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Treatment of ADHD in Adults

Treatment of ADHD in Adults

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Implications for People with ADHD

The daily doses of stimulants are similar for adults and children. Based on body weight, adults therefore generally receive a lower dose. Treatment should begin with a low dose at any age, and the dose should be increased gradually.

In studies, ADHD medications were slightly less effective in adults than in children, but still significantly effective. Stimulants (amphetamines, methylphenidate) were more effective than non-stimulants such as atomoxetine. Adults discontinued treatment more frequently due to side effects than those on placebo. According to a review, about 30% of people with ADHD did not respond to the available medications. In one study, methylphenidate also reduced emotional symptoms such as irritability and mood swings. In one study, methylphenidate altered the dopamine system and the cerebral cortex beyond the duration of treatment in children, but not in adults.

Medications do not cure ADHD. For most people with ADHD, a combination of medication and psychosocial treatment—such as psychoeducation and cognitive behavioral therapy—is considered most effective. In adults, cognitive behavioral therapy has also been shown to improve depression, anxiety, and emotional problems. The goal of treatment is not only to reduce symptoms but also to help individuals cope better with daily life and improve their quality of life. Since ADHD and the response to treatment can change over the course of a person’s life, regular follow-up visits are recommended.

Many adults with ADHD go untreated. In Germany, in 2023, approximately 44% of adults diagnosed with ADHD received neither medication nor psychotherapy. Many discontinue treatment, particularly when transitioning from child and adolescent psychiatry to adult care, even though their symptoms often persist. Reasons cited included a lack of knowledge about ADHD, difficulties with self-organization, the loss of parental support, and a shortage of specialized services for adults. A planned transition with a structured handoff is recommended.

In studies, symptoms often returned after discontinuing the medication. Cardiovascular diseases were not significantly more common among young and middle-aged adults taking ADHD medication.

In women, several studies suggested that ADHD symptoms worsened during the second half of the menstrual cycle. In a small case series, a higher dose of stimulants was helpful during the week before menstruation. In one study, methylphenidate during pregnancy did not increase the risk of major birth defects, but miscarriages were more common. Many women stopped or interrupted their ADHD medication around the time of pregnancy.

The recommended daily doses of stimulants differ barely, in absolute terms, between adults and children. For lisdexamfetamine, the initial dose (30 mg) and the recommended maximum dose (70 mg/day) are the same for children aged 6 and older and for adults. (E 4.)1 (E 4.)2 Based on body weight, adults therefore generally receive lower doses than children. Whether this is related to the fact that the number of dopamine transporters decreases with age remains unclear. (ADxS assessment)
Regardless of age, treatment with stimulants should be started at a low dose and gradually increased.

In healthy adults, the availability of dopaminergic target structures decreased per decade of life for: (Meta-analysis, k = 95, N = 2,611, E 3.)3

  • D1 receptors (k = 5, n = 106), −14.0%, correlation with age r = −0.77
  • striatal dopamine transporters (k = 29, n = 897), −8.9%, r = −0.68
  • D2 receptors (k = 42, n = 1,067), −8.2%, r = −0.56
  • Dopamine synthesis capacity (k = 10, n = 222), −3.7%, r = −0.06 (not significant)

The dose-response curves differed between children/adolescents and adults in the following cases: (dose-response network meta-analysis, k = 113, N = 25,154, E 1a.)4

  • Amphetamines in children and adolescents, with a peak at approximately 25 mg/day (dexamfetamine equivalent), SMD −1.06 (−1.35 to −0.78)
  • Methylphenidate in children and adolescents; peak effect at approximately 45 mg/day; SMD −0.89 (95% CrI −1.18 to −0.60)
  • Amphetamines in adults: plateau at approximately 50 mg/day (dexamfetamine equivalent); SMD −0.74 (−1.26 to −0.20)
  • Methylphenidate in adults: increasing efficacy across the entire dose range without a discernible plateau, with diminishing additional benefit as the dose approaches 50 mg/day

Discontinuation due to side effects increased in a dose-dependent manner for amphetamines at doses above 25 mg/day (children) and 50 mg/day (adults), and for methylphenidate at doses above 50 mg/day (adults). (Dose-effect network meta-analysis, k = 113, N = 25,154, E 1a.)4

(E 1a): The effectiveness of ADHD medications on core symptoms was lower in adults than in children and adolescents. (Network meta-analysis, k = 133 RCTs, n = 10,068 children and adolescents, 8,131 adults, E 1a.)5 (Umbrella review, k = 47, E 1a.)6 In adults, methylphenidate, atomoxetine, and cognitive behavioral therapy showed moderate effects on ADHD symptoms in the short term, with at least moderate certainty of evidence (GRADE). (Umbrella review, k = 47, E 1a.)6 The effect sizes (SMD compared to placebo) on core ADHD symptoms were

  • in adults for:
    • Amphetamines
      • SMD 0.72 to 1.07, reported in a meta-analysis (narrative review, E 4.)7
      • SMD −0.79 (95% CI −0.99 to −0.58), Clinical judgment, approximately 12 weeks (network meta-analysis, k = 133 RCTs, n = 10,068 children and adolescents, 8,131 adults, E 1a.)5
      • At least moderately supported efficacy only when limited to high-quality studies (umbrella review, k = 47, E 1a.)6
    • cognitive behavioral therapy
      • SMD 0.43 to 1.0, reported in a meta-analysis (narrative review, E 4.)7
      • SMD 0.53 (0.29 to 0.77), clinically assessed, moderate certainty of evidence (umbrella review, k = 47, E 1a.)6
    • Methylphenidate
      • SMD 0.42 to 0.72, reported in a meta-analysis (narrative review, E 4.)7
      • SMD 0.50 (0.39 to 0.61), clinically assessed, moderate certainty of evidence (umbrella review, k = 47, E 1a.)6
      • SMD −0.49 (95% CI −0.64 to −0.35), Clinical judgment, approximately 12 weeks (network meta-analysis, k = 133 RCTs, n = 10,068 children and adolescents, 8,131 adults, E 1a.)5
      • SMD 0.34 (0.26 to 0.42), self-assessed, high certainty of evidence (umbrella review, k = 47, E 1a.)6
    • mindfulness-based therapies
      • SMD 0.53 to 0.66, reported in a meta-analysis (narrative review, E 4.)7
    • Atomoxetine
      • SMD 0.38 to 0.60, reported in a meta-analysis (narrative review, E 4.)7
      • SMD −0.45 (95% CI −0.58 to −0.32), Clinical judgment, approximately 12 weeks (network meta-analysis, k = 133 RCTs, n = 10,068 children and adolescents, 8,131 adults, E 1a.)5
      • SMD 0.37 (0.26 to 0.47), self-assessed, high certainty of evidence (umbrella review, k = 47, E 1a.)6
  • in children and adolescents for: (network meta-analysis, k = 133 RCTs, n = 10,068 children and adolescents, 8,131 adults, E 1a.)5
    • Amphetamines SMD −1.02 (95% CI −1.19 to −0.85), clinician assessment, approximately 12 weeks
    • Methylphenidate SMD −0.78 (95% CI −0.93 to −0.62), clinician assessment, approximately 12 weeks
    • Methylphenidate SMD greater than 0.75 (95% CI 0.56 to 1.03) (umbrella review, k = 47, E 1a.)6
    • Atomoxetine SMD −0.56 (95% CI −0.66 to −0.45), clinician assessment, approximately 12 weeks

The effect sizes of stimulants and non-stimulants in adults with ADHD were of a similar magnitude to those previously reported for children. (Meta-analysis, k = 19, full text not available to us, E 1a.)8 Approximately 30% of people with ADHD do not respond to the available medications. (Narrative review, E 4.)7 No intervention was found to have highly reliable long-term evidence. (Umbrella review, k = 47, E 1a.)6

(E 1a): Stimulants were more effective than non-stimulants (atomoxetine, viloxazine) in adults with ADHD. (Meta-analysis, k = 19, full text not available to us, E 1a.)8 (Narrative review, E 4.)9 (Narrative review, E 4.)10 This was true in the short-term placebo-controlled studies. No significant difference was found between short- and long-acting stimulants. (Meta-analysis, k = 19, full text not available to us, E 1a.)8

(E 1a): The following were considered the first choice of medication for adults:

  • Stimulants, due to their greater efficacy compared to non-stimulants (narrative review, E 4.)10
  • Long-acting stimulants; once-daily dosing improves adherence (narrative review, E 4.)11
  • Amphetamines for short-term treatment; methylphenidate for children and adolescents (network meta-analysis, k = 133 RCTs, n = 10,068 children and adolescents, 8,131 adults, E 1a.)5

(E 1a): In adults, ADHD medications were less well tolerated than placebo. (Network meta-analysis, k = 133 RCTs, n = 10,068 children and adolescents, 8,131 adults, E 1a.)5 (Umbrella review, k = 47, E 1a.)6 Tolerability compared to placebo was

  • following discontinuations due to side effects (more participants than in the placebo group), with an OR of: (network meta-analysis, k = 133 RCTs, n = 10,068 children and adolescents, 8,131 adults, E 1a.)5
    • Modafinil OR 4.01 (95% CI 1.42 to 11.33)
    • Amphetamines OR 3.26 (95% CI 1.54 to 6.92)
    • Methylphenidate OR 2.39 (95% CI 1.40 to 4.08)
    • Atomoxetine OR 2.33 (95% CI 1.28 to 4.25)
  • as RR for: (umbrella review, k = 47, E 1a.)6
    • Amphetamines RR 0.40 (95% CI 0.22 to 0.72)
    • Atomoxetine RR 0.45 (95% CI 0.35 to 0.58)
    • Methylphenidate RR 0.50 (95% CI 0.36 to 0.69)

In children, the poorer tolerability of methylphenidate and atomoxetine was not significant. (Umbrella review, k = 47, E 1a.)6

(E 1a): In most analyses, age did not significantly influence the efficacy of ADHD medications. (Meta-analysis, k = 25, 13, and 29, respectively; n = 775, 559, and 956, respectively; E 1a.)12 (Post-hoc analysis of 2 RCTs, n = 536, 10 weeks, author(s) employed by the manufacturer, E 1a.)13 (Systematic review of RCTs, k = 62, full text not available to us, E 1a.)14 The effect sizes of methylphenidate on executive functions were independent of age (mean study age 4.8 to 50.1 years) and were as follows: (Meta-analysis, k = 25, 13 and 29, respectively; n = 775, 559, and 956, respectively; E 1a.)12

  • Sustained attention (k = 29, n = 956), ES 0.42 (95% CI 0.26 to 0.59)
  • Reaction inhibition (k = 25, n = 775), ES 0.40 (95% CI 0.22 to 0.58)
  • Working memory (k = 13, n = 559), ES 0.24 (95% CI 0.00 to 0.48), p = 0.053

Studies involving adolescents were largely absent. (Meta-analysis, k = 25, 13, and 29, respectively; n = 775, 559, and 956, respectively; E 1a.)12

Atomoxetine was equally effective in younger adults (ages 18 to 25) and older adults (over 25) (no significant interaction between treatment and age group). The effect sizes compared to placebo were as follows: (post hoc analysis of 2 RCTs, n = 536, 10 weeks, author(s) employed by the manufacturer, E 1a.)13

  • CGI-ADHD-S
    • 18- to 25-year-olds (n = 55) d = 1.121
    • People over 25 (n = 481) d = 0.346
  • CAARS-Inv:SV
    • 18- to 25-year-olds (n = 55) d = 0.797
    • People over 25 (n = 481) d = 0.326

The response rate was 56.4% among 18- to 25-year-olds and 47.8% among those over 25. (Post-hoc analysis of 2 RCTs, n = 536, 10 weeks, author(s) employed by the manufacturer, E 1a.)13

Of 171 RCTs on ADHD medications (children, adolescents, and adults), 62 examined clinical and demographic characteristics as predictors or moderators of efficacy and tolerability. Age was the most frequently examined characteristic (56.4%). Most RCTs found no significant associations. Preliminary evidence of an effect was found (proportion of RCTs) for: (Systematic review of RCTs, k = 62, full text not available to us, E 1a.)14

  • Age 17.7%
  • psychiatric comorbidity: 17.7%
  • ADHD severity at the start of treatment: 16.1%
  • Gender 11.3%
  • Presentation format 4.8%

Adults with ADHD onset after age 7 responded to methylphenidate at least as well as adults with earlier onset (F = 5.760, p = 0.018 in favor of late onset). (Cohort study, n = 291, 1 month, E 2b.)15

A 16-week course of methylphenidate produced changes in 10- to 12-year-old boys with ADHD, but not in 23- to 40-year-old men: (RCT, n = 99, 16 weeks, E 1b.)16

  • Response of cerebral blood flow to a methylphenidate challenge (a marker of dopamine function) in the striatum: increased (compared to placebo: 7.7, 0.7 to 14.8)
  • Response of cerebral blood flow to a methylphenidate challenge in the thalamus: increased (mean difference 6.5, 95% CI 0.4 to 12.6)
  • Thinning of the right medial cortex was reduced, even compared to placebo (time × medication × age interaction, F = 4.316, p < 0.05) (RCT, n = 99, 16 weeks, E 1b.)17

Cerebral blood flow was measured 1 week after the end of treatment. The authors interpreted this as an age-dependent, sustained effect on the developing dopamine system. (RCT, n = 99, 16 weeks, E 1b.)16

(E 1a): Cognitive behavioral therapy and methylphenidate reduced emotional symptoms in adults with ADHD. (Meta-analysis, k = 44, E 1a.)18 (RCT, n = 363, 24 weeks, manufacturer-funded, author(s) employed by the manufacturer, E 1b.)19 (Narrative review, full text not available to us, E 4.)20 The effect sizes for emotional symptoms were

  • for CBT after the end of treatment (small to moderate effect sizes) for: (meta-analysis, k = 44, E 1a.)18
    • Depression: SMD 0.42 (0.19 to 0.66)
    • Anxiety SMD 0.33 (0.15 to 0.50)
    • Emotional dysregulation: SMD 0.26 (0.06 to 0.45)
  • for sustained-release methylphenidate (MPH-ER, 50% immediate release, 50% sustained release, up to 60 mg/day, mean daily dose at week 24 41.2 mg and 0.55 mg/kg, respectively), which reduced emotional symptoms more effectively than placebo in adults with ADHD, for: (RCT, n = 363, 24 weeks, manufacturer-funded, author(s) employed by the manufacturer, E 1b.)19
    • Emotional dysregulation (as assessed by others, WRAADDS-EDS) 0.42 (PP)
    • emotional dysregulation (as assessed by others, WRAADDS-EDS) 0.37 (ITT)
    • emotional lability (self-reported, CAARS-ELS) 0.35 (PP)
    • emotional lability (self-reported, CAARS-ELS) 0.3 (ITT)

At follow-up, the effects of CBT on depression (SMD 0.59, 95% CI 0.04 to 1.15) and anxiety (SMD 0.47, 95% CI 0.12 to 0.82) persisted. In children with ADHD, however, parent training (emotional dysregulation: SMD 0.49, 95% CI 0.10 to 0.88) and social skills training (emotional dysregulation: SMD 0.49, 95% CI 0.07 to 0.91) after the end of treatment; however, at follow-up, no effects on emotional dysregulation or depression were found in children. The effectiveness of nonpharmacological interventions on emotional symptoms thus differed significantly between children and adults. (Meta-analysis, k = 44, E 1a.)18

The difference was significant starting in week 5 and remained stable through week 24. Compulsive symptoms and problems with self-concept decreased. Anxiety, depression, anger/hostility, phobic anxiety, paranoid thinking, and psychoticism did not improve. (RCT, n = 363, 24 weeks, manufacturer-funded, author(s) employed by the manufacturer, E 1b.)19

In adults with ADHD, methylphenidate reduced temperamental problems, affective instability, and emotional hyperreactivity, with varying degrees of effect size. Emotional side effects occurred primarily at high doses and in specific populations. (Narrative review, full text not available to us, E 4.)20

(E 1b): ADHD treatment improved SCT symptoms in adults with ADHD. (RCT, crossover, n = 38, 4 weeks each, manufacturer-funded, E 1b.)21 (Meta-analysis, k = 3, N = 432, E 2b.)22 (Cohort study, prospective, naturalistic, n = 37, 1 year, E 2b.)23 (Prospective case series, n = 32, E 4.)24 The effect sizes (Cohen’s d) for SCT were as follows: (RCT, crossover, n = 38, 4 weeks each, manufacturer-funded, E 1b.)21

  • Methylphenidate after one year (mean final dose 32.16 mg/day), Before-and-after comparison, SCT (BAARS-IV): median score decreased from 24 to 20, d = 1.02 (cohort study, prospective, naturalistic, n = 37, 1 year, E 2b.)23
  • Lisdexamfetamine versus placebo in the first treatment block, d = 0.68
  • Lisdexamfetamine versus placebo in the second treatment block, d = 0.61, not significant

Lisdexamfetamine (average dose 59.1 mg/day) also improved ADHD symptoms (d = 0.97 and 0.91, respectively) compared with placebo in adults with ADHD and comorbid SCT, executive function deficits, and functional impairment. The improvement in SCT was mediated by the improvement in executive functions (BRIEF-A). (RCT, crossover, n = 38, 4 weeks each, manufacturer-funded, E 1b.)21

For adults, only one placebo-controlled trial has been conducted to date on the pharmacological treatment of SCT/CDS (lisdexamfetamine, Hedges’ g = 0.68, 95% CI 0.22 to 1.14). In a pooled analysis of children and adults, ADHD medications improved SCT/CDS with g = 0.39 (0.01 to 0.78). (Meta-analysis, k = 3, N = 432, E 2b.)22

In an outpatient ADHD clinic for adults, medication and psychoeducation (treatment as usual) improved self-reported executive functions (p = 0.001), core ADHD symptoms (p = 0.007), and SCT (p = 0.002). Additional modular psychotherapy yielded similar improvements (p = 0.001, 0.004, and 0.002). (Prospective case series, n = 32, E 4.)24

After one year of methylphenidate treatment, scores for behavioral addictions decreased among adult ADHD patients. The proportion of patients with at least one comorbid behavioral addiction decreased from 51.4% to 35.1%. The decrease in internet addiction scores correlated with the decrease in SCT symptoms (r = 0.35). Change from: (cohort study, prospective, naturalistic, n = 37, 1 year, E 2b.)23

  • Total ADHD symptom score (BAARS-IV): Median 50 to 37, d = 1.1
  • Internet Addiction Test (IAT): Median 44 to 34, d = 0.53
  • Compulsive Shopping Scale (BSAS): Median 46 vs. 36, p = 0.022
  • Food addiction (YFAS) p = 0.039
  • Sex Addiction (SAST-R) p = 0.047

(E 4): For most people with ADHD, a combination of medication and psychosocial treatment is most beneficial. (Narrative review, E 4.)9 (Consensus, n = 15, industry-funded, E 4.)25 A multimodal treatment approach consisting of medication, psychoeducation, psychotherapy, and lifestyle changes was recommended, as well as a “treat-to-target” approach (defined clinical goals, adjustment of therapy until these goals are achieved) with regular, scheduled follow-up. (Consensus, n = 15, manufacturer-funded, E 4.)25

Medications do not cure ADHD. Difficulties beyond the core symptoms often do not improve sufficiently with medication and may require temporary or long-term psychotherapy or other support, as needed—possibly including case management. Research on ADHD coaching is still in its early stages. (Comment, E 4.)26

tDCS and neurofeedback showed moderate effects on inattention and executive functions; CBT-based approaches improved symptom management and emotion regulation, usually as an adjunct to medication. Acceptance and adherence remain key challenges. (Narrative review, E 4.)10

A literature search of 1,419 studies on ADHD in adults identified only five empirical studies on psychological treatment. Brief, structured interventions achieved moderate to large effect sizes. According to a panel of experts, psychological treatment is particularly suitable for motivated adults who are willing to learn new skills as their symptoms subside. (Expert panel with literature review, industry-funded, E 4.)27

(E 4): Response and remission criteria for adults with ADHD should take into account not only symptom reduction but also functional status, since symptom remission does not necessarily imply intact functional status. (Consensus, n = 15, industry-funded, E 4.)25 (Narrative review, industry-funded, author employed by manufacturer, E 4.)28 According to an expert consensus, this also includes comorbid symptoms, quality of life, and executive functions. Consensus was reached on 27 of 29 statements (93.1%). (Consensus, n = 15, manufacturer-funded, E 4.)25 For adults with ADHD, there is no general consensus on the definition of remission. Common criteria include a CGI-S score of 1 or 2 (no or minimal illness) or an ADHD-RS-IV total score of 18 or lower. Residual executive function impairments may persist. (Narrative review, manufacturer-funded, author employed by the manufacturer, E 4.)28

(E 4): ADHD requires regular follow-up. (Narrative review, industry-funded, author employed by the manufacturer, E 4.)28 (Consensus, n = 15, industry-funded, E 4.)25 As a chronic disorder, ADHD requires lifelong monitoring, since its presentation and response to treatment can vary greatly over time, even in the same individual. (Narrative review, industry-funded, author employed by the manufacturer, E 4.)28

The disorder causing the most significant impairment should be treated first; effective ADHD treatment facilitates the treatment of comorbid disorders. (Consensus, n = 15, manufacturer-funded, E 4.)25 According to a commentary, the order of priority in guidelines—treating comorbid depression first and then ADHD after remission or response—is not empirically supported. Since ADHD is a risk factor for treatment-resistant depression, concurrent treatment with antidepressants and stimulants may potentially increase remission rates. Warnings in the prescribing information for stimulants used to treat depression are predominantly theoretical. In bipolar disorder, a combination of stimulants and mood stabilizers (e.g., lithium) is considered safe with regard to the risk of switching. (Commentary, E 4.)29

In adults with ADHD and insomnia, the orexin receptor antagonist daridorexant (50 mg in the evening) improved insomnia to a clinically significant degree in 62.5% of participants in an open-label study and was associated with improved sustained attention. (Cohort study, open-label, naturalistic, n = 24, 1 month, manufacturer-funded, Phase 2b.)30

(E 2b): The prevalence of ADHD medication use among adults increased in several countries. (Registry study, n = 3,529,615, 6 years, manufacturer-funded, author employed by the manufacturer, E 2b.)31 (Registry study, n = 154.5 million, E 2b.)32 (Prescription registry study, N = 15.8 million, n = 76,896 users in 2012, 5 years, E 2b.)33 (General population cohort study, N = 5,149,791, n = 41,700, 4 years, E 2b.)34 (Prescription registry study, 17 years, E 2b.)35 (Cross-sectional study, routine data, E 3.)36 The prevalence of ADHD medication was

  • per 1,000 people: (registry study, n = 3,529,615, 6 years, manufacturer-funded, author employed by the manufacturer, E 2b.)31
    • 9.2 (95% CI 8.8 to 9.6) among 6- to 12-year-olds in the British primary care system in 2008; 4.8 (95% CI 4.5 to 5.1) in 2003
    • 7.4 (95% CI 7.0 to 7.8) among 13- to 17-year-olds in British primary care in 2008; 3.6 (95% CI 3.3 to 3.9) in 2003
    • 6.98 (prevalence of use) among 6- to 45-year-olds in Sweden in 2009; 2.93 in 2006 (PR 2.38, 95% CI 2.34 to 2.43) (Cohort study of the general population, N = 5,149,791, n = 41,700, 4 years, E 2b.)34
    • 5.3 (annual prevalence of use) among men aged 18 to 64 in the five Nordic countries in 2012, 2.4 in 2008 (prescription registry study, N = 15.8 million, n = 76,896 users in 2012, 5 years, E 2b.)33
    • 4.4 (annual prevalence of use) among women aged 18 to 64 in the five Nordic countries in 2012, 1.8 in 2008 (prescription registry study, N = 15.8 million, n = 76,896 users in 2012, 5 years, E 2b.)33
    • 1.1 (95% CI 1.0 to 1.3) among 18- to 24-year-olds in British primary care in 2008; 0.3 (95% CI 0.2 to 0.3) in 2003
    • 0.08 (95% CI 0.06 to 0.10) among 25- to 45-year-olds in the U.K. primary care system in 2008, 0.02 (95% CI 0.01 to 0.03) in 2003
    • 0.02 (95% CI 0.01 to 0.03) among people over 45 in British primary care in 2008; 0.01 (95% CI 0.00 to 0.01) in 2003
  • In 2010, among adults aged 19 and older, the rate ranged from 0.003% to 1.48% depending on the country; among children aged 3 to 18, it ranged from 0.27% to 6.69%; regionally among adults: (Registry study, n = 154.5 million, E 2b.)32
    • 1.42% in North America
    • 0.47% in Northern Europe
    • 0.05% in Asia and Australia
    • 0.03% in Western Europe

In the United Kingdom’s primary care system, the prevalence of ADHD treated with medication increased across all age groups from 2003 to 2008, but remained well below prevalence estimates among adults. (Registry study, n = 3,529,615, 6 years, manufacturer-funded, author employed by the manufacturer, E 2b.)31

The annual absolute increase among adults ranged from 0.0006% to 0.12%. (Registry study, n = 154.5 million, E 2b.)32

The treated prevalence of ADHD in Taiwan rose from 64.65 to 145.40 per 100,000 between 2000 and 2005 (p = 0.001), and the treated incidence rose from 44.67 to 81.20 per 100,000 (p = 0.013). The treated prevalence peaked between the ages of 7 and 12 and dropped sharply in the 13- to 18-year-old age group (p < 0.001). (Registry study, n = 6,173, 6 years, E 2b.)37

(E 2b): The relative increase in ADHD medication use was greater among adults than among children in Norway from 2006 to 2022 among 18- to 64-year-olds, although the prevalence among children remained consistently higher. (Prescription registry study, 17 years, E 2b.)35 (General population cohort study, N = 5,149,791, n = 41,700, 4 years, E 2b.)34 The prevalence ratio (PR) of dispensing prevalence in Sweden in 2009 compared to 2006 was: (Cohort study of the general population, N = 5,149,791, n = 41,700, 4 years, E 2b.)34

  • 3.40 for adults (ages 22 to 45)
  • 2.92 for women
  • 2.41 among adolescents and young adults (ages 15 to 21)
  • 2.19 for men
  • 1.90 for children (ages 6 to 14)

(E 2b): The percentage of individuals diagnosed with ADHD who received ADHD medication was:

  • 78.9% among adults in Sweden (register-based study, N = 44,364, manufacturer-funded, author employed by the manufacturer, E 2b.)38
  • 65.7% among newly diagnosed adults in Sweden (registry study, N = 44,364, manufacturer-funded, author employed by the manufacturer, E 2b.)38
  • The majority of those diagnosed across all age groups in Sweden; methylphenidate is the most commonly prescribed medication (registry study, manufacturer-funded, author employed by the manufacturer, E 2b.)39
  • 51.7% among AOK-insured individuals aged 13 to 14 in 2009 (peak age) (cross-sectional study, routine data, E 3.)36
  • 43.1% among AOK-insured individuals aged 13 to 14 in 2014 (peak age) (cross-sectional study, routine data, E 3.)36
  • 38% of adults in Bavaria with a continuously documented diagnosis; 22% received only other psychotropic medications, and 41% received no medication (comprehensive analysis of routine data, n = 10,529; author(s) employed by the manufacturer, E 3.)40
  • 33.4% among AOK-insured individuals aged 37 in 2014 (peak incidence in adulthood) (cross-sectional study, routine data, E 3.)36
  • approximately 30% within one year among adults with a newly diagnosed ADHD in Bavaria (2012) (comprehensive analysis of routine data, n = 10,529; author(s) employed by the data provider, E 3.)40
  • 19.2% among AOK-insured individuals aged 34 in 2009 (peak incidence in adulthood) (cross-sectional study, routine data, E 3.)36

Between 2009 and 2014, the medication rate increased among adults but decreased among children and adolescents. (Cross-sectional study, routine data, E 3.)36 In Sweden, one-third of adults received more than one additional medication. The mean daily dose was 51.5 mg and was higher among men, those with substance use disorders, during medication breaks, and when additional medications were prescribed. The most common concomitant medications were anxiolytics and hypnotics. (Registry study, N = 44,364, manufacturer-funded, author employed by manufacturer, E 2b.)38 In the five Nordic countries, 53% of men and 64% of women were taking other psychotropic medications at the same time, most commonly antidepressants and hypnotics. This co-medication increased with age. (Prescription registry study, N = 15.8 million, n = 76,896 users in 2012, 5 years, E 2b.)33

(E 2b): Methylphenidate was the most commonly used ADHD medication in most countries. (Registry study, n = 154.5 million, E 2b.)32 (Registry study, manufacturer-funded, author employed by manufacturer, E 2b.)39 (Registry study, N = 44,364, manufacturer-funded, author employed by manufacturer, E 2b.)38 (Comprehensive analysis of routine data, n = 10,529, author(s) employed by manufacturer, E 3.)40 (Cross-sectional study, routine data, E 3.)36 (Prescription registry study, N = 15.8 million, n = 76,896 users in 2012, 5 years, E 2b.)33 Its share was:

  • almost exclusively (atomoxetine accounted for less than 2% of prescriptions) among adults in Bavaria (comprehensive analysis of routine data, n = 10,529; author(s) employed by the manufacturer, E 3.)40
  • 75 to 100% of prescriptions in nearly all age groups among AOK-insured individuals, followed by atomoxetine (cross-sectional study, routine data, E 3.)36
  • 88% of adult users in the five Nordic countries (prescription registry study, N = 15.8 million, n = 76,896 users in 2012, 5 years, E 2b.)33

In Sweden, OROS methylphenidate was the most commonly used medication among adults. (Registry study, N = 44,364, manufacturer-funded, author employed by the manufacturer, E 2b.)38

(E 3): The administrative prevalence of ADHD in German health insurance data was: (routine data analysis, n = 78,919, manufacturer-funded, author(s) employed by the manufacturer, E 3.)41

  • 3.6% among children and adolescents in 2023
  • 0.6% among adults in 2023, up 89.7% since 2017
  • 0.4% in adulthood in a transition cohort (narrative review, secondary citation from Philipsen and Döpfner (2020), E 4.)42

The types of treatment for ADHD diagnoses in German health insurance data from 2023 were distributed as follows: (Routine data analysis, n = 78,919, manufacturer-funded, author(s) employed by the manufacturer, E 3.)41

  • medications only
    • 47.8% among children and adolescents
    • 38% among adults
  • no treatment
    • 44.4% among adults
    • 40.9% among children and adolescents
  • multimodal therapy
    • 10% in adults
    • 7.1% among children and adolescents
  • psychotherapy only
    • 7.6% among adults
    • 4.2% among children and adolescents

About half of the adults with a newly coded ADHD diagnosis in Bavaria received psychotherapy (62% of women, 43% of men). (Comprehensive analysis of routine data, n = 10,529; author(s) employed by the data provider, E 3.)40

(E 3): In German medical practices, ADHD prescriptions for adults shifted from primary care physicians to specialists (neurology, psychiatry). (Prescription data analysis, n = 77,504, E 3.)43 The proportion of prescriptions issued by specialists was: (Prescription data analysis, n = 77,504, E 3.)43

  • 80% among adults in 2018; 58% in 2008
  • approximately 75% of initial prescriptions for adults with a newly coded diagnosis in Bavaria (2012), Specialists in CNS disorders, approximately 25% general practitioners (comprehensive survey of routine data, n = 10,529, author(s) employed by the manufacturer, E 3.)40
  • 51% among children and adolescents in 2018; 38% in 2008

Adults with a primary diagnosis of hyperkinetic disorder (ICD-10 F90) received less intensive treatment than minors in German psychiatric hospitals (both inpatient and day treatment), even though they had more secondary diagnoses. Adults versus minors: (routine data analysis, 41 hospitals, 2015, N = 896, n = 164, E 3.)44

  • therapy sessions per week: 5.9 versus 28.5
  • average length of stay: 30.5 versus 45.3 days
  • Secondary diagnoses per case: 2.89 versus 1.23

The authors view this discrepancy as a possible indication of problems in the transition from child and adolescent psychiatry to adult psychiatry. (Routine data analysis, 41 clinics, 2015, N = 896, n = 164, E 3.)44

An editorial pointed out that a diagnosis rate among adults that is lower than the epidemiological prevalence does not necessarily indicate under-treatment, since not all people with ADHD require treatment in the strict sense—particularly pharmacotherapy. Reliable data on treatment needs were lacking. The authors identified care during the transition from adolescence to adulthood as a particular weak point. In a separate transition study conducted by the authors, more than one-third of respondents reported continuing to suffer from symptoms typical of ADHD and needing specialized treatment. (Editorial, E 4.)45

ADHD leads to age-specific impairments in all age groups, which is why age-specific diagnostic and therapeutic materials have been developed. In adulthood, there is a lack of ADHD-specific care, the establishment of which requires structural changes to existing healthcare services. (Narrative review; full text not available to us; E 4.)46

(E 2b): During the transition from child and adolescent psychiatry to adult care, many people with ADHD discontinued their ADHD treatment despite persistent symptoms and impairments. (Observational study, registry data from 9 countries and regions, n = 1,229,972, 5 years, full text not available to us, E 2b.)47 (General population cohort study, N = 5,149,791, n = 41,700, 4 years, E 2b.)34 (Registry study, n = 19,233, ages 18 to 21, manufacturer-funded, author(s) employed by the manufacturer, E 2b.)48 (Narrative review, E 4.)49 (Narrative review, full text not available to us, E 4.)50 (Narrative review, E 4.)7 (Narrative review, secondary citation of Philipsen and Döpfner (2020), E 4.)42 The proportion of patients receiving medication decreased:

  • from 80.1% at age 18 to 36.1% at age 21 during the transition to adult psychiatry in Sweden (2018 to 2020) (register-based study, n = 19,233, ages 18 to 21, industry-funded, author(s) employed by the sponsor, E 2b.)48
  • from 51.8% to 6.6% among 15- to 21-year-olds in a German transition cohort (narrative review, secondary citation from Philipsen and Döpfner (2020), E 4.)42

In the German transition cohort, the proportion of participants with a documented ADHD diagnosis also decreased from 100% to 31.1%. This decline cannot be explained solely by a reduction in symptoms and points to a gap in care during the transition phase. (Narrative review, secondary citation from Philipsen and Döpfner (2020), E 4.)42 In Sweden, 85.8% had entered adult psychiatry by age 21. At age 21, those who had received treatment were more likely than those who had not to be in treatment for autism, were more likely to be prescribed SSRIs, and had more frequent outpatient adult psychiatric contacts (p < 0.0001 for each). (Registry study, n = 19,233, ages 18 to 21, manufacturer-funded, author(s) employed by the manufacturer, E 2b.)48 15- to 21-year-olds were most likely to discontinue treatment. After 3 years and 11 months, only 27% of them were still in treatment—a lower rate than expected based on ADHD persistence rates. (General population cohort study, N = 5,149,791, n = 41,700, 4 years, E 2b.)34

Barriers to transition include young people’s limited knowledge of ADHD and treatment options, difficulties with self-management, a lack of interdisciplinary coordination, limited awareness of services for adults, regional shortages of specialized care, differing treatment cultures, and the loss of parental support upon reaching the age of majority. Structured handover processes and appropriate family involvement are recommended. (Narrative review, E 4.)49 Adolescence is associated with lower treatment adherence, more risky behaviors, the onset of substance use, and more comorbid Disorders. The transition to adult care requires close coordination between pediatric and adolescent care and adult care. (Narrative review, E 4.)11

One year after starting ADHD medication, the proportion of patients still receiving treatment was: (Observational study, registry data from 9 countries and regions, n = 1,229,972, 5 years, full text not available to us, E 2b.)47

  • Children (ages 4 to 11), 65% (95% CI 60 to 70)
  • Adults (age 25 and older), 48% (95% CI 44 to 52)
  • Adolescents (ages 12 to 17), 47% (95% CI 43 to 51)
  • young adults (ages 18 to 24), 39% (95% CI 36 to 42)

Most treatment discontinuations occurred between the ages of 18 and 19. Taking reinstitutions into account, after 5 years, 50 to 60 percent of children and 30 to 40 percent of adolescents and adults were receiving medication in most countries. The authors assessed treatment persistence among adolescents and young adults as lower than would be expected based on symptom persistence. (Observational study, registry data from 9 countries and regions, n = 1,229,972, 5 years, full text not available to us, E 2b.)47

Early discontinuation of ADHD medication (a gap of at least 180 days between dispensing dates) was common in all age groups. (Register-based cohort study, n = 1,000,411, E 2b.)51 Discontinuation rates in eight countries and regions were as follows, depending on the country: (Cohort study, registry data from 8 countries and regions, n = 1,000,411, E 2b.)52

  • Adults, 38% to 68%
  • Adolescents, 37% to 68%
  • young adults, 52% to 67%
  • Children, 19% to 61%

Early termination was predicted in: (cohort study, registry data from 8 countries and regions, n = 1,000,411, E 2b.)52

  • young adults with conduct disorder or oppositional defiant disorder, HR 1.42 (95% CI 1.30 to 1.55)
  • Children with intellectual disability, autism, and psychotropic medications, HR 1.32 to 1.51 (register-based cohort study, n = 1,000,411, E 2b.)51
  • Tic disorders in adults, HR 1.27 (95% CI 1.11 to 1.46)
  • Schizophrenia in adults, HR 1.25 (95% CI 1.09 to 1.44)

Starting in adolescence, only a few consistent clinical predictors were identified overall. Without ultrasound data, the associations with schizophrenia, tic disorders, and conduct disorder were no longer significant. (Cohort study, registry data from 8 countries and regions, n = 1,000,411, E 2b.)52

In the five Nordic countries, 21% of adult first-time users discontinued treatment within the first year. (Prescription registry study, N = 15.8 million, n = 76,896 users in 2012, 5 years, E 2b.)33 Among adults in Bavaria receiving ADHD medication following a newly coded diagnosis, only 26% received a prescription in all 4 quarters following the diagnosis. (Comprehensive survey of routine data, n = 10,529, author(s) employed by the manufacturer, E 3.)40

Overall adherence to oral stimulant treatment in Sweden (2015–2020) was high (78.2%) and similar for methylphenidate, lisdexamfetamine, and dexamfetamine. Adherence of 80% or more was achieved by: (registry study, n = 128,366, 158,413 treatment episodes, manufacturer-funded, author(s) employed by the manufacturer, E 2b.)53

  • Adults aged 25 and older: 69.3 to 71.8%
  • Adolescents (ages 12 to 17) 49.7 to 52.4%

Discontinuing ADHD medication after symptom remission led to a decline in quality of life compared with continued treatment in children and adolescents, but not in adults. Effect sizes (positive = worsening after discontinuation) for: (meta-analysis of RCTs, k = 5, N = 1,463, E 1a.)54

  • Children and adolescents (k = 3, n = 894) SMD 0.21 (0.06 to 0.36)
  • people with ADHD (k = 5, n = 1,463) SMD 0.19 (95% CI 0.08 to 0.30)
  • Adults (k = 2, n = 569) SMD 0.02 (−0.46 to 0.50), not significant

In randomized discontinuation studies involving children, adolescents, and adults, relapses occurred more frequently and earlier in the placebo group than in the group that continued medication. After discontinuation of stimulants and guanfacine, relapses occurred more frequently and more rapidly than after discontinuation of atomoxetine. Relapse rates in adults after discontinuation (various definitions of relapse) for: (Narrative review, k = 9, manufacturer-funded, authors employed by the manufacturer, E 4.)55

  • Lisdexamfetamine 75.0% after 6 weeks
  • Modified-release methylphenidate: 49.6% after 6 months
  • Atomoxetine 7.4% after 25 weeks

Among young and middle-aged adults, ADHD medications were not significantly associated with cardiovascular disease (RR 1.04, 95% CI 0.43 to 2.48). Neither stimulants (RR 1.24, 0.84 to 1.83) nor non-stimulants (RR 1.22, 0.25 to 5.97) showed a significant association. (Meta-analysis, k = 19, N = 3,931,532, E 2b.)56

(E 4): The effects of stimulants may depend on the phase of the menstrual cycle, with stronger effects during estrogen-rich phases. (Narrative review, E 4.)57 (Theoretical review, E 4.)58 In healthy women, the subjective effects of D-amphetamine were stronger during the follicular phase and positively correlated with estrogen levels; during the luteal phase, these effects were reduced compared to those observed in men. Four studies suggested a worsening of ADHD symptoms during the luteal phase; two studies tested a cycle-adapted intervention. The authors identify a research gap (gender health gap) regarding the cycle-dependent efficacy of stimulants. (Narrative review, E 4.)57 A theoretical review identifies five knowledge gaps regarding gender effects of stimulant treatment, including the influence of the menstrual cycle and reproductive transitions (puberty, pregnancy and the postpartum period, menopause). The authors hypothesize that stimulants have a stronger effect during estrogen-rich phases of the menstrual cycle and a weaker effect during estrogen-poor phases. (Theoretical review, E 4.)58

In women with ADHD who experienced premenstrual worsening of ADHD and mood symptoms, increasing the individual stimulant dose during the premenstrual week improved ADHD and mood symptoms (inattention, irritability, energy) with minimal side effects. All continued with the increased dose. (Case series, n = 9, 6 to 24 months, E 4.)59

Methylphenidate use during pregnancy (89.5% in the first trimester) did not increase the risk of major birth defects; however, miscarriages and abortions were more common. Methylphenidate compared with non-teratogenic exposure for: (Prospective cohort study, n = 382 exposed pregnancies, E 2b.)60

  • Miscarriage: aHR 1.98 (95% CI 1.23 to 3.20)
  • Major malformations: 3.2% (10 out of 309) versus 3.6% (13 out of 358); not statistically significant
  • Major malformations following exposure during organogenesis without genetic causes: 2.4% versus 3.4%, not statistically significant
  • cardiovascular malformations: 0.8% compared with 0.8%

About 60% of women who filled prescriptions for ADHD medications between one year before pregnancy and one year after childbirth stopped taking them around the time of pregnancy or interrupted their treatment. Proportions of medication use patterns for: (Registry cohort study, n = 4,717 pregnancies from 4,052 mothers, E 2b.)61

  • Withdrawal: 41.8%
  • Continuing operations 23.3%
  • Onset after birth: 17.7%
  • Interruption of pregnancy with resumption after birth: 17.2%

Those who continued treatment were older, smoked more frequently during pregnancy, took other psychotropic medications more often, and predominantly took methylphenidate (89.1%), which, according to the authors, may indicate more severe ADHD. (Register-based cohort study, n = 4,717 pregnancies from 4,052 mothers, E 2b.)61

Continuing dexamfetamine use during pregnancy was not associated with more adverse maternal or fetal consequences compared with discontinuation. Discontinuation was associated with a higher incidence of threatened miscarriage (OR 2.28, 95% CI 1.00 to 5.15). Women who did not take dexamfetamine during pregnancy had lower risks compared to those who continued taking it for: (Retrospective cohort study, n = 1,688, E 2b.)62

  • Admission of the newborn to a specialized unit: OR 0.16 (0.12 to 0.20)
  • High blood pressure OR 0.32 (0.11 to 0.93)
  • postpartum hemorrhage OR 0.57 (0.41 to 0.80)
  • Preeclampsia OR 0.58 (0.35 to 0.97)
  • fetal distress OR 0.73 (0.54 to 0.99)

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