Stephen V. Faraone, PhDAn international group of twelve experts recently published a consensus report examining the state of the evidence and offering recommendations to guide screening, diagnosis, and treatment of individuals with ADHD-SUD comorbidity.1

In a clear sign that we are still in the early stages of understanding this relationship, five of the thirteen recommendations received the lowest recommendation grade (D), eight received the next-lowest (C), and none received the highest (A and B).

The lower grades reflected the absence of the highest level of evidence, obtained from meta-analyses or systematic reviews of relevant randomized controlled trials (RCTs).

Nevertheless, with these limitations in mind, the experts agreed on the following points:

ADHD Diagnosis

  • The strongest recommendation, the only one based on a 2+ level of evidence (well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal) is that the “Short Version of the Adult ADHD Self-Report Scale (ASRS-SV) screener is currently the most widely used and investigated screening tool in individuals with ADHD and comorbid SUD, with good sensitivity and specificity across studies.”
  • Two other recommendations were graded C: The diagnostic process should include current and past substance abuse and seek to involve partners and relatives in evaluating symptoms and functional impairments.
  • Four recommendations got the lowest grade, D. The experts suggested starting the diagnostic process as soon as possible and focusing on drug- and alcohol-free periods in the patient’s life during history taking. They also recommended that physicians and clinical psychologists should only make diagnoses if they have extensive training in diagnosing ADHD, as well as experience with adults with ADHD and with addiction care, and that they should consider treating adults with sufficiently severe ADHD symptoms.

ADHD Treatment

  • In general, evidence was stronger in this area, and only one of the six recommendations was graded D. The other five recommendations were graded C, with the highest level of evidence being 2 (cohort or case and control studies with undetermined risk of bias), although in three cases it was level 3 (non-analytical studies, such as case reports and case series).
  • The grade D recommendation was to always consider a combination of psychotherapy and pharmacotherapy.
  • The grade C recommendations included considering adequate medical treatment of both ADHD and SUD; integrating ADHD treatment with SUD treatment as soon as possible; considering psychotherapy targeting both; use of long-acting methylphenidate, extended-release amphetamines, and atomoxetine because of their low potential for abuse; and careful clinical management to avoid abuse and diversion of prescribed stimulants.

Note: Andrew Reding is a co-author on this post.

REFERENCES
1Cleo L. Crunelle at al., “International Consensus Statement on Screening, Diagnosis and Treatment of Substance Use Disorder Patients with Comorbid Attention Deficit/Hyperactivity Disorder,” European Addiction Research, published online March 6, 2018, DOI: 10.1159/000487767.

Stephen V. Faraone, PhDA Dutch study compared the efficacy of mindfulness-based cognitive therapy (MBCT) combined with treatment as usual (TAU), with TAU-only as the control group. MBCT consisted of an eight-week group therapy consisting of mindfulness exercises (bodyscan, sitting meditation, mindful movement), psychoeducation about ADHD, and group exercises. TAU consisted of usual treatment in the Netherlands, including medications and other psychological treatment. Sixty individuals were randomly assigned to each group. MBCT was taught in subgroups of 8 to 12 individuals. Patients assigned to TAU were not brought together in small groups. Baseline demographic and clinical characteristics were closely matched for both groups.

Mindfulness Cognitive Behavioral TherapyOutcomes were evaluated at the start, immediately following treatment, and again after 3 and 6 months using well-validated rating scales. Following treatment, the MBCT + TAU group outperformed the TAU group by an average of 3.4 points on the Conners’ Adult Rating Scale, corresponding to a standardized mean difference of .41. Thirty-one percent of the MBCT + TAU group made significant gains, versus 5% of the TAU group. 27% of MBCT +TAU patients scored a symptom reduction of at least 30 percent, as opposed to only 4% of TAU patients. Three and six-month follow-up effects were stable, with an effect size of .43.

The authors concluded “that MBCT has significant benefits to adults with ADHD up to 6 months after post-treatment, with regard to both ADHD symptoms and positive outcomes.” Yet in their section on limitations, they overlook a potentially important one. There was no active placebo control. Those who were undergoing TAU-only were aware that they were not doing anything different from what they had been doing before the study. Hence no substantial placebo response would be expected from this group during the intervention period (post-treatment they were offered an opportunity to undergo MBCT). Moreover, MBCT + TAU participants were gathered into small groups, whereas TAU participants were not. We therefore have no way of knowing what effect group interaction had on the outcomes, because it was not controlled for. So, although these results are intriguing and suggest that further research is worthwhile, the work is not sufficiently rigorous to definitively conclude that MBCT should be prescribed for adults with ADHD.

Note: This post was co-authored by Andrew Reding.

REFERENCES
Janssen L, Kan CC, Carpentier PJ, Sizoo B, Hepark S, Schellekens MPJ, Donders ART, Buitelaar JK, Speckens AEM. “Mindfulness-based cognitive therapy v. treatment as usual in adults with ADHD: a multicentre, single-blind, randomised controlled trial,” Psychological Medicine (2018), https:// doi.org/10.1017/S0033291718000429

Stephen V. Faraone, PhDThough there have been numerous studies of the efficacy of cognitive behavioral therapy (CBT) for ADHD symptoms in children, adolescents, and adults, few have examined efficacy among adults over 50. A new study begins to fill that void.

Psychiatric researchers from the New York University School of Medicine, Massachusetts General Hospital, and Pfizer randomly assigned 88 adults diagnosed with elevated levels of ADHD to one of two groups. The first group received 12 weeks of CBT targeting executive dysfunction – a deficiency in the ability to properly analyze, plan, organize, schedule, and complete tasks. The second group was assigned to a support group, intended to serve as a control for any effects arising from participating in a group therapy. Each group was split into subgroups of six to eight participants. One of the CBT subgroups was run concurrently with one of the support-only subgroups and matched on the percent receiving ADHD medications.

Outcomes were obtained for different ADHD demographics, 26 adults aged 50 or older (12 in CBT and 14 in support) and compared with 55 younger adults (29 in CBT and 26 in support). The mean age of the younger group was 35 and of the older group 56. Roughly half of the older group, and 3/5ths of the younger group, was on medication. Independent (“blinded”) clinicians rated symptoms of ADHD before and after treatment.

In the blind structured interview, both inattentive scores and executive function scores improved significantly and almost identically for both older and younger adults following CBT. When compared with the controls (support groups), however, there was a marked divergence. In younger adults, CBT groups significantlyIs Cognitive Behavior Therapy Effective for Older Adults with ADHD? outperformed support groups, with mean relative score improvements of 3.7 for inattentive symptoms and 2.9 for executive functioning. In older adults, however, the relative score improvements were only 1.1 and 0.9, and were not statistically significant.

Given the nonsignificant improvements over placebo, the authors’ conclusion that “The results provide preliminary evidence that CBT is an effective intervention for older adults with ADHD” is premature. As they note, a similar large placebo effect was seen in adults over 50 in a meta-analysis of CBT for depression, rendering the outcomes nonsignificant. Perhaps structured human contact is the key ingredient in this age group. It may also be, as suggested by the positive relative gains on six of seven measures, that CBT has a small net benefit over placebo, which cannot be validated with such a small sample size. Awaiting results from studies with larger sample sizes, it is for now impossible to reach any definitive conclusions about the efficacy of CBT for treating adults over 50.

Note: Andrew Reding is co-author on this post.

REFERENCES
Mary V. Solanto, Craig B. Surman, Jose Ma. J. Alvir, “The efficacy of cognitive–behavioral therapy for older adults with ADHD: a randomized controlled trial,” ADHD Attention Deficit and Hyperactivity Disorders (2018)

Stephen V Faraone PhD AIA 2016 tatAj0

A recent CNN report, http://tinyurl.com/yannlfd6, highlighted a paper published in Pediatrics, which reported that pregnant women who use acetaminophen during pregnancy put their unborn child at two-fold increased risk for attention deficit hyperactivity disorder (ADHD).   In that study, acetaminophen use during pregnancy was common; nearly half of women surveyed used the painkiller during a pregnancy.   Other studies have reported similar associations of acetaminophen, also known as paracetamol with ADHD or with other problems in childhood (e.g., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300094/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177119/, https://www.ncbi.nlm.nih.gov/pubmed/24566677, https://www.ncbi.nlm.nih.gov/pubmed/24163279). Given these prior findings, it seems unlikely that the new report is a chance finding. But does it make any biological sense?   One answer to that question came from an epigenetic study. Such studies figure out if assaults from the environment change the genetic code. One epigenetic study found that prenatal exposure, changes the fetal genome via a process called methylation. Such genomic changes could increase risk for ADHD (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540511/)/ . Because all of these studies are observational studies, one cannot assert with certainty that there is a causal link between acetaminophen use during pregnancy. The observed association could be due to some unmeasured third factor. Although the researchers did a respectable job ruling out some third factors, we must acknowledge some uncertainty in the finding. That said, what should pregnant women do if they need a acetaminophen.   I suggest you bring this information to your physician and ask if there is a suitable alternative.

Stephen_Faraone_PhD_ADHD_in_Adults
In the popular media, ADHD is sometimes portrayed as a minor condition or not a disorder at all.   In fact, it is easy to find web sites claiming that ADHD is an invention of the medical profession and that the symptoms used to diagnose the disorder are simply normal behaviors that have been “medicalized”.   These claims are wrong.  They miss the main point of any psychiatric diagnostic process which is to identify people who experience distress or disability due to a set of well-defined symptoms.  So, does ADHD cause serious distress and disability?   It is a serious psychiatric condition?  To illustrate the strong evidence base for the “Yes” answer to that question, my colleagues and I constructed this infographic for our “Primer” about ADHD,
http://rdcu.be/gYyV.   It describes the many ways in which the symptoms of ADHD impact and impair the lives of children, adolescents and adults with the disorder.  We divided these ‘impacts’ into four categories: other disorders (both psychiatric and medical), psychological dysfunction, academic and occupational failure, social disability and risky behaviors.  Let’s start with other health problems.  We know from many studies that have followed ADHD children into adolescence and adulthood that having the disorder puts patients at risk for several psychiatric disorders, addictions, criminality, learning disabilities and speech/language disorders. ADHD even increases the risk for non-psychiatric disease such as obesity, hypertension and diabetes.  Perhaps most worrisome is that people with ADHD have a small increased risk for premature death.  This increased risk is due in part to their having other psychiatric and medical conditions and also to their risky behaviors which, as research documents, lead to accidents and traumatic brain injuries.   In the category of ‘psychological dysfunction’ we highlighted emotional dysregulation, which makes ADHD people quick to anger or to fail to tame extreme emotions.  Other serious psychological issues are low self-esteem and increased thoughts of suicide, which lead to more suicide attempts than for people without ADHD.  This increased risk for suicide is small, but it is real.    A more prevalent impact of ADHD is the broad category of social disability, which includes marital discord, poor parenting, legal problems, arrests and incarceration.   This typical starts in youth with poor social adjustment and conflict with parents, siblings and friends.  Another common impact of ADHD is on academic and vocational pursuits.  ADHD youth are at risk for underachievement in school, repeating grades and dropping out.  As adults, they are more likely to unemployed or underemployed, which leads to them having lower incomes than expected for their level of achievement in school.   So, don’t believe anyone who claims that ADHD is not a disorder or is only a mild one.   To be sure, there is a wide range of impairment among people with ADHD but, in the absence of treatment, they are at risk for adverse outcomes.  Fortunately, the medications that treat ADHD have been documented to reduce this risk, which is why they are typically the first line treatment for most people with ADHD.

REFERENCE

Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ;  http://rdcu.be/gYyV

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Stephen_Faraone_PhD_ADHD_in_Adults

If you’ve ever wondered how experts make treatment recommendations for patients with ADHD, take a look at this ADHD treatment decision tree that my colleagues and I constructed for our “Primer” about ADHD, http://rdcu.be/gYyV. Although a picture is worth a thousand words, keep in mind that this infographic only gives the bare bones of a complex process.   That said, it is telling that one of the first questions an expert asks is if the patient has a comorbid condition that is more severe than ADHD.  The rule of thumb is to treat the more severe disorder first and after that condition has been stabilized plan a treatment approach for the other condition.  Stimulants are typically the first line treatment due to their greater efficacy compared with non-stimulants.  When considering any medication treatment for ADHD, safety is the first concern which is why medical contraindications to stimulants, such as cardiovascular issues or concerns about substance abuse, must be considered.  For very young children (preschoolers) family behavior therapy is typically used prior to medication.  Clinicians also must deal with personal preferences.   Some parents and some adolescents and adults with ADHD simply don’t want to take stimulant medications for the disorder.  When that happens, clinicians should do their best to educate them about the costs and benefits of stimulant treatment.   If, as is the case for most patients, the doctor takes the stimulant arm of the decision tree, he or she must next decide if methylphenidate of amphetamine is more appropriate.  Here there is very little guidance for doctors.  Amphetamine compounds are a bit more effective but can lead to greater side effects.   Genetic studies suggest that a person’s genetic background provide some information about who will respond well to methylphenidate but we are not yet able to make very accurate predictions.    After choosing the type of stimulant, the doctor must next consider what duration of action is appropriate for each patient.  There is no simple rule here; the choice will depend upon the specific needs of each patient.  Many children benefit from longer acting medications to get them through school, homework and late afternoon/evening social activities.  Likewise for adults.  But many patients prefer shorter acting medications especially as these can be used to target specific times of day and can also lower the burden of side effects.   For patients taken down the non-stimulant arm of the decision tree, duration is not an issue but the patient and doctor must choose from among two classes of medications norepinephrine reuptake inhibitors or alpha-2-agonists.  There are not a lot of good data to guide this decision but, again, genetics can be useful in some cases.  Regardless of whether the first treatment is a stimulant or a non-stimulant, the patient’s response must be closely monitored as there is no guarantee that the first choice of medication will work out well.  In some cases efficacy is low or adverse events are high.  Sometimes this can be fixed by changing the dose and sometimes a trial of a new medication is indicated.  If you are a parent of a child with ADHD or an adult with ADHD, this trial and error approach can be frustrating.  But don’t lose hope.  In the end, most ADHD patients find a dose and a medication that works for them.   Last but not least, when medication leads to a partial response, even after adjusting doses and trying different medication types, doctors should consider referring the patient for a non-pharmacologic ADHD treatment.  You can read details about these in my other blogs but for here the main point is to find an evidenced-based treatment.  For children the biggest evidence base is for behavioral family therapy.  For adults, cognitive behavior therapy (CBT) is the best choice.   With the exception of preschoolers, the experts I worked with on this infographic did not recommend these therapies before medication treatment.  The reason is that the medications are much more effective and many non-pharmacologic treatments (such as CBT) have no data indicating they work well in the absence of medication.  

REFERENCE
Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ;  http://rdcu.be/gYyV

Stephen_Faraone_PhD_ADHD_in_Adults

If you’ve ever wondered how experts make treatment recommendations for patients with ADHD, take a look at this ADHD treatment decision tree that my colleagues and I constructed for our “Primer” about ADHD, http://rdcu.be/gYyV. Although a picture is worth a thousand words, keep in mind that this infographic only gives the bare bones of a complex process.   That said, it is telling that one of the first questions an expert asks is if the patient has a comorbid condition that is more severe than ADHD.  The rule of thumb is to treat the more severe disorder first and after that condition has been stabilized plan a treatment approach for the other condition.  Stimulants are typically the first line treatment due to their greater efficacy compared with non-stimulants.  When considering any medication treatment for ADHD, safety is the first concern which is why medical contraindications to stimulants, such as cardiovascular issues or concerns about substance abuse, must be considered.  For very young children (preschoolers) family behavior therapy is typically used prior to medication.  Clinicians also must deal with personal preferences.   Some parents and some adolescents and adults with ADHD simply don’t want to take stimulant medications for the disorder.  When that happens, clinicians should do their best to educate them about the costs and benefits of stimulant treatment.   If, as is the case for most patients, the doctor takes the stimulant arm of the decision tree, he or she must next decide if methylphenidate of amphetamine is more appropriate.  Here there is very little guidance for doctors.  Amphetamine compounds are a bit more effective but can lead to greater side effects.   Genetic studies suggest that a person’s genetic background provide some information about who will respond well to methylphenidate but we are not yet able to make very accurate predictions.    After choosing the type of stimulant, the doctor must next consider what duration of action is appropriate for each patient.  There is no simple rule here; the choice will depend upon the specific needs of each patient.  Many children benefit from longer acting medications to get them through school, homework and late afternoon/evening social activities.  Likewise for adults.  But many patients prefer shorter acting medications especially as these can be used to target specific times of day and can also lower the burden of side effects.   For patients taken down the non-stimulant arm of the decision tree, duration is not an issue but the patient and doctor must choose from among two classes of medications norepinephrine reuptake inhibitors or alpha-2-agonists.  There are not a lot of good data to guide this decision but, again, genetics can be useful in some cases.  Regardless of whether the first treatment is a stimulant or a non-stimulant, the patient’s response must be closely monitored as there is no guarantee that the first choice of medication will work out well.  In some cases efficacy is low or adverse events are high.  Sometimes this can be fixed by changing the dose and sometimes a trial of a new medication is indicated.  If you are a parent of a child with ADHD or an adult with ADHD, this trial and error approach can be frustrating.  But don’t lose hope.  In the end, most ADHD patients find a dose and a medication that works for them.   Last but not least, when medication leads to a partial response, even after adjusting doses and trying different medication types, doctors should consider referring the patient for a non-pharmacologic ADHD treatment.  You can read details about these in my other blogs but for here the main point is to find an evidenced-based treatment.  For children the biggest evidence base is for behavioral family therapy.  For adults, cognitive behavior therapy (CBT) is the best choice.   With the exception of preschoolers, the experts I worked with on this infographic did not recommend these therapies before medication treatment.  The reason is that the medications are much more effective and many non-pharmacologic treatments (such as CBT) have no data indicating they work well in the absence of medication.  

REFERENCE

Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ;  http://rdcu.be/gYyV

Stephen V. Faraone, PhD - ADHD in Adults


The diagnosis of ADHD should only be done by a licensed clinician and that clinician should have one goal in mind: to plan a safe and effective course of evidenced-based treatment.  The infographic below gives a summary of this diagnostic approach over time, which my colleagues and I prepared for our “Primer” about ADHD, referenced below.

.   A key point that parents of ADHD youth and adults with ADHD should keep in mind is that there is only one way to diagnose ADHD.  An expert clinician must document the criteria for the disorder as specified by either the Diagnostic and Statistical Manual of the American Psychiatric Association, which is now in its fifth edition (DSM-5) or the World Health Organizations International Classification of Diseases (ICD-10).  The two sets of criteria are nearly identical.  These criteria are most commonly applied by a clinician asking questions of the parent (for children) and/or patient (for adolescents and adults).  For children, information from the teacher can be useful.  Some clinicians get this information by having the parent ask the teacher to fill out a rating scale.  This information can be very useful if it is available.   

When diagnosing adults, it is also useful to collect information from a significant other which can be a parent for young adults or a spouse for older adults.  But when such informants are not available, diagnosing ADHD based on the patient’s self-report is valid.  As the infographic indicates, any diagnosis of ADHD should also assess for comorbid psychiatric disorders as these have implications for which ADHD medications will be safe and effective.  And because a prior history of cardiovascular disease or seizures frequently contraindicate stimulants, these must also be assessed.

REFERENCE

Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ;  http://rdcu.be/gYyV

 

Stephen_Faraone_PhD_ADHD_in_Adults
Although ADHD was conceived as a childhood disorder, we now know that many cases persist into adulthood.  My colleagues and I charted the progression of ADHD through childhood, adolescence and adulthood in our “Primer” about ADHD,
http://rdcu.be/gYyV.   Although the lifetime course of ADHD varies among adults with the disorder, there are many consistent themes, which we described in the accompanying infographic.   Most cases of ADHD start in utero, before the child is born.  As a fetus, the future ADHD person carries versions of genes that increase risk for the disorder.  At the same time they are exposed to toxic environments.  These genetic and environmental risks change the developing brain, setting the foundation for the future emergence of ADHD.  In preschool early signs of ADHD are seen in emotional lability, hyperactivity, disinhibited behavior and speech, language and coordination problems.  The full blown ADHD syndrome typically occurs in early childhood but can be delayed until adolescence.   In some cases, the future ADHD person is temporarily protected from the emergence of ADHD due to factors such as high intelligences or especially supportive family and/or school environments.  But as the challenges of life increase, this social, emotional and intellectual scaffolding is no longer sufficient to control the emergence of disabling ADHD symptoms.  Throughout childhood and adolescence the emergence and persistence of the disorder is regulated by additional environmental risk factors such as family chaos along with the age dependent expression of risk genes that exert different effects at different stages of development.  During adolescence, most cases of ADHD persist and by the teenage years, many youth with ADHD have onset with a mood, anxiety or substance use disorder.   Indeed, it is essential for parents and clinicians to monitor ADHD youth for early signs of these disorders.  Prompt treatment can prevent years of distress and disability.  By adulthood, the number of comorbid conditions has increased, including obesity, which likely has effects of future medical outcomes.   The ADHD adult tends to be very inattentive by shows fewer symptoms of hyperactivity and impulsivity.  They remain at risk for substance abuse, low self-esteem, occupational failure and social disability, especially if they are not treated for the disorder.   Fortunately, there are several classes of medicine available to treat ADHD that have been shown to be safe and effective.  And the effects of these medications are enhanced by cognitive behavior therapy as I’ve written about in prior blogs.

REFERENCE

Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ;  http://rdcu.be/gYyV

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Stephen_Faraone_PhD_ADHD_in_Adults

The Journal of Attention Disorders has published two papers about a new formulation of mixed amphetamine salts that uses a triple bead technology (MAS-TB). This technology allows for a delayed release of the medication and enables a duration of effect up to sixteen hours.

This 16-hour effect is significantly higher than existing stimulant medications which on average last for 8-10 hours. This new formulation is based on patient desire to experience beneficial medication effects from morning through evening.

Previously, Spencer et al. (https://www.ncbi.nlm.nih.gov/pubmed/19012813) reported a 7-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, dose-optimization study of 272 adults with ADHD.   They found that MAS-TB significantly reduced ADHD symptoms, behavioral measures of executive dysfunction and increased quality of life ratings. (Other studies have confirmed the benefit of select medications not only for ADHD symptoms, but for executive dysfunctions as well, although no ADHD medications treat executive dysfunction as well as they treat ADHD.)

An assessment of ADHD symptoms 13 to 16 hours post-dose confirmed the duration of action. The first new paper by Frick et al. (https://www.ncbi.nlm.nih.gov/pubmed/28413925) reported a 6 week, randomized controlled study comparing MAS-TB with placebo.   As with the prior study, MAS-TB significantly reduced ADHD symptoms. Mean ± SD pulse and systolic blood pressure increases at end of study were 3.5 ± 10.33 bpm and 0.3 ± 10.48 mmHg, which are medically non-consequential.  

In the second new study, Adler et al. (https://www.ncbi.nlm.nih.gov/pubmed/28412886) reported a long-term, open-label, safety study of MAS-TB in adults with ADHD. Of 505 enrolled participants, 266 completed the study.   Study discontinuation was more likely for patients taking higher (37.5-75 mg) vs. lower doses (12.5 and 25 mg). Blood pressure and pulse increases were observed at end-of-study. ADHD symptoms decreased modestly during the follow-up period.

The most frequently reported treatment emergent adverse events in both studies were insomnia, decreased appetite, and dry mouth. These observed side effects are similar to those seen for other stimulant medications, and are typically well managed by physicians when they occur by adjusting the dose or changing medications.