The diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD) in older adults

ABSTRACT

Introduction

There is a striking knowledge gap on ADHD in older adults, and the diagnosis as well as treatment for ADHD in this age group.

Areas covered

The authors first review the literature on the prevalence, functional impairment, and health comorbidities of ADHD across the lifespan. Next, they address the diagnostic criteria for ADHD in adults according to the DSM/ICD, available screening/diagnostic tools, differential diagnosis, and the validity of diagnostic criteria for ADHD in older adults. Finally, the authors focus on empirical evidence on the prevalence rates, medication response, and safety of pharmacological treatment of ADHD in older adults, and national and international clinical guidelines on the treatment of ADHD in this age group.

Expert opinion

It is expected that future editions of the DSM and ICD will provide specifiers to the standard ADHD criteria, to better inform the diagnosis of ADHD in older adults. It is also expected that the increasing number of epidemiological studies will provide rigorous estimates on the prevalence, incidence, and burden of ADHD in older adults. One may expect an increasing number of RCTs assessing the efficacy/effectiveness and tolerability/safety of pharmacological as well as non-pharmacological interventions which will inform future guidelines on ADHD in older adults.

KEYWORDS:

• Attention-deficit hyperactivity disorder (ADHD)
• older adults
• prevalence
• functional impairment
• comorbidity
• diagnosis
• treatment
• treatment recommendations

1. Introduction

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, estimated to affect about 5% of children and about 2.5% of adults [1,2]. It is characterized by age-inappropriate and impairing levels of inattention and/or hyperactivity/impulsivity [3]. ADHD is a highly heritable condition, yet adverse environmental risk factors (e.g. prenatal factors and early life adversities) and gene-environment interactions may increase the risk of ADHD [4]. Although ADHD was once thought to be a condition limited to childhood, it has been suggested that a substantial number of older adults still experience elevated levels of ADHD symptoms accompanied by functional impairment and health issues, without being recognized by clinicians and without receiving adequate healthcare [5–8]. We refer to older adults as individuals aged 50 years and older as this or a slightly higher (e.g. 55) cutoff for older age is typically used in the relevant literature [5–8]. Most studies on ADHD have been conducted in children and young adults, while older adults have been typically excluded from research. This has resulted in a striking knowledge gap on the presentation of ADHD, its functional impairment, adverse health outcomes, and proper diagnosis and treatment in older adults. As the world population continues to grow older [9], it is important to raise awareness among clinicians and researchers in order to improve the diagnostic assessment and treatment of ADHD in older adults. Furthermore, it is essential to investigate the efficacy and safety of different treatment strategies in this age group. On the one hand, adequate and timely treatment of ADHD and comorbid conditions is relevant to help reduce the risk of multimorbidity at an older age and ultimately improve the overall health and well-being of individuals aging with ADHD. On the other hand, the focus on safety should be paramount, given the possible adverse effects of the pharmacological treatment of ADHD, and the increased risk of psychiatric and physical multimorbidity in older adults [10–13].

Several important literature reviews [5–7] have provided much-needed insights in relation to the prevalence, functional impairment, and health outcomes of ADHD in older adults, as well as recommendations on the diagnosis and treatment of ADHD in this age group. However, since 2016, when these reviews were published, there has been an increasing interest and a significant influx of studies on ADHD in older adults. An updated review of the literature in the field is therefore needed. We searched PubMed for original and review articles using search terms in relation to ‘Attention-Deficit/Hyperactivity Disorder’ and ‘older adults’ from inception until 1 May 2023 We also hand-searched reference lists of relevant full-text articles and textbooks to identify any additional relevant articles. The review covers the following areas: (i) the prevalence of ADHD, related functional impairment, and comorbidities in older adults; (ii) diagnostic criteria of ADHD in adults according to the DSM and ICD, available screening and diagnostic tools, and differential diagnosis of ADHD in older adults, as well as the validity of current diagnostic criteria for ADHD in older adults; and (iii) empirical evidence on the efficacy and safety of pharmacological treatment for ADHD in older adults, and national and international clinical guidelines on the treatment of ADHD in this age group.

1.1. Prevalence and persistence of ADHD across the lifespan

It is estimated that ADHD affects between 5% (95% confidence interval (CI) = 5.0. 5.6) [1] and 7.2% (95% CI = 6.7, 7.8) [14] of children and adolescents, and around 2.5% (95% CI = 2.1, 3.1) of adults [2] worldwide. An earlier systematic review on ADHD in older adults published in 2016 [6] identified only four studies investigating the prevalence of ADHD in older adults, thus emphasizing a striking scarcity of research on ADHD in this age group. A more recent systematic review and meta-analysis of ADHD prevalence in adults aged 50 years and older published in 2020 included 20 studies with 32 data sets and provided significantly different prevalence estimates depending on the applied assessment method [8]. That review indicated that a substantial number of older adults may experience increased levels of ADHD symptoms with a pooled prevalence of a research diagnosis of ADHD based on validated scales around 2% (95% CI = 1.51, 3.16). However, the prevalence of individuals treated for ADHD, 0.09% (95% CI = 0.06, 0.15) was less than half of the prevalence of individuals with a clinical diagnosis of ADHD, 0.23% (95% CI = 0.12, 0.43) [8]. Further, prevalence estimates based on a research diagnosis were mostly based on community samples, while prevalence estimates for clinical diagnosis and treatment of ADHD were mostly based on electronic health records.

Most longitudinal studies assessing the persistence of ADHD symptoms across the lifespan have followed participants until they were young adults, up to 25 years of age [15–17]. These studies have concluded that the level of symptoms declines with age, although functional impairment may remain in a more substantial portion of individuals [15]. Additionally, these studies have revealed a striking heterogeneity in the estimates of persistent ADHD, ranging from 5 to 76% of individuals with ADHD diagnosed in childhood [18]. Potential sources of heterogeneity across studies may be related to changes in diagnostic criteria over time, differences in the duration of follow-up and age at the follow-up, and inconsistent application of functional impairment and childhood-onset criteria across studies [18]. One of the studies with the longest follow-up available, a longitudinal study conducted in New Zealand, investigated ADHD symptoms and clinical features in a sample of 1073 individuals who were followed from childhood until age 38 [19]. A follow-up assessment of ADHD at age 38, conducted using a structured interview, revealed that only three out of 61 individuals diagnosed with ADHD in childhood (5%) still met the full diagnostic criteria. However, the group with a childhood diagnosis of ADHD still experienced significantly more functional impairment and cognitive deficits in adulthood than those without childhood ADHD. These results support previous findings of older individuals reporting subthreshold levels of ADHD and thus not meeting the full diagnostic criteria, but still experiencing ADHD-associated functional impairment [6,8], which is further associated with a reduced quality of life [20].

Overall, the bulk of the available literature on the persistence of ADHD beyond mid-adulthood is based on community-based samples with the retrospective assessment of childhood symptoms of ADHD [21–24] and revealed that about 1.75% (95% CI = 1.01, 3.03) [8] of older adults aged 50 and older have symptoms of ADHD that persisted from childhood until older age. However, there are no prospective longitudinal studies assessing the persistence of ADHD symptoms into older age, and the risk of recall bias remains a major methodological issue accompanying the use of retrospective assessment of childhood ADHD symptoms in older adults. Thus, future longitudinal studies investigating ADHD symptoms from early until older age, as well as associated functional impairment and health comorbidities, are warranted.

1.2. Functional impairment and comorbidity of ADHD in older adults

Despite the lack of solid empirical evidence, it has been suggested that symptoms of ADHD may persist until older age in a substantial number of individuals, with a significant negative impact on one’s educational, occupational, and social functioning [2,6,8]. Although the clinical presentation of ADHD may differ among individuals, it is often accompanied by mood issues, emotion dysregulation, and irritability, as well as impairment in executive functions (e.g. issues with organization, response inhibition and working memory, sustained attention, and ability to perform complex tasks) [10,25,26]. Studies specifically investigating functional impairment and the health of older adults with ADHD are sparse, although it has been suggested that the burden of ADHD and associated professional/social/emotional/economic functional impairment in older people are comparable to the burden of ADHD experienced in younger and middle-aged adults [20,22,27–29]. Older individuals experience the cumulative negative impact of ADHD symptoms on their quality of life [20,27,28], self-esteem [28], health-related quality of life, and satisfaction with life [30].

Further, ADHD has been associated with an increased risk of psychiatric comorbidity across the lifespan [11–13,31,32], with anxiety, mood disorders, sleep disorders, behavioral disorders, and substance use disorder being the most commonly diagnosed psychiatric conditions in adults with ADHD [10,11,13]. It has been found that older adults (aged between 60 and 80) experience similar rates of psychopathology (i.e. depressive and anxiety symptoms, somatic problems, and antisocial personality) as middle-aged individuals (aged between 40 and 69) [33]. There is also evidence that a diagnosis of ADHD and ADHD symptom severity are associated with anxiety and depressive symptoms in older adults both cross-sectionally and longitudinally [34].

Furthermore, ADHD has been associated with increased mortality rates, primarily due to unnatural causes (e.g. accidents) [35], as well as an increased risk of physical multimorbidity [36], including diseases of the digestive and urinary system (e.g. celiac disease, inflammatory bowel disease, elimination disorders, etc.), endocrine and metabolic disorders (e.g. disorders of the thyroid gland, obesity, diabetes mellitus, etc.), autoimmune and allergic diseases (e.g. atopic disorders and allergies), cardiovascular diseases, and neurological disorders (e.g. epilepsy, migraine, neurodegenerative disorders, etc.) [12,37]. ADHD in older age has been found to be associated with chronic physical illness (e.g. chronic nonspecific lung disease, cardiovascular disease, and the number of chronic diseases) and poor self-perceived health [38]. Additionally, recent studies have identified a link between ADHD in older adults and an increased risk of mild cognitive impairment (MCI) and dementia [39–42].

Potential underlying mechanisms of the associations of ADHD with psychiatric and physical health comorbidities are still largely understudied and may differ depending on the disease category. Genome-wide association studies (GWAS) have found significant genetic correlations of ADHD with major depressive disorder, neuroticism, anorexia nervosa, smoking, migraine, obesity, insomnia, and mortality [10,43,44]. Further, Swedish family-based studies have suggested a shared familial risk between ADHD and dementia [45], other psychiatric disorders [46], and respiratory, musculoskeletal, and metabolic diseases [47]. Additionally, adverse functional, socio-economic, and lifestyle outcomes of ADHD (e.g. low educational attainment, employment and relationship issues, unhealthy eating behaviors, smoking, lack of physical activity, etc.), which accumulate across a person’s lifespan, might increase the risk of many psychiatric and physical disorders in older adults with ADHD [10]. In fact, several recent studies have suggested that different life course factors, such as socio-economic status, psychiatric comorbidity of ADHD, and lifestyle factors, may mediate the association of ADHD [48,49] or ADHD genetic liability [50] with cardiometabolic disorders in adults and older adults. Similarly, psychiatric comorbidity of ADHD (e.g. anxiety, depression, substance use disorder, bipolar disorder) may partially explain the association between ADHD and dementia and MCI [42], and ADHD symptoms may affect cognitive functions in older adults through depressive symptoms [26,51].

2. Diagnostic criteria and assessment of ADHD in older adults

Manifestation and balance between symptoms of inattention and hyperactivity/impulsivity of symptoms vary across individuals [10,52] and within individuals as they age, with symptoms of hyperactivity/impulsivity being more common in younger age, and symptoms of inattention becoming predominant in adulthood [17]. Diagnostic criteria for ADHD according to the latest versions of the Diagnostic and Statistical Manual of Mental Disorders, DSM-5-TR [53], and the International Statistical Classification of Diseases and Related Health Problems (ICD), ICD-11 [52], have both shifted toward a wider inclusion of adults, who would otherwise remain undiagnosed under previous versions of these diagnostic systems. For instance, some relevant changes made in the DSM-5 compared to the DSM-IV entail: (i) the change in the number of required symptoms, from six out of nine symptoms in either or both domains in the DSM-IV to five out of nine symptoms for older adolescents (aged 17 and older) and adults in the DSM-5; (ii) the age of onset, from requiring that symptoms and impairment need to be present by the age seven in the DSM-IV (TR), to several symptoms being present by age 12 in the DSM-5; and (iii) the severity of ADHD, with the DSM-5 allowing that ADHD can be specified into mild, moderate or severe, and the disorder can be coded as ‘in partial remission’ if the full diagnostic criteria are not being met [54]. While the core 18 symptoms of ADHD remained the same as in the DSM-IV (TR), examples of symptom manifestation to better account for clinical presentation in older adolescents and adults were added in the DSM-5. Similarly, the ICD-11 recognizes three presentation categories of ADHD (i) predominantly inattentive presentation, (ii) predominantly hyperactive-impulsive presentation, and (iii) combined presentation, with evidence of symptoms before age 12, while the ICD-10 required both symptom domains to be present with early childhood onset, typically at the age of five. Nonetheless, older adults are not considered separately in current diagnostic systems, and the diagnostic criteria have not been validated in the older age group.

2.1. Screening and diagnostic assessment of ADHD in older adults

The updated European Consensus Statement on diagnosis and treatment of adult ADHD issued by the European Psychiatric Association (EPA) recommends screening for ADHD in adults with a history of inattentiveness, hyperactivity/impulsivity, emotion dysregulation, other mental health disorders, behavioral problems, criminality, or family members diagnosed with ADHD [55]. Several screening tools have been validated in adults, such as Adult ADHD Self-Report Scale (ASRS) with 18 or 6 self-report items in accordance with the DSM-IV [56] and updated per the DSM-5 [57]. Diagnostic assessment, in general, should be conducted within specialist care and based on information from multiple sources, such as self-report, reports from family members, and, when available, documents/school records [55]. Several diagnostic interviews have been validated in adults, such as the semi-structured Diagnostic Interview for ADHD in adults (DIVA), according to the DSM-IV-TR and DSM 5 criteria [58], or the Conner’s Adult ADHD Diagnostic Interview for DSM-IV (CAADID), based on the DSM-IV criteria [59]. Unfortunately, there has been a lack of validation studies of screening and diagnostic tools in older adults. To the best of our knowledge, only one screening tool, developed by Barkley and Murphy [60], has been validated in older adults (aged 60–94 years old in the Netherlands) against a diagnostic interview (DIVA 2.0) [61]. This screening tool consists of nine questions covering seven executive functioning items and two DSM-IV-TR criteria, with the most common complaints of adult patients with ADHD in relation to working memory, emotional self-regulation, planning, verbal impulsiveness, and use of time. The screening list showed good sensitivity (0.80) and specificity (0.77), while test–retest validity was moderate, with an intraclass correlation of 0.56. The findings of this validation study also suggested that some of the questions may not be specific enough for the older age population to recognize ADHD symptoms (e.g. ‘Often has difficulty stopping his or her activities or behavior when he or she should do so’), or they may experience symptom manifestations which were not covered by the scale. Furthermore, for the screening tool to provide the results with the highest accuracy in older adults, the authors indicate that the symptom cutoff may need to be lowered from the one proposed for younger adults (6 points out of the maximum 9), as suggested earlier [60]. By keeping the same cutoff point adjusted for younger adults, the screening tool would capture only those older individuals with the most severe ADHD.

2.2. Differential diagnosis of ADHD in older adults

Establishing a differential diagnosis of ADHD in older adults can be challenging, as many medical conditions, such as depression and depressive pseudodementia, bipolar disorder, borderline and antisocial personality disorder, mild cognitive impairment (MCI), cognitive decline linked to menopause in women, and other neurocognitive disorders, and sleep disorders [5,62,63] have similar clinical presentations. Furthermore, older adults are more likely to receive medication for several medical conditions (i.e. polypharmacy) [64], which may similarly impact cognitive functioning to ADHD. Finally, normal cognitive aging itself may resemble some symptoms of ADHD. Thus, other psychiatric disorders in older adults should be primarily considered as potential causes of ADHD-like symptoms [7].

A particular challenge in establishing a differential diagnosis of ADHD may come from the similarities of ADHD symptoms with MCI, such as difficulty sustaining attention, issues with organizing activities, memory issues, and behavioral and psychiatric symptoms (e.g. mood swings, sleep disturbances, anxiety, and depression) [5,65]. These similarities are of relevance since MCI is quite common in older age. Indeed, findings from systematic reviews and meta-analyses have estimated that MCI is present in about 17.5% (95% CI = 13.8–20.8) of people aged 60 years and older in community samples [66], and 21.2% (95% CI = 18.7–23.6) of older adults living in nursing homes [67]. In the process of establishing a differential diagnosis in relation to MCI and dementia in older adults, there are several distinctive pointers that could be helpful [5,7,65]: (i) patients with ADHD typically report childhood onset of symptoms with a chronic course over time, while MCI is characterized by a more abrupt onset of symptoms in later life; (ii) patients with ADHD are usually more able to provide a detailed history of symptoms in comparison with patients with MCI, who often have issues with anterograde memory; (iii) history of learning difficulties or substance misuse is common in patients with ADHD, less so in those with MCI; (iv) a progressive and recent worsening of symptoms in later life, such as worsening of anterograde memory, not explained by any other psychiatric or medical conditions, is more likely a sign of MCI than ADHD, while patients with ADHD typically report fewer symptoms/less severe ADHD-like symptoms as they age; (v) patients with ADHD respond more positively to medication for ADHD than patients with MCI; and (vi) re-assessment of symptoms after 12–18 months should provide additional information in relation to the potential worsening of cognitive dysfunction, which is typical in individuals with MCI, with neuropsychological testing over time as an asset in establishing a differential diagnosis [7,68].

2.3. Validity of ADHD diagnostic criteria in older adults

Previous research on the validity of the ADHD diagnostic criteria in older adults has primarily focused on the age-of-onset criterion [69]. Sharma and colleagues argue that this criterion needs to be investigated and validated at a later age due to several issues linked to a later-life diagnosis [69]. A later-life diagnosis commonly heavily relies on self-report, primarily due to the unavailability of adequate collateral sources [70]. However, a retrospective assessment of childhood symptoms may be unreliable due to potential age-related issues with autobiographical memory [71] or ADHD-specific issues with long-term memory [72]. Indeed, issues with recall bias have been one of the reasons why older age individuals were typically excluded from previous research on ADHD in adults [73]. It has also been shown that self-reports in adults underestimate ADHD symptoms compared to reports from parents [16]. Furthermore, it is possible that cognitive/behavioral strategies and/or academic and work environments in earlier life, when well-structured/flexible enough, may compensate for the process deficits in ADHD. Consequently, with the increasing demands in occupational and/or social environments, individuals may start experiencing functional impairment due to ADHD symptoms when they also seek treatment. Additionally, due to low socio-economic status and poor access to health care at a younger age or ADHD being a relatively new clinical concept, symptoms of ADHD during childhood might not have been recognized as such. These reasons could impede the assessment in older individuals and lead to a missed diagnosis of ADHD. Furthermore, some authors suggest that age 16 may be a more appropriate age of onset to capture more adults with ADHD, rather than 12 years old, as it is currently required by the DSM-5 [55,74]. Nevertheless, confirmation of the age-of-onset criterion in adulthood should lessen the risk of misdiagnosis as other disorders with a similar clinical presentation, such as certain psychiatric disorders (i.e. anxiety, depression, substance abuse) [75] or neurological conditions at a later age [62,65]. Several alternative approaches to the age-of-onset criterion have been recommended, including confirmation of the persistence/chronicity of symptoms across years, the presence of symptoms during the developmental period, and using collateral informants and school records when possible [55,68].

Future longitudinal studies with follow-ups until older age are needed to investigate the validity of the age-of-onset criterion and other diagnostic criteria for ADHD in older adults.

3. Pharmacological treatment of ADHD in older adults: current evidence on treatment rates, medication response, and safety

A systematic review with meta-analysis from 2020 showed that the prevalence of individuals aged 50 and older who are treated for ADHD (0.09%, 95% CI = 0.06, 0.15) is less than half of the prevalence of those who received a clinical diagnosis in this age group (0.23%, 95% CI = 0.12, 0.43) [8]. An annual growth in the prevalence of pharmacologically treated ADHD in adults aged 45 and older has been reported in Nordic countries (i.e. Denmark, Finland, Norway, Iceland, and Sweden), US, UK, and Taiwan over the last two decades, but, overall, these prevalence estimates remain lower than the estimates of clinically diagnosed ADHD at the national level or community sample data [76–81]. Additionally, a Swedish register-based study has reported that among those diagnosed with ADHD, only 28.4% of older aged individuals (aged 65 and older) received pharmacological treatment for ADHD in comparison with 80% of those diagnosed with ADHD aged 22–64 years [80]. Also, a large epidemiological study from the US, with 35% of the participants being 45 years old and older, has reported that 44% of all adults diagnosed with ADHD have ever sought treatment, and 27.6% reported taking medication for ADHD [23]. Furthermore, a register-based study from Denmark [79], which has also identified an increase in the incidence of ADHD medication use in adults aged ≥50 years between 2000 and 2010 but a decrease in the incidence between 2010 and 2015, has found that ADHD medication is often used off-label as part of palliative care in older adults (e.g. in patients with cancer). Thus, the authors suggest that researchers should be wary of relying on ADHD medication data in identifying older individuals with ADHD.

Regarding the medication response and side effects of ADHD treatment in older adults, only a few observational and survey studies are available, while the evidence from randomized controlled trials (RCTs) is substantially lacking. In a survey study from Norway [82] conducted on 149 individuals (59.7% female) with ADHD aged 50 and older, 63.8% of them reported being on ADHD medication, with stimulant medications being the most commonly prescribed ones. Individuals who were currently treated for ADHD with medication reported significantly improved attention compared to the individuals who did not currently receive treatment. A study from the Netherlands [83] based on data from the Electronic Health Records (EHR) on 148 patients with ADHD (57% female) aged 55–79 years, from a specialized outpatient clinic, found that 65% of them reported a positive response (e.g. enhanced concentration, more overview, less restlessness, more stable mood, improved sleep) after a minimum seven days after their first dose of stimulant medication for ADHD. However, 42% of the patients discontinued their medication treatment due to side effects or nonresponse. Among the side effects reported as reasons to stop the medication, the most common were anxiety/depression, cardiovascular complaints, and sleep problems. Additionally, a small but significant decrease in weight and an increase in heart rate were identified during methylphenidate treatment. However, this study has several important limitations. Its findings were based on short-term response to treatment with an initial, low dose of stimulant medication for ADHD, without considering the personalized end dose of the medication for each patient; furthermore, the time between the start of treatment and the response assessment substantially varied between patients. Smaller observational studies from the US (24 individuals with ADHD, aged 60–77, 79% were currently taking ADHD medication) [27] and Israel (11 individuals with ADHD 55 years or older and treated with methylphenidate) [84] have also reported improvements in symptoms and no serious adverse effects due to medication treatment for ADHD.

A post-hoc analysis of data from a double-blind, placebo-controlled clinical trial from the US found that younger (until 25 years old, N = 55) and older adults with ADHD (ages 26–77, N = 481) showed similar improvements on several clinical scales with similar tolerability as a response to atomoxetine treatment, a non-stimulant ADHD medication [85]. Additionally, there was a slightly larger effect size in the younger age group but most likely due to a greater response variability than in the older group. However, the ‘older adults’ group covered individuals of younger and middle age as well (mean age = 43.4 years), which may limit the generalizability of the findings to the population of individuals aged 50 and older. Furthermore, a double-blind, placebo-controlled, two-period crossover trial conducted in 47 healthy adults aged 55 and older [86] found no significant correlation between age and changes in pulse or blood pressure changes with the administration of lisdexamfetamine dimesylate. However, clearance of the drug decreased with age. Moreover, a systematic review [87] has suggested that amphetamine and methylphenidate can be safely used in older adults, albeit based on limited evidence, and for treating conditions other than ADHD (e.g. apathy in dementia, stroke rehabilitation, poststroke depression).

3.1. Treatment of ADHD in older adults: clinical guidelines

Available national and international clinical guidelines provide detailed recommendations for children, adolescents, and adults. However, specific recommendations for older adults are limited [55,88–92]. Due to the lack of systematic empirical evidence in this age group, it is recommended to offer healthcare to older adults in the same manner as in younger and middle-aged adults, and to individualize treatment to the needs of each person through a multimodal and multidisciplinary approach which consists of psychoeducation, psychotherapy, behavioral/environmental adjustments, and pharmacological treatment [7]. After a full baseline assessment, medication should be offered to adult patients with ADHD after environmental modifications have been implemented and reviewed, with ADHD symptoms still causing significant impairment in at least one domain (e.g. education and occupational attainment, interpersonal relationships, risk awareness) [55,88,89,91,93]. The hierarchy in the choice of treatment should be established based on the presence of any comorbid conditions, with the most severe conditions or conditions causing the most severe functional impairment being treated first (e.g. severe depression or anxiety, psychosis, bipolar disorder, substance abuse). In contrast, milder conditions can be treated at the same time as ADHD, or symptoms of these conditions may be improved due to ADHD treatment.

Atomoxetine has been registered for use in adults by the European Medicines Agency (EMA) [93], and, as of 2021, at least one form of methylphenidate has been approved in 16 European countries even when ADHD treatment initiation is over age 18 [94,95]. In the US, the following ADHD stimulant medications are specifically approved for use in adults by the Food and Drug Administration (FDA): mixed amphetamine salts extended release (XR), osmotic release oral system (OROS) methylphenidate, dexmethylphenidate XR, and lisdexamfetamine, and non-stimulants atomoxetine [7] and viloxazine [96]. The upper age limit for these medications depends on the corresponding drug trials; for instance, the upper age limit is 55 years for lisdexamfetamine and 65 years for mixed amphetamine salts XR. An additional issue for the generalizability of the results from these clinical trials to the population of older adults is that such studies typically exclude individuals with comorbid physical and psychiatric conditions, which are common in older age. Furthermore, prescribing recommendations by the FDA list symptomatic and/or severe cardiovascular disease as a contraindication to amphetamines and atomoxetine treatment for ADHD, and a cardiovascular assessment is advisable in patients with a suspected increased cardiac risk [7].

The few available recommendations on the treatment of ADHD in older adults specifically can be found in the 2018 Canadian ADHD Practice Guideline [89] which recommends first-line medications (i.e. long-lasting psychostimulants) for ADHD as the treatment of choice, taking into account the overall health of the patient and potential drug interactions due to polypharmacy. Furthermore, the Guideline on the clinical investigation of medicinal products for the treatment of attention deficit hyperactivity disorder issued by the EMA in 2008 [93] provides a short section on older patients with ADHD, in which the emphasis is placed on the dosing and safety of central nervous system active drugs. However, no further updates to these guidelines have since been issued. Several expert literature reviews investigating the assessment and treatment of ADHD in older adults have tried to address the gap in clinical recommendations [5,7]. For instance, Kooij et al. [5] recommend considering somatic comorbidities in older adults, as well as drugs used to treat these comorbidities and potential medication interactions and their side effects. They also recommend starting with lower doses of stimulant medication until the optimal dosage has been reached based on the clinical evaluation of the achieved improvement and side effects. Due to a higher cardiovascular risk in older adults, the authors recommend: screening cardiovascular risk factors in all adults aged 50 and older for potential cardiac complaints in the last 6 months; a cardiac history (high cholesterol/triglycerides, hypertension, diabetes, and medications for these disorders); a family history of cardiovascular disease; and a physical exam including the assessment of pulse, blood pressure, weight, edema, and an electrocardiogram (ECG), conducted by a physician or cardiologist [5]. After each increase in dosage and stabilization, it is suggested to monitor blood pressure, pulse, and weight every 6 months. In case of cardiovascular side effects (e.g. hypertension, persistent elevated heart rate), the medication/dosage should be adjusted, or if a clinically significant improvement in symptom alleviation has been achieved, additional medications should be considered to treat the side effects (e.g. antihypertensive medications or low-dose beta-blockers). Further, Goodman et al. [7] recommend that special consideration should be in place in case of a positive history of psychosis and mania or substance use disorder, as these disorders may be exacerbated by ADHD pharmacological treatment. They also recommend that clinicians treating older adults should identify and monitor any conditions that might be exacerbated by increased sympathetic tone, such as hypertension, arrhythmia, urologic/sexual function, poor peripheral circulation, and to monitor potential issues with age-related decline in renal or hepatic function which could alter the effects of ADHD medication [7].

In relation to cardiovascular risk, it is worth highlighting some recent efforts aimed at optimizing the accuracy of cardiovascular disease (CVDs) risk prediction in adults with ADHD [97]. In particular, a two-year prediction model of CVDs in adults initiating pharmacological treatment has been developed. This model demonstrated that by considering novel CVD predictors which are relevant in the population with ADHD, such as substance use disorder and the use of other psychotropic medication, in addition to traditional cardiovascular risk factors (e.g. hypertension, obesity, smoking, diabetes mellitus, family history of cardiovascular disease) may improve the prediction of adults with ADHD at high risk of developing CVD. However, external validation of this model and studies assessing its clinical impact are needed, with a particular focus on older adults who are at high risk of developing CVD.

4. Conclusions

Although ADHD persists in a substantial number of individuals until older age, previous studies on ADHD have commonly excluded older individuals. Nevertheless, it has been suggested that older adults with ADHD report significant functional impairment, decreased quality of life, and increased risk of psychiatric and physical health multimorbidity, comparable to the adverse outcomes of ADHD experienced in younger adults. The latest editions of DSM (i.e. DSM-5(TR)) and ICD (i.e. ICD-11) have allowed the inclusion of adults – who were previously overlooked by clinicians – by, for instance, decreasing the number of symptoms needed for a diagnosis, increasing the upper age of symptom onset, allowing for the inclusion of individuals in partial remission, and providing more descriptions of symptom manifestation adjusted to adults. Yet, these diagnostic systems do not specifically address older adults. A particular challenge in establishing a differential diagnosis of ADHD in older adults may come from the similarities in the clinical presentation present in other medical conditions, due to medication/substance use, or changes accompanying normal cognitive aging. Therefore, other medical conditions should be primarily considered as a cause of ADHD-like symptoms in older individuals. Longitudinal studies following individuals until older age are needed to investigate the validity of diagnostic criteria for ADHD in older adults. Furthermore, validation studies of available screening and diagnostic tools in this age group are warranted.

Concerning the treatment for ADHD, available clinical guidelines provide very limited recommendations for older adults specifically. A general approach should correspond to the treatment recommendations in adults, with a multidisciplinary and multimodal approach consisting of psychoeducation, psychotherapy, and pharmacotherapy. Before the initiation of pharmacological treatment, particular attention should be placed on assessing and monitoring the general physical health, potential comorbidities that might be exacerbated by ADHD medication (e.g. increased blood pressure or heart rate), and co-medication due to potential medication interactions. Epidemiological studies have suggested an increasing prevalence of prescribing pharmacological treatment for ADHD in older adults, indicating an increased awareness of ADHD in adults. Nevertheless, treatment rates remain lower than the reported prevalence estimates of clinically diagnosed ADHD in older adults. Current evidence on the safety, effectiveness, and efficacy of ADHD medication in older adults is scarce. Although there have been some indications that pharmacological treatment may be safe and effective in treating ADHD in this age group, more studies, and RCTs in particular, are warranted. Such studies should provide evidence-based input for national and international ADHD treatment guidelines tailored for older adults specifically.

5. Expert opinion

It is expected that future editions of the DSM and ICD will address the current gaps in the diagnostic definition of ADHD in older adults by providing specifiers to the standard ADHD criteria, in terms of the required number of symptoms for the diagnosis (if any), the weight of each symptom and possibly, additional criteria specific for older adults. Notably, while the DSM-5-TR has retained a minimum number of symptoms in the criterion A as essential for the diagnosis (‘Six or more symptoms of inattention for children up to age 16 years, or five or more for adolescents age 17 years and older and adults; Six or more symptoms of hyperactivity-impulsivity for children up to age 16 years, or five or more for adolescents age 17 years and older and adults’), the ICD-11 does not require any minimum number of symptoms. This might lead to increased diagnostic rates, with a related increase in ADHD medication prescription rates. This may be particularly problematic in older adults whose cognitive symptoms can be exacerbated by physical and mental comorbidities. Pharmacovigilance studies will need to carefully assess such possible trends. Rather, it states that ‘Attention deficit hyperactivity disorder is characterized by a persistent pattern (at least 6 months) of inattention and/or hyperactivity-impulsivity that has a direct negative impact on academic, occupational, or social functioning.’ The lack of a minimum number of symptoms highlights the importance of impairment, rather than the mere count of symptoms which can be misleading (e.g. an individual with 5 symptoms of inattention and 5 symptoms of hyperactivity/impulsivity would not meet the criteria for the diagnosis, while another one with 6 symptoms of inattention and 0 of hyperactivity/impulsivity would). Should an approach without minimum symptoms be retained also for older adults, it will be important to clarify how impairment is established for this clinical population. Classification systems should also include specific differential diagnoses for older adults, and how differential diagnoses can be ruled out.

It is also expected that the increasing number of epidemiological studies will allow high-quality evidence synthesis – such as the one included in the Global Burden of Disease (GBD) study – providing rigorous estimates on the prevalence, incidence, and burden of ADHD in older adults that can inform policymakers. In terms of treatment, we predict an increasing number of RCTs assessing the efficacy/effectiveness and tolerability/safety of pharmacological as well as non-pharmacological interventions (e.g. cognitive behavioral therapy, cognitive training, mindfulness) – and adaptations of these interventions needed in this population. This body of research will be included in meta-analyses, network-meta-analyses, and individual patient data (network) meta-analyses, which, combined with data from rigorously conducted observational studies, will inform future guidelines and clinical guidance on the management of ADHD in older adults. It will be particularly relevant for guidelines to inform how ADHD symptoms can be managed within the framework of physical multimorbidity (e.g. cardiovascular and endocrinological morbidity) which is frequent in older adults. Also, it should be clarified what are the maximum recommended dose of stimulants and non-stimulants in older adults, based on safety/tolerability, and if these maximum doses differ in relation to what is recommended in guidelines and formularies for children, young people and young adults. Additionally, the safety of combining stimulants or non-stimulants with other medications in older adults would be a priority in psychopharmacology research for older adults with ADHD. Another line of research of interest would be around the establishment of factors that predict the persistence of ADHD or ADHD-impairing symptoms in older adults, which would potentially inform preventive strategies.

Article highlights

• Although significant functional impairment and health issues associated with ADHD may persist throughout the lifespan, ADHD has been largely understudied in older adults.

• Current DSM and ICD diagnostic criteria for ADHD allow for broader recognition of affected individuals across the lifespan. Yet, these criteria do not specifically address the clinical presentation of ADHD in older adults.

• In establishing a differential diagnosis of ADHD in older adults, particular attention should be paid to conditions with a similar clinical presentation, such as mild cognitive impairment.

• National and international treatment guidelines for ADHD provide very scarce or no recommendations for older adults.

• In general, a multimodal and multidisciplinary approach to the treatment of ADHD in older adults is recommended. Assessing and monitoring general physical health and comorbidities/co-medication prior to and during pharmacological treatment is particularly relevant in older adults due to high physical comorbidity rates and increased cardiovascular risk in older age.

• Limited evidence suggests that pharmacological treatment in older adults may be relatively safe with similar benefits as in younger adults. Additional studies, particularly randomized controlled trials, on the efficacy and safety of pharmacological treatment in older adults, are warranted.

Declaration of interest

H Larsson reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals and Evolan Pharma AB; all outside the submitted work. H Larsson is also the editor-in-chief of JCPP Advances. S Cortese declares honoraria and reimbursement for travel and accommodation expenses for lectures from the following nonprofit associations: the Association for Child and Adolescent Central Health (ACAMH), the Canadian ADHD Alliance Resource (CADDRA), the British Association of Pharmacology (BAP), and from the Healthcare Convention for educational activity on ADHD. S Cortese is Deputy Editor of BMJ Mental Health, Consulting Editor of the Journal of the American Academy of Child and Adolescent Psychiatry, and Joint Editor of the Journal of Child Psychology and Psychiatry. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

M Dobrosavljevic acknowledges funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No [754285]. H Larsson acknowledges financial support from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 965381, the Swedish Research Council [2018-02599; 2022-01119] and the Swedish Brain Foundation [FO2021-0115; FO2022-0327]. S Cortese acknowledges research support through grants from the National Institute for Health and Care Research (NIHR) [NIHR203684; NIHR203035; NIHR130077; NIHR128472; RP-PG-0618-20003] and the European Research Agency [101095568-HORIZON- HLTH-2022-DISEASE-07-03].