September 8, 2021

How do psychiatric comorbidities affect risk of premature death among children and adults with ADHD?


The Nordic countries maintain detailed registers of their inhabitants. This enables researchers to examine patterns over entire nations. An international research team used the Swedish national registers for a prospective cohort study of 2,675,615 persons in the Medical Birth Register born in Sweden over 27 years from January 1, 1983, through December 31, 2009. Follow-up was completed in December 2013, with the oldest cohort member aged 31. The mean age at study entry was 6, and the mean at follow-up was 11.

Using personal identification numbers, researchers were able to cross-reference with the National Patient Register and the National Drug Register. From this, they determined that 86,670 members of the cohort (3.2 percent) had ADHD, based either on records of clinical diagnosis or of prescription of ADHD drugs. Psychiatric comorbidities were likewise identified in the National Patient Register.

These comorbidities were significantly more prevalent in the ADHD population than in the rest of the cohort. For example, whereas only 2.2% of the non-ADHD group was diagnosed with substance use disorder (SUD), 13.3% of the ADHD group also had SUD, a six-fold difference. For depression, it was a seven-fold difference; for schizophrenia a nine-fold difference.

The ADHD group had a significantly higher risk of premature death from all causes than the non-ADHD group, with an adjusted hazard ratio(HR) of 3.94 (95% CI 3.51-4.43). Unintentional injury (36%) and suicide (31%)were the leading causes of death in the ADHD group. Those with ADHD were more than eight times more likely to die by suicide than non-ADHD individuals and roughly four times more likely to die from unintentional injury.

The vast majority of the increased risk appears to be associated with comorbid psychiatric conditions. Those with ADHD but no diagnosed comorbidities had an adjusted HR of 1.41 (95% CI 1.01-1.97). With a single comorbidity, the HR more than doubled to 3.71 (95% CI 2.88-4.78). With four or more comorbidities, it rose to a staggering 25.22 (95% CI 19.6-32.46).

The comorbid condition with the greatest impact was SUD, which increased the risk eight-fold by comparison with those with only ADHD (HR= 8.01, 95% CI 6.16-10.41). Anxiety disorder, schizophrenia, and personality disorder increased the risk about fourfold. Bipolar disorder, depression, and eating disorders increased risk by roughly two and a half times.

The co-variate analysis helped tease out what portion of the risk was associated with ADHD alone versus comorbid conditions. Adjusting for the year of birth, sex, birth weight, maternal age at birth, parental educational level, and parental employment status, those with ADHD (including comorbid conditions)were 2.7 times more likely to prematurely die of natural causes than those without. Adjusting for comorbid psychiatric conditions completely eliminated the risk from ADHD alone (HR = 1.01, 95% CI.72-1.42).

Likewise, those with ADHD (including comorbid conditions)were six times as likely to die of unnatural causes. Adjusting for early-onset comorbid disorders (such as conduct disorders, autism spectrum disorder, and intellectual disability) only modestly reduced the HR to 5.3, but further adjusting for later-onset comorbid disorders(including substance use disorder, depressive disorder, bipolar disorder, anxiety disorder, schizophrenia, personality disorder, and eating disorders)reduced the HR to 1.57 (95% CI 1.35-1.83), and reduced it to insignificance in the case of suicide (HR = 1.13, 95% CI .88-1.45).

Summing up, the lion's share of the greater risk of premature death in persons with ADHD is attributable to psychiatric comorbidities. Nevertheless, those with ADHD alone still face a 40 percent greater risk than those without ADHD.

The study did not examine the effects of ADHD medication, which the authors state should be analyzed because of documented potential benefits on ADHD symptoms and comorbid disorders.

The authors concluded, Among adults, early-onset psychiatric comorbidity contributed substantially to the premature mortality risks due to natural causes. On the other hand, later-onset psychiatric comorbidity, especially SUD, explained a substantial part of the risk for unnatural deaths, including all the risk of suicide deaths and most of the deaths due to unintentional injuries. These results suggest that overall health conditions and risk of psychiatric comorbidity should be evaluated clinically to identify high-risk groups among individuals with ADHD.

Shihua Sun, MD; Ralf Kuja-Halkola, Ph.D.; Stephen V. Faraone,  Ph.D.; Brian M. D'Onofrio, Ph.D.; Søren Dalsgaard, Ph.D.; Zheng Chang, Ph.D.; Henrik Larsson, Ph.D., "Association of Psychiatric Comorbidity With the Risk of premature Death Among Children and Adults With Attention-Deficit/hyperactivity disorder," JAMA Psychiatry doi:10.1001/jamapsychiatry.2019.1944Published online August 7, 2019.

Related posts

No items found.

Swedish Population Study Confirms Association Between ADHD and Height

Nationwide population study in Sweden confirms association between ADHD and shorter height in children and adolescents, suggests stimulant medications are not a factor

A commonly reported risk associated with ADHD medication is reduced growth in height. But studies to date have generally not adequately described or measured possible confounders, such as genetic factors, prenatal factors, or socioeconomic factors. What if ADHD were associated with reduced height even in the absence of medications? 

An international study team explored this question by performing a nationwide population study comparing data from before (1968-1991) and after (1992-2020) the adoption of stimulant therapy for ADHD in Sweden. 

The country’s single-payer health insurance system that connects patient records with all other national registers through unique personal identification numbers makes such analysis possible. Sweden also has military service conscription, which records the heights of 18-year-old males.

The participants were all 14,268 Swedish males with a diagnosis of ADHD who were drafted into military service at any time from 1968 through 2020. 

Up to five non-ADHD controls were identified for each ADHD case, matched by sex (they had to be male), birth year, and county. The total number of controls was 71,339.

Among 34,586 participants in the period before adoption of stimulant medications (1968-1991), those diagnosed with ADHD had roughly 30% greater odds of being shorter than normal (166-172 vs. 173-185 cm) than typically developing controls. That dropped to 20% greater odds among the 34,714 participants in the cohort following adoption of stimulant medications.

The odds of those diagnosed with ADHD being much shorter than normal (150-165 vs. 173-185 cm) remained identical (about 55% greater) among the almost 30,000 participants in both cohorts.

In other words, there was no increase in the odds of ADHD individuals being shorter than normal after adoption of stimulant therapy in Sweden compared with before such adoption.

Furthermore, after adjusting for known confounders, including birth weight, inflammatory bowel disease, celiac disease, hypothyroidism, anxiety disorders, depression, substance use disorder, and highest parental education, the odds of those diagnosed with ADHD being shorter than normal or much shorter than normal in the 1992-2020 cohort dropped to roughly 10% and 30% greater, respectively.

Could it be the disorder itself rather than stimulant treatment that is associated with reduced height in individuals diagnosed with ADHD?

To address effects of environmental and familial/genetic confounding, the team then compared the entire cohort of males diagnosed with ADHD from 1968 through 2020 with typically developing male relatives, ranging from first cousins to full siblings.

Among full siblings, the odds of those with ADHD diagnoses being shorter (over 90,000 participants) or much shorter (over 77,000 participants) were a statistically significant 14% and 18%, respectively.

The authors concluded, “Our findings suggest that ADHD is associated with shorter height. On a population level, this association was present both before and after ADHD-medications were available in Sweden. The association between ADHD and height was partly explained by prenatal factors, psychiatric comorbidity, low SES [socioeconomic status] and a shared familial liability for ADHD.”

January 9, 2024

Swedish nationwide population study finds mothers with ADHD have elevated risk of depression and anxiety disorders after childbirth

Swedish nationwide population study finds mothers with ADHD have elevated risk of depression and anxiety disorders after childbirth

In the general population, most mothers experience mood disturbances right after childbirth, commonly known as postpartum blues, baby blues, or maternity blues. Yet only about one in six develop symptoms with a duration and magnitude that require treatment for depressive disorder, and one in ten for anxiety disorder.

To what extent does ADHD contribute to the risk of such disorders following childbirth? A Swedish study team used the country’s single-payer health insurance database and other national registers to conduct the first nationwide population study to explore this question.

They used the medical birth register to identify all 420,513 women above 15 years of age who gave birth to their first child, and all 352,534 who gave birth to their second child, between 2005 and 2013. They excluded miscarriages. They then looked for diagnoses of depression and/or anxiety disorders up to a year following childbirth.

In the study population, 3,515 mothers had been diagnosed with ADHD, and the other 769,532 had no such diagnosis. 

Following childbirth, depression disorders were five times more prevalent among mothers with ADHD than among their non-ADHD peers. Excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.

Similarly, anxiety disorders were over five times more prevalent among mothers with ADHD than among their non-ADHD peers. Once again, excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.

The team cautioned, “There is a potential risk of surveillance bias as women diagnosed with ADHD are more likely to have repeated visits to psychiatric care and might have an enhanced likelihood of also being diagnosed with depression and anxiety disorders postpartum, compared to women without ADHD.”

Nevertheless, they concluded, “ADHD is an important risk factor for both depression and anxiety disorders in the postpartum period and should be considered in the post- pregnancy maternal care, regardless of sociodemographic factors and the presence of other psychiatric disorders. Parental education prior to conception, psychological surveillance during, and social support after childbirth should be provided to women diagnosed with ADHD.”

December 22, 2023

Meta-analysis suggests acupuncture might offer effective treatment for ADHD, but suffers from methodological flaws

Meta-analysis suggests acupuncture might offer effective treatment for ADHD, but suffers from methodological flaws

Noting that previous “systematic reviews concluded that currently available data on the clinical effectiveness of acupuncture for treating ADHD are yet to be sufficient to support its routine use,” a South Korean study team conducted an updated systematic search of the medical literature for randomized controlled trials (RCTs) comparing acupuncture with drug treatment for children and adolescents with ADHD. There were no restrictions on language or publication type.

Only two of the meta-analyses involved more than two RCTs. 

One of them, of six RCTs with a combined 541 participants, reported total treatment efficacy of acupuncture to be at least equal to that of conventional treatment with ADHD medicines. 

Another, of five RCTs with a total of 351 participants, reported total treatment efficacy of combined acupuncture and ADHD drugs to be at least equal to that of conventional treatment with ADHD medicines.

Two RCTs with a Noting that previous “systematic reviews concluded that currently available data on the clinical effectiveness of acupuncture for treating ADHD are yet to be sufficient to support its routine use,” a South Korean study team conducted an updated systematic search of the medical literature for randomized controlled trials (RCTs) comparing acupuncture with drug treatment for children and adolescents with ADHD. There were no restrictions on language or publication type.

Only two of the meta-analyses involved more than two RCTs. 

One of them, of six RCTs with a combined 541 participants, reported total treatment efficacy of acupuncture to be at least equal to that of conventional treatment with ADHD medicines. 

Another, of five RCTs with a total of 351 participants, reported total treatment efficacy of combined acupuncture and ADHD drugs to be at least equal to that of conventional treatment with ADHD medicines.

Two RCTs with a combined 152 participants reported a large effect size improvement in hyperactivity/impulsivity symptoms from acupuncture treatment versus conventional drug treatment.

From this one could superficially conclude that acupuncture is at least as effective for treating ADHD as the medicines currently considered to be the standard of care, and that there is no need to combine acupuncture with drug treatment.

However, there were numerous methodological shortcomings:

  • No effort was made to look for publication bias.
  • There were few RCTs, and the combined number of participants was relatively small.
  • Only one of the six RCTs in the first meta-analysis and none of the five RCTs in the second meta-analysis was rated “low risk of bias.”
  • Though nowhere stated in the journal article, there may have been cultural bias as well. All studies included in the meta-analyses were conducted in China. As China has emerged as a global superpower, it has been eager to portray its traditional medicine as at least equal if not superior to forms of medicine originating elsewhere.
  • The authors noted, “the quality of the studies included in this systematic review was poor. Assessing the blinding of studies is a major aspect in determining the risk of bias of a study, but most of the studies did not provide any relevant information.” 

The authors concluded, “The current evidence on AT [acupuncture treatment] is still too limited to support its routine use in treating ADHD.”

152 participants reported a large effect size improvement in hyperactivity/impulsivity symptoms from acupuncture treatment versus conventional drug treatment.

From this one could superficially conclude that acupuncture is at least as effective for treating ADHD as the medicines currently considered to be the standard of care, and furthermore that there is no need to combine acupuncture with drug treatment.

However, there were numerous methodological shortcomings:

  • No effort was made to look for publication bias.
  • There were few RCTs, and the combined number of participants was relatively small.
  • Only one of the six RCTs in the first meta-analysis and none of the five RCTs in the second meta-analysis was rated “low risk of bias.”
  • Though nowhere stated in the journal article, there may have been cultural bias as well. All studies included in the meta-analyses were conducted in China. As China has emerged as a global superpower, it has been eager to portray its traditional medicine as at least equal if not superior to forms of medicine originating elsewhere.
  • The authors noted, “the quality of the studies included in this systematic review was poor. Assessing the blinding of studies is a major aspect in determining the risk of bias of a study, but most of the studies did not provide any relevant information.” 

The authors concluded, “The current evidence on AT [acupuncture treatment] is still too limited to support its routine use in treating ADHD.”

January 4, 2024