Explanation of the terms life-limiting illness, palliative care, end-of-life care and advance care directives.
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People are at risk of diabetes due to genetic inheritance, epigenetic factors, age and lifestyle-related factors. The International Diabetes Federation (IDF) [1] estimated 123 million people aged 65–99 had diagnosed diabetes and predicted the number would increase to 438 million by 2045. Most older people have type 2 diabetes (T2DM), but people with type 1 diabetes (T1D) survive to older age. These data do not take account of the people with prediabetes who may already have one or more life-limiting diabetes complications at diagnosis.
\nAn estimated ~ 20 million people globally need palliative care the year before they die; a further 20 million need end-of-life care per year [2]. The World Health Organization (WHO) estimated that 71% of deaths in 2016 were associated with diabetes complications. Most (~67%) occur in people aged 60 and older [3]. Therefore, older people with diabetes may have more than one life-limiting condition.
\nAging is associated with reduced insulin production and insulin sensitivity that lead to insulin resistance, which increases by 1–2% per year [4]. Older age is generally defined as older than age 65 [5]. However, chronological age is not a good guide to disease, functional status, care needs or life expectancy. Biological age is a more accurate indicator of the rate at which body cells deteriorate but is more difficult to measure. Significantly, the individual’s chronological and biological age may be different [5].
\nMany older people have several coexisting comorbidities/geriatric syndromes, including cardiovascular disease, renal disease, sensory impairments, lower limb pathology, cognitive changes/dementia, some forms of cancer and frailty that individually and collectively affect life expectancy [6, 7, 8, 9]. Frailty predicts admission to a care home and mortality and increases the risk of death [10, 11]. Frailty is assessed in various ways, including phenotype and accumulation of deficits. The latter may be more useful to prognostication.
\nMany older people with diabetes have at least three coexisting comorbidities, but these are often managed as single entities that may not address the many diffuse symptoms [12, 13, 14] or the need to change the focus of care from achieving normoglycaemia to prevent complications to focus on comfort by managing existing complications and preventing hypoglycaemia and hyperglycaemia.
\nPeople with diabetes who can maintain near-normal glycaemia (~7%) and normal lipids and blood pressure are less likely to develop complications and may not have significantly reduced life expectancy. However, these parameters are often abnormal some 10–15 years before type 2 diabetes (T2DM) is diagnosed, and complications can be present and affect life expectancy from diagnosis [7, 12]. In addition, older people are less likely to benefit and more likely to be harmed by ‘tight blood glucose control’. Therefore, blood glucose and HbA1c target ranges need to be individualized to minimize risk, especially hypoglycaemia risk and other risk factors being managed [15, 16].
\nDiabetes and the associated comorbidities affect the quality of life, compromise function and self-care and increase the need for hospital admissions and readmissions and eventually lead to death [11, 13, 17]. Over 50% of people aged 65–80 experience moderate to severe disability and increased dependency. On average, they need care 24 hours/day between 1.3 and 6.9 years [18].
\nSignificantly, older people with diabetes and concomitant heart failure who have several recent hospital admissions and consult multiple prescribers are at risk of readmission within 30 days [19]. Hospital admissions near the end of life often result in burdensome and futile treatment that causes significant suffering and stress for the individual and their family [19, 20]. Likewise, people with cognitive impairment face many challenges, including decisions about their care.
\nThus, starting conversations about the likely prognosis early in the disease trajectory can enhance people’s capacity to make meaningful decisions and enable them to document their values and care preferences [21, 22]. In turn, clearly documented values and care preferences enhance family and health professionals’ capacity to make care decisions consistent with the person’s values and reduce decisional uncertainty.
\nQuality diabetes care is described in many clinical guidelines such as the IDF [7], American Association of Diabetes/European Association for the Study of Diabetes [23], Australian Diabetes Society [24] and Diabetes UK [25]. Many recommend ‘relaxing’ glycaemic targets in older people to reduce the risk of hypoglycaemia and its consequences: they usually do not include comprehensive guidance about other key aspects of palliative and end-of-life care. Exceptions are the IDF Global Guideline for Managing Older People with T2DM [7] and Guidelines for Managing Diabetes at the End of Life (currently under review) [8] and Diabetes UK [26].
\nQuality diabetes care encompasses achieving normoglycaemia (HbA1c <6.5 7%), controlling blood lipids and blood pressure using diet and exercise and commencing glucose-lowering (GLM), lipid-lowering and antihypertensive agents and other medicines when indicated, providing diabetes self-care education and undertaking regular health assessments. Self-care and adherence to recommendations are important to maintain health and meet metabolic targets.
\nAssessments could also encompass determining when the individual could benefit from palliative care and when to document an end-of-life care plan and an advance care directive (ACD). However, many clinicians find it difficult to discuss death and dying (giving bad news). Consequently, they miss opportunities to initiate conversations about these issues, and beneficial palliative care can be delayed [20, 21, 27]. Death cannot be cured: people’s end-of-life can be made comfortable, dignified and consistent with their values and care preferences when these are known, clearly documented and communicated.
\nMany clinicians regard death and dying as treatment failure [28]. The terms ‘failure’ and ‘bad news’ are inherently negative. People often know they are not going to recover and want affirmation from their health professionals [28]. Some people express the wish to die while their identity and personhood can be maintained and not when they are terminally ill and incapable of making rational thoughts and informed decisions [29]. When such discussion does occur, health professionals often present the options as a choice between continuing and withdrawing treatment.
\nPalliative care originated in the 1960s and largely focused on end-of-life care at that time. More recently, there is increasing recognition that people with chronic disease could benefit from palliative care; thus the term broadened in meaning and scope to include non-communicable chronic diseases [30]. Most adults with chronic disease need palliative care as a result of cardiovascular disease [9, 11]. Diabetes is the leading cause of cardiovascular disease, and, in turn, cardiovascular disease is the leading underlying cause of diabetes-related deaths [3, 6, 31]. All health professionals who care for people with diabetes have a role in timely implementation of palliative care. Therefore, health services need to integrate such care into the services they offer and policies [32].
\nThe patterns of dying are changing as more people follow the chronic disease trajectory, which is characterized by periods of deterioration followed by recovery until physiological reserves are depleted and the person reaches the terminal and end-of-life stages [32, 33, 34]. Many experts recommend palliative care should be implemented early in the disease trajectory, sometimes from diagnosis, for greatest benefit [30, 32]. In fact, Murray et al. recommend ‘[clinicians] should routinely and systematically consider whether our patients might benefit from early palliative care’ [34]. Table 1 explains the terms palliative care, life-limiting illness, end-of-life care and advance care planning.
\nTerm | \nExplanation | \nConsiderations | \n
---|---|---|
Life-limiting illness | \nThe term life-limiting illness (LLI) describes people at high risk of dying in the subsequent 12 months. Many people admitted to hospitals and ICUs have a life-limiting illness. The Gold Standards Framework Proactive Indicator [33] outlines indicators of life-limiting illnesses for cancer, chronic obstructive pulmonary disease, heart failure, renal disease, neurological diseases, frailty, dementia and stroke Diabetes is not specifically mentioned in the GSF. It does mention organ failure, kidney disease, dementia and multimorbidity. Diabetes is the main underlying cause of renal disease, cardiovascular disease and some forms of cancer, frailty and dementia. Therefore, it is often unclear what ‘initial’ disease commenced the underlying pathological changes, which could be an inflammatory process related to obesity | \nDiabetes experts recommend normalizing blood glucose, lipids and blood pressure to reduce the risk of complications that can reduce life expectancy Palliative care experts and many geriatricians recommend people to document their values and end-of-life preferences while they are able to make informed, autonomous decisions Fewer than 50% of people with life-limiting illnesses actually have documented goals of care, and < 24% has documented care goals [36] | \n
Palliative care | \nThe aim of palliative care is to improve the quality of life, relieve suffering and manage distressing symptoms Palliative care involves symptom management, prognostication, advance care planning and transition to the dying/terminal stage [36] Palliative care can be used at any time and can complement usual diabetes care. Palliative care should be commenced early for maximum benefit to archive these aims [3, 31]. Early palliative care also increases satisfaction with care [34] | \nMany older people with diabetes could benefit from combining palliative care into their usual diabetes care as function changes and the burden of medicines and complications increase They also benefit from the support to document advance care directives much earlier than it currently occurs [36, 37] Good communication is essential to support older people to make informed decisions and to document their values and care preferences and goals | \n
End-of-life care | \nThe last 12 months of life and includes imminent death in a few hours or days [2, 30, 33] Four phases are described: stable, unstable, deteriorating, terminal [38] | \nMany people want to die at home, but most older people with multiple comorbidities die in hospital [39] Recognize/diagnose dying Identify whether unstable disease is likely to be remediable or likely to continue to deteriorate and progress to the terminal stage Treat or implement end-of-life care | \n
Advance care directive (ACD) | \nAdvance care planning (ACP) is the process used to develop and ACD ACD is a document that clearly describes an individual’s values and the type of treatment they want if they are not capable of deciding for themselves and guides their medical treatment decision-maker and clinicians to make decision on their behalf that accord with their values and care preference [40] ACDs are often first documented when the individual has a rapid response team (RRT) call to assess sudden deterioration [41, 42] It is important to consider cultural and religious conventions when discussing ACDs. These differ among cultures and within cultures and influence laws and regulations and the way individual’s view end of life and ACDs | \nImportant information for older people with diabetes to document in their ACD are the things they value and give meaning and purpose to their life (values directive), the care they want to receive and the care they do not want to receive [40]. Generally the ACD does not have to be completed all at once. Older people need time to think about the issue and discuss them with relevant people. So, start the conversation and follow up at a later time It is important to check the persons’ care preferences as part of ongoing care because they can change over time. Values remain relatively constant | \n
Explanation of the terms life-limiting illness, palliative care, end-of-life care and advance care directives.
It is certain that everybody will die eventually. The uncertainty lies in when and how an individual will die. The trajectory to death for people with diabetes can be a long and healthy one but is often a long process of physical and social decline followed by recovery until the final stages of life: the so-called chronic disease trajectory [2, 43, 44]. People can die, seemingly suddenly, during a disease exacerbation. However, most of these people have one or more indicators of limited life expectancy. Thus, their death was possibly predictable: the time of death might not have been. Episodes of deterioration become increasingly frequent over time and reduce the remaining physiological reserve and the person’s ability to recover from subsequent exacerbations.
\nThe chronic disease trajectory to end of life is unpredictable and includes many periods of deterioration and recovery before death occurs [38, 43, 44], which creates a degree of diagnostic uncertainty for many health professionals, people with diabetes and families. The uncertainty is compounded by challenges associated with prognostication and, sometimes, from misinterpreting individual’s questions such as ‘how long have I got Doc?’ Mostly the individual wants an idea about how long they have left ‘to put their house in order’ and ‘say my goodbyes’. Such questions could be a cue to health professionals to begin advance care planning to document the individual’s values and care goals and preferences. Some strategies to enhance such conversations are shown in Table 2.
\n\n
\n
Older people need time to process the question in order to respond—a complex cognitive process, especially when the topic is emotive. Interrupting can cause confusion and change the discussion, and important issues might not be identified Understand and accept that not everybody is capable of making informed decisions during a crisis and some people prefer certainty, i.e. to be ‘told what to do’ | \n
Diagnostic uncertainty encompasses cognitive, emotional and ethical reactions, which are affected by the need to discuss care options with the individual and often their families as well as organizational culture and personal experience [31] and individual tolerance of uncertainty [45]. Some degree of uncertainty occurs in nearly every aspect of health care and influence clinician and patient outcomes. Types of uncertainty include disease, therapeutic (risk and benefit) and prognosis [46].
\nInformed shared decision-making requires the individual to understand their illness, their treatment options and prognosis. Clinicians may not be comfortable disclosing their uncertainty to the individual [22, 46] and may refer them for a second opinion, admit them to hospital and/or order a barrage of diagnostic investigations [47]. These actions may or may not be indicated/warranted.
\nSudden, unexpected death occurs in ~ 25% of deaths [2, 20]; however, diabetes-related deaths are often multifactorial, which makes it more difficult to predict life expectancy. A number of changes and well-defined patterns accompany functional decline to the end of life. These patterns are described in a series of disease trajectories [43, 44]. Prognostic indicators, include the Gold Standards Framework Proactive Identification Guidance (PIG) [35], life expectancy and risk calculators, the Diabetes Complications Severity Index (DCSI) [47], Cardiovascular risk tools and life expectancy calculators. These tools and calculators can help health professionals tailor care with the individual and start conversations about advance care planning.
\nSome experts recommend using absolute risk to decide which people are most likely to benefit from treatment because it considers the whole person and their individual determinates of risk [48]. These tools do not predict death. They are a guide to self-care education and care planning.
\nGeneral indicators described in the GSF that indicate palliative care could be beneficial include:
Decline in health and function.
Unplanned hospital admissions.
Symptoms that are difficult to manage.
The person becomes less responsive to treatment.
Person chooses not to accept active treatment.
> 10 Kg progressive weight loss in the preceding 6 months.
Serum albumin <25 g/L—other guidance suggests <5% in people with sarcopenia.
More than 50% have a significant life event such as a fall, admission to a care home or bereavement.
In addition, a range of diabetes-related factors associated with reduced life were identified in a targeted literature review [49, 50, 51] and include:
Long duration of diabetes.
Macro- and microvascular complications [49]. Diabetes significantly increases the risk of all-cause and cardiovascular mortality in men and women by two- to fourfold [50].
Glucose variability (fluctuation between high and low blood glucose levels) and rapid reduction in HbA1c [52, 53, 54].
Multimorbidity: 80% of people 80 years and older have an average of 3.6 morbidities [54, 55].
Severe hypoglycaemia [56, 57, 58] especially in older people and those on sulphonylureas or insulin and those with hypoglycaemic unawareness, including dementia.
Polypharmacy [61].
Cancer contributes to increased mortality in T2DM.
Comorbid depression [62]: it is important to recognize and explore suicide ideation; suicide is twice as common in older people, and depressive symptoms are present in 80% of people > aged 74 who commit suicide. The severity of depression is a determinant of suicidal ideation [63].
This information and other prognostic indicators can be used independently or together to guide discussions with people with diabetes about advance care planning, their ACD and when to initiate palliative care. Documenting and ACD are part of holistic, evidence-based quality care.
\nUncertainty occurs in all areas of health care, not just palliative and end-of-life care. A number of strategies can help clinicians reduce decisional uncertainty. These include:
Acknowledging their uncertainty to themselves, colleagues, the individual and their family [46]. Not acknowledging uncertainty leads to further uncertainty and other problems. Acknowledging it can help build rapport and trust with the individual and their family.
Accepting that death is normal and being able to recognize common disease patterns and their consequences that compromise life expectancy, signs of deterioration and signs that death is approaching. Guidance concerning these issues is described in the GSF [33], Murtagh et al. [31] and a suite of three tailored versions of information for older people with diabetes, family carers and clinicians [64].
Understanding that many people choose comfort and quality of life over a longer life.
Being able to recognize deterioration beyond the clinical parameters used in acute care. For example, using the GSF, which recommends asking the ‘surprise question’: ‘would I be surprised if this person died soon?’ The answer, yes or no, can guide treatment decisions, including whether and when to implement palliative care and aspects of usual diabetes care such as HbA1c, blood glucose monitoring and other metabolic parameters and when to initiate conversations about advance care planning with the individual older person and relevant others.
Developing communication skills and the confidence to discuss palliative and end-of-life care. These skills increase following communication skills training [65] and include asking ‘good/appropriate’ questions, listening to the answers and using relevant probing and clarifying questions when relevant; see Table 2.
Understanding that ACP is an iterative process that can be achieved using structured ACP communication tools and processes.
Consulting the individual’s ACD. ACDs are an outcome of advance care planning; they inform clinicians and families about the individual’s values and preferences and enable medical treatment decision-makers, family and clinicians to make decisions consistent with the person’s values when they are unable to decide for themselves [40, 64, 65].
Asking about subjective life expectancy such as will to live is a strong predictor of survival in all age groups and genders [66, 67].
Asking questions about self-rated future health, e.g. in 5 years, and adjusting for known mortality risk factors [67].
Considering the health and care burden of informal/family carers: their subjective care burden is linked to various health outcomes for the care recipient including mortality risk [67, 68].
Considering relevant policies, regulations and legislation that apply where the clinician works [51, 66].
These strategies show that subjective information and shared decision-making is an important part of the health assessment and risk calculations. After all, death is a very personal experience. They can help clinicians can include palliative and end-of-life care in usual diabetes clinical practice guidelines, is important.
\nFigure 1 depicts a framework for integrating diabetes and palliative and end-of-life care based on function and the chronic disease trajectory. The information can be used as a basis for developing a personalized care plan and with usual diabetes and palliative care guidelines.
\nProposed framework for integrating diabetes care with palliative care that supports function and proactive care planning. Reproduced from Dunning et al. [72] with permission. The framework has not been formally evaluated at this stage.
Commencing palliative care does not mean usual diabetes care is abandoned. All care must be based on the best evidence. Care must be personalized and, ideally, developed in consultation with the older individual and often their family carers. People with diabetes do receive ‘usual’ palliative care, but it may not encompass important diabetes-specific issues that need to be considered. Specific information about these issues can be found in Dunning et al. [8] and Diabetes UK [26].
\nPreventing hyperglycaemia is important to prevent ketoacidosis and hyperosmolar states, both of which cause considerable discomfort and can be fatal. Likewise, preventing hypoglycaemia is imperative. It is often missed because of the changed symptomatology and can become chronic. Hypoglycaemia is a risk factor for frailty [69] and cardiovascular disease [70] and leads to short-term cognitive changes and dementia in the longer term.
\nT2DM is associated with brain aging and cognitive changes that affect memory and learning and contribute to depression in the longer term. Thus, blood glucose monitoring in a suitable regimen tailored to the medicine regimen and hypo-hyperglycaemia risk profile can provide important information about glucose variability, the medicine regimen and care needs.
\nPharmacovigilance is important and includes regular medicine reviews, stopping medicines and using non-medicine options where possible and selecting the lowest effective dose when medicines are indicated. Insulin might be a safer option than some other glucose-lowering medicines and can be used with a palliative intent, that is, to improve comfort by managing unpleasant symptoms associated with hyperglycaemia. Some medicines are diabetogenic, and it is important to diagnose hyperglycaemia caused by medicines such as glucocorticoids and manage it appropriately.
\nUndernutrition can contribute to frailty, hypoglycaemia, slow wound healing and falls and can be present in overweight individuals. Eating disorders, depression, difficulty swallowing and other causes can be present. Likewise cancer, thyroid disease and other diseases can cause weight changes. These factors highlight the value of comprehensive geriatric assessments and collaborative interdisciplinary care.
\nFamily carers play a vital role in the care of children and older people with diabetes by helping with diabetes self-care and other activities of daily living. They are at risk of sleep deprivation, reduced immunity, depression and unresolved bereavement after their relative dies [68]. It is important to monitor their health and provide counseling and support.
\nLong-standing diabetes and associated complications significantly increase the risk of disability and frailty and reduce life expectancy. Palliative care can be used with usual diabetes care. Proactively planning for diabetes palliative care is important. Diabetes reduces life expectancy and can cause significant suffering. Considering the indicators of reducing life expectancy and implementing palliative care early into the diabetes care plan has many benefits, including reducing the suffering and the burden on the individual and family carers. Atypical symptoms associated with older age can make it difficult to recognize deterioration and underlying causes.
\nPeople admitted to hospital near their end of life are more likely to receive burdensome treatment such as admission to intensive care, resuscitation, dialysis and blood transfusions that are often futile [45, 46] and distressing for the individual and their families. Health professionals have an important role in helping older people with diabetes to plan for predictable changes in health status and to initiate timely palliative and EOL care to prevent unnecessary admissions to hospital and/or invasive intensive care that have little benefit, even when it prolongs life, and may not accord with the individual’s core values. It is difficult for health professionals and family to make care decisions when the individual’s values and wishes are not known, documented and communicated.
\nThe authors acknowledge the older people with diabetes and their families and health professionals who served on research advisory groups for their research. The Diabetes Australia Research Program funded the research that enabled them to develop a suite of information to help older people with diabetes, family members and clinicians initiate discussions about palliative and end-of-life care. It is referenced in the chapter.
\nThe authors have no conflicts of interest to declare.
The authors conceived and wrote the chapter.
\nAttention-deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent symptoms of inattention and/or hyperactivity-impulsivity. There are three subtypes of ADHD, marked by predominantly inattentive symptoms, or by hyperactivity and impulsiveness, either a combination of inattentiveness and hyperactivity [1]. Studies suggest that the prevalence of ADHD among children may be as high as 15.5%, with approximately 20% of cases persisting into adulthood [2, 3]. A lower prevalence of ADHD in adults compared with children is consistent with the age-dependent decline of the disorder, which has been confirmed in a meta-analysis [4]. ADHD is diagnosed twice as often in boys as in girls. Boys with ADHD tend to present with more impulsivity, while girls with ADHD tend to have more inattentiveness [5].
The etiology and pathophysiology of ADHD are incompletely understood. There is evidence of a genetic basis for ADHD and secondary environmental risk factors. Differences in the dimensions of the frontal lobes, caudate nucleus, and cerebellar vermis have been demonstrated. Neuropsychological studies have demonstrated deficits in executive functioning and alterations in the motivation and reward among individuals with ADHD [6]. There is both empirical and theoretical support for an association between ADHD and SUD. ADHD and SUD are believed to have shared pathophysiology. Dopaminergic dysregulation of the motivational and reward system of the midbrain the basal ganglia and the frontal cortical regions influence executive functions and response inhibition which are key characteristics in both disorders [6, 7].
The essential feature of a substance use disorder (SUD) is a cluster of cognitive, behavioral, and physiological symptoms. This indicates that the individual continues using the substance despite significant substance-related problems. An essential characteristic of SUD is an underlying change in brain circuits. These changes may persist beyond detoxification, particularly in individuals with severe disorders. The behavioral effects of these brain changes may be exhibited in the repeated relapses and intense drug craving when the individuals are exposed to drug-related stimuli. The diagnosis of a SUD is based on a pathological pattern of behaviors related to use of the substance, which includes impaired control over substance use, the consummation of substance in more significant amounts or over a longer period, persistent desire to cut down or regulate substance use, a great deal of time spent in using the substance, craving for the drug, social impairment, risky use of the substance, and pharmacological criteria including tolerance and withdrawal [1].
One of the most frequent co-occurring disorders with adult ADHD is SUD. A meta-analysis reported a prevalence of 15–20% of ADHD in adults diagnosed with SUD (nicotine excluded) [8, 9].
International consensus statement concluded that screening questionnaires such as the Adult ADHD Self-Report Scale (ASRS) are useful in screening patients presenting with SUD followed by in-depth diagnostic assessment if the screener is positive or if the clinician has a strong clinical feeling about the possible presence of ADHD. ADHD and SUD experts agreed that the simultaneous and integrated treatment of ADHD and SUD using a combination of pharmaco- and psychotherapy is recommended [10].
The aim of this study is to summarize extant scientific literature concerning the comorbidity of ADHD and SUD on the etiology, prevalence, diagnosis, and treatment.
Publications on adults with combined ADHD and SUD were included focusing on etiology, prevalence, diagnosis and treatment. PubMed search was performed for articles published between 2010 and 2020 using the terms: adult ADHD, drug abuse, substance use disorder, addiction, and dependence. Publications were limited to articles published in English and were discarded if: they did not include adults; ADHD or SUD was not the primary diagnosis; they were reviews before a meta-analysis; they were personal opinion papers; and they were study protocols. The search was conducted on August 17, 2020.
A total of 143 articles were found on initial search and screened on title and abstract. Of these, 68 articles did not discuss a combination of ADHD and SUD specifically. Articles focusing solely on children or discussing other topics were excluded (n = 9) and also those in other languages (n = 7) or they were too old (n = 13). A total of 46 peer-reviewed studies were included for full-text review. Additional five articles were found with cross-referencing cited by authors that had not been found by initial research.
All together 51 articles were focusing either on etiology (n = 6), prevalence and symptom severity (n = 28), screening (n = 4), and treatment (n = 13) of adult ADHD and SUD.
A study exploring childhood trauma exposure in SUD patient with ADHD and control group found higher rates of childhood trauma in ADHD and SUD patients, but not with the persistence of childhood ADHD into adulthood [11]. A familial risk analysis of probands followed from childhood to young adulthood found that SUDs in probands increased the risk for SUDs in relatives irrespective of ADHD status [12].
A large trans-ancestral genome-wide association study (GWAS) of alcohol dependence revealed common genetic underpinnings with ADHD, which indicates shared etiology between the two disorders [13]. Shared genetic susceptibility ADHD and SUD is also reported in Spanish study with polygenic scores based on GWAS [14]. Study on shared genetic contribution of the ADHD and SUD showed significantly increased frequency of the dopamine beta-hydroxylase (DBH) rs2519152 and the opioid receptor mu-1 (OPRM1) risk genotypes rs1799971 [15]. Dutch International Multicenter ADHD Genetics study reported that the serotonin genetic risk score significantly predicted alcohol use severity, but no significant serotonin × dopamine risk score or effect of stimulant medication was found [16]. An Italian study reported that patients with ADHD showed a higher intensity of craving for heroin than patients without ADHD in the absence of withdrawal symptoms. We can conclude on shared neurobiological mechanisms that mutually influence the evolution of both disorders where dopamine dysfunction within various brain circuits may influence impulsivity levels, motivation, inhibitory control, executive functions, and behavior and, consequently, the intensity of craving [17].
A study which analyzed commercial health-care claims from adolescent and adult ADHD patients shows results that receiving ADHD medication is unlikely to be associated with a higher risk of substance-related problems in adolescence or adulthood. Instead, medication was associated with lower concurrent risk of substance-related events and, at least among men, with lower long-term risk of future substance-related events [18].
Existing evidence shows a prevalence of 15–20% of ADHD in adults diagnosed with SUD [8]. International European study exploring the prevalence of DSM-IV and DSM-5 adult ADHD varied from 5.4 to 32.6%. Prevalence estimates for DSM-5 were slightly higher than for DSM-IV [19]. Another study on inpatients with alcohol dependence showed that ADHD prevalence was 20.5% [20]. Nigerian study observed an ADHD prevalence of 21.5% with the combined subtype being the most prevalent [21].
Adult ADHD was reported to be associated with fewer years of education, earlier initiation of regular tobacco use and more extensive lifetime poly-drug [22], as also with a more severe pattern of cocaine consumption [23]. ADHD in the cocaine-dependent patient was associated with factors such as male gender, age at the start of cocaine use and dependence, the amount of cocaine consumed weekly, increased occupational alteration, alcohol consumption, general psychological discomfort, depressive disorder, and antisocial personality disorder [24]. A large study reported that high rate of ADHD symptoms was found among heroin-dependent patients, particularly those affected by the most severe form of addiction. These individuals had higher rates of unemployment, other comorbid mental health conditions, and heavy tobacco smoking [25]. Another study reported that ADHD in long-term methadone maintenance treatment of patients is characterized by greater addiction severity and more comorbid psychopathology [26]. Mexican study reported that adolescents diagnosed with ADHD were more likely to have problems with use or abuse of or dependence on inhalants, and an elevated prevalence of parental SUDs was found in both the adolescent and adult groups [27].
Data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) on ADHD symptoms (DSM-IV) for the period when they were 17 years old or younger showed that hyperactive-impulsive symptoms were more consistently associated with lifetime substance use and SUD compared to inattentive symptoms [28]. Large American study investigated associations of lifetime hyperactive-impulsive ADHD and inattention ADHD. Both hyperactive-impulsive and inattention group were associated with the majority of dependence diagnoses in a linear pattern, such that each additional symptom was associated with a proportional increase in odds of dependence. Both were uniquely associated with alcohol, nicotine, and polysubstance dependence, but only hyperactive-impulsive ADHD was uniquely associated with dependence on illicit substances [29].
Prospective outcome study reported that adults with childhood ADHD are more susceptible than peers to developing alcohol (adjusted OR 14.38, 95% CI 1.49–138.88) and drug dependence (adjusted OR: 3.48, 95% CI: 1.38–8.79) [30]. A recent Dutch study confirmed this, where results showed that individuals with persistent ADHD were at significantly higher risk of development of SUD relative to healthy controls (OR = 4.56, CI 1.17–17.81). In contrast, levels of SUD in those with remittent ADHD were not different from healthy controls (OR = 1.00, CI: 07–13.02). They concluded that SUD and nicotine dependence are associated with a negative ADHD outcome [31]. Similar results were reported in Italian study where patients with ADHD symptoms and high-dose benzodiazepine dependence showed a significantly larger prevalence of poly-drug abuse than ones without them [32].
A French study reported that a history of ADHD was associated with an earlier onset of addiction, poly-dependence, and borderline personality disorder [33]. An Australian study reported that conduct disorder, rather than ADHD, is the strongest predictor of differences in patterns of drug use severity. The extensive comorbidity of those two highlights the great potential for misattributing drug use risks to ADHD [34]. A Dutch study on opioid-dependent patients found that conduct disorder patients had significantly higher problem severity scores, more frequent comorbid SUD, and more severe psychiatric comorbidity. ADHD was found to increase the risk of psychiatric comorbidity [35]. Another study on British prisoners, on the contrary, show that combined ADHD type is significantly associated with the need for coping as a way of managing primary and comorbid symptoms, but not conduct disorder [36]. Brazilian study also found no difference in drug use or dependence prevalence between ADHD and non-ADHD patients but observed different addiction patterns such as earlier use of cocaine and more severe use of cocaine correlated to earlier contact with cannabis [37]. The longitudinal study followed participants with childhood-limited ADHD and persistent ADHD compared to controls and found that there were no significant group differences in change in rates of substance dependence over time. However, individuals whose ADHD persisted into adulthood were significantly more likely to meet DSM-IV criteria for alcohol, marijuana, and nicotine dependence [38]. An Australian study conducted in drug and alcohol treatment centers reported increased drug dependence complexity and chronicity in treatment-seeking SUD patients who screen positively for ADHD, specifically for amphetamine, alcohol, opiates other than heroin or methadone, and benzodiazepines [39].
A recent large study reported that symptoms of hyperactivity/restlessness and problems with self-concept increased the odds of having a diagnosis of ADHD and that impulsivity mediated the relationship between adult ADHD symptoms and alcohol dependence severity [40]. A Dutch study showed higher levels of motor and cognitive impulsivity in ADHD patients with comorbid cocaine dependence compared to ADHD patients without cocaine dependence and controls [41]. Belgian study also reported higher impulsivity in cocaine-dependent individuals to controls, regardless of whether they have concomitant ADHD or not [42]. Similar was reported by Brazilian study where patients who had ADHD and cocaine dependence had impairments in both cognitive and affective regulation [43]. Another study on cocaine dependence reported that the Barkley’s executive dysfunction items showed statistically significant differences between cocaine-dependent patients with ADHD and those patients without ADHD diagnosis [44].
Swiss study reported that patients with probable adult ADHD showed higher craving, more withdrawal and psychiatric symptoms, and rated withdrawal symptoms as more severe than did patients without ADHD symptoms [45]. Hungary study of drug-dependent patients with and without ADHD symptoms reported the highest severity of aggression when the ADHD positive status co-occurred with heroin use, while the lowest severity of aggression was detected when ADHD negative status co-occurred with the use of marijuana. ADHD positive patients showed a marked increase in depression symptoms, suicidal ideation, suicidal attempts, as well as self-injuries associated with suicidal attempts [46]. Study on Scottish prisoners reported that ADHD symptoms were the strongest predictor, followed by alcohol dependence for violent offending. Hence, the authors pointed out the importance to treat drug addiction and ADHD symptoms in order to reduce offending among the most persistent offenders [47]. Taiwan study among heroin-dependent participants entering methadone maintenance treatment showed that ADHD-screened positive patients showed higher depression scores (p = .003), and more severe heroin dependence (p = .006) [48]. Childhood ADHD was associated with obsessive-compulsive disorder, and both conditions were highly prevalent among former heroin addicts on methadone maintenance treatment [49].
ADHD is a common comorbid disorder that is frequently overlooked in adults with SUD. DIVA diagnostic interview is important tool to diagnose ADHD in adult patients. Since it is an interview, it has greater diagnostic power then screening questioners. DIVA-5 is the successor to DIVA 2.0, the structured Diagnostic Interview for Adult ADHD, and is based on the criteria for ADHD in DSM-5 [50]. A most used screening questionnaire for screening ADHD patients presenting with SUD is the ASRS followed by in-depth diagnostic assessment [10]. In a Norwegian study, 33% of patients on opioid maintenance therapy [51] and in the Italian study, 19.4% [25] were positive for ADHD using the ASRS. Among patients with benzodiazepine dependence, 32% of them screened positive on ADHD [32].
Brazilian study validated the translated version of the adult self-report The Brown Attention-Deficit Disorder Scale (BADDS) using the ASRS as the gold standard [52], but ASRS appears to be more appropriate screener that BADDS in SUD patients [53]. Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID) proved to be a diagnostic tool that can also be used during active substance use [54]. Study investigating the clinical utility of two self-report screening instruments such as Conners’ Adult ADHD Rating Scale screening Self-Rating (CAARS-S-SR) and the ASRS in alcohol use disorder showed many false-negative results (ASRS: 89.5%; CAARS-S-SR: 92.3%) which indicates underreporting of ADHD symptoms. Authors suggested that underreporting of ADHD symptoms in ASRS and CAARS-S-SR of alcohol use disorder patients requires lower cut-off values to detect the majority of ADHD [55].
In a recent study from international multi-center, the Mini-International Neuropsychiatric Interview (MINI-Plus) on patients with substance use disorders was validated for the screening of adult ADHD in treatment-seeking SUD patients [56]. Another tool in understanding the possible causes and motivations behind substance misuse and its dependency is Substance Transitions in Addiction Rating Scale (STARS) where the subscales produced meaningful and reliable factors that supported the self-medication and behavioral disinhibition hypotheses of substance use motivation [36].
Comorbid ADHD and SUD represent a challenge for health-care providers as the pharmacological trials have found mix results for efficacy [8]. The reviews on ADHD medications for ADHD with SUD point out limited efficacy of treatment, but more recent trials using psychostimulants in robust dosing have demonstrated positive results [57, 58, 59, 60].
Guidelines recommend that when ADHD coexists with other psychopathologies in adults, the most impairing condition should generally be treated first [58]. Another approach is to first achieve abstinence before treating ADHD, where the main goal is to reduce the risk of diversion of stimulant medication [57]. The international consensus statement recommends long-acting stimulant medication [10].
While previous concerns arose whether stimulant therapy would increase the ultimate risk for substance abuse, recent studies have indicated that pharmacologic treatment appears to reduce the risk of substance abuse in individuals with ADHD [61]. Findings from 19 large open studies and controlled clinical trials show that the use of atomoxetine or extended-release methylphenidate formulations, together with psychological therapy, yield promising though inconclusive results about short-term efficacy of these drugs in the treatment of adult ADHD in patients with SUD and no other severe mental disorders. However, the efficacy of these drugs is scant or lacking in treating concurrent SUD [62]. The concern is as indicated by American study that ADHD is prevalent among chronic methamphetamine users, who are at increased risk for persistence of childhood diagnoses of ADHD into their adult years. ADHD also appears to play an important role in methamphetamine-associated disability, indicating that targeted ADHD screening and treatment may help to improve real-world outcomes for individuals with methamphetamine use disorders [63].
A meta-analysis on the efficacy of atomoxetine in treating adult ADHD showed atomoxetine is efficacious in treating adult ADHD compared to placebo, though the efficacy is significantly superior for inattention than hyperactivity/impulsivity [64]. Study on alcohol-dependent patients with and without a diagnosis of ADHD hypothesized that atomoxetine could reduce the impulsivity trait [65]. A small study reported that atomoxetine may improve some ADHD symptoms but does not reduce marijuana use in marijuana-dependent adults with ADHD [66].
A small study on ADHD patient with cocaine use disorder showed that behaviors reflecting cocaine addiction were sharply reduced during the stimulant treatment of adult ADHD, and were not correlated with age, gender, familiarity, length of treatment, or medication used. Cocaine use disorder improvement was closely correlated with adult ADHD improvement [67]. Earlier data show that patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with methylphenidate, where Dutch study showed that low dopamine transporter occupancy is not the reason for that. Authors also suggest that higher dosages of methylphenidate in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients [68]. ADHD patients with cocaine dependence are a distinctly more impulsive subpopulation compared to ADHD patients without cocaine dependence on objective measures of impulsivity. These findings are relevant for optimizing psycho-education and treatment of ADHD patients with comorbid SUD [41].
Sweden placebo-controlled double-blind study reported that methylphenidate treatment reduces ADHD symptoms and the risk for relapse to substance use in criminal offenders with ADHD and substance dependence [69]. Norway study reported about the safety and utility of central stimulant medications for patients with ADHD who are receiving opioid maintenance treatment [70]. Sustained-release methylphenidate in a double-blind, placebo-controlled trial for the treatment of ADHD in amphetamine abusers found no difference with regards to the craving for amphetamine or in retention in treatment [71]. Another double-blind, placebo-controlled study in adults with ADHD reported that extended-release methylphenidate was statistically superior to placebo in reducing emotional symptoms and a decline of obsessive-compulsive symptoms and those of problems with self-concept. Symptoms of anxiety, depression, anger and hostility, phobia, paranoid ideations and psychoticism were not improved [72]. A study that examined if stimulants would decrease marijuana use in a randomized controlled trial of extended-release mixed amphetamine salts for the treatment of co-occurring ADHD and cocaine use disorders found no significant baseline differences in marijuana use frequency and quantity [73].
A recent Dutch randomized clinical trial among SUD and ADHD patients reported that integrated cognitive behavioral therapy resulted in a significant improvement in ADHD symptoms in comorbid SUD and ADHD patients [74]. This finding leads to the conclusion that nonpharmacological interventions can contribute to ADHD symptom reduction in patients with comorbid ADHD and SUD. ADHD and SUD experts recommend that simultaneous and integrated treatment of ADHD and SUD, using a combination of pharmaco- and psychotherapy, is effective [10].
ADHD is highly comorbid with SUD, being diagnosed up to 20% in SUD patients. ADHD and SUD are believed to have shared pathophysiology. ADHD is associated with the majority of dependence diagnoses. A most used screening questionnaire for screening ADHD patients presenting with SUD is the ASRS. Evidence on pharmacological treatment is limited, but new trials support the use of a higher dose of long-acting stimulants as also recommended with a combination of psychotherapy by expert opinion. Finally, the decision to treat adult ADHD in the context of SUD depends on various factors, so clinical decisions should be individualized and based on a careful analysis of the advantages and disadvantages of pharmacological treatment for ADHD in the context of SUD. Given the prevalence of both ADHD and SUD, more research is needed to understand the theoretical and clinical implications of this comorbidity.
The authors declare no conflict of interest.
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I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. 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I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. 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