Lenard A. Adler, – Page 3

mTBI and ADHD

Lenard A. Adler, on May 14, 2015

A 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.

Atomoxetine, ADHD and Executive Function Deficits

Lenard A. Adler, on April 30, 2015

Atomoxetine and the Treatment of Executive Dysfunction
ADHD Patients with Executive Dysfunction: Atomoxetine vs Placebo Studies

Although they are not included in the formal DSM-5 criteria for adult ADHD, studies have shown that clinically significant executive dysfunction can occur in one-third to one-half of all adults with ADHD. Executive functions are a set of neuropsychological parameters including: 1) working memory, 2) awareness of one’s self in the environment, 3) higher level cognitive functions of prioritization, planning and time estimation/planning and 4) emotional control. Symptoms of ADHD are separate from executive dysfunction and both should be considered in possible treatment design for the particular patient.

There have been two recent reports on the response of executive functions to the non-stimulant atomoxetine used to control ADHD symptoms. (Adler LA, Clemow DB, Williams DW, Durell TM.. Atomoxetine Effects on Executive Function as Measured by the BRIEF-A in Young Adults with ADHD: A Randomized, Double-Blind, Placebo-Controlled Study. PLoS One. 2014 Aug 22;9(8):e104175. doi: 10.1371/journal.pone.0104175. eCollection 2014. and Adler L, Tanaka Y, Williams D, Trzepacz PT, Goto T, Allen AJ, Escobar R, Upadhyaya HP, Executive function in adults with attention-deficit/hyperactivity disorder during treatment with atomoxetine in a randomized, placebo-controlled, withdrawal study. J Clin Psychopharmacol. 2014 Aug;34(4):461-6. doi: 10.1097/JCP.0000000000000138.) Both studies present data on changes in the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A, which is a 75 item, self-report clinical measure of executive function).

The first study presents the changes in BRIEF-A ratings in a study of atomoxetine (40-100 mg/day) versus placebo in young adults with ADHD. Significant effects of atomoxetine vs. placebo were seen on the major indices in the BRIEF, Global Executive Composite (GEC), Behavioral Regulation Index (BRI), and Metacognitive Index (MI), and a number of brief subscales. In other words, the non-stimulant atomoxetine had measureable effects on both ADHD symptoms and executive dysfunction when compared with the administration of a placebo.

The second trial was a randomized, withdrawal study of atomoxetine vs. placebo in patients who previously responded to an open label trial of atomoxetine. Atomoxetine significantly improved the executive function major indices and some subsets compared with placebo, which was maintained for 25 weeks or more. The executive function of patients in the placebo group worsened but did not return to baseline levels after randomization.

In both of these studies the overall effect size on measures of executive dysfunction was less than core ADHD symptoms observed for atomoxetine. Also, the effect on symptoms of emotional control subsets was somewhat less than seen on other subsets. Clinicians should be aware of co-travelling symptoms of executive dysfunction in their adult patients with ADHD and should consider whether to target these symptoms as part of the treatment plan.

PTSD and ADHD

Lenard A. Adler, on April 17, 2015

J Atten Disord. 2014 Feb 24.
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.

ADHD and Epilepsy

Lenard A. Adler, on April 16, 2015

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.

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.

Depression and ADHD Life Events

Lenard A. Adler, on March 26, 2015

This article** examines the co-occurrence of adverse life events and depression in a cohort of older adults with ADHD. The study is important as ADHD and depression are highly co-morbid in both younger and older adults. The authors examined the co-occurrence of life events as a possible link with ADHD and depression. Patients (n=230) in the Longitudinal Aging Study Amsterdam (LASA) were examined for the presence of ADHD with the DIVA (Diagnostic Interview for ADHD in Adults).

The authors found that the older adults with ADHD had significantly more depressive symptoms and life events than the older adults without ADHD. One caveat to the interpretation of this data is that non-DSM diagnostic criteria were employed. Never the less, this association of depression and life events is of interest as it may highlight another potential consequence of the inattention or impulsivity seen with ADHD and highlights the need for future study of this association.

Logistic and linear regression analyses were used to examine the relationship between ADHD symptoms, depressive symptoms and life events. Subjects with significant cognitive decline were excluded from the sample to remove this potential confound. ADHD symptom criteria were defined as having four significant symptoms of inattention and/or hyperactivity-impulsivity in the six months prior to the interview, which is more liberal than the cut-off of five significant symptoms in DSM-5 and six significant symptoms in DSM-IV; however a stricter cut-off than DSM criteria was used of requiring six symptoms of inattention and/or hyperactivity-impulsivity in childhood. Depressive symptoms were assessed with the Center for Epidemiological Studies-Depression scale (CES-D).

** E.J. Semeijn, H.C. Comijs, J.J.S. Kooij, M. Michielsen, A.T.F. Beekman, D.J.H. Deeg. The role of adverse life events on depression in older adult with ADHD. Journal of Affective Disorders. DOI: http:

ADHD and PTSD

Lenard A. Adler, on March 6, 2015

J Atten Disord. 2014 Feb 24. The Neuropsychological Profile of Comorbid Post-Traumatic Stress Disorder in Adult ADHD. Antshel KM, Biederman J, Spencer TJ, Faraone SV.

This article describes an examination of potential differences in neuropsychological functioning between a cohort of adults with ADHD (n=186), ADHD and 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).

CME LEARN HERE Improving Executive Function in Adult ADHD

Overall the group with ADHD (whether they had PTSD or not) had significantly lower scores on the battery of neuro-psychological tests than the non-ADHD controls. However, the group with ADHD and 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. Additionally, in this study, 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 and PTSD patients. Never the less, 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 that should be accounted for in making the adult ADHD diagnosis.

Driving and ADHD

Lenard A. Adler, on February 15, 2015

Zheng Chang, PhD; Paul Lichtenstein, PhD; Brian M. D’Onofrio, PhD; Arvid Sjölander, PhD; Henrik Larsson, PhD. “Serious Transport Accidents in Adults With Attention-Deficit/Hyperactivity Disorder and the Effect of Medication: A Population-Based Study” JAMA Psychiatry. doi:10.1001/jamapsychiatry.2013.4174. Published online January 29, 2014.

This study examines the association of adult ADHD with transport accidents and potential effects of ADHD treatment. The authors note that transport accidents exert a substantial burden on the world economy, such that they account for 2% of the global GNP. Untreated adult ADHD has been previously associated with increased rates of transport accidents or poor driving (increased accidents, false brakes and speeding) when adults with ADHD are examined on a driving stimulator. ADHD pharmacotherapy has also been shown to ameliorate performance on the driving simulator in these adults (Barkley RA, Cox D. J Safety Res. 2007;38(1):113-28. Epub 2007 Feb 15.) However, these studies are of relatively small sample sizes and concerns have been raised regarding potential referral bias influencing the study results.

Chang and co-authors examined over 17,000 individuals with ADHD over a four year period in the Swedish national registries. Cox proportional hazards regressions were used to examine the association between ADHD and serious traffic accidents (resulting in death or emergency room visit). Stratified Cox regressions were used within patients to examine the rates of accidents on and off medication. ADHD treatment was defined as filling a prescription for an ADHD medication within a six month period.

The study found significantly higher rates of transport accidents in men (adjusted hazard ratio, 1.47; 95%CI, 1.32-1.63) and women (1.45; 1.24-1.71) with ADHD, compared to the control group. Medication treatment was associated with a 58% risk reduction in men, but no significant risk reduction in women. The potential reasons for this gender difference is not fully known, but the 40% lower base rate of accidents in women versus men may have created a floor effect, where the base rates were lower in women to an extent which minimized potential ameliorative effects of medication. It was estimated that continuous medication treatment would have cut accident rates almost in half, presumably from positive effects on ADHD related symptoms and impairment and resulting improvement in driving (the ameliorative effects of medication on accidents is associative not causative in this trial).

This is a very important trial as it extends observations of increased motor vehicle accidents in untreated adults with ADHD to a large community based sample. It further highlights the ameliorative effects of ADHD pharmacotherapy observed in driving simulator studies to a large population based sample, which further emphasizes the importance of adults with ADHD receiving treatment. Of note, the definition of being on medication in the study, of filling a prescription in the last six months, is a fairly liberal definition of adherence to treatment; therefore, the potential beneficial effects of medication may if anything be under-estimated by this study given the long period of time individuals presumed to be treated with medication might have been off medication. Furthermore, the authors did examine whether defining medication treatment as filling a prescription within three months, would influence the findings; this tighter definition of treatment yielded similar results.

Overall adherence rates to treatment in ADHD are fairly poor, whereby most adults and young adults do not fill beyond their second prescription of psychostmulants. (Adler LD, Nierenberg AA. Review of medication adherence in children and adults with ADHD. Postgrad Med. 2010 Jan;122(1):184-91. doi: 10.3810/pgm.2010.01.2112.) It is important, given the earlier findings and results of the current study, for ADHD adults and young adults to be treated pharmacologically in periods when they are driving motor vehicles. Overall treatment principles for adults and young adults with ADHD suggest treatment throughout the day, to ensure symptomatic relief for longer periods of time during the day and especially during periods when driving (Adler LA, Barkley RA, Newcorn JH. Performance improvement CME: adult ADHD. J Clin Psychiatry. 2011 Apr;72(4):e15. doi: 10.4088/JCP.9066pi4c.). Clinicians may use the increased risk of motor vehicle accidents in untreated adults with ADHD as means of reinforcing the importance of medication adherence, when discussing adherence to pharmacotherapy with patients.

Atomoxetine and the Treatment of Executive Dysfunction

Lenard A. Adler, on January 23, 2015

DHD Patients with Executive Dysfunction: Atomoxetine vs Placebo Studies

ADHD in Older Adults

Lenard A. Adler, on January 9, 2015

Just as there have been concerns about the treatment and potential increased societal burden as we improve disease recognition with adolescents recently diagnosed with ADHD aging into adulthood, there are similar concerns as middle aged adults recently diagnosed with ADHD become older adults with ADHD. In fact, the largest percentage growth in stimulant prescriptions in the last year is in adults over the age of 50 years of age (Adler LA. ADHD in Older Adults. Paper Presentation at the Annual Meeting of the American Psychiatric Association, New York , New York, May 2014). However, there are special concerns re: the diagnosis and treatment of older adults which merit heightened attention.

The evidence basis for ADHD in older adults is quite small, when compared to the literature for childhood and adult ADHD. In fact a recent Pubmed search found 100 times fewer peer-reviewed publications on geriatric and older adults with ADHD, than for adult ADHD in general (Adler LA 2014).

The epidemiology of ADHD in older adults indicates:

Similar prevalence to overall adult ADHD
Some diminution in symptom severity with age – this is true through the lifespan, not just true with geriatric ADHD.
Impairment: Notable deficits in social interactions, which is larger than younger adults with ADHD
The diagnosis of ADHD in older adults is complicated by potential overlap with disorders of cognitive decline, such as Mild Cognitive Impairment (MCI).
Inattentive (IA) symptoms (relative to hyperactive-impulsive (HI) ones) increase with the transition from childhood to adulthood (Kessler RC. Arch Gen Psychiatry 2010). It is not clear that this pattern continues with the transition to older adulthood. It is also not clear if the number and burden of IA symptoms might be limited with retirement as individuals perform less cognitively challenging tasks.
The co-morbidities seen in adults with ADHD are similar to those seen in adult ADHD in general.
Symptoms also seem similar. However, there is some support in the literature for increasing rates of depression as adults with ADHD become geriatric adults.

A specific co-morbidity which must be addressed in the evaluation of adults for ADHD is Mild Cognitive Impairment (MCI). It is critical that physicians examine whether there are formal memory deficits. Deficits in MCI are more memory-related as compared with attentional issues seen in ADHD. Other potential issues in establishing this differential include that executive function deficits are somewhat less common in MCI as compared with ADHD in general (except for amnestic MCI).

The time courses of the illnesses differ with an older onset in life for MCI, while ADHD is more or less present throughout the lifespan. A MMSE may be quite helpful in establishing whether memory deficits are present, or formal neuro-psychological testing can be obtained to further delineate the presence of memory vs. attentional issues.

There are special treatment considerations for older adults with ADHD. ADHD medications should be used carefully, with regular cardiovascular monitoring and consultation with primary care physicians as all FDA approved medications for adult ADHD (sustained release stimulants and atomoxetine) have a small risk for increasing the heart rate (on the average 5 beats/minute) and blood pressure (on the average 3 mm Hg); this is especially important as geriatric adults have higher rates of cardiovascular illness and hypertension. Geriatric adults with ADHD should also be monitored for potential agitation or activating effects of the medication.

In conclusion, just as ADHD persists from the transition from adolescence into young adulthood, it also persists in the transition to older adulthood. As always, clinicians should perform careful clinical evaluations and establish appropriate treatment programs, taking into account the special issues involved with the older adults.

Diagnosing and Monitoring ADHD

Lenard A. Adler, on December 8, 2014

The American Academy of Pediatrics (AAP) published guidelines for the diagnosis and treatment of ADHD, which include using DSM-IV criteria to evaluate ADHD, using rating scales from multiple sources to assist in making the diagnosis and monitoring for treatment effects and side effects and inclusion of psychosocial treatment paradigms in treatment recommendations (American Academy of Pediatrics. (2000). Clinical practice guideline: Diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics, 105, 1158–1170. http://dx.doi.org/10.1542/peds.105.5.1158.) This just published study by Epstein and colleagues examined the rates of evidence based care and potential sources of clinician and patient centered variability in a chart review of over 1500 patients, 188 pediatricians in 50 different practice settings in Ohio since the publication of the AAP guidelines for ADHD. The authors found:

Diagnosis: There was an underutilization of parent and teacher rating scales in making the ADHD diagnosis (occurring in slightly over 55% of the sample); about 30% of the patients did not fulfill DSM-IV criteria for ADHD.

Treatment Initiation: Medications were used in the vast majority of cases (93.4%); psychosocial treatments were not commonly recommended or used (13% of the time). Less than ½ the sample had a visit or a phone call with the pediatrician’s office within the first month of starting treatment.

Monitoring Treatment: Only 10% and 8% of the charts indicated that parent or teacher rating scales, respectively, were used to assess treatment response or side effect. The average time to collection of these scales was quite long – over a year from the time of treatment initiation.

Practice Variables: Urban and rural practices used psychosocial treatments more commonly than suburban ones, while suburban practices had shorter times for follow up visits after starting treatment than urban practices.

The authors concluded that there is a need to improve the quality of ADHD care in the pediatric practices they surveyed. Advances could be achieved in applying DSM criteria for ADHD, using rating scales from parents and teachers and using psychosocial treatments. They suggest that improvements could be made in terms of education and the use of technology in the practice and patient level.

Even though this study was of pediatric PCPs (pediatricians), it has significant implications for the treatment of adults with ADHD by PCPs. As there are no US practice guidelines for adults with ADHD, there is a clear need to educate PCPs about the appropriate use of the DSM for diagnosis and rating scales to monitor ADHD adults during treatment. The above study does not address the issue of whether the cost of potential psychosocial treatments might create a barrier to their use, which could also be the case for adult ADHD (along with a smaller network of providers of these treatments for adults as compared to children). The study did not assess the consequences of failing to document and monitor treatment efficacy and side effects. The need for ongoing monitoring of patients with ADHD is certainly important when using stimulant and non-stimulant medications.

Source:

Variability in ADHD Care in Community-Based Pediatrics, Jeffery N. Epstein, Kelly J. Kelleher, Rebecca Baum, William B. Brinkman, James Peugh, William Gardner, Phil Lichtenstein and Joshua Langberg. Pediatrics; originally published online November 3, 2014; DOI: 10.1542/peds.2014-1500.