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September 13, 2024

Population Study: Stimulants Shown to Reduce Hospitalization and Suicidality

Swedish Population Study Suggests Stimulants Reduce Hospitalization and Suicidality, Have No Significant Effect on Work Disability

A meta-analysis of short-term, placebo-controlled, randomized clinical trials (Cortese et al. 2018), looking at both efficacy and safety, supported prescribing stimulants – methylphenidate use in children and adolescents and amphetamine use in adults – as first-choice medications. 

However, these were short-term studies, and they focused on relieving ADHD symptoms. What about longer-term outcomes, especially looking more broadly at functional impairment and overall quality of life? 

Sweden has a single-payer health insurance system that encompasses virtually every resident and is linked to national registers that enable researchers to conduct nationwide population studies. 

A joint Finnish-Swedish research team used Sweden’s registers to study outcomes for all individuals of working age, 16 to 65 years old, living in Sweden who had received a diagnosis of ADHD from 2006 through 2021. The resulting study cohort encompassed 221,714 persons with ADHD. 

The team adjusted for the following confounding variables: Genetics, baseline severity of symptoms, baseline comorbidities, temporal order of treatments (which medication was used as first, second, third, and so forth, including also nonuse of ADHD medications), time since cohort entry, and time-varying use of psychotropic drugs, including antidepressants, anxiolytics, hypnotics, mood stabilizers (carbamazepine, valproic acid, and lamotrigine), lithium, antipsychotics, and drugs for addictive disorders. 

With these adjustments, they discovered that amphetamine treatment was associated with a roughly 25% reduction in psychiatric hospitalization relative to unmedicated ADHD. Lisdexamphetamine was associated with a roughly 20% reduction, dexamphetamine with a 12% reduction, and methylphenidate with a 7% reduction. All four medications are stimulants

None of the non-stimulant medications – atomoxetine, guanfacine, clonidine – had any significant effect on psychiatric hospitalization. Nor did modafinil a drug that is not FDA approved for ADHD but is sometimes used when other drugs fail. 

Amphetamine was also associated with the greatest reduction in suicide attempts or deaths, with a roughly 40% decline relative to unmedicated ADHD. Dexamphetamine was associated with a roughly 30% decline and lisdexamphetamine with a roughly 25% decline. The stimulant methylphenidate was only associated with an 8% reduction, and modafinil had no significant effect. 

Surprisingly, non-stimulant medications were associated with significant increases in suicide attempts or deaths: 20% for atomoxetine, 65% for guanfacine, and almost double for clonidine

Amphetamine and lisdexamphetamine also reduced the risk of nonpsychiatric hospitalization by more than a third compared to unmedicated ADHD. Dexamphetamine was associated with a risk reduction of more than 25%, methylphenidate with 20% lesser risk.  

The non-stimulant atomoxetine was associated with a roughly 15% reduction in risk of nonpsychiatric hospitalization. But neither guanfacine nor clonidine had any significant effect. 

Turning to work disability, atomoxetine was the only ADHD medication associated with a reduction – a roughly 10% improvement. All other medications had no significant effect

The team concluded, “In this cohort study of adolescents and adults with ADHD, the use of medications for ADHD, especially lisdexamphetamine and other stimulants, was associated with decreased risk of psychiatric hospitalizations, suicidal behavior, and nonpsychiatric hospitalizations during periods when they were used compared with periods when ADHD medication was not used. Non-stimulant atomoxetine use was associated with decreased risk of work disability.” 

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Addressing the challenge of under-diagnosed adult ADHD

Addressing the challenge of under-diagnosed adult ADHD

There is a well-documented gap between the known prevalence of adult ADHD and rates of diagnosis and treatment. In Germany, epidemiological studies of nationally representative community samples have found prevalence rates ranging from 3.1% to 4.7%. Yet, studies of publicly insured individuals aged 18 to 69 years old report rates of diagnosed ADHD between 0.04% and 0.4%. So, even in a country with universal health insurance, more than nine out of ten adults with ADHD go undiagnosed.

Many factors contribute to under-diagnosis: stigma, culturally influenced perceptions, and lack of motivation by those affected. Another crucial factor is the lack of recognition of ADHD symptoms by clinicians.

A research team surveyed 144 psychologists, 32 physicians, and two occupational therapists. Almost three in five participants were psychotherapists, a quarter were neuropsychologists, and one in seven were psychiatrists.

Four out of five clinicians stated they had received only a few hours of ADHD-specific training. One in four stated they had not examined guidelines for diagnosing ADHD. A lack of formal training among the vast majority, and unfamiliarity with current diagnostic guidelines in a significant minority, were surprising findings among clinicians who regularly work with adults with ADHD.

Many clinicians had difficulty identifying core features of adult ADHD as defined by the DSM-5 and International Classification of Diseases, Tenth Revision (ICD-10). Roughly one in five stated that hyperactivity had little relevance to adult ADHD. The only core feature correctly identified by more than half the respondents was having difficulties concentrating. Impairments in social behavior or aggression and memory impairment were not identified as being clearly relevant or irrelevant to adult ADHD.

The authors concluded that these findings appear to indicate some uncertainty or at least a lack of consensus among clinicians about what symptoms are relevant to ADHD in adulthood, and it is likely that this uncertainty contributes to diagnostic inaccuracy.

Most respondents reported using self-report scales of ADHD symptoms and using unstructured interviews. While slightly more than half agreed that collateral reports are important to diagnosis, only about a third reported regularly using them. This is a problem given the limited accuracy of self-reported childhood symptoms for documenting the childhood-onset of the disorder. Semi-structured interviews are also known to improve the accuracy of diagnosis, but are rarely used in clinical practice.

Over half of psychologists and a quarter of physicians reported using cognitive or neuropsychological testing, even though this is at variance with German (and other) guidelines, which specify that such testing is suitable for clarifying strengths and weaknesses, but not for ruling out or confirming a diagnosis of ADHD. The European Consensus Statement also states that cognitive/neuropsychological testing should only be used as a secondary or supplementary assessment tool.

While three out of four clinicians recommended stimulant drug treatment, psychologists tended to be more hesitant to do so. This is likely because German psychologists receive little training in pharmacotherapy, and do not have prescription privileges. Given the demonstrated efficacy of stimulant treatment, this points to a need to better educate psychologists in this regard.

Almost three in four respondents cited a lack of clinician knowledge and experience as a barrier to ADHD diagnosis. Most clinicians also stated they were either uncertain or only somewhat certain of their ability to diagnose ADHD. That suggests that more extensive ADHD-specific training is needed.

A limitation of the survey was the relatively low participation by physicians. It is also likely that the findings are not reflective of practices in ADHD specialty clinics.

The authors concluded, Further training is needed to improve clinicians' understanding of ADHD in adulthood and to align diagnostic practices with guideline recommendations. Whereas discrepancies between respondents regarding the relative importance of peripheral symptoms (e.g., memory problems) were most common, a lack of consensus was found even for core symptoms listed by diagnostic criteria. Particularly among psychologists improved awareness regarding the benefits of stimulant medications is needed to bring their treatment recommendations in line with evidence-based guidelines.

September 22, 2023
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Trigeminal nerve stimulation may be an effective non-drug treatment for ADHD

Trigeminal nerve stimulation may be an effective non-drug treatment for ADHD

A University of California at Los Angeles (UCLA) team has just reported on the first-ever, double-blinded, sham-controlled study of trigeminal nerve stimulation (TNS) for treating ADHD. The trigeminal nerve is the largest cranial nerve. It enables facial sensation, as well as biting and chewing.

Over four weeks, researchers fitted 62 eight-to-twelve-year-old children with electrodes while they slept; 32 got an active low current, the rest none at all. The active and sham setups were identical in appearance. The children were told, pulses may come so fast or so slowly that the nerves in the forehead might or might not detect a sensation. After the four weeks, there was an additional-blinded week without intervention.

The primary efficacy outcome measure was the clinician-completed ADHD-RS total score, derived from parent interviews and available clinical information. It was completed at the onset of the study, and repeated over subsequent weeks. The Clinical Global Impression (CGI) score was used as a secondary outcome measure.

Both groups of children showed significant reductions in ADHD symptoms over the first week. But University of California at Los Angeles (UCLA) teams leveled off during the remaining three weeks for the group with sham treatment, while scores continued to decline for those in the group with actual stimulation. The standardized mean difference (SMD) between groups was 0.5.

By the conclusion of week 4, 52 percent of those in active treatment were improved or very much improved, as indicated by CGI scores; only a 14percent did as well with the sham treatment. The number needed to treat was just 3.

After discontinuation of treatment, total scores in both groups rose at similar rates. At the end of week 5, CGI ratings for active treatment showed 13 percent improvement over baseline, versus 7 percent for sham treatment. The SMD was 0.46, once again indicating the persistence of a medium effect size a week after treatment cessation.

The effect sizes computed for TNS are roughly comparable to effect sizes for non-stimulant medication, but less than those for stimulants.

Though the active group had significant gains in weight and pulse over the sham group, there were no serious adverse events in either group.

The authors concluded: Results from the Early Impressions Questionnaire showed no differences in outcome expectations between treatment groups after 1 week of using the randomized device, suggesting that our sham procedures successfully accomplished double-blinding of group assignment. Improvements seen in the active and sham groups at week 1 likely reflect some placebo response secondary to the high level of parental involvement in administering treatment. Nonetheless, a further improvement over subsequent weeks with active TNS suggests the emergence of true treatment effects TNS is a non-medication, minimal-risk intervention with proven efficacy in alleviating ADHD symptoms. Although the present study finds that only slightly more than half of those receiving therapy have clinically meaningful improvement, the virtual lack of significant side effects should make it a popular treatment choice for many patients with ADHD, particularly for parents who prefer to avoid psychotropic medication.

Nevertheless, one must keep in mind that this is a single uncomplicated study with a small sample size. Further, studies with larger numbers of participants are needed, both to confirm the efficacy and to further explore the weight gains and higher pulse rates in the treatment group.

August 31, 2021
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Meta-analysis Finds Association Between ADHD and Suicidal Behaviors

Meta-analysis finds association between ADHD and suicidal behaviors

A newly published meta-analysis of 57 studies encompassing almost a third of a million participants has uncovered a very strong association between ADHD and suicide, a strong association with suicidal ideation, and a small-to-medium association with suicide attempts.

The population examined included children, adolescents, and adults. Only persons formally diagnosed were considered to have ADHD. Studies that included self-injuries without suicidal intent were excluded. Most of the studies focused on European and American populations, with one in six from other locations, mostly Asian.

The most striking result was for actual suicides. The odds ratio (OR) for four datasets encompassing roughly one hundred forty thousand participants was 6.69 (95% CI 3.24 to 17.39, p <.0001). As a frame of reference, an OR of 1.5 is a small effect size, 2.5 is a medium one, and 4.3 is a large one. That means the effect size, in this case, is very large.

For suicidal ideation, 23 datasets with a combined total of just over 73,000 participants produced a medium-to-large OR of 3.5 (95% CI 2.94 to 4.25, p < .0001). In three datasets with more than nine thousand participants that adjusted for confounders, the adjusted OR was 4.5 (95% CI 1.72 to 11.63, p < .0001), indicating a large effect size.

For suicide attempts, 44 datasets encompassing over 228,000 participants produced an OR of 2.4 (95% CI1.64 to 3.43, p < .0001). In six datasets with over 65,000 participants that adjusted for confounders, the adjusted OR dropped to 2.1 (95% CI 1.27 to 3.47,p = .005).

There was no evidence of publication bias for studies on suicides or suicidal ideation, but significant evidence of bias for studies on suicide attempts (Eager's p = .03). This means that studies with positive findings were more likely to be published than negative studies.

There was, however, strong statistical evidence for differences between studies in the size of their ORS.  This indicates that the pooled OR cannot summarize results from all datasets, and more work is needed to clarify why the ORS differs among studies.

The authors appropriately caution that their meta-analysis is not informative on cause-effect relationships, but offer as a hypothesis that ADHD contributes to suicidal spectrum behaviors (SSBs) through Impulsivity, a core symptom of ADHD, along with impaired decision-making and risk-taking, that characterize several individuals with ADHD Additionally, a sizeable portion of individuals with ADHD present with deficits in executive functions. As executive functions are implicated in the regulation of impulse control and emotions, executive dysfunctions may contribute to SSBs.

Given the large to very large effect sizes for suicide and suicidal ideation, the authors advise: Awareness of this association should prompt practitioners to systematically screen for SSBs in patients with ADHD at the first assessment and at each follow-up, which in turn should contribute to decreasing the risk of SSB's. This is particularly noteworthy considering that questionnaires/scales commonly used to screen/assess ADHD symptoms generally do not include suicide-related items.

August 29, 2021
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Stigma: Public attitudes towards children and adults with ADHD

Stigma: Public attitudes towards children and adults with ADHD

To gauge the extent of stigma towards persons with ADHD, a European research team hired a company specialized in market and social research to conduct a poll of some five thousand randomly selected Germans. Just over a thousand completed the interview, representing a response rate of only one in five. The team acknowledged, “Although non-responder bias has to be considered to be important, ethical considerations prohibited the collection of any detailed information on non-respondents.” The sample had slightly more women and elderly persons, and a higher average level of educational attainment relative to the German population as a whole. Sampling weights were used to compensate for these discrepancies.

The poll relied on computer-assisted telephone interviews. Interviews began with prerecorded vignettes of either a 12-year-old child or 35-year-oldadult exhibiting core symptoms of ADHD (such as “careless mistakes in schoolwork,” “does not follow through on instructions,” “easily distracted by extraneous stimuli”, “loses things”, “leaves his place in the classroom or when sitting at the dining table”). Half of those interviewed were presented with child vignettes, and half with adult vignettes. The gender of the person described varied randomly.

On a scale of one to five, respondents were asked to indicate levels of agreement with two statements: 1. ‘‘Basically, we are all sometimes like this person. It’s just a question of how pronounced this state is.’’ 2. “All in all, the problems of Robert / Anne are abnormal.” For both child and adult vignettes, two out of three respondents agreed that “we are all sometimes like this person.” One in three respondents considered the problems depicted in the child vignettes as abnormal. That dropped to one in four in the adult vignettes.

Next, respondents were asked whether they ever had a problem like this, and whether someone among their family or close friends ever had to deal with such a problem. For both vignettes, one in four acknowledged having had a problem like this, and half said a close friend or family member had such a problem.

On the assumption that “negative emotional reactions are an important consequence of negative stereotypes, leading to separation, discrimination and status loss,” respondents were probed for their specific emotional reactions. “I feel annoyed,” “I react angrily,” and “provokes my incomprehension” were interpreted as indicating varying levels of anger.“Provokes fear” and “Makes me feel insecure” were seen as indicating fear. “I feel uncomfortable” was viewed as indicating somewhere between fear and anger. On the other hand, “I feel the need to help,” “I feel pity,” and “I feel sympathy” were interpreted as “pro-social” responses.

Pro-social reactions were by far the most common. Over two-thirds felt a need to help a child, and over half to help an adult, in such a situation. In both instances, almost half felt sympathy, and a half or more felt pity. On the other hand, a quarter of respondents in each case felt annoyed, and just under one in five felt uncomfortable. Almost one in seven reacted angrily to the child vignette, and almost one in six to the adult vignette. Fear was the least frequent emotional reaction.

In the case of adults, respondents were also asked about their willingness to accept the person described in the vignette in seven social situations:

·        Working together
·        As a neighbor
·        Marrying into the family
·        Introducing to a friend
·        Renting a room
·        Recommending for a job
old adult·        Taking care of chi

While three out of four respondents were willing to accept such persons as co-workers, only one in three would recommend them for a job. Two out of three would accept such persons as neighbors, and almost as many to marry into the family. Three out of five would very willingly introduce such persons to friends. Slightly over half would rent a room to them. But less than one in three would be willing to have such individuals take care of their own children.

Older respondents were more likely to see the problems as“abnormal” and to seek greater social distance. Women, and respondents with higher levels of education, were less likely to see the problems as abnormal and more likely to respond in pro-social ways.

Though showing most Germans to be accepting of persons with ADHD, these findings still indicate a significant degree of stigma, though less than for other psychiatric conditions such as depression, schizophrenia, or alcohol dependence.

August 27, 2021
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Exploring The Long-term Effects of Treating ADHD with Methylphenidate

Are there adverse effects to long-term treatment of ADHD with methylphenidate?

Methylphenidate (MPH) is one of the most widely-prescribed medications for children. Given that ADHD frequently persists over a large part of an individual's lifespan, any side effects of medication initiated during childhood may well be compounded over time. With funding from the European Union, a recently released review of the evidence looked for possible adverse neurological and psychiatric outcomes.

From the outset, the international team recognized a challenge: ADHD severity may be an important potential confounder, as it may be associated with both the need for long-term MPH therapy and high levels of underlying neuropsychiatric comorbidity. Their searches found a highly heterogeneous evidence base, which made meta-analysis inadvisable. For example, only 25 of 39 group studies reported the presence or absence of comorbid psychiatric conditions, and even among those, only one excluded participants with comorbidities. Moreover, in only 24 of 67 studies was the type of MPH used (immediate or extended-release) specified. The team, therefore, focused on laying out an evidence map to help determine priorities for further research.

The team found the following breakdown for specific types of adverse events:

·        Low mood/depression. All three non-comparative studies found MPH safe. Two large cohort studies, one with over 2,300 participants, and the other with 142,000, favored MPH over the non-stimulant atomoxetine. But many other studies, including a randomized controlled trial (RCT), had unclear results. Conclusion: the evidence base regarding mood outcomes from long-term MPH treatment is relatively strong, includes two well-powered comparative studies, and tends to favor MPH.

·        Anxiety. Here again, all three non-comparative studies found MPH safe. But only two of seven comparative studies favored MPH, with the other five having unclear results. Conclusion: while the evidence about anxiety as an outcome of long-term MPH treatment tends to favor MPH, the evidence base is relatively weak.

·        Irritability/emotional reactivity. A large cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: the evidence base is limited, although it includes one well-powered study that found in favor of MPH over atomoxetine.

·        Suicidal behavior/ideation. There were no non-comparative studies, but all five comparative studies favored MPH. That included three large cohort studies, with a combined total of over a hundred thousand participants, that favored MPH over atomoxetine. Conclusion: the evidence base is relatively strong, and tends to favor MPH.

·        Bipolar disorder. A very large cohort study, with well over a quarter-million participants, favored MPH over atomoxetine. A much smaller cohort study comparing MPH with atomoxetine, with less than a tenth the number of participants, pointed toward caution. Conclusion: the evidence base is limited and unclear, although it includes two well-powered studies.

·        Psychosis/psychotic-like symptoms. By far the largest study, with over 145,000 participants, compared MPH with no treatment, and pointed toward caution. A cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: These findings indicate that more research is needed into the relationship between ADHD and psychosis, and into whether MPH moderates that risk, as well as research into individual risk factors for MPH-related psychosis in young people with ADHD.

·        Substance use disorders. A cohort study with over 20,000 participants favored MPH over anti-depressants, anti-psychotics, and no medication. Other studies looking at dosages and durations of treatment, age at treatment initiation, or comparing with no treatment or alternative treatment, all favored MPH except a single study with unclear results. Conclusion: the evidence base is relatively strong, includes one well-powered study that compared MPH with antipsychotic and antidepressant treatment, and tends to favor MPH.

·        Tics and other dyskinetic. Of four non-comparative studies, three favored MPH, the other, with the smallest sample size, urged caution. In studies comparing with dexamphetamine, pemoline, Adderall, or no active treatment, three had unclear results and two pointed towards caution. Conclusion: more research is needed regarding the safety and management of long-term MPH in those with comorbidities or tic disorder.

·        Seizuresor EEG abnormalities. With one exception, the studies had small sample sizes. The largest, with over 2,300 participants, compared MPH with atomoxetine, with inconclusive results. Two small studies found MPH safe, one had unclear results, and two others pointed towards caution. Conclusion: While the evidence is limited and unclear, the studies do not indicate evidence for seizures as an AE of MPH treatment in children with no prior history more research is needed into the safety of long-term MPH in children and young people at risk of seizures.

·        Sleep Disorders. All three non-comparative studies found MPH safe, but the largest cohort study, with over 2,300 participants, clearly favored atomoxetine. Conclusion: more research is needed into the relationship between ADHD, sleep, and long-term MPH treatment.

·        Other notable psychiatric outcomes. Two noncomparative studies, with 118 and 289participants, found MPH safe. A cohort study with over 700 participants compared with atomoxetine, with inconclusive results. Conclusion: there is limited evidence regarding long-term MPH treatment and another neuropsychiatric outcome, and that further research may be needed into the relationship between long-term MPH treatment and aggression/hostility.

Although this landmark review points to several gaps sins in the evidence base, it mainly supports prior conclusions of the US Food antidrug Administration (FDA) and other regulatory agencies (based on short-term randomized controlled trials) that MPH is safe for the treatment of ADHD in children and adults.  Given that MPH has been used for ADHD for over fifty years and that the FDA monitors the emergence of rare adverse events, patients, parents, and prescribers can feel confident that the medication is safe when used as prescribed.

August 25, 2021
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Outcomes of Mindfulness-Based Interventions on Adults with ADHD

Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with ADHD

A Canadian team has published a systematic review examining the effectiveness of Mindfulness-Based Interventions (MBIs) for treating adults with ADHD. MBIs usually involve three forms of meditation “ body scan, sitting meditation, and mindful yoga “ that are intended to cultivate nonjudgmental awareness of the present-moment experience. The team reviewed thirteen studies.

Three were single-group studies with no control group. One used dialectical behavior therapy (DBT). It reported mild to moderate improvements in ADHD symptoms, and substantial improvements in neurocognitive function (with standardized mean difference effect sizes from .99 to 2.22). A second enrolled both adults and adolescents in a mindful awareness program (MAP)which included a psychoeducational component. It found improvements in itself-reported ADHD symptoms, with standardized mean difference (SMD) effect sizes running from .50 to.93. Following training, it also reported improvement in attentional conflict (.93) set-shifting (.43). The third study also used DBT, which focused on acceptance, mindfulness, functional behavioral analysis, and psychoeducation. ADHD symptoms showed mild improvement (.22), and functional impairment was slightly reduced (.15) and remained stable at the 3-month follow-up.

The other ten studies used control groups. One used MAP and carefully stratified participants based on their ADHD medication status, then randomly assigned them to mindfulness treatment or waitlist. It reported large effect sizes in the improvement of self-reported and clinician ratings of ADHD symptoms (1.35 to 3.14), executive functioning (1.45 to 2.67), and self-reported emotion regulation (1.27 to 1.63). Another study non randomly assigned adults to either mindfulness-based training (MBT) or skills training. Effect sizes were small to medium (.06 to .49), with 31% of MBT participants showing some improvement, versus only 11% of skills training participants.

Another study involved a controlled trial of college students with ADHD, randomized to receive either MBT or skills treatments. Treatment response rates were higher for MBT (59-65%, vs. 19-25%). In follow-up, the effect size for MBT on ADHD symptoms was large (.84), and similarly large on executive functioning (.81).

Another study tried a year's worth of mindfulness training for poor responders to medication. Participants who received the treatment were compared to others who were waitlisted. The study reported a medium effect size(.63) in reducing the severity of ADHD.

Another looked at the impact of MAP on affective problems and impaired attention. It compared adults with ADHD and healthy controls who participated in MAP sessions with similar patients and controls who did not. The authors reported that MAP improved sustained attention and mood, with medium to large effect sizes (.50 to .80).

A recent study explored the impact of MAP on neurocognitive performance with a randomized controlled trial. Following an 8-week mindfulness training, researchers found a significant decrease in ADHD symptoms and significant improvement in task performance in both the MAP and the psychoeducation comparison group post- versus pre-intervention but did not find evidence for a significant main effect of treatment or a significant interaction effect on any ADHD symptoms (self-and observer-rated) nor on task performance (WM).

Another study randomly assigned adults with ADHD either to the waitlist or mindfulness-based cognitive therapy (MBCT). It found that MBCT led to a medium-to-large reduction in self-reported ADHD symptoms (.64) and a large reduction in investigator-reported symptoms (.78). It also found large(.93) improvements in executive functioning.

An 11th study looked at the effects of MBCT on neuropsychological correlates (event-related potentials (ERPs)) of performance monitoring in adults with ADHD. Half the patients were randomly assigned tomb cut, and the other half to the waitlist. MBCT produced reduced inattention, hyperactivity/impulsivity, and global ADHD index symptoms with medium to large effect sizes (.49 to .93).

A 12th study randomly assigned college students to MBCT or waitlist. At follow-up, participants who had received MBCT exhibited large (1.26) reductions in ADHD symptoms as well as greater treatment response rates (57%-71% vs. 23%-31%) versus waitlist. They also registered a greater improvement in most neuropsychological performance and attentional scores.

Finally, another study compared the efficacy of MBCT plus treatment as usual (TAU) versus TAU only in reducing core symptoms in adults with ADHD. Participants were randomly assigned to an 8-weekly group therapy including meditation exercises, psycho-education, and group discussions, or TAU only, including pharmacotherapy and/or psychoeducation. At 6-month follow-up, MBCT+TAU patients reported large (SMD = .79) improvements in ADHD symptoms relative to patients.

Overall, these are promising results of mindfulness-based interventions, and all the more so for those who do not respond well to drug therapy. Nevertheless, they must be seen as tentative. The total of participants overall in thirteen studies was just 753, or an average of only 58 per study. There was too much variation in the studies to perform a meta-analysis. Only one of the studies included a healthy (non-ADHD) control group. And only one study received a perfect score from Cochrane Collaboration standards.  Most studies did not use a suitable control group, i.e., one in which there was an expectation of benefit from participating.  As the authors noted, "Attrition bias was found to have high or unclear risk in more than a half of the studies. The reason for dropout of participants was not always clearly specified in those studies, so it is difficult to decide if it might be related to adverse effects or some discomfort with treatment or instead to some incidental reasons."

August 23, 2021
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Can ADHD be Treated With Mindfulness-Based Interventions?

How effective are mindfulness-based interventions in treating attention deficit symptoms?

Mindfulness has been defined as intentionally directing attention to present moment experiences with an attitude of curiosity and acceptance. Mindfulness-based interventions (MBIs) aim to improve mindfulness skills.

A newly-published meta-analysis of randomized controlled trials (RCTs) by a team of British neurologists and psychiatrists explores the effectiveness of MBIs in treating a variety of mental health conditions in children and adolescents. Among those conditions is the attention deficit component of ADHD.

A comprehensive literature search identified studies that met the following criteria:

1)     The effects of mindfulness were compared against control conditions “either no contact, waitlist, active, or attention placebo. The waitlist means the control group receives the same treatment after the study concludes. Active control means that a known, effective treatment (as opposed to a placebo) is compared to an experimental treatment. Attention placebo means that controls receive a treatment that mimics the time and attention received by the treatment group, but is believed not to have a specific effect on the subjects. Participants were randomly assigned to the control condition.
2)     The MBI was delivered in more than one session by a trained mindfulness teacher, involved sustained meditation practice, and was not mixed in with another activity such as yoga.

Eight studies evaluating attention deficit symptoms, with a combined total of 1,158 participants, met inclusion criteria. The standardized mean difference (SMD) was 0.19, with a 95% confidence range of 0.04 to 0.34 (p= .02). That indicates a small effect size for MBIs in reducing attention deficit symptoms. Heterogeneity was low (I2 = 35, p = .15), and teenager test showed little sign of publication bias (p = 0.42).

When looking only at studies with active controls, five studies with a total of 787 participants yielded an SMD of 0.13, with a 95%confidence interval of -0.01 to 0.28 (p = .06), indicating a tiny effect size that failed to reach significance. Active controls most commonly received health education, with a few receiving social responsibility training or Hath a yoga.

Overall, this meta-analysis suggests limited effectiveness, especially when compared with active controls.  If MBIs are effective for ADHD, their effect on symptoms is very small.  Thus, such treatments should not be used in place of the many well-validated, evidenced-based therapies available. Whether longer periods of MBI (training times varied between 2 and 18 hours spread out over 2to 24 weeks) might result in greater effect sizes remains unexplored.

August 21, 2021
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Link Found Between ADHD Risk Genes and Reduced Estimated Life Expectancy

Association found between ADHD risk genes involved in dopamine signaling and reduced estimated life expectancy

Behavioral disinhibition is a trait associated with both ADHD and several genes that affect dopamine signaling. A new study by three American medical researchers set out to examine how these ADHD risk genes - DRD4 (dopamine 4 receptor density), DAT1 (dopamine 1 transporter), and DBH(dopamine beta-hydroxylase) - affect estimated life expectancy in young adulthood.

The method used was a longitudinal study of 131 hyperactive children and 71 matched controls through early adulthood. The original evaluations were done in 1979-1980, when both groups were children in the 4 to 12 age range. They were reevaluated in1987-1988 as adolescents aged 12 to 20. The next follow-up was in 1992-1996 in early adulthood, aged 19 to 25. The final follow-up was in 1998-2004, for adults aged 24 to 32. All agreed to physical examinations that formed the basis for calculating estimated life expectancy using actuarial tables that factor in the effects of smoking, body mass index, alcohol, and other risk factors of on expected longevity. Participants also provided blood samples that enabled gene typing.

For the DAT1 gene, participants who had the homozygous-repeat allele (9/9) had a five-year reduction in estimated life expectancy relative to those with the ten-repeat allele (10/10). Those with the intermediate (9/10) configuration had a three-year reduction in estimated life expectancy.

For the DBH Taq1 gene, those with a heterozygous (A1/A2) combination had almost a three-year reduction in estimated life expectancy relative to those with homozygous (A1/A1 or A2/A2)configurations.

For DRD4, on the other hand, no significant differences were found in estimated life expectancy.

In a related study, several background traits were found to be significantly predictive of variance estimated life expectancy. The largest of these was behavioral disinhibition, followed by verbal IQ, self-rated hostility, and a nonverbal fluency test. But no significant differences were found between any of the gene polymorphisms on any of these four measures, indicating that the present gene associations were independent of the background traits.

The researchers next sought to determine which variables used in the estimated life expectancy calculations were associated with the two significant genes. For DBH, one variable stood out. Those with the A1/A2 heterozygous pairings had almost twice the alcohol consumption of those with homozygous pairings (p = 0.023).

For DAT1, two variables stood out. Overall, the 9/9 pairings smoked two and a half times as much as the 10/10pairings, with the 9/10 pairings midway between the extremes (p = 0.036). They were also 73 percent more likely to be smokers relative to the 10/10 pairings, and 61 percent more likely relative to the 9/10 pairings. They also had significantly less education than the 10/10 pairings, with the 9/10 pairings again being intermediate (p = 0.027).

An obvious limitation of the study was its small sample size. The authors cautioned, our findings should be considered quite preliminary and in need of much greater research before being given much weight in the literature or public policy.

"With these limitations in mind, they concluded, the present study demonstrated that two ADHD risk genes (DB Hand DAT1) independently contributed to a reduction in ELE [estimated life expectancy] beyond the second-order variables of behavioral disinhibition, IQ, hostility, and nonverbal fluency that contributed in the related study to variation in ELE. The gene polymorphisms seemed to be influencing ELE through their affiliation with first-order or more proximal factors related to ELE such as education, smoking, alcohol use, and possibly exercise."

August 19, 2021
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The Economic Burden of ADHD

The Economic Burden of ADHD

ADHD, especially when untreated, impairs patients and creates difficulties in families.  

Although these are the proximal targets of treatment, ADHD also burdens society due, for example, to underemployment and the use of health resources.   A recent study assessed the economic burden using the Danish population registries, researchers, which link medical information with employment, education, crime, and social care registers while maintaining confidentiality. They identified 5,269 adults with adult ADHD who had not been diagnosed with ADHD in childhood and, we can assume, were probably not treated for the disorder. They excluded patients with other psychiatric diagnoses and cases without a same-sex sibling free of any diagnosed psychiatric diagnoses. That left 460 pairs of same-sex siblings, one with an adult with ADHD and the other with no psychiatric diagnosis. They selected the non-ADHD sibling closest in age to the ADHD sibling. Using siblings mitigated the effects of genetics and upbringing between the ADHD group and normally developing controls.

Looking at personal income (combining work income and public transfers), adults with ADHD on average brought home about 12,000 Euros less - almost a third less - than their sibling counterparts. They also paid 40% less tax. Balancing that out, their after-tax income was roughly 7,500 Euros less than their siblings. With the additional personal cost of prescribed medication(prescriptions are relatively inexpensive in Denmark, and co-payments even more so) the net personal cost to adults with ADHD was 7,700 Euros.

The net public costs were considerably greater. That was primarily due to the reduction in taxes paid (about 4,500 Euros) and the increase in income replacement transfers (just over 5,500 Euros). The cost of additional crimes committed by adults with ADHD added another 1,000 Euros. Additional primary and secondary health care costs contributed another 1,000 Euros. Subsidies for prescribed medicines added 661 Euros, but that was partly counterbalanced by a reduction of 344 Euros in education costs. There were no significant differences in costs from traffic accidents or adult continuation of foster care. Overall, the net per capita public cost of adults with ADHD was just over 12,400 Euros each year.

Combining public and private costs, the per capita economic burden of adult ADHD was just over 20,000 Euros each year.

The study could not evaluate the extent to which ADHD treatment may reduce the economic burden, but given many studies that show treatment for ADHD reduces impairments, we would expect treatment to have a positive impact on the economic burden.  These results are extremely important for policymakers and for those who control the allocation of treatment in healthcare systems.  Although treating ADHD incurs costs, not treating it incurs even greater costs in the long run

May 5, 2023
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Driving, Safety, and ADHD

How to Improve Driving Safety for Teens and Adults With ADHD

Drivers with ADHD are far more likely to be involved in crashes, to be at fault in crashes, to be in severe crashes, and to be killed in crashes. The more severe the ADHD symptoms, the higher the risk. Moreover, ADHD is often accompanied by comorbid conditions such as oppositional-defiant disorder, depression, and anxiety that further increase the risk.

What can be done to reduce this risk? A group of experts has offered the following consensus recommendations:

·        Use stimulant medications. While there is no reliable evidence on whether-stimulant medications are of any benefit for driving, there is solid evidence that stimulant medications are effective in reducing risk. But there is also a “rebound effect” in many individuals after the medication wears off, in which performance becomes worse than it had been before medication. It is therefore important to time the taking of medication so that its period of effectiveness corresponds with driving times. If one has to drive right after waking up, it makes sense to take a rapid-acting form. The same holds for late-night driving that may require a quick boost.
·        Use a stick shift vehicle wherever possible. Stick shifts make drivers pay closer attention than automatic transmissions. The benefits of alertness are most notable in city traffic. But using a stick shift is far less beneficial in highway driving, where shifting is less frequent.
·        Avoid cruise control. Highways can be monotonous, making drivers more prone to boredom and distraction. That is even more true for those with ADHD, so it is best to keep cruise control turned off.
·        Avoid alcohol. Drinking and driving is a bad idea for everyone, but, once again, it’s even worse for those with ADHD. Parents should consider the no-questions-asked policy of either picking up their teenager anytime and anywhere or setting up an account with a ride-sharing service.
·        Place the smartphone out of reach and hearing. Cell phone use is as about as likely to impair as alcohol. Hands-free devices only reduce this risk moderately, because they continue to distract. Texting can be deadly. Sending a short text or emoticon can be the equivalent of driving 100 yards with one’s eyes closed. Either turn on Do Not Disturb mode or, for even greater effectiveness, place the smartphone in the trunk.
·        Make use of automotive performance monitors. These can keep track of maximum speeds and sudden acceleration and braking, to verify that a teenager is not engaging in risky behaviors.
·        Take advantage of “graduated driver’s licensing laws” wherever available. These laws forbid the presence of peers in the vehicle for the first several (for example, six) months of driving. Parents can extend that period for teenagers with ADHD, or set it as a condition in states that lack such laws.
·        Encourage practicing after obtaining a learner’s permit. Teenagers with ADHD generally require more practice than those without. A “pre-drive checklist” can be a good place to start. For example: check the gas, check the mirrors, make sure the view through the windows is unobstructed, put your cell phone in Do not disturb mode and place it out of reach, put on a seatbelt, and scan for obstacles.
·        Consider outsourcing. Look for a driving school with a professional to teach good driving skills and habits.

Experts do not agree on whether to delay licensing for those with ADHD. On the one hand, teenagers with ADHD are 3-4 years behind in the development of brain areas responsible for executive functions that help control impulses and better guide behavior. Delaying licensing can reduce risk by about 20 percent. On the other hand, teens with ADHD are more likely to drive without a license, and no one wants to encourage that, however inadvertently. Moreover, graduated driver’s licensing laws only have a legal effect on teens who get their licenses at the customary age.

August 13, 2021
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