ADHD in Focus – Medical Update on Adult ADHD

The 4th Congress of the UK Adults ADHD Network (UKAAN), in conjunction with ENAA (European Network Adults ADHD) and APSARD (American Professional Society of ADHD and Related Disorders), was held in London from 10 to 12 September 2014. What follows are highlights, latest trends, salient points and new ways of thinking emanating from some of the presentations.

ADHD as a lifelong condition – Eric Taylor

  • Functional remission of adult ADHD is uncommon as demonstrated by a 33-year follow-up study (Klein et al) demonstrating lower levels of education and employment and higher divorce and death rates in adults with ADHD.
  • Conduct Disorder (CD) is a common co-occurrence with childhood ADHD; CD is difficult to distinguish from ADHD in terms of educational consequences and social impairment and “ADHD in childhood should be taken serious”.
  • “Adult onset” ADHD caused by CNS infections, substances, degenerative conditions and traumatic brain injury needs further investigation.
  • The co-morbidities with ADHD (e.g. Substance Use Disorders, mood dysregulation, antisocial behaviour, etc.), the impact on relationships, concerns about possible long term structural brain effects and other consequences of ADHD makes it important to consider the persistence of ADHD into adulthood.

Cultural differences between US and Europe – Ilina Singh

  • Reference was made to the qualitative VOICES study (of ADHD in the age group 9-14yr) where people were asked about their perceptions of ADHD and its treatment. In The UK ADHD was perceived more as “a disorder of aggression/anger” where treatment improved mood regulation and impulsivity (“conduct niche”) whereas in the USA it was perceived as a disorder of academic functioning and treatment improved classroom performance (“performance niche”). Therefore context should be taken into account when considering matters of compliance and perceived efficacy of treatment.

Panel Discussion (Philip Asherson, Sandra Kooij, Tony Rostain, Susan Young and others)

  • “Resilience factors” (e.g. environmental compensation, using of strengths, right career choice, parenting styles, lowering comorbidity, etc.) and their impact on ADHD should be a focus of future research.
  • Although clinical “remission” of ADHD might be achieved, the “baggage” and disadvantages from previous ADHD might not remit.
  • “Adult onset” ADHD might be explained by good “scaffolding” (e.g. IQ, structure) during school years without causing impairment – hence the DSM 5 requiring presence of “symptoms that interfere with, or reduce the quality of… functioning” (and not “clinically significant impairment” as in DSM-IV-TR).
  • It was felt that, after the MTA study, ADHD was ”medicalized” and that psychotherapy for ADHD was not recognized anymore. Psychotherapy in ADHD should be aiming help individuals accept and accommodate to the new diagnosis, reframing the “baggage of ADHD” of their past and reintegrating it into their current situation. Addressing comorbidity is also vital.

Long term outcomes (LTO) of treatment: a multi-modal approach – Susan Young

  • The estimated prevalence of ADHD in adult prisons in the UK is 25%.
  • Discontinuation of care in the “twilight zone” between adolescence to adulthood is of great concern as this missed opportunity leads to more adverse LTO, including substance use disorders, poor academic outcomes, antisocial behaviour, etc.
  • Two third of adults benefitted from treatment, irrespective of the age of onset of treatment – the most improvement was with driving, obesity, self esteem, social and academic functioning.
  • There is a bigger effect size with combination treatment (pharmacological end non-pharmacological).

Comparative studies of stimulants and Atomoxetine – Jeff Newcorn

  • Atomoxetine, a highly selective NA reuptake inhibitor, produces long-lasting increases in NA and DA neurotransmission in the PFC which may be linked to neuroadaptation in the brain and extended duration of therapeutic effect in ADHD.
  • One third of people chose Atomoxetine over Methylphenidate; preference seems to be determined by response.
  • Reference is made to the MACRO study (crossover study in children comparing Methylphenidate OROS (MPH) vs. Atomoxetine (ATX)):
    • With MPH, somewhat larger overall response and larger number of excellent responders.
    • More people who are treated with both medications prefer MPH.
    • Poor responders to MPH are unlikely to be excellent responders to ATX, though they may achieve a moderate response.
    • With ATX, comparable symptom improvement to MPH when used first, though fewer excellent responders and more non-responders.
    • Relatively better response when used first than after stimulant.
    • Preferred equally to MPH among excellent responders of both.
    • Non-responders or moderate responders to ATX likely to have better response to MPH.

ADHD drugs: Pharmacological mechanisms and clinical outcomes – David Heal

  • Monoamine release (vs. reuptake inhibition by MPH) is achieved by medications like lisdexamfetamine and is especially powerful to increase DA transmission in the PFC.
  • Lisdexamfetamine (inactive prodrug) has a slow and prolonged enzymatic liberation of dextroamfetamine and was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse.
  • DA-reuptake inhibition (e.g. Buproprion) does not seem to be very effective for ADHD.

Clinical trials in adults with ADHD – Ulrich Müller

  • In a meta-analysis of pharmacotherapy for adult ADHD, Castells et al (CNS Drugs, 2011) reports an effect size of 0.5 for MPH and 0.4 for ATX.
  • New treatments that are being considered for ADHD includes Desipramine, Duloxetine, Reboxetine and Metadoxine. There were negative studies for the efficacy of Modafinil and Venlafaxine for the treatment of ADHD.

Metadoxine – Iris Manor

  • Phase III trials are being conducted on this monoamine independent GABA/glutamate modulator currently registered for use in alcohol intoxication and alcohol related liver disorders.
  • It seems to have an immediate onset and the optimum dose seems to be 1400mg with the maximal response after 5 hours and no response after approx. 8 hours.
  • It might be more effective for inattentive type ADHD.
  • It has a very favourable side-effect profile.

Trajectory and maintenance of response in adult ADHD: How does Atomoxetine compare with stimulants? – Chris Bushe

  • Because of a slower onset of action with Atomoxetine, “non-responders” can become responders if enough time is given.
  • Five patterns of response to Atomoxetine has been identified; e.g.:
    • In 5% there is no response for unknown reasons.
    • In 2 groups (the “slow burners”) there was ongoing response up to 25 weeks.
  • After discontinuation of stimulants, benefits were lost rapidly (50% relapse rate after 6 months vs. 20% with Atomoxetine). This raises the question whether Atomoxetine causes longer term changes (neuroadaptation) explaining ongoing benefits after discontinuation.

ADHD and Bipolar Disorder – Andreas Reif

  • ADHD is a trait-like condition with stable deficits vs. Bipolar Disorder which is phasic/state-like.
  • When considering the overlapping of symptoms, Bipolar depression is often not considered.
  • The “mood swings” in ADHD is of higher frequency, lower amplitude and mostly reactive to triggers.
  • Comorbidity is estimated at 10-20%, which raises the question of a shared genetic basis.
  • To help distinguish between ADHD and Bipolar Disorder, the following is suggested: take time to make the diagnosis; use rating scales like the WURS, CAARS, DIVA, etc.; defer the diagnosis in a manic/mixed state; combination treatment should be used if both conditions co-occur.

Emotional lability in adult ADHD – Philip Asherson

  • Emotional dysregulation or “emotional impulsivity” is a common associated feature in ADHD and should maybe be considered a 3rd cluster of symptoms (together with the inattention and hyperactive/impulsive clusters) as it has an independent impact on impairment.
  • It should be distinguished from state-like lability of Bipolar Disorder as it is more stable/trait-like.
  • Treatment also has a sustained effect on emotional regulation.

ADHD and Personality Disorders (PD) – Tony Ramos

  • There is significant overlap with many personality traits from all 3 clusters (e.g. A – Paranoid traits and C – OC and Dependant traits), but most notably with cluster B (Borderline, Histrionic and Antisocial traits). Comorbidity is estimated to be around 25%.
  • In cluster B personality traits, the hyperactive/impulsive presentation is more common; in cluster C personality traits the inattentive presentation is more common.
  • There is a 7 fold increased risk of antisocial behaviour in adult ADHD patients.
  • OCPD should be distinguished from ADHD patients compensating with OC behaviours for their executive dysfunction.

Providing support during the transition from child to adult services – Iris Manor

  • There is often poor communication between paediatric and adult ADHD services leading to patients “falling through the cracks” and not entering adult ADHD services. Treatment is often discontinued after school as it’s still believed that ADHD is “outgrown”.
  • Possible solutions include
    • “Lifespan clinics” where children and adults are being treated by the same health care provider.
    • “Specialized” GPs with special interest, training and experience in treating adult ADHD.
    • Adults ADHD clinics – this is probably the most practical solution; psychiatrist leading the team; “task-shifting” to other health care professionals to enlarge service delivery.

ADHD and addictions seminar

  • There is a high prevalence (estimated at 15-25%) of ADHD in primary Substance Use Disorders (SUD); screening for ADHD in this population is vital.
  • The prevalence of SUD in adult ADHD patients is estimated at 45%.
  • The ASRS is a valuable tool to screen for ADHD in SUD.
  • There is a strong association with the hyperactive/impulsive presentation and SUD; in the inattentive presentation cannabis is often the drug of choice.
  • Underlying mechanisms of comorbid ADHD and SUD include impulsivity, “reward deficiency” and self medication of negative emotional states.
  • It is suggested that the impulsivity trait should be measured independently from the ADHD assessment as it could constitute a separate phenotype which is highly predictive of later SUD.
  • Treatment considerations for impulsive ADHD and SUD include the use of Atomoxetine, Lisdexamfetamine, Guanfacine or Buproprion instead of stimulants.
  • In a recent meta-analysis by Cunill et al (J Psychopharmacol August 20, 2014) it is reported that, while pharmacological interventions improved ADHD symptoms, no beneficial effect on drug abstinence or on treatment discontinuation was noted.
  • If stimulants are used in co-occurring SUD, Methylphenidate OROS or Lisdexamfetamine is preferred. High dose Methylphenidate OROS treatment holds promise. Atomoxetine should be considered 1st line if there is a risk of diversion (NICE, RACP and BAP guidelines).
  • Order of treatment: treat what is clinically most relevant – often ADHD treatment is lower on the priority list.
  • Research on “substitution treatment” in stimulant abuse/dependence is lacking.