Stephen_Faraone_PhD_ADHD_in_AdultsEditor’s Note:  It is important to read the FULL Blog post.

Suicide is one of the most feared outcomes of any psychiatric condition.  Although its association with depression is well known, a small but growing research literature shows that ADHD is also a risk factor for suicidality.  

Suicide is difficult to study. Because it is relatively rare, large samples of patients are needed to make definitive statements.  Studies of suicide and ADHD must also consider the possibility that medications might elevate that risk. 

For example, the FDA placed a black box warning on atomoxetine because that ADHD medication had been shown to increase suicidal risk in youth.   A recent study of 37,936 patients with ADHD now provides much insight into these issues (Chen, Q., Sjolander, A., Runeson, B., D’Onofrio, B. M., Lichtenstein, P. & Larsson, H. (2014). Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: register based study. BMJ 348, g3769.).    In Sweden, such large studies are possible because researchers have computerized medical registers that describe the disorders and treatments of all people in Sweden.  Among 37,936 patients with ADHD, 7019 suicide attempts or completed suicides occurred during 150,721 person years of follow-up.  This indicates that, in any given year, the risk for a suicidal event is about 5%. 

 

Ask the ADHD Experts  Prescribing ADHD Medications

For ADHD patients, the risk for a suicide event is about 30% greater than for non-ADHD patients.  Among the ADHD patients who attempted or completed suicide,the risk was increased for those who had also been diagnosed with a mood disorder, conduct disorder, substance abuse or borderline personality.  This is not surprising; the most serious and complicated cases of ADHD are those that have the greatest risk for suicidal events.  

The effects of medication were less clear.   The risk for suicide events was greater for ADHD patients who had been treated with non-stimulant medication compared with those who had not been treated with non-stimulant medication.  A similar comparison showed no effect of stimulant medications. 

This first analysis suffers from the fact that the probability of receiving medication increases with the severity of the disorder.  To address this problem, the researchers limited the analyses to ADHD patients who had had some medication treatment and then compared suicidal risk between periods of medication treatment and periods of no medication treatment.  This analysis found no increased risk for suicide from non-stimulant medications and, more importantly, found that for patients treated with stimulants, the risk for suicide was lower when they were taking stimulant medications.  This protective effect of stimulant medication provides further evidence of the long-term effects of stimulant medications which have also been shown to lower the risks for traffic accidents, criminality, smoking and other substance use disorders.

Stephen_Faraone_PhD_AIA_2016_XM7MQd

Adult ADHD is a Risk Factor for Broken Bones

Although some people view the impulsivity and inattentiveness of ADHD adults as a normal trait, these symptoms have adverse consequences, which is why doctors consider ADHD to be a disorder. The list of adverse consequences is long and now we can add another: broken bones.   A recent study by Komurcu and colleagues examined 40 patients who were seen by doctors because of broken bones and 40 people who had not broken a bone.  After measuring ADHD symptoms in these patients, the study found that the patients with broken bones were more impulsive and inattentive than those without broken bones.

These data suggest that, compared with others, adults with ADHD symptoms put themselves in situations that lead to broken bones.  What could those situations be?  Well, we know for starters that ADHD adults are more likely to have traffic accidents.   They are also more likely to get into fights due to their impulsivity.   As a general observation, it makes sense that people who are inattentive are more likely to have accidents that lead to injuries.  When we don’t pay attention, we can put ourselves in dangerous situations. 

Who should care about these results?  ADHD adult patients need to know about this so that they understand the potential consequences of their disorder.  They are exposed to so much media attention to the dangers of drug treatment that it can be easy to forget that non-treatment also has consequences.  Cognitive behavior therapy is CBT_treats_Executive_Dysfunction_Free_ADHD_CME_CJkZtualso useful for helping patients learn how to avoid situations that might lead to accidents and broken bones.

This study also has an important message for insurance administrators and how they make decisions about subsidizing or reimbursing treatment for ADHD.  They need to know that treating ADHD can prevent outcomes that are costly to the healthcare system, such as broken bones.   For example, in a study of children and adolescents, Leibson and colleagues showed that healthcare costs for ADHD patients were twice the cost for other youth, partly due to more hospitalizations and more emergency room visits. 

Do these data mean that every ADHD patient is doomed to a life of injury and hospital visits?   Certainly not.  But they do mean that patients and their loved ones need to be cautious and need to seek treatments that can limit the possibility of accidents and injury.

REFERENCES

Komurcu, E., Bilgic, A. & Herguner, S. (2014). Relationship between extremity fractures and attention-deficit/hyperactivity disorder symptomatology in adults. Int J Psychiatry Med 47, 55-63.

Leibson, C. L., S. K. Katusic, et al. (2001). “Use and Costs of Medical Care for Children and Adolescents With and Without Attention-Deficit/Hyperactivity Disorder.” Journal of the American Medical Association 285(1): 60-66.

Len_Adler_AIA_ttvZJn.png.jpgEttinger AB1, Ottman R, Lipton RB, Cramer JA, Fanning KM, Reed ML. Attention-deficit/hyperactivity disorder symptoms in adults with self-reported epilepsy: Results from a national epidemiologic survey of epilepsy. Epilepsia. 2015 Jan 15. doi: 10.1111/epi.12897. [Epub ahead of print]

The purpose of this study was to examine symptoms of ADHD and resulting functional consequences in a large community cohort of individuals with epilepsy. There is a somewhat higher rate of ADHD observed in pediatric samples of ADHD, but little data exists in terms of the comparative rates of ADHD, co-morbidity and quality of life in adults with epilepsy.

This study is important because it extends the observation of higher rates of ADHD seen in studies of pediatric ADHD to adult ADHD; the observed prevalence rate of ADHD (using a proxy of being screen positive on the ASRS v1.1) was nearly three times in this population of adults with epilepsy as compared to the general population, with substantial functional consequences in these individuals. The study also highlights the need to examine adults with epilepsy for the possibility of co-morbid ADHD.

This study examined through telephone survey as part of The Epilepsy Comorbidities and Health Study (EPIC), 1361 respondents who had been told they had epilepsy and were receiving anti-epileptic drugs (AEDs). The group was divided into a likelihood of having ADHD via the ASRS v1.1 Screener, if they had a total score on these six items > 14 (ASRS v1.1 Screen positive and ASRS v1.1 Screen negative). Measures of co-morbidity included depression: the Physicians Health Questionnaire (PHQ-9), and generalized anxiety disorder: the Generalized Anxiety Disorder Assessment 7 (GAD-7). Quality of life and disability were assessed with the Quality of Life in Epilepsy Inventory 10 (QOLIE-10), Quality of Life and Satisfaction Questionnaire (Q-LES-Q) and the Sheehan Disability Scale (SDS). 251 of the 1361 (18.4%) respondents were found to be at risk for having adult ADHD (ADHD+). ASRS v1.1 Screener positive vs. negative cases were significantly more likely to have seizures and AED use, along with significantly higher depression and anxiety symptom scores. The ASRS v1.1 Screen positive cohort (controlling for covariates) had lower QoL and social functioning (Q-LES-Q) and increased family and occupational disability (SDS). Potential confounds in the data include: 1) that a formal diagnosis of adult ADHD was not obtained (just individuals at risk for the disorder (but prior trials have found that a substantial proportion of screen positive individuals when assessed, actually have adult ADHD) and 2) the possible presentation of ADHD-like symptoms from epilepsy or treatment with AEDs.

Anthony L. Rostain, MD MA - ADHD in Adults

This article reviews existing evidence for the use of locomotor activity measures in diagnosing ADHD. The authors conducted a meta-analysis of published studies on ADHD using motion measures to compare patients with ADHD with controls and then conducted a case control study using the McLean motion activity test (MMAT) on a sample of child, adolescent and adult ADHD patients (N=81) and matched controls (N=91).

Methods
The meta-analysis procedure involved searching several electronic medical databases and selecting only articles which used validated methods for diagnosing ADHD, which compared ADHD subjects to healthy controls and which reported data in ways that enabled the authors to calculate the effect sizes as measured by standardized mean differences (SMD) between study groups. A total of 18 studies were chosen, 13 of which involved actigraphy measures and 5 which used motion tracking systems. The combined sample sizes were 570 ADHD patients (305 children and adolescents and 265 ADHD adults) and 515 controls (equally divided between youth and adults). The SMD (or effect size) between ADHD subjects and controls was 0.64 using actigraphy measures and 0.92 using the motion tracking systems. The SMD or pooled effect size for youth was 0.75 and for adults was 0.73, indicating that excessive motion is seen as often in adult ADHD patients as in children and adolescents. This contradicts the prevailing view that excessive motor activity is less prominent in adults as compared to youth with ADHD.

The authors then conducted a case control study comparing ADHD patients and controls. Patients were diagnosed using a comprehensive assessment procedure consisting of structured psychiatric interviews, Conners’ rating scales and the BRIEF (a measure of executive functioning). Subjects were administered the MMAT, an infrared motion tracking system that measures the micro-movements of participants during a Go/No-Go task (15 minutes for youth and 20 minutes for adults). ADHD groups differed significantly from controls on most motion measures, with an effect size of 0.83 for adults and 0.45 for children and adolescents. Reaction time variability was also significantly greater in the ADHD sample across all ages (p<0.05). Interestingly, there were no differences in excessive motion seen among the different ADHD subtypes (combined vs inattentive vs hyperactive vs NOS).

Ask the ADHD Experts - Prescribing Medications

Conclusions
The authors conclude that locomotor hyperactivity is a core constituent feature of ADHD even in adults and across all diagnostic subtypes. They further suggest that objective locomotion measures may be useful in improving the process of diagnosing difficult cases of ADHD. While it is still premature to suggest that movement measurement devices like the MMAT are necessary for ADHD diagnosis in most patients, there is certainly a role for using them in clinical practice along with established ADHD resources. Future research will help delineate additional uses for these tools in diagnosing other neurodevelopmental disorders.

Murillo LG, Cortese S, Anderson D, DiMartino A, Castellanos FX (2015). “Locomotor activity measures in the diagnosis of attention deficit hyperactivity disorder: Meta-analyses and new findings.” Journal of Neuroscience Methods Epub ahead of print March 11, 2015. DOI: 10.1016/j.jneumeth.2015.03.001.

 

Stephen_Faraone_PhD_AIA_2016_XM7MQd.png.jpgADHD itself is associated with sleep difficulties, independent of ADHD medications. Thus, it is very important that sleep quality is assessed prior to treatment so that the changes due to treatment can be correctly inferred.

In clinical trials of stimulant medications for ADHD, insomnia is typically noted a side effect of the medications. But most of these studies have used subjective patient or parent reports of sleep quality. A new meta analysis, reviews 9 studies of a total of 246 patients enrolled in randomized controlled trials of a stimulant medication. To be included, studies must have had an objective measure of sleep quality, either polysomnography or actigraphy. The analysis showed that stimulant medications led to a) a longer time to get to sleep; b) worse sleep efficiency and c) a shorter duration of sleep. Some of these sleep measures worsened with an increasing number of doses and a shorter time on medication.
Given the adverse effects that lack of sleep can have on cognition and behavior, these data provide further impetus for clinicians, parents and patients to monitor the effects of stimulant ADHD medication on sleep and to take appropriate action (e.g., dose reduction, change of medication) as warranted.
 

REFERENCES
http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+26598454
http://www.ncbi.nlm.nih.gov/pubmed/?term=cortese%5Bau%5D+sleep%5Bti%5D+meta%5Bti%5D

Stephen_Faraone_PhD_ADHD_in_Adults

ADHD itself is associated with sleep difficulties, independent of ADHD medications. Thus, it is very important that sleep quality is assessed prior to treatment so that the changes due to treatment can be correctly inferred.

(Editor’s Note: See our Ask the ADHD Experts session on ADHD and Sleep.)

In clinical trials of stimulant ADHD medications, insomnia is typically noted a side effect of the medications. But most of these studies have used subjective patient or parent reports of sleep quality. A new meta analysis, reviews 9 studies of a total of 246 patients enrolled in randomized controlled trials of a stimulant medication.

Ask_the_ADHD_Experts_-_Prescribing_MedicationsTo be included, studies must have had an objective measure of sleep quality, either polysomnography or actigraphy. The analysis showed that stimulant medications led to a) a longer time to get to sleep; b) worse sleep efficiency and c) a shorter duration of sleep. Some of these sleep measures worsened with an increasing number of doses and a shorter time on medication.

Given the adverse effects that lack of sleep can have on cognition and behavior, these data provide further impetus for clinicians, parents and patients to monitor the effects of stimulant ADHD medication on sleep and to take appropriate action (e.g., dose reduction, change of medication) as warranted.

REFERENCES

J Am Acad Child Adolesc Psychiatry. 2009 Sep;48(9):894-908. doi: 10.1097/CHI.0b013e3181ac09c9.
Sleep in children with attention-deficit/hyperactivity disorder: meta-analysis of subjective and objective studies.
Cortese S1, Faraone SV, Konofal E, Lecendreux M.

Pediatrics. 2015 Dec;136(6):1144-53. doi: 10.1542/peds.2015-1708.
Stimulant Medications and Sleep for Youth With ADHD: A Meta-analysis.
Kidwell KM1, Van Dyk TR2, Lundahl A2, Nelson TD2.

Len_Adler_AIA_ttvZJn.png.jpgA systematic review of the literature and a meta-analysis investigating the relationship between mild traumatic brain injury (mTBI) and ADHD has been completed. The study indicates that mTBI is cerebral concussion and that there has been increasing interest from the coverage in the lay press re: the effects of mTBI in professional sports.

The authors hypothesize that individuals with ADHD commonly have a history of being risk-takers and have higher accident rates, which may predispose them to mTBI. Conversely, it has been hypothesized that mTBI could create a secondary ADHD-like condition.

The authors used reasonable inclusion criteria re: the studies included in the analyses (including being original research which examined ADHD and mTBI, used diagnostic criteria for ADHD and differentiated ADHD from learning disorders and mTBI from other types of TBI). They found five articles which met entry criteria for the meta-analysis; most, but not all, of the trials involved children.

They then examined the relative risk for one disorder being associated with the other disorder, based upon the temporal sequence of disorder onset. The authors found that there was no increased risk for TBI if ADHD occurred first.
However, if mTBI occurred first or if the temporal sequence was unclear there was about a two times elevated risk for ADHD. The overall finding of increased relative risks of ADHD and mTBI is important and highlights the need for clinicians to screen for the potential of these co-occurring disorders.
 

Reference:
J Atten Disord. 2014 Oct;18(7):576-84. doi: 10.1177/1087054714543371. Epub 2014 Jul 21. Mild traumatic brain injury and ADHD: a systematic review of the literature and meta-analysis. Adeyemo BO1, Biederman J2, Zafonte R1, Kagan E3, Spencer TJ3, Uchida M3, Kenworthy T3, Spencer AE3, Faraone SV4.

PTSD and ADHD

Lenard Adler, MD ADHD in AdultsJ Atten Disord. 2014 Feb 24. [Epub ahead of print]
The Neuropsychological Profile of Comorbid Post-Traumatic Stress Disorder in Adult ADHD.
Antshel KM, Biederman J, Spencer TJ, Faraone SV.

This study is important as it is the first investigation to examine neuropsychological deficits in individuals with ADHD and PTSD; it also adds to our increasing understanding of the increased burden of having ADHD and PTSD. Prior studies have shown that PTSD may be a vulnerability factor for developing future ADHD. These studies indicate that clinicians should be careful in screening individuals with ADHD for co-morbid PTSD and that the combination of disorders may carry a higher neuropsychological burden.

Overall the group with ADHD (whether they had PTSD or not) had significantly lower scores on the battery of neuropsychological tests; however, the group with ADHD+PTSD had lower neuropsychological test scores on a number of measures versus the group with ADHD alone (WAIS full scale IQ and block design, ROCF copy accuracy and copy time and Stroop Color T-score). Measures of quality of life were not shown to be predictors of PTSD status.

This article describes an examination of potential differences in neuropsychological functioning between a cohort of adults with ADHD (n=186), ADHD with PTSD (n=20) and a non-ADHD control group (n=123) who received psychiatric evaluations and neuropsychological tests (including WAIS intelligence, tests of frontal executive function (Wisconsin Card Sorting Test, Stroop Color and Word Test) the California Verbal Learning Test (CVLT) the Rey-Osterrieth Complex Figure Test (ROCF) and an auditory working memory continuous performance task (CPT). The group with ADHD had lower socio-economic status and were more likely to be of non-Caucausian ethnicity. Interpretation of the findings of this trial is somewhat limited by the small cohort of ADHD+PTSD patients.

Lenard A. Adler, MD, ADHD in Adults
Ettinger AB1, Ottman R, Lipton RB, Cramer JA, Fanning KM, Reed ML. Attention-deficit/hyperactivity Len_Adler_AIAdisorder symptoms in adults with self-reported epilepsy: Results from a national epidemiologic survey of epilepsy. Epilepsia. 2015 Jan 15. doi: 10.1111/epi.12897. [Epub ahead of print]

The purpose of this study was to examine symptoms of ADHD and resulting functional consequences in a large community cohort of individuals with epilepsy. There is a somewhat higher rate of ADHD observed in pediatric samples of ADHD, but little data exists in terms of the comparative rates of ADHD, co-morbidity and quality of life in adults with epilepsy.

This study is important because it extends the observation of higher rates of ADHD seen in studies of pediatric ADHD to adult ADHD; the observed prevalence rate of ADHD (using a proxy of being screen positive on the ASRS v1.1) was nearly three times in this population of adults with epilepsy as compared to the general population, with substantial functional consequences in these individuals. The study also highlights the need to examine adults with epilepsy for the possibility of co-morbid ADHD.

ASRS Professional Screener Download

This study examined through telephone survey as part of The Epilepsy Comorbidities and Health Study (EPIC), 1361 respondents who had been told they had epilepsy and were receiving anti-epileptic drugs (AEDs). The group was divided into a likelihood of having ADHD via the ASRS v1.1 Screener, if they had a total score on these six items > 14 (ASRS v1.1 Screen positive and ASRS v1.1 Screen negative). Measures of co-morbidity included depression: the Physicians Health Questionnaire (PHQ-9), and generalized anxiety disorder: the Generalized Anxiety Disorder Assessment 7 (GAD-7).

Quality of life and disability were assessed with the Quality of Life in Epilepsy Inventory 10 (QOLIE-10), Quality of Life and Satisfaction Questionnaire (Q-LES-Q) and the Sheehan Disability Scale (SDS). 251 of the 1361 (18.4%) respondents were found to be at risk for having adult ADHD (ADHD+). ASRS v1.1 Screener positive vs. negative cases were significantly more likely to have seizures and AED use, along with significantly higher depression and anxiety symptom scores. The ASRS v1.1 Screen positive cohort (controlling for covariates) had lower QoL and social functioning (Q-LES-Q) and increased family and occupational disability (SDS).

Potential confounds in the data include: 1) that a formal diagnosis of adult ADHD was not obtained (just individuals at risk for the disorder, but prior trials have found that a substantial proportion of screen positive individuals when assessed, actually have adult ADHD) and 2) the possible presentation of ADHD-like symptoms from epilepsy or treatment with AEDs.

Graziano PA, Reid A, Slavec J, Paneto A, McNamara JP, Geffken GR.  “ADHD Symptomatology andTony_Rostain_AIA-5Risky Health, Driving, and Financial Behaviors in College: The Mediating Role of Sensation Seeking and Effortful Control” Journal of Attention Disorders (2014) Epub ahead of print April. DOI: 10.1177/1087054714527792.

This study explores the relative contributions of “top-down” (i.e. effortful control) and “bottom up” (i.e. sensation seeking) mental processes to maladaptive risky behaviors in college students with ADHD.  The authors review these constructs by pointing out that effortful aspects of self-regulation involve intact prefrontal circuits underlying executive functions whereas reactive behaviors not requiring conscious mental resources are influenced by emotional stimuli and are mediated by subcortical brain structures.  Given that ADHD involves difficulties in both these domains of psychological functioning, it makes sense to explore which contribute to the onset of maladaptive risk-taking in college students with ADHD.

The authors studied 555 college students attending a southeastern university using an online survey for which they received class credit.   Participants filled out standardized rating scales to assess outcomes.  Of the total sample, 5.7% reported a history of an ADHD diagnosis and 10.8% reported elevated ADHD symptoms (> 1.5 SD above the mean) on an ADHD rating scale. There were two distinct patterns of risk behaviors: risky driving/financial behaviors and risky health behaviors.  ADHD symptoms were highly correlated with these two factors as well as with sensation seeking and effortful control.   More ADHD symptoms were associated with risky behaviors ONLY when effortful control was low.   Sensation seeking was more highly associated with risky health behaviors but not risky driving/financial behaviors. 

The authors note that the study’s reliance on self-report scales and measures limits its validity.  ADHD individuals are known to underreport severity of symptoms.  Moreover, it was not possible to detect the presence of antisocial behaviors (e.g. Conduct Disorder) that might have a greater impact on risky behaviors than ADHD symptoms.  Finally, the fact that the study was conducted on a single campus may limit the generalizability of its findings to the entire population of US college students.  (Note: Watch our Ask the ADHD Experts Session on ADHD and College Students.)

Despite these limitations, this paper reports interesting results suggesting that ADHD symptoms may not be as important as effortful control deficits and as high stimulus seeking in mediating the onset of risk behaviors in this population.    These could be important targets for psychological therapies.  It also points to the relevance of these two aspects of psychological functioning for preventive health efforts to reduce health, driving and financial risk behaviors, and for clinical approaches to dealing with patients presenting with maladaptive coping mechanisms.