August 12, 2024
Quality of life (QoL) is defined as a person’s satisfaction with their life, measured across several dimensions including psychological, social, health, biological, and economic well-being. For adults, these are usually self-reported. QoL for children and adolescents is usually reported by parents.
Medications for ADHD include stimulants (methylphenidate and amphetamines) and non-stimulants (e.g., atomoxetine, clonidine, guanfacine, viloxazine). As QoL is related to ADHD symptoms’ severity, management of ADHD via medication could improve not only core symptoms but also QoL in people with ADHD.
Noting the absence of meta-analytic evidence on the effects of ADHD medications on QoL, an international research team conducted a systematic review and meta-analysis of parallel or cross-over randomized clinical trials (RCTs) to estimate the effects of ADHD medication on QoL. They also performed secondary analyses to see if these effects differed in children and adolescents versus adults, as well as by class of medications, and if they were moderated by length of treatment.
Meta-analyses of four RCTs with a combined total of 950 participants with ADHD (45% adults) found a medium effect size improvement among those receiving amphetamines by comparison with those receiving placebo. There was no sign of publication bias, but there was wide variation (heterogeneity) in effect size estimated among the studies.
Meta-analysis of four RCTs with a combined total of 1,094 participants with ADHD (57% adults) found a small-to-medium effect size improvement among those receiving methylphenidate by comparison with those receiving placebo. Again, there was no sign of publication bias, but wide variation in effect sizes among the studies.
Due to lack of sufficient data, the team could not explore whether length of treatment affected the results, or if there were differences between children/adolescents and adults.
Finally, a meta-analysis of eleven RCTs with a combined total of 3,344 participants with ADHD (63% adults) likewise found a small effect size improvement among those taking atomoxetine compared with those receiving placebo. Once again, there was no sign of publication bias, but wide variation in effect sizes among the studies.
The team was able to establish that for atomoxetine treatment, length of intervention – the studies ranged from 6 to 24 weeks – had no significant moderating effect. Similarly, they found no significant differences in effect on children and adolescents versus adults.
A single RCT evaluating modafinil treatment in adults found no improvements at any dose, whereas a single RCT testing non-stimulant guanfacine reported a medium effect size improvement in QoL. Modafinil is not FDA approved for ADHD but is sometimes used as a last resort if other treatments fail.
The team concluded that the FDA approved medications for ADHD were significantly more efficacious than placebo in improving QoL in people with ADHD. The improvements in Q0L were, however, smaller than what has been found for improvements is the symptoms of ADHD (inattention, hyperactivity, impulsivity). More work is needed to detect differences by age and length of treatment.
Alessio Bellato, Nadia J. Perrott, Lucia Marzulli, Valeria Parlatini, David Coghill, and Samuele Cortese, “Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life,” Journal of the American Academy of Child & Adolescent Psychiatry (2024), https://doi.org/10.1016/j.jaac.2024.05.023.
A Chinese research team performed two types of meta-analyses to compare the risk of suicide for ADHD patients taking ADHD medication as opposed to those not taking medication.
The first type of meta-analysis combined six large population studies with a total of over 4.7 million participants. These were located on three continents - Europe, Asia, and North America - and more specifically Sweden, England, Taiwan, and the United States.
The risk of suicide among those taking medication was found to be about a quarter less than for unmediated individuals, though the results were barely significant at the 95 percent confidence level (p = 0.49, just a sliver below the p = 0.5 cutoff point). There were no significant differences between males and females, except that looking only at males or females reduced sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications produced divergent outcomes. A meta-analysis of four population studies covering almost 900,000 individuals found stimulant medications to be associated with a 28 percent reduced risk of suicide. On the other hand, a meta-analysis of three studies with over 62,000 individuals found no significant difference in suicide risk for non-stimulant medications. The benefit, therefore, seems limited to stimulant medication.
The second type of meta-analysis combined three within-individual studies with over 3.9 million persons in the United States, China, and Sweden. The risk of suicide among those taking medication was found to be almost a third less than for unmediated individuals, though the results were again barely significant at the 95 percent confidence level (p =0.49, just a sliver below the p = 0.5 cutoff point). Once again, there were no significant differences between males and females, except that looking only at males or females reduced the sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications once again produced divergent outcomes. Meta-analysis of the same three studies found a 25 percent reduced risk of suicide among those taking stimulant medications. But as in the population studies, a meta-analysis of two studies with over 3.9 million persons found no reduction in risk among those taking non-stimulant medications.
A further meta-analysis of two studies with 3.9 million persons found no reduction in suicide risk among persons taking ADHD medications for 90 days or less, "revealing the importance of duration and adherence to medication in all individuals prescribed stimulants for ADHD."
The authors concluded, "exposure to non-stimulants is not associated with a higher risk of suicide attempts. However, a lower risk of suicide attempts was observed for stimulant drugs. However, the results must be interpreted with caution due to the evidence of heterogeneity ..."
Older adults are at greater risk for cardiovascular disease. Psychostimulants may contribute to that risk through side effects, such as elevation of systolic blood pressure, diastolic blood pressure, and heart rate.
On the other hand, smoking, substance abuse, obesity, and chronic sleep loss - all of which are associated with ADHD - are known to increase cardiovascular risk, and stimulant medications are an effective treatment for ADHD.
So how does this all shake out? A Dutch team of researchers sets out to explore this. Using electronic health records, they compared all 139 patients 55 years and older at PsyQ outpatient clinic, Program Adult ADHD, in The Hague. Because a principal aim of the study was to evaluate the effect of medication on cardiovascular functioning after first medication use, the 26 patients who had previously been prescribed ADHD medication were excluded from the study, leaving a sample size of 113.
The ages of participants ranged from 55 from 79, with a mean of 61. Slightly over half were women. At the outset, 13 percent had elevated systolic and/or diastolic blood pressure, 2 percent had an irregular heart rate, 15 percent had an abnormal electrocardiogram, and 29 percent had some combination of these (a "cardiovascular risk profile"), and 21 percent used antihypertensive medication.
Three out of four participants had at least e comorbid disorder. The most common are sleep disorders, affecting a quarter of participants, and unipolar mood disorders (depressive or more rarely manic episodes, but not both), also affecting a quarter of participants.
Twenty-four patients did not initiate pharmacological treatment. Of the 89 who received ADHD medication, 58 (65%) reported positive effects, and five experienced no effect. Thirty-eight (43%) discontinued ADHD medication while at the clinic due to lack of effect or to side effects. The most commonly reported positive effects were enhanced concentration, more overview, less restlessness, more stable mood, and having more energy. The principal reasons for discontinuing medication were anxiety/depression, cardiovascular complaints, and lack of effect.
Methylphenidate raised heart rate and lowered weight, but had no significant effect on systolic and diastolic blood pressure. Moreover, there was no significant correlation between methylphenidate dosage and any of these variables, nor between methylphenidate users taking hypertensive medication and those not taking such medication. There was no significant difference in systolic or diastolic blood pressure and heart rate before and after the use of methylphenidate among patients with the cardiovascular risk profiles.
Systolic blood pressure rose in ten out of 64 patients, with two experiencing an increase of at least 20 mmHg. It descended in five patients, with three having a decrease of at least 20 mmHg. Diastolic blood pressure rose by at least 10 mmHg in four patients, while dropping at least 10 mmHg in five others.
The authors concluded "that the use of a low dose of ADHD-medication is well tolerated and does not cause clinically significant cardiovascular changes among older adults with ADHD, even among those with an increased cardiovascular risk profile. Furthermore, our older patients experienced significant and clinically relevant improvement of their ADHD symptoms using stimulants, comparable with what is found among the younger age group," and that "the use of methylphenidate may be a relatively safe and effective treatment for older adults with ADHD, under the condition that all somatic complaints and especially cardiovascular parameters are monitored before and during pharmacological treatment."
Yet they cautioned that "due to the observational nature of the study and the lack of a control group, no firm conclusions can be drawn as to the effectiveness of the stimulants used. ... Important factors that were not systematically reported were the presence of other risk factors, such as smoking, substance (ab)use, aspirin use, and level of physical activity. In addition, the response to medication was not systematically measured"
The stimulants methylphenidate and amphetamine are well known for their efficacy in treating symptoms of ADHD in both youth and adults. Although these medications have been used for several decades, relatively little is known about the mechanisms of action that lead to their therapeutic effect.
New data about the mechanism comes from a meta-analysis by Katya Rubia and colleagues. They analyzed 14 functional magnetic resonance imaging (fMRI) data sets comprising 212 youth with ADHD. Each of these data sets assessed the short-term effects of stimulants on fMRI-assessed brain activations. In the fMRI paradigm, ADHD and control participants are asked to do a neurocognitive task while the activity of their brains is being measured. Dr. Rubia and colleagues analyzed data from fMRI assessments of time discrimination, inhibition, and working memory, each of which is known to be deficient in ADHD patients.
The meta-analysis found that the most consistent brain activations were seen in a region comprising the right inferior frontal cortex(IFC) and insula, even when the analysis was limited to previously medication-naïve patients. The implicated region of the brain is known to mediate cognitive control, time estimation, and attention. Dr.Rubia also notes that other studies show that the IFC/Insula is needed for updating information and allocating attention to relevant stimuli.
Another region implicate by the meta-analysis was the right putamen, a region that is rich in dopamine transporters. This finding is consistent with the fact that the dopamine transporter is the main target of stimulant medications.
What is the potential clinical implication of these findings? As Dr. Rubia and colleagues note, it is possible that the fMRI anomalies they identified could be used as a biomarker for ADHD or a biomarker to select patients who should respond optimally to stimulant medication. Although fMRI cannot be used as a clinical tool at this time, research of this sort is opening up new horizons for how we understand the etiology of ADHD and the mechanisms whereby medications exert their effects.
Given the persistence of ADHD and its adverse effects on children and adolescents, one might expect caregivers to face greater parenting challenges, with potential effects on their own mental health.
To what extent do parenting stress, depression, and – at the extreme – even suicidal ideation manifest themselves among caregivers of ADHD patients as opposed to caregivers of children and adolescents without ADHD?
A pair of Korean researchers made use of their country’s single-payer health insurance system, which maintains records on virtually the entire population, to perform a nationwide population study. They used data from the Korean National Health and Nutrition Examination Surveys (KNHANES) covering the decade from 2011 to 2020. KNHANES is an annual survey using a sophisticated sampling design conducted by the Korean Ministry of Health and Welfare to represent the entire population of South Korea.
The analysis included 14,428 individuals who had children younger than 19 at the time of participation. All were asked whether their child had ever been diagnosed with ADHD by a physician. The mental health problems of the parents were assessed in terms of perceived stress, depressive symptoms, and suicidality.
Of the 14,428 participants, 8,298 (57.5 %) were mothers and 6,130 (42.5 %) were fathers. Of the mothers, 116 (1.4 %) had a child with ADHD, and of the fathers, 86 (1.4 %) had a child with ADHD.
The researchers adjusted for the following confounders: age of caregiver, education level, household income, area of residence, employment status, alcohol consumption, smoking status, cohabitation status, number of children, and child’s age.
After adjustment, mothers of ADHD patients fared significantly worse than mothers of typically developing children on all three categories of mental health problems. They were 67% more likely to report higher stress, three times as likely to report symptoms of depression, and 2.5 times more likely to report suicidal ideation.
Yet that pattern did not carry over to fathers, where there was no significant difference in mental health indicators between fathers of children with ADHD and fathers of children without ADHD.
The authors concluded, “Parents of children with ADHD, especially mothers, need community support and public health attention to help alleviate their mental health problems.”
Background:
ADHD is commonly accompanied by psychiatric comorbidities that complicate its diagnosis and treatment. Roughly two out of three affected children and adolescents have one or more comorbid psychiatric disorder.
Because the peak age of ADHD onset is typically a decade or more earlier than those for schizophrenia, depressive disorder, or bipolar disorder, it is essential to explore these comorbidities over an extended period. Populations studies help researchers identify broader patterns and trends within an entire population and includes adults as well as children. This type of study provides unique insights into the population at large, rather than a sample group.
In earlier studies the maximum follow-up period was twelve years, insufficient in view of the roughly ten years between onset of ADHD and onset of major psychiatric disorders. Also, previous nationwide population studies have included less than 150,000 participants.
This study, relying on data from South Korea’s universal single-payer health insurance system, included over one and a half million individuals. Persons previously diagnosed with depression, bipolar disorder, tic disorder, or schizophrenia were excluded.
382,434 individuals had been diagnosed with ADHD, while 1,169,279 were without an ADHD diagnosis.
Propensity score matching ensured that potential confounders, both sociodemographic and clinical, were equalized for the ADHD and control groups. After matching, there were 353,898 individuals in each group.
After these adjustments, individuals in the ADHD group were at least an order of magnitude more likely to subsequently be diagnosed with psychiatric disorders than their peers without an ADHD diagnosis:
Conclusion:
The Korean study team concluded, “Overall, our findings suggest that upon prolonged examination, the risk of subsequent diagnoses of other psychiatric disorders in individuals with ADHD appears to be higher than that reported previously. … Therefore, patients with ADHD should be carefully screened for the presence of other psychiatric symptoms on a regular basis from an earlier age … It is advisable to have a follow-up period extending beyond 10 years to sufficiently identify the occurrence of comorbid disorders in patients with ADHD.”
Children with ADHD often face challenges in social interactions, leading to long-term consequences if not properly addressed. While various interventions exist, many fail to consider the broader social context in which these children interact. A recent study conducted in Bergen, Norway, explored how primary school teachers perceive their role in supporting children with ADHD who struggle socially and the strategies they use to assist them.
Researchers conducted semi-structured interviews with five focus groups of primary school teachers. Using reflexive thematic analysis, they identified two major themes:
Rather than relying on standardized interventions, teachers tailored their strategies to foster an inclusive and supportive social environment. Their methods included both active participation in social situations and behind-the-scenes efforts to encourage peer inclusion and understanding.
This study underscores the need to move beyond labels and recognize children with ADHD as individuals with distinct social needs. Teachers play a crucial role in shaping these children’s experiences, using flexible and personalized approaches to promote positive social interactions. By integrating social context and individualized support, educators can help children with ADHD build meaningful connections and navigate their social world more effectively.
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