Over the course of the 2-day meeting, delegates were able to attend a range of clinical seminars, which covered a wide range of topics such as ADHD and psychiatric comorbidities, the psychopharmacology of ADHD medications, utilising ADHD treatment choice for children and adolescents, diagnostic issues and management of late-onset ADHD, and ‘tips and tricks’ for greater success in patient consultations. Here are some highlights.
ADHD, depression and anxiety in adults
Professor Martin Katzman (Stress, Trauma, Anxiety, Rehabilitation and Treatment [START] Clinic for Mood and Anxiety Disorders, Canada) got this stimulating clinical seminar underway by presenting results from the National Comorbidity Survey (n=3199 adults), where the 1-year prevalence of major depressive disorder (MDD) and generalised anxiety disorder (GAD) in adults with ADHD was 18.6% and 8.0%, respectively.1 The 1-year prevalence of ADHD in patients with MDD and GAD was 9.4% and 11.9%, respectively.1 He noted that misdiagnosis can occur due to the overlap of symptoms between ADHD and other psychiatric comorbidities.2
He went on to show that in a study of first-year college students with (n=220) and without (n=233) ADHD, the odds ratio for having an anxiety disorder in students with ADHD was 10.8.3 Furthermore, in a Spanish observational study of psychiatric comorbidity at the time of adult ADHD diagnosis (n=367), the majority of patients had at least one comorbid psychiatric disorder (66.2%) and the mean number of psychiatric comorbidities per patient was 2.4.4
Professor Katzman went on to talk about the impact of untreated ADHD on lifetime outcomes. He began by presenting data from a cross-sectional study of 414 adults with ADHD (mean age: 34.5 years) within the Norwegian National Registry of Adult ADHD, which showed that individuals who did not receive treatment for their ADHD in childhood were significantly more likely than those individuals who were treated to have an adult diagnosis of depression and/or anxiety (72.5% versus 58.9%; p=0.031).5 Professor Katzman continued by explaining the results from a 10-year follow-up study in patients (mean age: 22 years) who had received stimulant therapy at some point in their life (n=82) compared with those who had not received stimulant therapy (n=30), which demonstrated that stimulant therapy for ADHD significantly lowered cumulative morbidity risk for major depression, conduct disorder, multiple (≥2) anxiety disorders, oppositional defiant disorder and repeating a year at school.6
He also summarised the variables associated with the development of anxiety in adults with ADHD, such as childhood aggression, employment status, difficulties making friends, caffeine intake, number of children and comorbid MDD.7,8
Professor Katzman then went on to discuss which disorder should be prioritised when treating ADHD and anxiety, highlighting the importance of distinguishing anxiety disorders such as GAD, obsessive-compulsive disorder and panic disorder from performance anxiety. Canadian guidelines recommend treating the most impairing condition first, and highlight that stimulant therapy may increase anxiety, particularly during treatment initiation.9 If anxiety becomes too intense, the guidelines recommend that the ADHD medication should be reduced or withdrawn and the anxiety treated until the symptoms have stabilised, and only then should treatment for ADHD be restarted.9
Professor Katzman continued his review of the data by showing that ADHD may be significantly more prevalent in adults with depression than those without depression.10 He asserted that those patients with MDD and comorbid ADHD may exhibit more severe depressive symptoms, more chronic depression, earlier age of onset of depressive symptoms and additional comorbid anxiety symptoms,10 and that individuals with ADHD and lifetime MDD may have a significantly higher number of negative life events compared with individuals with ADHD without lifetime MDD.11
During the presentation, he explained how low prefrontal activity manifests as low hedonic tone, and that patients with low hedonic tone try to reach euthymia via internalising activities (e.g. using fantasy) and externalising activities (e.g. taking cocaine). He highlighted that chronically low hedonic tone could predict treatment-resistant depression and could be understood as a manifestation of the presence of ADHD.12
When diagnosing comorbid ADHD in patients with MDD, he explained the impact of executive dysfunction on predicting ADHD in these patient populations. Professor Katzman explained that if you improve executive function in these patients with ADHD, you move them from just reacting to what is going on around them to planning and pursuing goals. He related this to the default mode network, a network which activates when a person’s mind wanders when they are not fully involved in a task.13
Professor Katzman went on to summarise the role of the prefrontal cortex in impulse control, whereby the prefrontal cortex is more active when patients successfully inhibit an action (delayed gratification), and that those individuals who cannot achieve delayed gratification show exaggerated recruitment in the ventral striatum.14
Professor Katzman discussed the intolerance of uncertainty that is experienced by patients with anxiety, highlighting that uncertainty increases fear responses, i.e. the more an individual dislikes uncertainty, the more worried they get and the more anxious they become.
In his conclusion, Professor Katzman outlined the involvement of the amygdala and neural circuits in bottom-up and top-down systems in the prefrontal cortex and the role of dopamine, noradrenaline and serotonin in monoaminergic pathways in MDD, and the role of selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors on dopamine and noradrenaline.
Professor Katzman: “If you manage patients with ADHD and comorbid depression or anxiety you can change their life trajectory.”
ADHD and substance-use disorder
This interactive clinical seminar was led by Dr Larry Klassen (Eden Health Care Services, Canada), and discussed the similarities and relationship between substance-use disorder (SUD) and ADHD, the most appropriate ways to screen for and identify these comorbid psychiatric diagnoses, and common dilemmas in the treatment of comorbid SUD and ADHD.
Dr Klassen began the seminar by highlighting the risk factors for addiction, such as family history, being male, comorbidities, peer groups, psychosocial adversity, early exposure to drugs and alcohol, and the kind of drugs that patients were addicted to. ADHD symptoms are also important in determining risk, for example, boredom, fidgetiness, irritability, sleep problems and impulsivity (e.g. binge eating, binging on drugs/alcohol).15
He then described the developmental relationship between ADHD and SUD across the lifespan, from gestation (where familial-genetic factors can link ADHD and SUD risk, and where alcohol and nicotine exposure in utero increases ADHD risk) through to adulthood (where ADHD is linked to more cigarette smoking, more severe and chronic SUD, and less remission from cigarette smoking and SUD).16
Dr Klassen then went on to describe the similarities between the neurobiology of ADHD and SUD, the possible common genetic contribution (dopamine receptor genes [D2 and D4], dopamine transporter genes and synaptosomal-associated protein 25), highlighting that family, twin, adoption and molecular genetic studies have shown that genes influence the likelihood of developing each disorder and that neuropsychological deficits have consistently been observed in studies of adults with ADHD that are similar to those observed in adults with SUDs.17
In a meta-analysis of patients with SUD (29 studies), results showed that 23.1% (95% confidence interval 19.4–27.2) of patients were diagnosed with ADHD, and that cocaine dependence was associated with lower ADHD prevalence than alcohol and opioid dependence and other addictions.18 He also noted that patients with SUD with comorbid ADHD were more likely to experience additional psychiatric comorbidities than if they had SUD or ADHD alone.19 He then went on to show that SUD with comorbid ADHD can be linked to worse disease outcomes than SUD alone, including a more severe course of SUD, earlier onset of substance abuse, lower remission rates, more substance dependence and an elevated risk of transition from drug abuse to drug dependence.20
Dr Klassen then evaluated studies in relation to ADHD and specific SUDs, highlighting the following:
- An increased prevalence of cigarette smoking in patients with ADHD (around 40% versus 20% in general population).21,22 Cigarette smoking can be a gateway to drug and alcohol abuse, with results from a study by Biederman et al. showing that individuals with ADHD are more likely to abuse other types of substances if they are a smoker compared with a non-smoker.23
- The importance of recognising gambling addiction in patients with ADHD. Results from a study by Faregh and Derevensky have demonstrated that 17.4% of individuals with ADHD had a gambling addiction and that those with combined subtype ADHD had greater gambling problems than those with inattentive subtype ADHD.24
- In patients with ADHD and cocaine dependence, significantly higher levels of both motor and cognitive impulsivity have been demonstrated, with patients with ADHD with cocaine dependence shown to be more impulsive than patients with ADHD without cocaine dependence.15
The following screening tools available to assess alcohol and substance use were discussed:
- CAGE questionnaire – a patient-reported rating scale, which asks four questions surrounding: 1) cutting down; 2) annoyance by criticism; 3) guilty feeling; 4) eye openers (hence the acronym ‘CAGE’).25
- Alcohol, Smoking and Substance Involvement Screening Test [ASSIST] – a clinician-rated scale.26
- Adult ADHD Self-Report Scale (ASRS) for ADHD screening.27
Dr Klassen then continued the seminar by discussing Canadian ADHD Resource Alliance (CADDRA) treatment considerations for patients with ADHD and comorbid SUD. The CADDRA guidelines state that the best approach to treatment sequencing in patients with ADHD and comorbid SUD is concurrent intervention with specific interventions for each disorder. If SUD is severe, sequential treatment may be considered, with immediate attention paid to the SUD.9
Dr Klassen described his own clinical experience surrounding prescription medications and abuse potential, highlighting that misuse, diversion, abuse and addiction are inherent risks of prescribing controlled medications, and noted that all patients prescribed controlled substances should be assessed at each visit for signs of misuse, abuse or addiction. He noted that results from a study of 545 patients in an ADHD clinic reported that 14.3% abused stimulants and, of those, 79.8% abused short-acting stimulants, 17.2% long-acting stimulants, 2.0% both and 1.0% other,28 and that reasons for abusing stimulant medication were not always about the euphoric effects, but to stay awake to study, concentrate on work, help memorise, have fun and make work more interesting.29
Dr Klassen went on to describe the abuse potential of ADHD medication and some of the red flags that he uses in his clinical practice to identify misuse/diversion:
- Symptoms of intoxication or symptoms associated with heavier use (agitation, psychosis, shortness of breath, palpitations)
- Demands for a particular, usually fast-acting, medication (amfetamine immediate release) [“Extended-release doesn’t work for me”]
- Repeated lost prescriptions
- Discordant pill count (escalation of doses)
- Excessive preoccupation with securing medication supply
- Multiple prescribers.
In the final part of the clinical seminar, Dr Klassen described general trends associated with pharmacotherapy in patients with ADHD and comorbid SUD. ADHD symptoms tended to improve in both active-treatment and placebo groups, with active treatment struggling to show significant difference. However, most studies suggested some benefit of active treatment on ADHD symptoms and even in terms of substance use, particularly if ADHD responded to treatment. A single study using a sustained-release formulation using high dosing reported positive results for both ADHD symptom severity and reduction in substance use.30
In his conclusion, Dr Klassen summarised that ADHD and SUD are frequently comorbid, with significantly higher rates of ADHD found in patients presenting with SUD, and that treatment goals which include stabilising ADHD symptoms, and reducing substance use and promoting abstinence, were key.
Dr Klassen: “The starting point should be a clear ADHD diagnosis through psychiatric assessment and prioritising the problems to treat.”
Psychopharmacology of ADHD medications
This practical clinical seminar was led by Professor David Coghill (Royal Children’s Hospital Melbourne, Australia), and discussed the underlying science of ADHD medications and how this knowledge can be applied to clinical practice.
Professor Coghill began the seminar by emphasising that there are several efficacious therapies to choose from in the current ADHD treatment landscape; however, these treatments are not always utilised by clinicians in the best way possible. Professor Coghill explained that a good understanding of the mechanisms of action of the available treatments can be an important tool in understanding how to use these drugs effectively.
During this seminar, Professor Coghill briefly described the structure of the human brain, demonstrating with a series of engaging diagrams that the brain is made up of a series of interlinking circuits. These circuits are predominantly controlled by gamma-aminobutyric acid and glutaminergic neurons; however, noradrenaline and dopamine have important roles in modulating the efficiency, drive and activity of these circuits.31 Noradrenergic and dopaminergic neurons show different patterns of distribution throughout the brain, a fact that helps to explain both the manifestations of ADHD in the brain and also the effect of ADHD medications.31
To explain the role of noradrenaline and dopamine in the brain, the analogy of noise and signal was introduced, with noise representing dopamine and signal representing noradrenaline. For transmission to work effectively in the brain, the balance between noise and signal must be optimal – for example, too much noise can lead to fidgeting and shifting attention, while too little signal can lead to an inability to sit still. Optimising transmission in the circuits of the brain is ultimately the purpose of the pharmacological treatment of ADHD on a neuropharmacological level.32
Methylphenidate is thought to act by blocking dopamine and noradrenaline transporters, and subsequently increasing concentrations of dopamine and noradrenaline in the extraneuronal spaces.33-35 This is believed to be effective in treating ADHD because of the lack of dopamine transporters in the prefrontal cortex; methylphenidate acts to block reuptake of noradrenaline, while having less of an effect on dopamine, thus improving the ratio of noise to signal. Similar to methylphenidate, amfetamines are thought to block dopamine and noradrenaline transporters. However, amfetamines can also be taken up by the dopaminergic neuron to stimulate release of dopamine.33 Atomoxetine binds to the noradrenaline transporter and is thought to block reuptake of dopamine in the prefrontal cortex.36,37 In contrast, guanfacine acts on α2 receptors where it is believed to optimise catecholamine modulation of the prefrontal cortex.32
Professor Coghill’s conclusion was that individual patients with ADHD may respond differently to each of the different medications, and that some patients will respond better to certain mechanisms of action. Professor Coghill recommended discussing with patients that medication choice may be able to be a case of trial and error to find the drug that is most effective in an individual patient. By understanding the mechanisms of action of ADHD medications, the physician may be able to make more informed decisions about the next choice of treatment following a suboptimal response to initial therapy.
Professor Coghill: “Understanding psychopharmacology at this level won’t change what you say to your patients, but it may help you to understand the science behind the medication choice.”
Utilising ADHD treatment choice for children and adolescents
This engaging clinical seminar was led by Professor Michael Huss (Rheinhessen-Fachklinik, Germany) and Professor Jeffrey Newcorn (Mount Sinai Medical Center, NY, USA), and consisted of a lively discussion with the attendees regarding the rationale behind treatment choices for children and adolescents with ADHD.
Professor Huss started with a brief overview of some of the factors that he considers when facilitating the choice of medication in children and adolescents with ADHD. Examples included national and international treatment guidelines, the licensing status of ADHD medications in a given country, the medical history of an individual patient including past exposures to ADHD medication, patient or parent preferences and also the clinical experience of the treating clinician.
Professor Huss and the audience discussed the ways in which these factors can influence a treatment decision in clinical practice. In particular, prior exposure to ADHD medications was highlighted as a useful way to predict what medications a patient may respond positively to, and vice versa. Professor Newcorn and Professor Huss then went on to debate the importance of considering other family members with ADHD when making a treatment choice. While Professor Huss felt that knowing what treatments for ADHD had been effective in a family member could help to guide treatment choice, Professor Newcorn highlighted the difficulties he has experienced with patients or parents who are determined for a particular drug to be prescribed because a family member is receiving the same one, despite it not being the best choice for the current patient.
Both Professor Huss and Professor Newcorn agreed that it is important to be open to changing medications in patients who do not show a satisfactory response to a chosen treatment, despite optimisation of dose. The consensus in the room was that clinicians should always evaluate whether they can do any better for the patient, for example, in patients who do show some response to medication, the clinician should consider whether it might be possible to get an even better response by either optimising or changing therapy.
Professor Huss: “When treating our patients with ADHD, we must always ask ourselves if we can do better for this patient.”
Late-onset ADHD: diagnostic issues and management
This case study-based seminar was led by Professor Luis Rohde (Federal University of Rio Grande do Sul, Brazil) and Professor Philip Asherson (King’s College London and Maudsley Hospital, UK), and focused on adult-onset ADHD.
Professor Rohde began by providing background information on some of the controversies that have surrounded the diagnosis of ADHD in adults. For example, ADHD is currently categorised as a neurodevelopmental disorder, requiring an onset during infancy or childhood for a diagnosis.38,39 However, Professor Rohde explained that he sees many adults in clinical practice with suspected ADHD who do not report the presence of any symptoms during childhood. With these patients, many clinicians assume that either the patient is simply failing to remember any symptoms experienced during childhood or that the patient cannot have ADHD. Professor Rohde presented his opinion that the onset of ADHD in adults with no prior history should be accepted in the same way that clinicians accept that the first episode of anxiety or depression can occur in adulthood.
To demonstrate his point, Professor Rohde shared a previously published case study documenting a case of late-onset ADHD.40 The case study documented the story of a 22-year-old man, Mr B, who presented for evaluation following problems with poor performance at work, at home and in personal relationships. Mr B reported problems with procrastination, organisation and executive functions. Mr B failed to complete paperwork, failed to pay monthly bills and was experiencing tension with his girlfriend due to not meeting expectations for managing daily adult life. Professor Rohde explained that in the current scenario, it should be assumed that following a detailed medical history, anxiety and depression were excluded. Professor Rohde said that Mr B reported five symptoms of ADHD on Part A of the ASRS; however, self- and parent-reports recalled no academic difficulties or symptoms of ADHD during childhood.
Professor Rohde and Professor Asherson agreed that they would both treat Mr B for ADHD based on the details provided in the case study, despite the lack of childhood symptoms. However, it was acknowledged that the presented case study was a very straightforward case, and that in clinical practice, the diagnosis of late-onset ADHD is likely to be more complex.
An interesting discussion then developed between the facilitators and the audience regarding the nature of adult ADHD. Different theories were discussed, including the idea that certain individuals with a genetic profile that exposes them to a moderate risk of ADHD might only experience symptoms of ADHD in adulthood once they are exposed to certain environmental triggers. Alternatively, it is possible that patients who develop late-onset ADHD have an entirely different genetic profile to those patients who develop ADHD in childhood or adolescence. The impact of coping mechanisms and a high IQ were also discussed, with a suggestion that some patients may be able to compensate for their symptoms of ADHD in childhood when they are surrounded by a supportive environment at school and at home. In these patients, the additional complexities of adult life after leaving home and becoming self-sufficient may become too much to cope with, and symptoms of ADHD may become apparent.
Following these discussions, Professor Asherson stated his conclusion that more research is required to determine if late-onset ADHD is a different condition versus early-onset ADHD, or if they are simply different trajectories of the same condition. Professor Asherson used the hypothetical example of type I and II diabetes as an analogy for how late-onset ADHD may be viewed in the future. Regardless of the nature of late-onset ADHD, Professor Rohde and Professor Asherson agreed that there is a need to increase the profile of late-onset ADHD to increase its detection and diagnosis.
Professor Rohde: “We do not have a definitive conclusion on adult ADHD, but the consideration of different phenotypes and trajectories can be useful.”
Patient consultations: ‘tips and tricks’ for greater success
The objectives of this lively and interactive clinical seminar led by Dr Ari Tuckman (Clinical Psychologist, PA, USA) were to discuss the diagnosis of ADHD, especially with psychiatric comorbidities, and to learn how to inform and educate the patient and their family about their diagnosis and treatment, and successful ways to measure success.
Dr Tuckman opened the session by highlighting that ADHD is relatively straightforward to diagnose; however, ADHD rarely travels alone and psychiatric comorbidities increase in prevalence across the lifespan. Psychiatric comorbidities not only ‘muddy the waters’ but may also require the prioritisation of some treatments over others. For example, if a patient is anxious at work because they struggle to concentrate, it could be anxiety or distractibility, or it could be anxiety and distractibility. In this instance, the clinician can wonder if they should treat the distractibility first and hope the anxiety goes away, or treat the anxiety first to help the patient cope at work.
Discussion question: Which do you prioritise first?
The audience agreed that they would treat the condition which has the most impact on the patient. They noted that the job of the physician is to provide the patient with the correct information to see the bigger picture and to address their specific goals, not the goals of the physician. However, it was also agreed that it was dependent on the services and treatment available to them in their country/clinic.
Dr Tuckman continued by asking how you prioritise for the patient if it is not clear which condition is more severe. The approach the audience agreed on was if the patient does not respond quickly to treatment then they would switch approaches. An example would be if a child was anxious at school and did not pay attention, then anxiety would be the primary condition and ADHD the secondary; however, if the child did not want to go to school and they forgot their homework and they were worried, it could be that ADHD was the primary condition and anxiety was the secondary condition.
Dr Tuckman described ADHD as a diagnosis of contradictions as follows:
- ADHD is a deficit in attention regulation, not in attention per se, and is strongly influenced by interest.
- ADHD impacts executive functions and working towards the future, not task performance per se.
- ADHD is not a disorder of knowing what to do, it is a disorder of doing what you know.
Discussion question: How do you use understanding as an intervention?
The audience agreed that knowledge is power, and the more knowledge the patient and their family have, the less insecure and confused they are. One of the audience members told the group that she shows a slide to her patients about executive function and the symptoms, highlighting that it is not just about attention. They discussed the importance of developing strategies to solve executive function deficits and practical solutions. The group noted the importance of also educating teachers because they have a huge impact on the child. Dr Cesar Soutullo (Clínica Universidad de Navarra, Spain) told the group that he sends an ADHD rating scale to the teachers and asks them to not only score the patient but to give examples as well, because he finds that teachers do not like to ‘diagnose’ their pupils.
Dr Tuckman went on to say that, in his experience, patients and family members will believe the diagnosis more if you explain your reasoning, for example, educating patients and family members about how ADHD can explain past struggles can help them understand the need for appropriate treatment and can explain why previous interventions may not have been sufficiently effective. This improves the patient’s trust in the physician, which in turn can improve treatment adherence.
Discussion question: How do you use patient education as a foundation for treatment?
The audience agreed the importance of patient and family members having a group discussion to discuss the diagnosis and the next steps in treatment – it may be that during these discussions, the parent or family member can relate to the symptoms and their past history of ADHD symptoms can be discovered.
Dr Tuckman described a four-part treatment programme, which he uses with his patients and their families to help them target their efforts, and highlighted that each aspect of the multimodal treatment programme supports the effectiveness of the others:
- ADHD education
- ADHD-friendly strategies
- Effective medication regimen
- Therapy, which can help to develop a stronger mindset to take the steps to address issues in a positive way, for example, quality of life and quality of function.
Discussion question: How do you discuss treatment options with patients?
One of the audience members explained that they create a pictorial diagram with ADHD symptoms surrounded by circles with the treatment options and how they work. This method allows the patient to visualise how each of the treatments could work for them.
Dr Tuckman described satisfaction as a function of expectations versus experience. He went on to note that physicians work hard to improve patients’ experiences (e.g. symptoms and impairments), but it is important to recognise their expectations as well. He asserted the importance of patients striving to have high enough expectations that they will work hard and not settle prematurely, and that the patient needs to realise that ADHD does not just go away or that treatment is only needed until skills are learned.
Discussion question: How do you walk this balance with patients’ expectations?
Dr Soutullo noted that he recommends asking the patients about their treatment expectations, and recommended questions such as, “What do you do all day and how will treatment fit in?”, “What happens at the weekend? Do you have different expectations?” – it is important to show patients what they are missing without treatment, for example friendships, social activities, improved relationships etc. The audience agreed that if a patient comes with the opinion that they ‘don’t believe in medication’, it is important to get them to understand that they do not need to struggle, and that a more functional/satisfying life is available to them and their families.
The group went on to discuss the importance of asking the right questions at follow-up appointments. For example, if you have a patient who is not seeing the improvements they need, then it is important to get them to try different doses and different medications, and for them to have the energy to push for their goals and have high expectations – “It needs to be as good as it can be!”. Conversely, you will have patients who have high expectations at the outset that are not achievable, and you still need to manage these patients’ expectations, otherwise they will discontinue treatment.
Regarding tolerability, it was discussed that physicians should discuss the pros and cons of treatments, for example, if a patient feels emotionally flat they may want to reduce their dose, but it is important to highlight that they may lose some of the benefits in doing so – it is important to ensure that the patient recognises what is important to them as well as their family, friends and those around them.
In his conclusion, Dr Tuckman stated that it is important to give patients and their families the information to be able to make informed choices.
Dr Tuckman: “Some patients don’t see the need for ADHD treatment and they just think they need to try harder. Nobody says that about diabetes! We should be saying that they need to have the treatment so they don’t need to try harder.”
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