the reliability of the data.
1.1.2.6. Behavioral Training: 0.54
- extracurricular 0.29 (meta-analysis, k = 1 study)163; however, antidepressants were assigned an effect size of 0.85, stimulants an effect size of 0.35, and multimodal treatment an effect size of 0.28, which raises questions regarding the reliability of the data.
- academic: 0.50 (meta-analysis, k = 3 studies)163; however, antidepressants were assigned an effect size of 0.85, stimulants an effect size of 0.35, and multimodal treatment an effect size of 0.28, which raises questions regarding the reliability of the data.
1.1.2.7. Food diets: 0.51
Effective only when the diet is followed correctly.
High levels can be achieved under test conditions if a food intolerance is present.
An elimination diet places very high demands on compliance during the elimination phase and, as a form of treatment, represents a major disruption to one’s lifestyle, with a high risk of errors in daily life. For children, this is barely possible to follow and carries significant social consequences.
Studies:
- Oligoantigenic diet:
- Avoiding known antigens
- Elimination diet
- Avoiding dietary supplements/food coloring: 0.2 (0.08 to 0.44)
- 0.42: Avoidance of colorants, based solely on blinded studies; of 8 studies, 6 showed no statistically significant results; 0.32 when all studies are included172
- 0.21 to 0.44 in the parent rating100
- 0.21 to 0.283 (when including smaller, lower-quality studies as well)173
- 0.12 to 0.25169
- 0.08 to 0.11 (teacher and observer ratings)100
Meta-analyses of dietary interventions:
- 1.48 (0.2 to 5.13) when all studies are included, 0.51 (0.2 to 1.9) when only blinded studies are included; 172
- 0.51 to 0.8100
There is evidence that an elimination diet is effective only for certain people with ADHD (“subgroup”).174
In our view, this is simply the nature of the matter, since eliminating certain foods can only lead to an improvement if a food intolerance exists. However, these intolerances vary greatly from person to person.
1.1.2.8. Repetitive Transcranial Magnetic Stimulation (rTMS) up to 0.45
Improvement
- Overall ADHD Symptoms
- 0.48 (meta-analysis, k = 8, N = 325, compared to placebo)175
- 0.45 (meta-analysis, k = 7)176
- 0.24, treatment of the left or right PFC (meta-analysis of k = 6 RCTs with N = 169 participants compared to sham treatment)177
- 0.01, treatment of the left PFC (meta-analysis of k = 6 RCTs with N = 169 participants compared to sham treatment)177
- 0.49, treatment of the right PFC, not statistically significant (meta-analysis of k = 6 RCTs with N = 169 participants compared to sham treatment)177
- Individual ADHD symptoms
- Depression
1.1.2.9. Cognitive training: 0.22 to 0.45
Other terms: Cognitive Rehabilitation, Cognitive Remediation.
- 0.45, based on a meta-analysis of k = 4 studies with N = 159 participants.180
A meta-analysis examined the effect size of cognitive training181
- Clinician reports (unblinded):
- 0.37 for ADHD overall
- 0.47 for symptoms of inattention
- 0.79 reduction in ADHD overall through interventions targeting multiple neuropsychological deficits
- (presumably) blinded reports:
- 0.20 for ADHD overall
- 0.32 for symptoms of inattention
Children and Adolescents:
-
0.78 for attention symptoms (meta-analysis of k = 10 studies involving N = 446 children compared with placebo)182
-
0.56 for executive functions (meta-analysis of k = 10 studies involving N = 446 children compared with placebo)182
-
0.37 for ADHD symptoms in children and adolescents (meta-analysis, k = 12, N = 655)29
-
0.22 (meta-analysis)183
One review found limited to minor improvement in symptoms through computer-assisted cognitive training (CCT):184
* 0.12 for total ADHD symptoms when limited to the “likely blinded” results (PBLIND; k = 14 studies)
* 0.12 for hyperactivity/impulsivity symptoms when limited to the “likely blinded” results (PBLIND; k = 14 studies)
* 0.17 for inattention symptoms when limited to the “likely blinded” results (PBLIND; k = 14 studies)
* 0.40 on inattention symptoms when assessed immediately after training (indicating rater bias)
* 0.38 on verbal working memory
* 0.49 on visual-spatial working memory
* No improvement in attention, inhibition, reading, or math*
Overall, there were improvements:185
- 0.52 verbal working memory
- 0.3 Executive functions in the parent rating
- No significant effects were observed with regard to
- Hyperactivity/Impulsivity
- Academic performance
1.1.2.10. Psychological behavioral interventions overall: 0.35 for children and adolescents
A meta-analysis found an effect size of 0.35 (k = 14, N = 1,686) for ADHD symptoms across all psychosocial behavioral interventions targeting children and adolescents.29 When limited to RCTs, the effect size remained at 0.36. Eight of the six studies found no statistically significant effect.
The psychological behavioral interventions included in the study comprised
- Skills training (e.g., executive function training, homework training, or organizational skills training)
- Social Skills Training
- Executive Function Therapy for Preschoolers
- Driving program for young drivers
- sleep-focused intervention
- dialectical behavior therapy
- cognitive behavioral therapy
- Attention Training
- complex behavioral modification intervention
- Behavioral counseling with both school-based and home-based components
- Parent-Child Psychotherapy for Mothers and Their Children with ADHD
- Mindfulness Training
- Music Therapy
- playful intervention
- dog-assisted therapy
With an effect size of 0.007 (k = 3, N = 459), no improvement in academic performance was found.29
1.1.2.11. Social Skills Training: 0.26 to 0.31
A Cochrane meta-analysis found that, based on teacher ratings, social skills training for children and adolescents aged 5 to 17 had an effect size that was of little therapeutic benefit:186
-
Overall ADHD symptoms: 0.26 (k = 14 RCTs with N = 1,379)
-
0.11 social competence (k = 11 RTC, N = 1,271)
-
0.02 emotional competence (k = 2, N = 129)
-
0.06 General Behavior (k = 8, N = 1,002)
In this meta-analysis, the term “social skills training” was defined to include:
- Social Skills Training
- cognitive behavioral therapy
- multimodal behavioral/psychosocial therapy
- Addressing children’s life skills and attention skills
- Life Skills Training
- the “Program for Challenging Horizons”
- verbal self-instruction
- metacognitive training (a form of cognitive behavioral therapy)
- Behavioral therapy
- Treatment for behavioral and social skills
- Psychosocial treatment
Skills training also includes, among other things, leadership training, homework assignments, and training in organizational skills.29
- Meta-analysis of k = 3 studies163
- 0.31; However, in this study, antidepressants were simultaneously assigned an effect size of 0.85, stimulants an effect size of 0.35, and multimodal treatment an effect size of 0.28, which raises questions regarding the robustness of the data and suggests that the effect size results may be inflated
1.1.2.12. Neurofeedback: 0.13 to 0.30
0.13 to 0.30 refers to blinded studies.
Meta-analyses:
-
Meta-analyses consisting solely of blinded studies
-
0.35 for the Theta-Beta Protocol (meta-analysis)187
-
0.30 (teacher rating, blinded, k = 5, N = 246)188
-
0.30 impulse control (not statistically significant; k = 13, N = 520)189
-
0.29172
-
0.21, independent of age (k = 9 RCTs with established standard protocols (out of a total of k = 38 RCTs, N = 681))190191
-
0.13 Attention (not statistically significant; k = 13, N = 520)189
-
No significant improvement in global or frontal-midline theta activity during the resting state following theta-beta training (double-blind RCT)192
-
-0.76 for the SMR protocol (worse than standard treatment); not statistically significant (meta-analysis)187
-
0.81 for the SCP protocol, not statistically significant (meta-analysis)187
-
-
(also) open-label studies:
-
1.10 for adults in the patient assessment after 52 weeks (meta-analysis)34; not significantly better than placebo in the expert assessment
-
0.59172
-
0.61 (meta-analysis of k = 6 studies with a total of N = 203 participants193 Unfortunately, no comparison was made with the effect size of medication.
-
0.49 (parent rating); k = 5, N = 246188
-
0.35 overall ADHD symptoms (meta-analysis with k = 13 open-label RCTs, involving N = 520 participants):194 Additional results regarding individual symptoms:
- 0.36 Inattention
- 0.26 Hyperactivity/Impulsivity
-
Individual studies
-
only blinded observation according to Sonuga-Barke et al. (2013):172
-
including open-label observation:
Children and Adolescents:
- 0.49 (parent rating); k = 5, N = 246188
- 0.44 for ADHD symptoms (statistically significant, meta-analysis, k = 12, N = 945)29
- 0.30 (blinded teacher rating, k = 5, N = 246)188
By symptoms:
-
Attention: 0.8 to 1.2
-
0.64 immediately after treatment compared to untreated controls (MPH, by contrast, was 1.08)203
-
0.80 at the 2- to 12-month follow-up (compared to 1.06 for MPH)203
-
0.8204
-
0.48 for inattention on the EEG-NF compared to the waiting list/TAU (k = 5; N = 279)205
-
0.46 (parent rating); k = 5, N = 246188
-
after 40 sessions: 1.2206
-
-
for hyperactivity/impulsivity: 0.5 to 0.61
-
0.50 immediately after treatment compared to untreated controls203
-
0.61 at the 2- to 12-month follow-up203
-
0.39 after 20 sessions; cannot be improved further by increasing the number of sessions206
-
0.03 for hyperactivity/impulsivity in the EEG-NF group compared to the waiting list/TAU group (k = 5; N = 279)205
-
0.34 (parent rating); k = 5, N = 246188
-
-
impulsivity:
-
Processing speed 0.35
By comparison:
- Neurofeedback is not as effective as MPH.207
- In one study, MPH showed a 46.9% improvement in symptoms (SMD 2.03), while neurofeedback resulted in a 26.7% improvement in symptoms (SMD 0.89).208
- The effect may persist after treatment ends
1.1.2.13. Transcranial Direct Current Stimulation (tDCS): 0.23
- 0.78 for adults in the expert assessment (meta-analysis)34; not significantly better than placebo in the self-assessment
- 0.23 (meta-analysis, k = 102)209
- Attention
- 0.66 (meta-analysis, 8 experiments from k = 7 studies with N = 277 participants)179
- Inhibition
- 0.21 (meta-analysis, 17 experiments from k = 13 studies with N = 582 participants)179
- Working memory
- 0.31 (meta-analysis, 12 experiments from k = 9 studies with N = 390 participants)179
- Cognitive flexibility
- 0.61, though not statistically significant (meta-analysis, 4 trials from k = 2 studies with N = 94 participants)179
- Hyperactivity
- 0.41, though not statistically significant (meta-analysis, 4 trials from k = 4 studies with N = 94 participants)179
1.1.2.14. Teacher Training
A meta-analysis of k = 22 studies found the following for a teacher training program:210
- A 0.71 to 0.78 improvement in the behavior of children with ADHD as a consequence of adjustments in teacher behavior
In addition, there was a significant improvement in the trained teachers’ knowledge of ADHD immediately after the training (1.96); however, this score decreased by 1.21 within 3 months.
1.1.2.15. Virtual Reality Interventions
A meta-analysis of k = 4 studies involving N = 125 people with ADHD found an effect size of211
- 1.38 for omission errors (errors of omission)
- 1.50 for correct answers
- 1.07 for perceptual sensitivity
- 0.62 due to a commission error
- 0.67 for reaction time
- No effect on impulsivity
1.1.2.16. Online Interventions
A meta-analysis of k = 6 RCTs involving N = 261 participants found an effect size of 0.59 for online interventions in improving attention deficits and social functioning in adults and children with ADHD, compared to the waiting list.212
1.1.2.17. Working Memory Training
A meta-analysis of k = 12 studies found that working memory training is effective for children and adults with and without ADHD:213214
- 0.37 for inattention in everyday life
- 0.62 on visual-spatial working memory tasks
- 0.41 on verbal working memory tasks
1.1.2.18. Digital Interventions
A meta-analysis (k = 25 RCTs, N = 1,780) found an effect size of215
- 0.33 for ADHD symptoms overall
- 0.31 for inattention
- 0.15 for hyperactivity/impulsivity
1.1.2.19. Digital Therapy Games
A meta-analysis of k = 20 studies found the following effect size for digital therapeutic games in ADHD:216
- Inattention
- 0.21 in the teacher rating
- 0.28 in the parent rating
- Hyperactivity/Impulsivity
- a decrease of 0.01 in the teacher rating
- 0.16 in the parent rating
The study results were overwhelmingly not statistically significant.
1.1.2.20. School-Based Interventions
- 0.50 for ADHD symptoms; not statistically significant; meta-analysis of k = 5 studies involving N = 822 children and adolescents29
- 0.36 (not statistically significant) Meta-analysis of k = 39 studies on school-based interventions in low- and middle-income countries217
1.1.2.21. Acupuncture
A Chinese meta-analysis of k = 13 studies with N = 1,304 participants reported an effect size for acupuncture of:218
- 0.94 in terms of the overall response rate and the reduction rate of the Conners Index for Hyperactivity compared to other treatment groups
- 1.14 in improving the Traditional Chinese Medicine syndrome (liver-kidney yin deficiency) in children with ADHD (and thus comparable to methylphenidate)
- less severe side effects than with drug therapy (loss of appetite, dry mouth, nausea, and constipation)
We would like to note that the German ADHD forum run by ADxS does not report any reproducible treatment successes with acupuncture, even though readers there have a strong interest in successful non-pharmacological treatment options.
1.1.2.22. Age Differences Within School Classes
A population-based study with N = 14,643 participants in the UK found an effect on general mental health, as rated by parents, of:219
- 0.22 for a 1-year difference at age 11
- 0.02 for a 1-year difference at age 25
- 0.02 for a 1-year difference before starting school
1.1.2.23. Weighted Blankets and Anxiety Symptoms
0.47 compared to placebo (meta-analysis of k = 6 studies)220
1.1.2.24. Mind-Body Techniques (yoga, tai chi, dance, Pilates, etc.)
- 0.97 for attention (meta-analysis, k = 7)221
- No significant improvement in executive functions (meta-analysis, k = 7)221
- No significant improvement in emotional symptoms (meta-analysis, k = 7)221
- No significant improvement in hyperactivity/impulsivity (meta-analysis, k = 7)221
1.1.2.25. Relaxation Therapy
- 1.00 in the patient assessment of adults after 52 weeks (meta-analysis)34; not significantly better than placebo in the expert assessment
1.1.2.26. DBT
No effect on ADHD in adults (meta-analysis).34
1.1.2.27. Behavioral Sleep Intervention
A small study reports an effect size of 1.5 for behavioral sleep interventions on ADHD.222 This does not align with our experience.
1.2. Comparison Based on Risk Reduction
In a comparison based on risk reduction, a lower hazard ratio indicates an improvement.
1.2.1. Reducing the Risk of Psychiatric Hospitalization
Factors influencing the risk of psychiatric hospitalization:223
- Amphetamine (adjusted hazard ratio, aHR: 0.74 = 26% reduction)
- Lisdexamfetamine (aHR: 0.80 = 20% reduction)
- Polytherapy with ADHD medications (aHR: 0.85 = 15% reduction)
- Dexamphetamine (aHR: 0.88 = 12% reduction)
- Methylphenidate (aHR: 0.93 = 7% reduction)
- Modafinil: unchanged
- Atomoxetine: unchanged
- Clonidine: unchanged
- Guanfacine: unchanged
1.2.2. Reducing the Risk of Nonpsychiatric Hospitalization
Impact on the risk of nonpsychiatric hospitalization:223
Amphetamine, lisdexamfetamine, polytherapy (combination medication), dexamfetamine, methylphenidate, and atomoxetine reduced the risk of nonpsychiatric hospitalizations.
1.2.3. Reducing the Risk of Suicidal Behavior
Factors influencing the risk of suicidal behavior:223
- Dexamphetamine (aHR: 0.69)
- Lisdexamfetamine (aHR: 0.76)
- Methylphenidate (aHR: 0.92)
1.2.4. Reducing the Risk of Work Disability
Impact on the risk of work disability:223
- Atomoxetine (aHR: 0.89)
- particularly among adolescents and young adults aged 16 to 29 (aHR: 0.82)
All other ADHD medications studied: not significant.
- particularly among adolescents and young adults aged 16 to 29 (aHR: 0.82)
1.3. Comparison by Odds Ratio (OR)
Overview based on Catalá-López et al. (2017).13 The data compare the probability of treatment success relative to placebo. An OR of 1 would be equivalent to placebo; an OR greater than 1 favors the treatment method.
Placebo: 1 (reference value)
1.3.1. Pharmacological Interventions
Comparison by Odds Ratio (OR)
-
Total stimulants: 6.21
- Amphetamine-based medications: 7.45
- Methylphenidate: 5.26
-
Total non-stimulants: 3.95
- Modafinil: 5.51
- Atomoxetine: 3.63
- Guanfacine: 3.29
- Clonidine: 3.96
- Bupropion: 2.41
- Venlafaxine: 4.07
- Reboxetine: 3.58
- Antipsychotics: 1.36
- Thioridazine: 1.04
- Carbamazepine: 0.18
1.3.2. Minerals / Vitamins / Amino Acids / Herbal Remedies
Comparison by Odds Ratio (OR)
- Zinc: 2.42
- Polyunsaturated fatty acids (or PUFAs): 2.14
- Omega-3 and omega-3/6 fatty acids: 1.99
- L-carnitine: 1.20
- Amino acids: 1.19
- St. John’s Wort (Hypericum perforatum): 1.00 (0.23–4.26)
- Ginkgo biloba: 0.21
1.3.3. Non-pharmacological interventions
Comparison by Odds Ratio (OR)
- Behavioral therapy: 2.97
- Neurofeedback: 1.96
- Parent training: 1.19
- Training for children, parents, and/or teachers: 2.73
- Cognitive training: 0.70
- Working memory training: 0.34
1.4. Multimodal Therapy
Individual studies
In the “Multimodal Treatment Study of Children with ADHD” (MTA Study) conducted in the late 1990s, 579 children aged 7 to 10 were treated for 14 months with medication, behavioral interventions, or both.224 The MTA study consisted exclusively of group interventions (parent group training, children’s summer camp, and school support) and did not include individual behavioral therapy.
Teachers and parents rated the reduction in core ADHD symptoms as greater among children treated with medication alone than among those treated only with parent and behavioral training. The children who received medication along with parent and behavioral training fared slightly better than those treated with medication alone, although they required a reduced dosage of medication. When all symptoms—not just the core symptoms—were considered, the children treated with medication combined with parent and behavioral training performed significantly better. In contrast, the effect of parent and behavioral training alone was less than that of medication alone.11
Meta-analyses
- A comprehensive meta-analysis of multimodal treatment for children and adolescents with ADHD found an effect size of
- 0.36 for ADHD symptoms compared to medication alone (k = 7, N = 841, statistically just not significant, low risk of bias)29
- The greatest effect sizes were observed in a course on behavior and social skills for children and their parents, as well as in cognitive behavioral therapy for adolescents
- 0.42 for a wide range of symptoms compared to medication alone (k = 3, N = 171, not statistically significant, high risk of bias)29
- The studies compared multimodal psychosocial treatment plus MPH with MPH alone; cognitive group behavioral therapy plus MPH with MPH alone; and individual cognitive behavioral therapy plus FDA-approved medications with these medications alone.
- 0.36 for ADHD symptoms compared to medication alone (k = 7, N = 841, statistically just not significant, low risk of bias)29
- Another meta-analysis found
- 0.1 for parent and behavioral training alone versus no treatment
- minus 0.4 when only the blinded raters were included, indicating a deterioration compared to no parenting or behavioral training.172
2. Latency of Effect for Different Forms of Treatment
By “onset of action,” we mean how long it takes for a treatment to take effect.
- Medications
- Stimulants: take effect immediately; when dosed optimally, they are fully effective right away
- Norepinephrine reuptake inhibitors: 2–3-week titration phase
- Atomoxetine: a build-up phase lasting several weeks to 6 months
- Therapy
- Behavioral therapy: several months for initial steps, 3 years for adequate treatment outcomes
- Neurofeedback: several months for initial progress, 6 to 15 months for adequate therapeutic results
3. The Target of the Various Forms of Treatment
By “target of efficacy,” we mean which symptoms the individual treatment modalities affect.
3.1. Medications
- Stimulants:
- Attention
- Hyperactivity
- Impulsivity (MPH more than amphetamine medications)
- internal pressure
- emotional dysregulation
- Mood swings / emotional stability
- Aggression/Anxiety
- Dysphoria (primarily amphetamine-based medications; MPH, on the other hand, to a lesser extent)
- Non-stimulants:
- Impulsivity
e.g., low doses of SSRIs - emotional regulation
- Attention
- Impulsivity
- Norepinephrine reuptake inhibitors:
- Impulsivity
- Depression
- Mood swings / emotional stability
- Hyperactivity
3.2. Psychotherapy
- Behavioral therapy:
- Cognitive VT:
Self-esteem, Social Behavior, Stress Reduction
To a certain extent, this also involves changes in stress response, including hormonal and immunological changes in the body225 - Mindfulness-Based CBT:
Mindfulness, Empathy, Stress Reduction
- Cognitive VT:
- Mindfulness training:
Changes in stress perception; changes in stress processing in the central nervous system; impulsivity
An enhanced perception of pleasant aspects brings about immediate changes in the dopaminergic focus and reinforcement system. The same effects are produced by perceptions of the nature of an individual’s spatial environment and (sustained) high social status.226
However, it remains unclear whether these changes (with the exception of social status) have a lasting effect—which is a prerequisite for therapeutic use—or whether they are merely activated during perception. - Neurofeedback:
Attention; Impulsivity; Hyperactivity; Relaxation; Sleep - Environmental interventions:
Reduction of stressors through their elimination and a better understanding of the environment - Psychoeducation:
Elimination of stressors and improved regulatory capacity through a greater understanding on the part of the person with ADHD
Boosting self-esteem through the feeling of coming home, through encounters and interactions with other people with ADHD
4. Duration of Effectiveness of Treatment Methods
4.1. Early Medication
There is evidence that treatment with methylphenidate at a dose of 2 mg/kg/day in very young rats caused a lasting reduction in dopamine transporters in the striatum (which would correspond to a lasting therapeutic effect), whereas methylphenidate administration in slightly older animals (“after puberty”) no longer produced this effect.227 These results have not yet been replicated.
In the treatment of humans, including children before puberty, no sustained reduction in DAT in the striatum has been observed with MPH.
Despite the immense importance of this issue, no further studies are known that confirm these findings. Although short-term decreases in DAT counts were observed in rats administered a dose of 5 mg/kg twice daily from day 7 through day 35 after birth, these decreases were no longer detectable by day 135 of life.228
No structural changes in the brain were found either immediately after the end of treatment on day 35 or on day 135.228 Given the extremely high dosage, this further demonstrates that MPH poses a low risk.
4.2. Short-term medication
The benefits of drug treatment end (at least in the case of stimulants) immediately upon discontinuation of the medication; for other medications that affect blood levels, the effects wear off after approximately 14 days at the latest.
The learning outcomes of neurofeedback and behavioral therapy are better when combined with medication.
The effects of non-pharmacological therapy are long-lasting; however, treatment must be sufficiently long and intensive (6 months to 3 years).
In neurofeedback, the treatment benefits were found to persist even 6 months after the end of treatment14229 Kühle observed that in some cases, the treatment benefits persisted even years later, while in others they did not.
4.3. Long-term medication
There is evidence that long-term medication may promote the maturation of those brain structures that are affected by developmental delays in ADHD.
In ADHD, dysfunctional executive functions are associated with a reduced volume of brain matter in the cortex.230 In children with ADHD, the growth of brain matter in the cortex is significantly reduced, with the greatest delays occurring in the PFC and the ACC.230
Adults with ADHD who are treated with stimulants have significantly greater brain mass in the relevant brain regions than people with ADHD who have not been treated with stimulants.231 This could suggest that treatment with stimulants can help make up for or compensate for developmental delays.230
People with ADHD who continued to exhibit the full range of ADHD symptoms even as adults did not show any late maturation (in the sense of growth) of brain mass in the relevant brain regions.232
4.4. Multimodal Treatment: Non-Pharmacological Therapy and Medication
There is evidence suggesting that dopaminergic ADHD medications—specifically, D-amphetamine-based medications in this study (levodopa, which is also mentioned, is not suitable as an ADHD medication)—may increase neuroplasticity and thereby enhance the effectiveness of psychotherapy.233
We are convinced that psychotherapeutic interventions are significantly less effective for people with ADHD who are not on medication, since ADHD itself severely impairs learning and cognitive capacity. Since ADHD medications improve the impaired neuroplasticity associated with ADHD—and thus often establish the capacity to learn in the first place—we strongly recommend that medication be initiated prior to psychotherapy to ensure its success.
That said, in our view, psychotherapy makes little sense if the patient has no idea what the state they are supposed to achieve through therapy actually feels like. Only a prolonged period (at least one year) of properly adjusted medication can help the person with ADHD experience this feeling.
This is especially true for people with ADHD, since ADHD is characterized by a shift in motivation toward significantly increased intrinsic control. After all, one of the defining features of ADHD is that it makes it extremely difficult to comply with extrinsic requests.
5. Compatibility
A higher odds ratio (OR) indicates poorer tolerability compared to placebo.
- Amphetamine-based medications
- Atomoxetine (OR: 2.33)43
- Methylphenidate (OR: 2.39)43
- Guanfacine in children and adults (OR: 2.64)43
- Modafinil (OR: 4.01)43
6. Comparative Data: Effect Size for Other Clinical Conditions
6.1. Depression
6.1.1. Psilocybin treatment integrated into psychotherapy (PAP): 0.78 to 1.5
Treatment of severe depression using psilocybin therapy integrated into psychotherapy (PAP) demonstrated a high effect size for depression.
Meta-analyses:
- Meta-analysis (k = 10, N = 208)234
- 0.75 on Day 1
- 1.74 after 1 week
- 1.35 after 1 month
- 0.91 after 3 months
- 1.12 after 6 months.
- Meta-analysis (k = 8) on the use of psychedelics to treat depression235
- 1.5 on Day 1 (k = 5)
- 1.07 after 6 months (k = 5)
- No serious adverse effects.
- A temporary increase in heart rate and in systolic and diastolic blood pressure.
-0.78 (meta-analysis, k = 9, N = 596, p < 0.001)236
Studies:
- N = 15, Cohen’s d237
- 4.08, 3 weeks after treatment; a 24-point improvement on the MADRS
- 3.39 12 weeks after treatment
- N = 24, Cohen’s d238
- 2.6 on Day 1 after treatment
- 2.5 5 weeks after treatment
- 2.6 8 weeks after treatment
- N = 24, Cohen’s d239
- 2.3 1 month after treatment
- 2.0, 3 months after treatment
- 2.6 6 months after treatment
- 2.4 12 months after treatment
- N = 20, Cohen’s d, open-label without controls240
- 2.2 after 1 week
- 2.3 after 5 weeks
- 1.5 after 3 months
- 1.3 after 6 months.
- N = 29, Cohen’s d, depression in cancer patients241
- 1.23 after 1 day
- 1.12 after 2 weeks
- 1.32 after 6 weeks
- 0.98 after 7 weeks
- N = 29, Hedges’ g
- 1.07242
A meta-analysis identified 9 studies on psilocybin, ayahuasca, and LSD. The effect sizes of the three psychedelics were roughly the same:243
- 1.36 for depression
- 1.26 for anxiety
The effect size of ketamine on depression is significantly lower (0.4 to 0.65).244
6.1.2. Effect size of psychotherapy for depression: 0.34
Effect size in SMD.
NNT: Number needed to treat. If the treatment were 100% effective, the NNT would be 1. The higher the NNT, the lower the efficacy.
Psychotherapy is effective for acute depression with an effect size of 0.35 to 0.67, and for relapse prevention with an effect size of 0.37.5
Effect size of Psychotherapy for Depression:21245
- Behavioral activation: 0.82 (NNT = 2; 11 studies)
- Mindfulness-Based Cognitive Behavioral Therapy (MBCT): 0.73 (NNT = 3; 6 studies)
- Cognitive behavioral therapy: 0.71 (NNT = 3; 159 studies) to 0.79 (409 studies)246
- Interpersonal psychotherapy: 0.67 (NNT = 3; 22 studies)
- Problem-solving therapy: 0.48 (NNT = 4; 21 studies)
- Supportive therapy: 0.52 (NNT = 4; 17 studies)
- Psychodynamic therapy: 0.44 (NNT = 4; 8 studies)
The studies are subject to significant bias. Take cognitive behavioral therapy, for example:
When only the higher-quality studies were considered, the effect size decreased by 0.2.247
When all studies comparing the intervention to a waiting list were excluded, the effect size decreased by 0.17.21
When all studies with a high risk of bias were excluded, the effect size decreased by 0.32 to 0.39 (NNT = 5; 34 studies)21
When publication bias was also taken into account, the effect size decreased to 0.34 (NNT = 5; 38 studies)21
A comprehensive meta-analysis found the following effect size for depression in children and adolescents: (k = 92 RCTs)248
- Psychotherapy 1.16
- Placebo psychotherapy 0.58
- Medication 2.08
- Placebo medication 1.88
These four figures seem exaggerated to us.
If only those studies that meet all basic quality criteria are included, the effect size is just 0.22 (instead of 0.74).245249
For dysthymia, the average effect size of psychotherapy is only about 0.2.250
6.1.3. Traditional antidepressants: 0.30
Effect size of traditional antidepressants (SMD):
| According to Cipriani et al., 20185 | Effect size (SMD) | Remission rates (ranking) | Treatment discontinuations (ranking) |
|---|---|---|---|
| Amitriptyline | 0.48 | 1 | 13 |
| Duloxetine | 0.37 | 2 | 11 |
| Venlafaxine | 0.33 | 3 | 12 |
| Clomipramine | 0.32 | 4 | 14 |
| Paroxetine | 0.32 | 5 | 8 |
| Bupropion | 0.25 | 6 | 10 |
| Mirtazapine | 0.37 | 7 | 9 |
| Escitalopram | 0.29 | 8 | 4 |
| Milnacipran | 0.3 | 9 | 3 |
| Sertraline | 0.27 | 10 | 7 |
| Vortioxetine | 0.28 | 11 | 2 |
| Fluoxetine | 0.23 | 12 | 5 |
| Agomelatine | 0.26 | 13 | 1 |
| Citalopram | 0.24 | 14 | 6 |
The average dose of the classic antidepressants mentioned is thus 0.305250 , and 0.5 for relapse prevention5.
For dysthymia, the average effect size of antidepressants is around 0.5.250
A comprehensive meta-analysis found the following effect size for depression in children and adolescents: (k = 92 RCTs)248
- Psychotherapy 1.16
- Placebo psychotherapy 0.58
- Medication 2.08
- Placebo medication 1.88
These four figures seem exaggerated to us.
6.1.3. Electroconvulsive Therapy
Electroconvulsive therapy showed an effect size of 0.69 for depression compared to ketamine.251
6.2. Effect size of Medications for Mania / Bipolar Disorder
The average effect size for medications used to treat an acute manic episode is 0.4 (N = 11,000), as is the effect size for relapse prevention in bipolar disorder. By contrast, the mean effect size for depressive episodes of bipolar disorder is only 0.2.250
6.3. Effect size of Medications When Taking ASA
According to a meta-analysis, ASS overall improved due to
- Methylphenidate: 0.53 on the teacher rating scale (k = 2, N = 36)252
A meta-analysis examined k = 125 RCTs involving N = 7,450 children and adolescents and k = 18 RCTs involving N = 1,104 adults compared with placebo:253
Social Communication Problems:
- Children and Adolescents
- 0.27 Aripiprazole (k = 6)
- 0.51 methylphenidate (k = 3, N = 63)252
Repetitive behavior:
- Children and Adolescents
- 0.60 risperidone (k = 6)
- 0.49 atomoxetine (k = 3)
- 0.35 bumetanide (k = 4)
- 0.34 methylphenidate (k = 3, N = 69)252
- Adults
- 1,2 Fluoxetine (k = 1)
- 1.0 Fluvoxamine (k = 1)
- 0.97 risperidone (k = 1)
- 0.41 Oxytocin (k = 6)
Irritability:
- 0.90 Atypical antipsychotics compared with placebo; k = 12, N = 973254
- 0.18 neurohormones compared to placebo; k = 8, N = 466254
- 0.20 ADHD medication compared to placebo; k = 10, N = 400254
- 0.06 for antidepressants compared to placebo; k = 3, N = 267254
Aggression:
- 0.44 Atypical antipsychotics compared to placebo; k = 1, N = 77254
Reducing self-harm:
- 1.43 Atypical antipsychotics compared to placebo; k = 1, N = 30254
- 0.62 ADHD medication compared to placebo; k = 1, N = 16254
ADHD Symptoms in Children and Adolescents with ASD:
- Methylphenidate
- Atomoxetine
Intranasal immunotherapy with the M2 macrophage secretome improved speech disorders and autism-like behaviors in children. Unfortunately, no SMD was reported.258
6.4. NNT for Other Clinical Presentations
Number Needed to Treat for Various Clinical Conditions:21
- Schizophrenia Response
- Antipsychotics: NNT = 7
- Schizophrenia Relapse Prevention
- Antipsychotics: NNT = 3
- Depression – Response
- SSRI: NNT = 7
- Depression – Relapse Prevention
- SSRI: NNT = 5
- Depression - Remission
- Cognitive Behavioral Therapy vs. Medication: NNT = 34
- Alcohol – Relapse
- Acamprosate: NNT = 10
- Naltrexone: NNT = 50
7. Other Sources on the Effect Size of Treatment Modalities
“Stuff that works” is a website where people with ADHD share their experiences with different forms of treatment (not just for ADHD).
The results of treatment for ADHD in children (more than 12,000 participants: methylphenidate > lisdexamfetamine > amphetamine salts > dexmethylphenidate > guanfacine > atomoxetine; melatonin is effective for sleep problems) and on the treatment of ADHD in adults (more than 55,000 participants: lisdexamfetamine > amphetamine salts > dextroamphetamine sulfate > methylphenidate > sports > psychotherapy > atomoxetine > bupropion; surprisingly: cannabinoids are more effective than MPH) are essentially consistent with the study results we have compiled.
Faraone, Banaschewski, Coghill, Zheng, Biederman, Bellgrove, Newcorn, Gignac, Al Saud, Manor, Rohde, Yang, Cortese, Almagor, Stein, Albatti, Aljoudi, Alqahtani, Asherson, Atwoli, Bölte, Buitelaar, Crunelle, Daley, Dalsgaard, Döpfner, Espinet, Fitzgerald, Franke, Gerlach, Haavik, Hartman, Hartung, HinshawP, Hoekstra, Hollis, Kollins, Sandra Kooij, Kuntsi, Larsson, Li T, Liu J, Merzon, Mattingly , Mattos, McCarthy, Mikami, Molina, Nigg, Purper-Ouakil, Omigbodun, Polanczyk, Pollak, Poulton, Rajkumar, Reding, Reif, Rubia, Rucklidge, Romanos, Ramos-Quiroga, Schellekens, Scheres, Schoeman, Schweitzer, Shah H, Solanto, Sonuga-Barke, Soutullo, Steinhausen, Swanson, Thapar, Tripp, van de Glind, Brink, Van der Oord, Venter, Vitiello, Walitza, Wang Y (2021): The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder. Neurosci Biobehav Rev. 2021 Sep;128:789-818. doi: 10.1016/j.neubiorev.2021.01.022. PMID: 33549739; PMCID: PMC8328933. ↥
Goulet-Pelletier JC, Cousineau D (2018): A review of effect sizes and their confidence intervals, Part I: The Cohen’s d family. The Quantitive Methods for Psychology, 2018, 242-265. ↥ ↥ ↥
Fritz CO, Morris PE, Richler JJ (2012): Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012 Feb;141(1):2-18. doi: 10.1037/a0024338. PMID: 21823805. ↥ ↥ ↥
Möller (2023): Psychopharmakotherapie und Psychotherapie haben gleiche und schwache Wirksamkeit. Psychopharmakotherapie 2023; 30(01):1-4, german ↥
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JPT, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JPA, Geddes JR (2018): Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-1366. doi: 10.1016/S0140-6736(17)32802-7. PMID: 29477251; PMCID: PMC5889788. REVIEW ↥ ↥ ↥ ↥ ↥
Böhlke: Psychedelika in der Pailliativmedizi, Interview SZ 25.09.24, S. 14 german ↥
Waltereit, Müller (2018): Weiterbildungs-Curriculum Psychopharmakologie/Pharmakotherapie, Teil 4: Psychopharmakologie und klinische Psychopharmakotherapie der Stimulanzien, Psychopharmakotherapie 2018;25: 199–207. german ↥ ↥
Leucht S, Hierl S, Kissling W, Dold M, Davis JM (2012): Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. Br J Psychiatry. 2012 Feb;200(2):97-106. doi: 10.1192/bjp.bp.111.096594. PMID: 22297588. REVIEW ↥
Nageye, Cortese (2019): Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD. Expert Rev Neurother. 2019 Jul;19(7):707-717. doi: 10.1080/14737175.2019.1628640. PMID: 31167583.) ↥ ↥ ↥ ↥ ↥
Edel, Vollmoeller (2006): Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung bei Erwachsenen, Springer Seite 55 ↥
Müller, Candrian, Kropotov (2011): ADHS – Neurodiagnostik in der Praxis, Springer, Seite 23 ↥ ↥
Edel, Vollmoeller (2006): Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung bei Erwachsenen, Springer, Seite 55 ↥
Catalá-López, Hutton, Núñez-Beltrán, Page, Ridao, Macías Saint-Gerons, Catalá, Tabarés-Seisdedos, Moher (2017): The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials. PLoS One. 2017 Jul 12;12(7):e0180355. doi: 10.1371/journal.pone.0180355. PMID: 28700715; PMCID: PMC5507500. METASTUDY ↥ ↥
Daley D, van der Oord S, Ferrin M, Danckaerts M, Doepfner M, Cortese S, Sonuga-Barke EJ; European ADHD Guidelines Group (2014): Behavioral interventions in attention-deficit/hyperactivity disorder: a meta-analysis of randomized controlled trials across multiple outcome domains. J Am Acad Child Adolesc Psychiatry. 2014 Aug;53(8):835-47, 847.e1-5. doi: 10.1016/j.jaac.2014.05.013. PMID: 25062591. METASTUDY ↥ ↥
Evans SW, Langberg J, Raggi V, Allen J, Buvinger EC (2005): Development of a school-based treatment program for middle school youth with ADHD. J Atten Disord. 2005 Aug;9(1):343-53. doi: 10.1177/1087054705279305. PMID: 16371680. ↥
Epstein JN, Rabiner D, Johnson DE, Fitzgerald DP, Chrisman A, Erkanli A, Sullivan KK, March JS, Margolis P, Norton EC, Conners CK (2007): Improving attention-deficit/hyperactivity disorder treatment outcomes through use of a collaborative consultation treatment service by community-based pediatricians: a cluster randomized trial. Arch Pediatr Adolesc Med. 2007 Sep;161(9):835-40. doi: 10.1001/archpedi.161.9.835. PMID: 17768282. RCT ↥
Lieb (2019): Fake news in der Psychopharmakotherapie, Vortrag Uni Mainz, german ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Aderhold (2014): Neuroleptika minimal – warum und wie german ↥
Faraone SV (2008): Interpreting estimates of treatment effects: implications for managed care. P T. 2008 Dec;33(12):700-11. PMID: 19750051; PMCID: PMC2730804. ↥ ↥
Swift JK, Callahan JL, Vollmer BM (2011): Preferences. J Clin Psychol. 2011 Feb;67(2):155-65. doi: 10.1002/jclp.20759. PMID: 21120917. METASTUDY ↥ ↥
Delevry D, Le QA (2019): Effect of Treatment Preference in Randomized Controlled Trials: Systematic Review of the Literature and Meta-Analysis. Patient. 2019 Dec;12(6):593-609. doi: 10.1007/s40271-019-00379-6. PMID: 31372909. METASTUDY ↥
Windle E, Tee H, Sabitova A, Jovanovic N, Priebe S, Carr C (2020): Association of Patient Treatment Preference With Dropout and Clinical Outcomes in Adult Psychosocial Mental Health Interventions: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2020 Mar 1;77(3):294-302. doi: 10.1001/jamapsychiatry.2019.3750. PMID: 31799994; PMCID: PMC6902231. METASTUDY ↥
Türk S, Korfmacher AK, Gerger H, van der Oord S, Christiansen H (2023): Interventions for ADHD in childhood and adolescence: A systematic umbrella review and meta-meta-analysis. Clin Psychol Rev. 2023 Jun;102:102271. doi: 10.1016/j.cpr.2023.102271. PMID: 37030086. UMBRELLA REVIEW, k = 16 Metastudies ↥ ↥
Riera M, Castells X, Tobias A, Cunill R, Blanco L, Capellà D (2017): Discontinuation of pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder: meta-analysis of 63 studies enrolling 11,788 patients. Psychopharmacology (Berl). 2017 Sep;234(17):2657-2671. doi: 10.1007/s00213-017-4662-1. PMID: 28631099. METASTUDY ↥ ↥ ↥ ↥
Peterson BS, Trampush J, Maglione M, Bolshakova M, Brown M, Rozelle M, Motala A, Yagyu S, Miles J, Pakdaman S, Gastelum M, Nguyen BT, Tokutomi E, Lee E, Belay JZ, Schaefer C, Coughlin B, Celosse K, Molakalapalli S, Shaw B, Sazmin T, Onyekwuluje AN, Tolentino D, Hempel S (2024): ADHD Diagnosis and Treatment in Children and Adolescents [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2024 Mar. Report No.: 24-EHC003Report No.: 2023-SR-03. PMID: 38657097. METASTUDY ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Cunill R, Castells X, Tobias A, Capellà D (2016): Efficacy, safety and variability in pharmacotherapy for adults with attention deficit hyperactivity disorder: a meta-analysis and meta-regression in over 9000 patients. Psychopharmacology (Berl). 2016 Jan;233(2):187-97. doi: 10.1007/s00213-015-4099-3. PMID: 26446868. METASTUDY, k = 44, n = 9.952 ↥ ↥ ↥
De Crescenzo F, Cortese S, Adamo N, Janiri L (2017): Pharmacological and non-pharmacological treatment of adults with ADHD: a meta-review. Evid Based Ment Health. 2017 Feb;20(1):4-11. doi: 10.1136/eb-2016-102415. PMID: 27993933; PMCID: PMC10699262. REVIEW ↥ ↥
Cerrillo-Urbina AJ, García-Hermoso A, Pardo-Guijarro MJ, Sánchez-López M, Santos-Gómez JL, Martínez-Vizcaíno V (2018): The Effects of Long-Acting Stimulant and Nonstimulant Medications in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials. J Child Adolesc Psychopharmacol. 2018 Oct;28(8):494-507. doi: 10.1089/cap.2017.0151. PMID: 29897263. Metastudy ↥
Moukhtarian TR, Cooper RE, Vassos E, Moran P, Asherson P (2017): Effects of stimulants and atomoxetine on emotional lability in adults: A systematic review and meta-analysis. Eur Psychiatry. 2017 Jul;44:198-207. doi: 10.1016/j.eurpsy.2017.05.021. PMID: 28646732. REVIEW ↥ ↥ ↥ ↥ ↥ ↥
Ostinelli EG, Schulze M, Zangani C, Farhat LC, Tomlinson A, Del Giovane C, Chamberlain SR, Philipsen A, Young S, Cowen PJ, Bilbow A, Cipriani A, Cortese S (2025): Comparative efficacy and acceptability of pharmacological, psychological, and neurostimulatory interventions for ADHD in adults: a systematic review and component network meta-analysis. Lancet Psychiatry. 2025 Jan;12(1):32-43. doi: 10.1016/S2215-0366(24)00360-2. PMID: 39701638. METASTUDY ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Faraone SV, Buitelaar J (2010): Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis. Eur Child Adolesc Psychiatry. 2010 Apr;19(4):353-64. doi: 10.1007/s00787-009-0054-3. PMID: 19763664., METASTUDY ↥ ↥ ↥ ↥ ↥ ↥
Endrass, G (2024): ADHS aktuell – Mythen und Bedenken versus Fakten; NeuroTransmitter 2024; 35 (1-2) ↥ ↥ ↥
Castells X, Blanco-Silvente L, Cunill R (2018): Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2018 Aug 9;8(8):CD007813. doi: 10.1002/14651858.CD007813.pub3. PMID: 30091808; PMCID: PMC6513464. METASTUDY, k = 19 ↥ ↥ ↥
Castells X, Ramos-Quiroga JA, Bosch R, Nogueira M, Casas M (2011): Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults. Cochrane Database Syst Rev. 2011 Jun 15;(6):CD007813. doi: 10.1002/14651858.CD007813.pub2. Update in: Cochrane Database Syst Rev. 2018 Aug 09;8:CD007813. PMID: 21678370. METASTUDY, k = 7, n = 1.091 ↥
Rutledge-Jukes H, Jonnalagadda P, McIntosh AP, Krstovski S, Andriani N, Smith IR, Prendergast L, Lynch JM (2024): Lisdexamfetamine’s Efficacy in Treating Attention Deficit Hyperactivity Disorder (ADHD): A Meta-Analysis and Review. Cureus. 2024 Aug 31;16(8):e68324. doi: 10.7759/cureus.68324. PMID: 39350825; PMCID: PMC11441986. REVIEW ↥
Faraone SV (2009): Using Meta-analysis to Compare the Efficacy of Medications for Attention-Deficit/Hyperactivity Disorder in Youths. P T. 2009 Dec;34(12):678-94. PMID: 20140141; PMCID: PMC2810184. METASTUDY ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Pelham, Aronoff, Midlam, Shapiro, Gnagy, Chronis, Onyango, Forehand, Nguyen, Waxmonsky (1999): A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder. Pediatrics. 1999 Apr;103(4):e43. ↥
Metaanalyse einer hohen Anzahl von Studien durch Taylor (Eric), European guidelines on diagnosis and treatment of ADHD, Vortrag auf dem internationalen Symposium in Aachen, 14.03.2007, zitiert nach Kühle, Dr. med. Hans-Jürgen, Neurofeedbacktherapie bei ADHS, Giessen 2010 (PDF von Webseite Dr. Kühle, Download Februar 2018), Kapitel 7 ↥ ↥ ↥ ↥ ↥
Cortese, Adamo, Del Giovane, Mohr-Jensen, Hayes, Carucci, Atkinson, Tessari, Banaschewski, Coghill, Hollis, Simonoff, Zuddas, Barbui, Purgato, Steinhausen, Shokraneh, Xia, Cipriani (2018): Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis; The Lancet Psychiatry, VOLUME 5, ISSUE 9, P727-738, SEPTEMBER 01, 2018; Open Access; DOI:https://doi.org/10.1016/S2215-0366(18)30269-4 METASTUDY ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Punja S, Shamseer L, Hartling L, Urichuk L, Vandermeer B, Nikles J, Vohra S (2016): Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2016 Feb 4;2(2):CD009996. doi: 10.1002/14651858.CD009996.pub2. PMID: 26844979; PMCID: PMC10329868. METASTUDY ↥ ↥ ↥
Coghill D, Banaschewski T, Lecendreux M, Soutullo C, Johnson M, Zuddas A, Anderson C, Civil R, Higgins N, Lyne A, Squires L (2013): European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder. Eur Neuropsychopharmacol. 2013 Oct;23(10):1208-18. doi: 10.1016/j.euroneuro.2012.11.012. PMID: 23332456. ↥
Stuhec M, Munda B, Svab V, Locatelli I (2015): Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis with focus on bupropion. J Affect Disord. 2015 Jun 1;178:149-59. doi: 10.1016/j.jad.2015.03.006. PMID: 25813457. METASTUDY ↥ ↥ ↥ ↥
Nagy, Häge, Coghill, Caballero, Adey, Anderson, Sikirica, Cardo (2015): Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate.Eur Child Adolesc Psychiatry. 2016 Feb;25(2):141-9. doi: 10.1007/s00787-015-0718-0. ↥
Coghill D, Banaschewski T, Cortese S, Asherson P, Brandeis D, Buitelaar J, Daley D, Danckaerts M, Dittmann RW, Doepfner M, Ferrin M, Hollis C, Holtmann M, Paramala S, Sonuga-Barke E, Soutullo C, Steinhausen HC, Van der Oord S, Wong ICK, Zuddas A, Simonoff E (2023): The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG). Eur Child Adolesc Psychiatry. 2023 Aug;32(8):1337-1361. doi: 10.1007/s00787-021-01871-x. PMID: 34677682; PMCID: PMC8532460. REVIEW ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Banaschewski T, Coghill D, Santosh P, Zuddas A, Asherson P, Buitelaar J, Danckaerts M, Döpfner M, Faraone SV, Rothenberger A, Sergeant J, Steinhausen HC, Sonuga-Barke EJ, Taylor E (2008): Langwirksame Medikamente zur Behandlung der hyperkinetischen Störungen1. Eine systematische Ubersicht und europäische Behandlungsleitlinien Teil 2: Ein quantitativer Vergleich der langwirksamen Präparate [Long-acting medications for the treatment of hyperkinetic disorders - a systematic review and European treatment guidelines. Part 2: a quantitative evaluation of long-acting medications]. Z Kinder Jugendpsychiatr Psychother. 2008 Mar;36(2):97-106; quiz 106-7. German. doi: 10.1024/1422-4917.36.2.97. PMID: 18622939. REVIEW ↥ ↥ ↥ ↥ ↥ ↥
Faraone SV, Childress AC, Gomeni R, Rafla E, Kando JC, Dansie L, Naik P, Pardo A (2023): Efficacy of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder: Effect Size Across the Day. J Child Adolesc Psychopharmacol. 2023 Feb;33(1):14-19. doi: 10.1089/cap.2022.0093. PMID: 36730749. ↥
Maneeton, Maneeton, Suttajit, Reungyos, Srisurapanont, Martin (2014): Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD; Drug Des Devel Ther. 2014; 8: 1685–1693. doi: 10.2147/DDDT.S68393; PMCID: PMC4199984 ↥
Kooij, Bijlenga, Salerno, Jaeschke, Bitter, Balázs, Thome, Dom, Kasper, Filipe, Stes, Mohr, Leppämäki, Brugué, Bobes, Mccarthy, Richarte, Philipsen, Pehlivanidis, Niemela, Styr, Semerci, Bolea-Alamanac, Edvinsson, Baeyens, Wynchank, Sobanski, Philipsen, McNicholas, Caci, Mihailescu, Manor, Dobrescu, Krause, Fayyad, Ramos-Quiroga, Foeken, Rad, Adamou, Ohlmeier, Fitzgerald, Gill, Lensing, Mukaddes, Brudkiewicz, Gustafsson, Tania, Oswald, Carpentier, De Rossi, Delorme, Simoska, Pallanti, Young, Bejerot, Lehtonen, Kustow, Müller-Sedgwick, Hirvikoski, Pironti, Ginsberg, Félegeházy, Garcia-Portilla, Asherson (2018): Updated European Consensus Statement on diagnosis and treatment of adult ADHD, European Psychiatrie, European Psychiatry 56 (2019) 14–34, http://dx.doi.org/10.1016/j.eurpsy.2018.11.001, Seite 22, 7.4.3. ↥
Fridman, Hodgkins, Kahle, Erder (2015): Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: Estimates based on indirect analysis using a systematic review and meta-regression analysis; Eur Psychiatry. 2015 Jun;30(4) :521-7. doi: 10.1016/j.eurpsy.2015.01.001. METASTUDY, k = 22 ↥
Maneeton N, Maneeton B, Suttajit S, Reungyos J, Srisurapanont M, Martin SD (2014): Exploratory meta-analysis on lisdexamfetamine versus placebo in adult ADHD. Drug Des Devel Ther. 2014 Oct 3;8:1685-93. doi: 10.2147/DDDT.S68393. PMID: 25336914; PMCID: PMC4199984. METASTUDY, k = 5 RCT, N = 806 ↥
Stuhec, Lukić, Locatelli (2018): Efficacy, Acceptability, and Tolerability of Lisdexamfetamine, Mixed Amphetamine Salts, Methylphenidate, and Modafinil in the Treatment of Attention-Deficit Hyperactivity Disorder in Adults: A Systematic Review and Meta-analysis. Ann Pharmacother. 2018 Aug 17:1060028018795703. doi: 10.1177/1060028018795703. n = 701 ↥ ↥ ↥ ↥
Tripp G, Wickens J (2012): Reinforcement, dopamine and rodent models in drug development for ADHD. Neurotherapeutics. 2012 Jul;9(3):622-34. doi: 10.1007/s13311-012-0132-y. PMID: 22806330; PMCID: PMC3441939. REVIEW ↥ ↥ ↥ ↥ ↥
Faraone et al (2004), Biedermann et al (2006), Biedermann et al (2007), zitiert nach Safren, Perlman: Kognitive Verhaltenstherapie des ADHS des Erwachsenenalters, Seite 9 ↥
Sudnawa, Chirdkiatgumchai, Ruangdaraganon, Khongkhatithum, Udomsubpayakul, Jirayucharoensak, Israsena (2018): Effectiveness of Neurofeedback Versus Medication in Treatment of ADHD. Pediatr Int. 2018 Jun 22. doi: 10.1111/ped.13641., n = 40 ↥ ↥
Kortekaas-Rijlaarsdam AF, Luman M, Sonuga-Barke E, Oosterlaan J (2019): Does methylphenidate improve academic performance? A systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2019 Feb;28(2):155-164. doi: 10.1007/s00787-018-1106-3. PMID: 29353323. METASTUDY ↥
Tamminga HG, Reneman L, Huizenga HM, Geurts HM (2016): Effects of methylphenidate on executive functioning in attention-deficit/hyperactivity disorder across the lifespan: a meta-regression analysis. Psychol Med. 2016 Jul;46(9):1791-807. doi: 10.1017/S0033291716000350. PMID: 27019103. METASTUDY ↥ ↥ ↥
Lenzi, Cortese, Harris, Masi (2017); Pharmacotherapy of emotional dysregulation in adults with ADHD: A systematic review and meta-analysis; Neurosci Biobehav Rev. 2017 Aug 25. pii: S0149-7634(17)30443-8. doi: 10.1016/j.neubiorev.2017.08.010. REVIEW ↥
Metaanalyse einer hohen Anzahl von Studien durch Taylor (Eric), European guidelines on diagnosis and treatment of ADHD, Vortrag auf dem internationalen Symposium in Aachen, 14.03.2007, zitiert nach Kühle, Dr. med. Hans-Jürgen, Neurofeedbacktherapie bei ADHS, Giessen 2010 (PDF von Webseite Dr. Kühle, Download August 2015), Kapitel 4 ↥ ↥ ↥ ↥ ↥
Storebø OJ, Krogh HB, Ramstad E, Moreira-Maia CR, Holmskov M, Skoog M, Nilausen TD, Magnusson FL, Zwi M, Gillies D, Rosendal S, Groth C, Rasmussen KB, Gauci D, Kirubakaran R, Forsbøl B, Simonsen E, Gluud C (2015): Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. BMJ. 2015 Nov 25;351:h5203. doi: 10.1136/bmj.h5203. PMID: 26608309; PMCID: PMC4659414. COCHRANE MATASTUDY ↥ ↥
Storebø OJ, Storm MRO, Pereira Ribeiro J, Skoog M, Groth C, Callesen HE, Schaug JP, Darling Rasmussen P, Huus CL, Zwi M, Kirubakaran R, Simonsen E, Gluud C (2023): Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database Syst Rev. 2023 Mar 27;3(3):CD009885. doi: 10.1002/14651858.CD009885.pub3. PMID: 36971690; PMCID: PMC10042435. METASTUDY, k = 424, N = 32.718 ↥
Coghill DR, Seth S, Pedroso S, Usala T, Currie J, Gagliano A (2014): Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis. Biol Psychiatry. 2014 Oct 15;76(8):603-15. doi: 10.1016/j.biopsych.2013.10.005. PMID: 24231201. METASTUDY ↥ ↥ ↥ ↥ ↥
Maia CR, Cortese S, Caye A, Deakin TK, Polanczyk GV, Polanczyk CA, Rohde LA (2017): Long-Term Efficacy of Methylphenidate Immediate-Release for the Treatment of Childhood ADHD. J Atten Disord. 2017 Jan;21(1):3-13. doi: 10.1177/1087054714559643. PMID: 25501355. METASTUDY ↥ ↥ ↥ ↥
Punja S, Zorzela L, Hartling L, Urichuk L, Vohra S (2013): Long-acting versus short-acting methylphenidate for paediatric ADHD: a systematic review and meta-analysis of comparative efficacy. BMJ Open. 2013 Mar 15;3(3):e002312. doi: 10.1136/bmjopen-2012-002312. PMID: 23503579; PMCID: PMC3612754. ↥ ↥ ↥
Jaeschke, Sujkowska, Sowa-Kućma (2021): Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review. Psychopharmacology (Berl). 2021 Oct;238(10):2667-2691. doi: 10.1007/s00213-021-05946-0. PMID: 34436651; PMCID: PMC8455398. METASTUDY ↥ ↥
Koesters M, Becker T, Kilian R, Fegert JM, Weinmann S (2009): Limits of meta-analysis: methylphenidate in the treatment of adult attention-deficit hyperactivity disorder. J Psychopharmacol. 2009 Sep;23(7):733-44. doi: 10.1177/0269881108092338. PMID: 18562416. REVIEW ↥
Castells X, Ramos-Quiroga JA, Rigau D, Bosch R, Nogueira M, Vidal X, Casas M (2011): Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis. CNS Drugs. 2011 Feb;25(2):157-69. doi: 10.2165/11539440-000000000-00000. PMID: 21254791. METASTUDY, k = 18 RCT, n = 2.045 ↥
Bushe C, Day K, Reed V, Karlsdotter K, Berggren L, Pitcher A, Televantou F, Haynes V (2016): A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients. J Psychopharmacol. 2016 May;30(5):444-58. doi: 10.1177/0269881116636105. PMID: 27005307. METASTUDY ↥ ↥
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