Dr Duncan Manders (Child and Adolescent Mental Health Service, NHS Lothian, UK) welcomed delegates back to Day 2 of the 11th Meeting of Minds. The second day of the meeting included three plenary sessions focussing on ADHD in girls and women, headlines in ADHD and management optimisation of ADHD. There was also a semi-plenary session in the morning regarding complex cases of ADHD and psychiatric comorbidities. Delegates could choose to attend either the child and adolescent ADHD semi-plenary session or the session on differential diagnosis for adult ADHD. Meeting of Minds 2019 concluded with Professor Tobias Banaschewski (Central Institute of Mental Health, Mannheim, Germany) thanking the speakers and delegates for another excellent meeting.
Plenary 3: ADHD in girls and women
Moderator: Dr Duncan Manders
Professor Susan Young (Psychology Services Ltd., London, UK) opened her presentation by discussing the findings of some of her own research. The study aimed to clarify the developmental risk for interpersonal relationship problems and ineffective coping strategies associated with girls with hyperactive behaviour.1 This was a follow up study of girls aged 6‒7 years who were identified as demonstrating pervasive hyperactivity or conduct problems by their parents or teachers.1 During the study, Professor Young interviewed these girls at the age of 14‒16 years and found that childhood hyperactivity was a risk factor for disrupted relationships in adolescence with peers, as well as the opposite sex, but not parents.1 Moreover, hyperactivity was linked to use of a wide variety of coping strategies.1 These findings were independent of existing conduct problems and although girls with conduct problems reported using specific coping strategies, they were reportedly ineffective.1
Professor Young also highlighted the symptom profile of females with ADHD compared with males. For example, although the symptoms of ADHD are similar, their severity (especially hyperactivity and impulsivity) may be lower in females.2 In addition, females with ADHD may develop better coping strategies than males and may be better at masking their ADHD during childhood.2 There is evidence to suggest that differences in hormones could explain this effect.2 Professor Young noted that mortality rates, mainly driven by accidental deaths, are higher for individuals with ADHD than for those without; this rate is even higher for females with ADHD.3 Professor Young then stated that for her, the presentation and the perception of ADHD as a ‘behavioural disorder’ differs between males and females. Males are characterised by aggression, boisterousness, conduct and oppositional problems, whereas females are more emotionally and impulsively driven, in her opinion.
Professor Young indicated that she was currently involved in developing a consensus statement for the identification and treatment of females with ADHD and presented examples of the unpublished guidelines. Throughout her presentation, Professor Young peppered these consensus statements with quotes from the girls she had interviewed in her previous study. The quotes were accompanied by a voice-over from one of the interviewees and it was very poignant for delegates to hear the affect ADHD can have on young girls.
Professor Young: “These girls will be adults now and I wonder what became of them?”
(Semi) Plenary 4: ADHD and comorbidities – complex cases
ADHD in children and young people: ADHD and comorbid conditions
Moderator: Dr Duncan Manders
This session focussed on hypothetical clinical examples of children and adolescents with ADHD. The panel worked through each case study and invited delegates to comment and participate in the discussion. Dr Declan Quinn (University of Saskatchewan, Canada) and Professor David Coghill (University of Melbourne, Australia) were also involved in the panel discussion.
The first fictional case study was presented by Dr Anthony Rostain (University of Pennsylvania, USA) who discussed a child with ADHD displaying symptoms of oppositional defiant disorder. Dr Rostain pointed out that in these cases it may be important to obtain information on the child’s behaviour at school and at home and speak to the child about their behaviour. Following an active discussion, Dr Rostain provided the following tips for clinical practice:
- Careful history taking and interviews with child and parents are the basis for all clinical decisions
- Scales should be selected to determine type and severity of symptomatology and functional impairments
- Differential diagnosis should be considered to rule out other conditions (e.g. bipolar affective disorder, disruptive mood dysregulation disorder and post-traumatic stress disorder)
- Psychoeducation is crucial before undertaking treatment planning
- Combining behavioural interventions and medication are most likely to affect positive outcomes
Jakob Ørnberg (Aarhus University Hospital, Denmark) presented the second fictional case study, which described a teenager with ADHD with a history of depression and social phobia, and provided his clinical impression based on the rating scales that could be used.
The third fictional case study was presented by Dr Sam Chang (University of Calgary, Canada) who discussed a teenager with ADHD and a history of cannabis abuse and mood problems. In this hypothetical example, Dr Chang recommended regular drug screening tests and rating scales for psychiatric comorbidities.
|Take-home messages from the panel:
Dr Quinn: “Use rating scales to educate individuals with ADHD and help identify their strengths and weaknesses”
ADHD in adults: differential diagnosis of ADHD
Moderator: Professor Philip Asherson
Dr Peter Mason (ADHD and Psychiatry Services Ltd., UK) opened this exciting plenary session by highlighting that psychiatric comorbidity in ADHD is the rule rather than the exception.4 He went on to present results from a Spanish clinical record data study of adults with ADHD (n = 367; aged 18‒65 years) which showed that 66.2% of individuals had ≥1 comorbid psychiatric condition, with individuals on average having 2.4 psychiatric comorbidities. He then explained that the most common psychiatric comorbidities were anxiety disorders, mood disorders and substance use disorders,5 which he noted was similar to what he saw in his own clinical practice.
Dr Mason presented the overall prevalence of ADHD and selected psychiatric comorbidities from the National Comorbidity Survey Replication,6 which showed that the 12-month prevalence of psychiatric comorbidities in adults with ADHD was highest for bipolar disorder (19.4%) and major depression (18.6%) and that the 12-month prevalence of ADHD in adults with psychiatric comorbidities was highest for dysthymia (22.6%) and bipolar disorder (21.2%). He then presented findings from a multinational European study of adult psychiatric outpatients (n = 2284), in which 47.2% of individuals had screened positive for ADHD. The results showed that the most frequent comorbid psychiatric diagnosis was depression. This was more common in individuals who were diagnosed with ADHD during the study compared with those who had received an ADHD diagnosis previously (43.0% vs 53.9%).7
|Dr Mason then went on to emphasise that in his clinical experience many adults with ADHD still remain un- or mis-diagnosed and since many symptoms of psychiatric comorbidities may mask ADHD symptoms it is important to conduct a thorough differential diagnosis and evaluate any co-occurring symptoms.
He also stressed the importance of considering psychiatric comorbidities as part of the ADHD treatment plan tailored to the individual.
Dr Mason: “Differential diagnosis is incredibly important to identify the presence of ADHD alongside comorbidities”
This opening presentation was followed by a hypothetical patient case study presented by Professor Toni Ramos (Universitat Autònoma de Barcelona, Spain) which was discussed with the audience. In this example, Professor Ramos presented a patient case with ADHD in their mid-20s with a history of substance-use disorder. Following an active discussion, the following key points were summarised:
|Key learning points: summary
A second hypothetical patient case study was then presented by Professor Alexandra Philipsen (University of Bonn, Germany) which was discussed with the audience. Professor Philipsen described a student in their early 20s with bipolar disorder with a history of suicide attempts. The following key points were summarised:
|Key learning points: summary
Plenary 5: headlines in ADHD: review of selected publications from 2018/19
Moderator: Dr Joseph Sergeant (Free University, Amsterdam, The Netherlands)
The purpose of this plenary session was for five experts in the field to provide a quick overview of selected publications from 2018/19. Professor Johan Wiklund (Syracuse University, NY, USA) opened the session and presented his research paper proposing that the relationship between mental disorders and entrepreneurship should be explored.15 He stated that there is evidence to suggest that individuals with mental disorders can flourish and contribute productively to society via entrepreneurship.15 This paper shows how by studying entrepreneurship and ADHD, this will advance this new field.15 Moreover, Professor Wiklund highlighted that by examining the relationship between mental disorders and entrepreneurship, novel insights will be developed and this could contribute to new theories on the psychology of work, career-choice and clinical psychology.15
Dr Paulo Mattos (Federal University of Rio de Janeiro, Brazil) was next to present a recent publication. He discussed the association of psychiatric comorbidity and risk of premature death among children and adults with ADHD.16 Dr Mattos opined that it is important that clinicians always pay attention to psychiatric comorbidities, and this paper highlighted the role that these play in both all-cause and cause-specific mortality risks in ADHD.16 Early-onset psychiatric comorbidity in adulthood primarily contributes to death due to natural causes; however, later-onset psychiatric comorbidity is linked to death due to unnatural causes, e.g. suicide and unintentional injury.16 In line with the conclusions of the paper, Dr Mattos agreed that clinicians should closely monitor for all psychiatric comorbidities in individuals with ADHD as a means to identify high-risk groups for prevention efforts.16
The next presenter was Dr Quinn, who discussed what he described as a very informative paper on neuroimaging studies, which included 36 collaborators.17 These studies showed that there are subtle differences in the cortical surface area of children with ADHD, but not adolescents or adults.17 This may confirm the involvement of the frontal cortex in ADHD and highlights additional areas of the brain that require further attention in ADHD research.17 Dr Quinn pointed out that in the paper it is stated that these alterations behave like endophenotypes in families and are linked to symptoms of ADHD in the population.17 This further extends the evidence that ADHD behaves as a continuous trait in the population.17
Professor Jeffrey Newcorn (Mount Sinai Medical Center, USA) next described a paper which presents four areas of pharmacotherapy research on ADHD that could be improved.18 This includes: the use of appropriate trial designs; the need for outcome measures targeting effectiveness beyond symptom control; the need for safety outcome measures; and the application of clinical and administrative research databases to assess real-world outcomes.18 Professor Newcorn believes that although these types of study are expensive to conduct, they have the potential to influence clinical care.
Professor Coghill concluded this session by discussing emotional dysregulation in ADHD and its implications for clinical recognition and intervention.19 Professor Coghill opened his presentation by questioning how emotional dysregulation can be recognised as part of ADHD and opined that the nomenclature for emotional dysregulation is not clearly defined. This paper echoed his sentiment and demonstrated that emotional symptoms of ADHD may cause significant clinical impairments; however, there is no consensus of how emotional impulsivity and deficient emotional self-regulation are specific to ADHD.19 The article also stated that using an instrument to measure emotional impulsivity and self-regulation aside from irritability and other emotional symptoms may improve the accuracy of ADHD diagnostic criteria.19
Professor Coghill: “Nomenclature for emotional dysregulation is all over the place and none are clarified and precisely defined for ADHD”
Plenary 6: optimising the management of ADHD
Moderator: Dr Duncan Manders
Updated guidelines and consensus on ADHD treatment
National Institute for Health and Care Excellence (NICE) 2018 guidelines
Researching clinicians from the UK, Germany and Canada participated in this part of the plenary session. Dr Mason began by describing the evidence- and health economic-based NICE 2018 guidelines for ADHD in the UK. He described how in the UK, medication can be offered to children and young people if their ADHD is causing a persistent significant impairment in at least one domain (e.g. interpersonal relationships, educational/occupational attainment and risk awareness).20 This is offered after the individual and their parents have received and discussed ADHD-focused information, after group-based support has been offered, and after environmental modifications have been implemented and reviewed.20
According to the NICE 2018 guidelines, methylphenidate is the first-line pharmacological treatment for children (aged ≥5 years) and adolescents with ADHD.20 This is followed by second-line lisdexamfetamine if enough benefit has not been derived from a 6-week trial of methylphenidate.20 If an individual responds to second-line lisdexamfetamine but cannot tolerate the longer effect profile, then third-line dexamfetamine can be offered.20 Alternatively, if first-line methylphenidate and second-line lisdexamfetamine are not tolerated or if symptoms have not responded to separate 6-week trials of these therapies, then third-line atomoxetine or guanfacine can be initiated.20
For adults with ADHD, the NICE 2018 guidelines recommend that medication should only be offered under the same circumstances as children (aged ≥5 years) and adolescents with ADHD.20 If medication is required then either lisdexamfetamine or methylphenidate can be offered as first-line therapies; switching between therapies is appropriate if enough benefit has not been derived from a 6-week trial of either lisdexamfetamine or methylphenidate alone.20 Second-line therapy options include dexamfetamine (if an individual responds to lisdexamfetamine but cannot tolerate the longer effect profile) or atomoxetine (if an individual cannot tolerate lisdexamfetamine or methylphenidate, or if symptoms have not responded following separate 6-week trials of either therapy).20
For adults who have made an informed decision not to have medication or for those who may have difficulty adhering to medication or have found medication ineffective or intolerable, non-pharmacological therapy should be considered.20 Non-pharmacological options should also be considered in combination with medication in adults who have benefitted from medication but whose symptoms still cause significant impairments in at least one domain (e.g. interpersonal relationships, educational/occupational attainment and risk awareness).20 The NICE 2018 guidelines recommend a structured, supportive psychological intervention focused on ADHD with regular follow up either in person or via phone as a minimum for non-pharmacological management. This form of treatment may involve elements of or a full-course of cognitive behavioural therapy (CBT).20
German guidelines 2018
Professor Banaschewski next presented the 2018 update to the German guidelines for ADHD, and indicated that these were evidence- and consensus-based guidelines. Professor Banaschewski stated that these guidelines emphasise that treatment should be delivered via a multimodal treatment plan, combining psychosocial (including psychotherapeutic), pharmacological (when appropriate) and supplementary interventions.21 This is according to the individual’s symptoms, level of functioning, participation and the preferences of the individual and their social network.21 The severity (mild, moderate, severe) of ADHD is based on the DSM – 5th Edition (DSM-5TM), combining symptom severity and level of functional impairment.21
The first-line pharmacological treatment for ADHD in children (aged ≥6 years) and adolescents is stimulants (methylphenidate, dexamfetamine or lisdexamfetamine*).21 If these stimulants are not suitable, effective or tolerated then second-line, non-stimulants atomoxetine or guanfacine can be trialled.21 For adults, first-line pharmacological treatment (methylphenidate, dexamfetamine or lisdexamfetamine*) is stimulants, but if they are not sufficiently effective or tolerated, then second-line atomoxetine can be initiated.21
Professor Banaschewski highlighted that for children (aged ≥6 years), adolescents and adults with mild ADHD, psychosocial treatment and psychotherapy is recommended.21 For individuals with moderate ADHD, intensified psychosocial intervention and psychotherapy or pharmacological therapy can be initiated following comprehensive psychoeducation.21 In the cases of severe ADHD, the German guidelines recommend that intensive psychoeducation should be followed by pharmacotherapy for children (aged ≥6 years), adolescents and adults.21 In addition, intensive psychosocial treatment and psychotherapy can be integrated in parallel for severe ADHD.21
*Lisdexamfetamine is indicated for ADHD in children (aged ≥6 years) and adolescents when responses to previous methylphenidate treatment is considered clinically inadequate, and is not indicated in all adults;22,23 however, Professor Banachewski indicated that approval status is not considered in the German guidelines
Canadian ADHD Resource Alliance (CADDRA) guidelines 2018
Dr Chang presented the Canadian CADDRA guidelines for ADHD. Dr Chang emphasised that the goal of these guidelines was to enable consistency across diagnosis, treatment and care. He stated that an integrated and multimodal treatment plan for ADHD should be used, including medication, educational and psychosocial interventions.24 Dr Chang highlighted that as with all pharmacological treatments, the risk/benefit ratio must be considered before initiating any medication; however, the high morbidity of ADHD makes it important that the risk of not treating ADHD is weighed.24
For children (aged ≥6 years) and adolescents, long-acting psychostimulants (e.g. lisdexamfetamine, methylphenidate and amfetamine mixed salts) are initial treatment options for ADHD.24 An adequate trial of methylphenidate and amfetamine is recommended before moving on to second-line therapies.24 Only if an individual has significant side effects, suboptimal response, lack of access to first-line therapies or if stimulants are contraindicated (e.g. high risk of misuse), then second-line therapies can be considered.24 These include short- and immediate-acting psychostimulants (e.g. methylphenidate and dexamfetamine) or long-acting non-stimulants (e.g. atomoxetine or guanfacine).24 Note that only guanfacine has been approved for the adjunctive treatment of ADHD in combination with psychostimulants in children (aged ≥6 years) and adolescents in Canada.24 The recommendations for adults with ADHD is the same as that for children and adolescents; however, guanfacine is not licensed in adults by CADDRA.24
Professor Coghill: “Guidelines are important and continue to evolve over time… they reduce variability in care within and between countries”
Psychopharmacology of ADHD medications; what’s the difference?
The next session was presented by Professor Coghill who provided some insight into the mode of action of pharmacotherapies for ADHD. He began by highlighting the areas of the brain involved in executive control and the reward network and stated that noradrenaline (NA) and dopamine (DA) act as cognitive modulators within these areas.25 He then indicated that the levels of NA and DA are suboptimal within the prefrontal cortex of individuals with ADHD and that NA is responsible for the ‘signal’ (e.g. ‘sit in seat’/’focus’) and DA is important for ‘noise’ (e.g. ‘fidget’/’shift attention’).26 Therefore, treatment for ADHD should aim to optimise NA (increase the ‘signal’) and DA levels (decrease ‘noise’).26
Professor Coghill then described the proposed mode of action of ADHD pharmacotherapies. This evidence is based on animal studies, as the precise mechanism in humans with ADHD is unknown. Methylphenidate is thought to target the NA and DA transporters, inhibiting NA and DA reuptake, thereby increasing NA and DA levels within the synaptic cleft.27-34 Professor Coghill highlighted that the mode of action of amfetamine was similar to that of methylphenidate, in that amfetamine targets NA and DA transporters, thereby inhibiting NA and DA reuptake and increasing their levels within the synapse.27,28,35-37 For atomoxetine, only the NA transporter is targeted such that the reuptake of NA is inhibited and levels of NA increase in the synaptic cleft and the ‘signal’ is increased.38,39 The mode of action of guanfacine is different as it binds to postsynaptic α2A-adrenergic receptors, mimicking NA to enhance the ‘signal’.40
Professor Coghill stated that the pharmacokinetic and pharmacodynamic properties of each drug is highly predictive of how it will work over time and this aids the development of a treatment plan for those with ADHD. He felt that it allowed clinicians to tailor doses, and monitor and respond to ADHD symptoms over time.
Professor Coghill: “The pharmacokinetics and pharmacodynamics of a drug are highly predictive of how it will work over time”
Optimising and sustaining treatment strategies for ADHD | Clinical discussion and audience Q&A
Optimising and sustaining treatment strategies for ADHD
The final session was concluded by Dr Rostain who began his presentation by discussing the diagnostic assessment criteria of ADHD based upon DSM-5TM. The inclusion criteria for ADHD are core symptoms of inattention, impulsivity and hyperactivity; chronicity and pervasiveness of symptoms; and impairment caused by ADHD symptoms.41 Dr Rostain felt that it is important for clinicians to know how each individual’s symptom profile fits in with the symptoms of ADHD, and discussed how clinicians can implement and optimise strategies for management of ADHD across the lifespan.
- Psychoeducation is important42
- Often lower doses of methylphenidate are needed to achieve results in children and adolescents42-44
Setting measurement-based treatment goals
- Dr Rostain opined that it is important to measure functional outcomes (e.g. completing homework on time or not being late for school) and what matters to the individual with ADHD
Pharmacotherapy for ADHD
- Dr Rostain opined that it is difficult to predict which individual will respond to which pharmacotherapy; however, one study showed that most children and adolescents with ADHD (n = 287/316 [91%]) responded to either methylphenidate and/or amfetamine; the adverse event profile was similar for both therapies45
- In addition, a network meta-analysis demonstrated that when taking efficacy and safety into account, the preferred first-choice medications for short-term treatment of ADHD is methylphenidate in children and adolescents and amfetamine in adults46
- For individuals who have a suboptimal response to treatment, Dr Rostain recommended the following: dose adjustment (amount/timing); medication switching (alternative release mechanism or alternate stimulant); use of a non-stimulant; combination strategies; and re-evaluation for other diagnoses
- Dr Rostain said that it is also important to be aware of the potential adverse effects of pharmacotherapy, e.g. effects on appetite/growth, the cardiovascular system, development of tics, misuse/abuse, psychotic symptoms, seizures, sleep disturbances and suicidal thoughts47
Non-pharmacological interventions for ADHD
- Dr Rostain presented results from a systematic review and meta-analysis which showed statistically significant effects of dietary and psychological treatments for ADHD48
- He also emphasised that he felt there should be collaboration between family, school and healthcare systems (primary and specialty care) and highlighted the Incredible Years® parenting training programme49
- Barriers to treatment may include: personal characteristics (e.g. age, comorbidity, ethnicity and gender); perceptions of ADHD (e.g. cause, knowledge and severity); structural barriers (e.g. financial burden and system barriers); and perceptions of treatment (e.g. acceptability and stigma)50
Common barriers/obstacles to medication adherence
- Dr Rostain highlighted that in his opinion, individuals with ADHD do not always follow advice and this may potentially lead to problems with adherence, for example:
- Suboptimal or inadequate treatment response
- Physical and psychological adverse effects
- Inconvenience/effortful demands of taking regular medication or multiple dosing
- Financial expenses/insurance policy
- Availability of medications/supply issues
- Forgetfulness/disorganisation and deficits in executive functioning
- Oppositional behaviour/defiance/testing autonomy
- Negative attitudes about medication
- Demoralisation, defeatism and feelings of hopelessness
- Social stigma/embarrassment
Educational and employment accommodations
- Based on his clinical experience, Dr Rostain said that common academic accommodations for college/university students with ADHD include: extended time on exams; alternate exam format; testing in a reduced distraction room; access to lecture materials/slides prior to class; note-taking service; course substitution; texts in audio format; and reduced course load and extended graduation timeline
- In Dr Rostain’s view, learning support services can help college/university students with ADHD develop and implement effective learning strategies and use coping skills to address time-management and organisation problems that may affect academic studies. In addition, use of assistive technologies (e.g. consistent use of organisational features of mobile phone, computer, personal organisers, voice-activated software for writing) and academic coaching may aid students with ADHD
- Dr Rostain highlighted that, in the United States, qualified employees with ADHD may be eligible for workplace accommodations if there are significant functional impairments affecting work performance. These ‘informal’ accommodations and coping strategies can be implemented without disclosure of the ADHD diagnosis. ‘ADHD coaching’ is an emerging psychological support service that may be helpful for workplace functioning and focuses on helping adults with ADHD develop and implement coping skills that can be used to improve work efficiency51
- Other employment accommodations recommended by Dr Rostain included: computer software; books/manuals in audio format; dictation service; frequent meetings with boss to track project tasks; breakdown of large projects into individual tasks; modification of job demands; quiet workspace; and written reminders of task assignments
CBT for adults with ADHD
- An adaptation of CBT addresses the common problems faced by adults with ADHD and examines the impact dysfunctional behaviour can have. CBT can assist in the development of coping strategies and can explore how events influence completion of tasks and goals, but is different from ‘ADHD coaching’ or counselling52
- Specific adaptations and/or components for adults include psychoeducation, dialectical behavioural therapy, cognitive remediation therapy, problem-focused therapy and metacognitive therapy52
- Dr Rostain highlighted one meta-analysis of CBT for adult ADHD that showed that in adults, CBT had medium-to-large effects from pre- to post-treatment and small-to-medium effects versus control for self-reported functioning; these effect sizes are comparable to behavioural treatments for children with ADHD53
Dr Rostain concluded his presentation by pointing out that ADHD is a life-long disorder and that he felt that a chronic care model is most suitable. He emphasised that it was important for clinicians to constantly re-evaluate treatment effectiveness, especially during periods of transition, and that remaining hopeful and open to changing treatment approaches will enable individuals with ADHD and clinicians to stay engaged.
Dr Rostain: “Functional outcomes are preferable to symptom-based outcomes insofar as they reflect the most salient goals of treatment”
Professor Newcorn then provided his thoughts on the final plenary session. He said that clinicians want to do what works best for most people and treating individuals over a lifespan is important, as ADHD is gaining recognition as a lifelong disorder. Professor Banaschewski congratulated the speakers and delegates on such an excellent meeting and the 11th Meeting of Minds ended with each presenter in this session leaving delegates with their final take-home messages:
|Take-home messages from the panel:
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- Kooij JJS, Bijlenga D, Salerno L, et al. Updated European Consensus Statement on diagnosis and treatment of adult ADHD. Eur Psychiatry 2019; 56: 14-34.
- Dalsgaard S, Ostergaard SD, Leckman JF, et al. Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study. Lancet 2015; 385: 2190-2196.
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- Piñeiro-Dieguez B, Balanzá-Martinez V, García-García P, et al. Psychiatric comorbidity at the time of diagnosis in adults with ADHD: the CAT study. J Atten Disord 2016; 20: 1066-1075.
- Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163: 716-723.
- Deberdt W, Thome J, Lebrec J, et al. Prevalence of ADHD in nonpsychotic adult psychiatric care (ADPSYC): a multinational cross-sectional study in Europe. BMC Psychiatry 2015; 15: 242.
- Thapar A, Cooper M, Eyre O, et al. What have we learnt about the causes of ADHD? J Child Psychol Psychiatry 2013; 54: 3-16.
- Cortese S, Tessari L. Attention-deficit/hyperactivity disorder (ADHD) and obesity: update 2016. Curr Psychiatry Rep 2017; 19: 4.
- Roncero C, Ros-Cucurull E, Daigre C, et al. Prevalence and risk factors of psychotic symptoms in cocaine-dependent patients. Actas Esp Psiquiatr 2012; 40: 187-197.
- Crunelle CL, van den Brink W, Moggi F, et al. International Consensus Statement on screening, diagnosis and treatment of substance use disorder patients with comorbid attention deficit/hyperactivity disorder. Eur Addict Res 2018; 24: 43-51.
- Kuja-Halkola R, Lind Juto K, Skoglund C, et al. Do borderline personality disorder and attention-deficit/hyperactivity disorder co-aggregate in families? A population-based study of 2 million Swedes. Mol Psychiatry 2018.
- Distel MA, Carlier A, Middeldorp CM, et al. Borderline personality traits and adult attention-deficit hyperactivity disorder symptoms: a genetic analysis of comorbidity. Am J Med Genet B Neuropsychiatr Genet 2011; 156b: 817-825.
- Prada P, Nicastro R, Zimmermann J, et al. Addition of methylphenidate to intensive dialectical behaviour therapy for patients suffering from comorbid borderline personality disorder and ADHD: a naturalistic study. Atten Defic Hyperact Disord 2015; 7: 199-209.
- Wiklund J, Hatak I, Patzelt H, et al. Mental disorder in the entrepreneurship context: when being different can be an advantage. Acad Manage Perspect 2018; 32: 1-26.
- Sun S, Kuja-Halkola R, Faraone SV, et al. Association of psychiatric comorbidity with the risk of premature death among children and adults with attention-deficit/hyperactivity disorder. JAMA Psychiatry 2019: Epub ahead of print.
- Hoogman M, Muetzel R, Guimaraes JP, et al. Brain imaging of the cortex in ADHD: a coordinated analysis of large-scale clinical and population-based samples. Am J Psychiatry 2019; 176: 531-542.
- Wong ICK, Banaschewski T, Buitelaar J, et al. Emerging challenges in pharmacotherapy research on attention-deficit hyperactivity disorder-outcome measures beyond symptom control and clinical trials. Lancet Psychiatry 2019; 6: 528-537.
- Faraone SV, Rostain AL, Blader J, et al. Practitioner Review: Emotional dysregulation in attention-deficit/hyperactivity disorder – implications for clinical recognition and intervention. J Child Psychol Psychiatry 2019; 60: 133-150.
- NICE guideline 2018. Attention deficit hyperactivity disorder: diagnosis and management. Available at: https://www.nice.org.uk/guidance/ng87. Accessed November 2019.
- Banaschewski T, Hohmann S, Millenet S. Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Kindes-, Jugend- und Erwachsenenalter. DGKJP, DGPPN and DGSPJ German guidelines. 2018.
- Shire Pharmaceuticals Ltd. Elvanse Summary of Product Characteristics. Last updated July 2019.
- Shire Pharmaceuticals Ltd. Elvanse Adult Summary of Product Characteristics. Last updated July 2019.
- Canadian ADHD Resource Alliance (CADDRA). Canadian ADHD Practice Guidelines. Fourth Edition. Toronto, ON; CADDRA, 2018.
- Faraone SV, Asherson P, Banaschewski T, et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers 2015; 1: 15020.
- Stahl SM, Mignon L. Stahl’s Illustrated Attention Deficit Hyperactivity Disorder. New York, NY; Cambridge University Press, 2009.
- Heal DJ, Cheetham SC, Smith SL. The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety. Neuropharmacology 2009; 57: 608-618.
- Han DD, Gu HH. Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacol 2006; 6: 6.
- Volkow ND, Wang GJ, Fowler JS, et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 1998; 155: 1325-1331.
- Hannestad J, Gallezot JD, Planeta-Wilson B, et al. Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry 2010; 68: 854-860.
- Crunelle CL, van den Brink W, Dom G, et al. Dopamine transporter occupancy by methylphenidate and impulsivity in adult ADHD. Br J Psychiatry 2014; 204: 486-487.
- Somkuwar SS, Kantak KM, Dwoskin LP. Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder. J Neurosci Methods 2015; 252: 55-63.
- Volkow ND, Wang G, Fowler JS, et al. Therapeutic doses of oral methylphenidate signficantly increase extracellular dopamine in the human brain. J Neurosci 2001; 21: RC121.
- Volkow ND, Wang GJ, Tomasi D, et al. Methylphenidate-elicited dopamine increases in ventral striatum are associated with long-term symptom improvement in adults with attention deficit hyperactivity disorder. J Neurosci 2012; 32: 841-849.
- Kahlig KM, Galli A. Regulation of dopamine transporter function and plasma membrane expression by dopamine, amphetamine, and cocaine. Eur J Pharmacol 2003; 479: 153-158.
- Schiffer WK, Volkow ND, Fowler JS, et al. Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine. Synapse 2006; 59: 243-251.
- Zhu MY, Shamburger S, Li J, et al. Regulation of the human norepinephrine transporter by cocaine and amphetamine. J Pharmacol Exp Ther 2000; 295: 951-959.
- Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit / hyperactivity disorder. Neuropsychopharmacology 2002; 27: 699-711.
- Swanson CJ, Perry KW, Koch-Krueger S, et al. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology 2006; 50: 755-760.
- Wang M, Ramos BP, Paspalas CD, et al. Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell 2007; 129: 397-410.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 2013.
- Pliszka S, AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007; 46: 894-921.
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