The prevalence of ADHD in the general adult population is 2.5% and it is associated with substantial personal and individual burden.
The most frequent comorbid psychopathologies include mood and anxiety disorders, substance use disorders, and personality disorders.
There are strong familial links and neurobiological similarities between ADHD and the various associated psychiatric comorbidities.
The overlapping symptoms between ADHD and comorbid psychopathologies represent challenges for diagnosis and treatment.
Guidelines recommend that when ADHD coexists with other psychopathologies in adults, the most impairing condition should generally be treated first.
Early recognition and treatment of ADHD and its comorbidities has the potential to change the trajectory of psychiatric morbidity later in life.
The use of validated assessment scales and high-yield clinical questions can help identify adults with ADHD who could potentially benefit from evidence-based management strategies.
Prevalence of ADHD
Recent evidence supports the view that children with ADHD do not “outgrow” the disorder when they reach adulthood, and furthermore, that adult ADHD is not necessarily a continuation of childhood ADHD since a substantial proportion of adults with ADHD lack a history of the disorder in childhood [11, 12, 13]. Taken together, such observations suggest the existence of two separate syndromes that have distinct developmental trajectories .
The general population prevalence of ADHD in adults has been estimated to be 2.5% (95% confidence interval [CI] 2.1–3.1) , with adults with ADHD presenting with symptoms such as: failing to pay attention to detail, difficulty organizing tasks and activities, excessive talking or fidgeting, difficulty relaxing, overworking, forgetfulness, and distractibility [15, 16, 17].
Nonetheless, despite the relatively high prevalence of ADHD in adults, it is often unrecognized in patients who present to the clinic (reviewed by Ginsberg et al., 2014) . This is particularly true for females, who are a largely unrecognized population for several reasons.
Notably, childhood ADHD is usually diagnosed after a referral from parents or teachers, with boys being more likely to be referred for treatment since they present primarily with external symptoms such as hyperactivity, which are inevitably more noticeable to others .
Conversely, females with ADHD are more likely to have internalizing symptoms, resulting in a later diagnosis, and greater time for developing strategies to mask core symptoms . Despite this, one meta-analysis reported that females with ADHD often have greater intellectual impairments than males with the disorder , highlighting the importance of recognizing and appropriately managing this under-represented population.
Burden of adult ADHD
Adult ADHD is associated with profound functional and psychosocial disability, leading to serious personal and societal costs.
Its most prominent feature is attentional dysfunction, associated especially with impairment in focused and sustained attention . Individuals with ADHD also experience neuropsychological difficulties associated with deficient inhibition , memory , executive functioning [23, 24], decision making , and emotional dysregulation .
Adult ADHD can have negative consequences for individuals’ self-esteem and the quality of interpersonal relationships, with both colleagues and significant others [27, 28]. For example, in a community sample of 1001 adults, those with ADHD were significantly more likely to have been divorced (28% vs 15% controls, P ≤ 0.001) and were significantly less satisfied with their personal, social and professional lives .
ADHD is associated with educational difficulties, requiring extra help, attending special classes, repeating grades , as well as higher rates of academic suspension and drop outs . College students with ADHD have reduced grade point averages and are less likely to graduate than students without ADHD .
Later in life, adults with ADHD experience challenges with time management, organization, and self-regulation, which can result in employment and financial problem [27, 33]. One study estimated the individual income reduction in adults with ADHD in the United States to be between $8900 and $15,400 annually .
Along with these functional and psychosocial impairments, ADHD is associated with a higher risk of developing mood and anxiety disorders. In many studies, ADHD has been associated with comorbid depression, anxiety disorders, bipolar disorder, and substance use disorder [27, 30, 40, 41, 42].
The National Comorbidity Survey reported that adults with ADHD are three times more likely to develop major depressive disorder (MDD), six times more likely to develop dysthymia, and more than four times more likely to have any mood disorder .
Most notably, individuals with ADHD are twice as likely to experience substance abuse or dependence . These comorbidities present important clinical challenges since their co-occurrence results in greater disease burden and more severe illness courses than ADHD or mood and anxiety disorders alone .
Neurobiological and genetic concepts
There are strong familial links between ADHD and psychiatric comorbidities such as bipolar disorder, suggesting a genetic contribution .
One possible explanation is that ADHD and mood disorders stem from similar neurobiology. Recent studies have demonstrated that similar regions of the brain are involved in ADHD and psychiatric disorders .
Neuroimaging studies have implicated differences in volume and activity in the frontal lobe, which is responsible for attention, behaviour selection, and emotion .
Studies of neurotransmitters have also pointed to abnormalities in dopamine (DA) and norepinephrine (NE) signaling [16, 45], thus corroborating Volkow et al.’s (2012) conclusion that methylphenidate-elicited dopamine increases were associated with therapeutic response in individuals with ADHD .
Overlapping symptomology between ADHD and mood, anxiety, or SUDs present several barriers to diagnosis and treatment.
Similarly, ADHD symptoms may be masked by substance use . Physicians are often more familiar with mood and anxiety disorders, which may contribute to misdiagnosis and delays in treating ADHD in adults .
It has been suggested that stress, depression, and anxiety could manifest as a consequence of undiagnosed and untreated ADHD . The result is that many individuals with ADHD receive treatment for comorbid mood disorders, but not for ADHD [37, 71, 72].
Overall, these challenges have contributed to an under-diagnosis and under-treatment of adult ADHD . According to a National Comorbidity Survey Replication in the United States (n = 3199), only 11% of adults with ADHD were receiving treatment .
In part, these situations are exacerbated by the development of mistaken beliefs regarding the over-diagnosis and over-treatment of ADHD , which further lower the likelihood of patients receiving the diagnosis and targeted treatment to change their life trajectory.
The Spectrum of ADHD and other psychopathologies
The most common psychiatric comorbidities that co-occur with ADHD in adults are depression, anxiety disorders, bipolar disorder, SUDs and personality disorders.
The overlapping and distinctive features of these disorders are summarized in Fig. 1.
Given the considerable overlap between these disorders, the conceptualization of ADHD as a spectrum using a dimensional rather than a categorical approach to diagnosis and treatment has been proposed .
This framework is in keeping with work in other areas of psychiatry, notably the National Institute of Mental Health’s Research Domain Criteria (RDoC) initiative and the most recent Diagnostic and Statistical Manual of Mental Disorders 5th Edition , which both espouse dimensional approaches to the diagnosis and classification of mental disorders as a strategy to facilitate mental health research .
An important driver of this paradigm shift towards dimensional approaches to mental health research is the effort “to better understand basic dimensions of functioning underlying the full range of human behaviour from normal to abnormal” .
ADHD has a high prevalence of comorbidity with bipolar disorder. Rates of ADHD comorbidity in bipolar disorder have been estimated between 9.5% and 21.2%, and rates of comorbid bipolar disorder in ADHD at 5.1% and 47.1% . Bipolar I disorder is more common in individuals with comorbid ADHD than is bipolar II disorder .
Characteristics of the manic or elevated phase of bipolar disorder that overlap with ADHD include restlessness, talkativeness, distractibility, and fidgeting . The distinctive features of bipolar disorder, largely characterized by the depressive phase, as well as the episodic course of symptoms, can help to elucidate a differential diagnosis .
Several studies have suggested that comorbid ADHD hastens an earlier age of onset of bipolar disorder. In one study, 65% individuals with ADHD had early onset of bipolar disorder (at under 18 years of age), compared with only 20% of individuals who did not have comorbid ADHD .
Other studies have reported that bipolar patients with comorbid ADHD experienced an earlier average age of mood disorder onset by 5 years  or 6 years  compared to individuals without ADHD. In addition to an earlier age of onset, bipolar individuals with comorbid ADHD have demonstrated worse overall course of illness with shorter periods of wellness, more frequent episodes of mania and depression, and higher instance of additional comorbid psychiatric conditions including anxiety and substance use disorders .
Questions regarding the role of stimulants in bipolar depression remain unresolved [79, 80]. This might be related to raised hedonic tone in bipolar depression . Furthermore, the use of long-acting stimulants in individuals with ADHD and bipolar disorder has been advocated by some once mood has been stabilized with an appropriate mood stabilizer . Still, concerns remain in regards to the potentially increased risk of stimulant-associated mania/hypomania in bipolar disorder patients .
ADHD and dysthymia/depression co-occur frequently, with studies reporting prevalence rates of depression in individuals with ADHD ranging from 18.6%  to 53.3% . Similarly, studies have reported comorbid ADHD in individuals with depression at rates of 9% to 16% , with a mean rate of 7.8% .
The risk for anxiety disorders is higher in individuals with ADHD than in the general population [85, 86] with rates approaching 50% . Comorbid ADHD is more common in individuals with a primary diagnosis of social phobia than panic disorder .
Substance Use Disorder
Possibly the most common comorbid condition with ADHD is SUD, particularly alcohol and/or nicotine, cannabis and cocaine use . Substance abuse or dependency is approximately twice as common in individuals with ADHD as it is in the general population . There is a particularly strong association between ADHD and cigarette use, with these populations demonstrating stronger physical dependence to nicotine when compared to individuals without ADHD .
The literature on comorbid ADHD and personality disorders is sparse compared to other psychiatric comorbidities. Reports suggest that personality disorders are present in more than 50% of adults with ADHD, most commonly cluster B and C personality disorders, and 25% of individuals have two or more personality disorders .
ADHD and personality disorders often co-occur with other axis I disorders. For instance, 18% of adults with ADHD and depression and 23% of adults with ADHD and bipolar disorder are estimated to also have a personality disorder .
The substantial burden of comorbid ADHD and personality disorders is underscored by the high co-occurrence of these conditions in incarcerated individuals. In one study, a staggering 96% of imprisoned adults with ADHD had a lifetime history of antisocial personality disorder .
Other types of personality disorders were also over-represented in this population, including borderline (74%), paranoid (74%), narcissistic (65%), obsessive-compulsive (52%), passive-aggressive (48%), and avoidant (48%).
Distinguishing ADHD from common psychiatric comorbidities
It is important to determine if a patient presenting with one of the above-listed psychiatric disorders also has comorbid ADHD. This may be difficult, in part because of the difficulties associated with establishing a correct diagnosis.
Nonetheless, some individuals will be able to overcome their deficits such that diagnosis will be delayed. Compensating skills may delay or prevent diagnosis if one follows the strict DSM definition.
In fact, as noted by Moffitt et al. (2015) , when one looks at individuals with early onset (i.e. diagnosed before age 12), they exhibit fewer university degrees, lower intelligence quotients (IQs) by almost one standard deviation, more requirements for government support, more disability, more criminal convictions, more childhood depression and more conduct disorder.
Thus, those with delayed onset of symptoms may in fact be able to compensate thereby delaying diagnosis, but they may eventually require treatment nonetheless.
This compensation and delayed diagnosis may contribute to unrecognized ADHD, which has been associated with poor treatment response or noncompliance due to forgetfulness, or perceived lack of improvement of symptoms , or mismanagement where the medication will only address the problems it is designed to target (e.g. SSRIs will not address the primary premorbid ADHD contributing to the trajectory of depression, bipolarity, anxiety and substance abuse problems).
Treatment selection must be informed first and foremost by efficacy in terms of functional outcomes. Functional outcomes include symptom reduction, but also extend to improved daily functioning and increased quality of life .
Indicators of improved functioning include more efficient at working or studying, more stable relationships, success in containing aggressive impulses, and improved parenting . Long-term efficacy as well as adherence to treatment is also crucial to success.
Pharmacologic treatments for ADHD are usually divided into stimulants and non-stimulants. Stimulant medications include methylphenidate, mixed amphetamine salts, and lisdexamfetamine dimesylate. Non-stimulants used in ADHD treatment include atomoxetine and alpha-2-adrenergic agonists.
One systematic review and meta-analysis of treatments for ADHD concluded that immediate-release methylphenidate was superior to other treatments in terms of benefits and harms .
It also supported the efficacy of atomoxetine, long-acting bupropion, and extended-release stimulants, but found that short-acting stimulants had similar risk-profiles to these other options, with greater efficacy in terms of symptom reduction. Recommendations for the pharmacologic management of adult ADHD are described in Table 1.
Another important treatment consideration is the potential for the effective treatment of ADHD to improve functional outcomes of patients with comorbid conditions.
Many studies have reported improvements in comorbid psychiatric symptoms when ADHD is effectively treated. For instance, atomoxetine has been associated with improvements in both ADHD and comorbid anxiety  and depressive  symptoms.
Other studies have demonstrated the efficacy of co-administration of SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs) with stimulants on functional outcomes in ADHD with comorbid anxiety or depressive symptoms [113, 114].
Perhaps more exciting is the concept that early and optimal treatment of ADHD could potentially prevent the later development of psychiatric comorbidities.
In a 10-year longitudinal follow-up study of male youths with ADHD, Biederman et al. (2009)  found that those who were treated with stimulants had a significantly lower risk of developing comorbid depressive and anxiety disorders as adults, and were also significantly less likely to have impaired functional outcomes, than those who were not treated. Similarly, adolescents with ADHD treated with stimulants were found to have a significantly lower risk of cigarette smoking and subsequent development of SUD after 5 years of follow-up . Taken together, these observations suggest that pharmacologic therapy for ADHD in young adults could change the trajectory of psychiatric morbidity in adulthood. Such findings provide powerful support for the early and aggressive treatment of ADHD.
A final important treatment consideration is safety and tolerability. Both stimulant and non-stimulant medications have possible side effects, which must be taken into account. Common side effects of stimulants include headache, appetite suppression, nausea, dry mouth, mood fluctuations, difficulty sleeping, jitteriness, increased heart rate, and increased blood pressure .
Generally the severity and risk of these side effects is considered minimal. However, due to the possibility of serious cardiac adverse events, it is recommended that patients be screened for both family and personal histories of cardiac conditions prior to prescription of stimulant medications .
Side effects vary depending on the type of non-stimulant employed, but common side effects of atomoxetine include appetite suppression, dry mouth, insomnia, constipation, vomiting, dizziness, fatigue, nausea, dyspepsia and mood swings .
However, most experts agree that minimal lab investigations are needed prior to the initiation of ADHD medications in adults, particularly the psychostimulants. For instance, routine bloodwork is not necessary in most individuals, and only at-risk individuals may require monitoring of blood pressure, heart rate, and electrocardiogram prior to starting psychostimulants.
Non-pharmacological interventions play a central role in the management of ADHD. Evidence supports the superiority of multimodal approaches utilizing pharmacotherapy and psychosocial and/or behavioural interventions to target the core symptoms of ADHD and for the improvement of functional outcomes [107, 117].
Similarly, the addition of psychotherapeutic approaches to pharmacotherapy in adults with ADHD whose symptoms persist despite medication has been shown to improve symptoms and functioning .
Notably, recent research suggests that cognitive behavioural therapy (CBT) has bidirectional efficacy for both ADHD and depressive disorders . Table 2 lists non-pharmacological strategies recommended by the CADDRA guidelines for ADHD.
The consensus in the literature is that the most severe, functionally impairing or destabilizing illness should be treated first, and comorbidities should be addressed in a stepwise fashion once the patient has responded to treatment [17, 69, 107].
Generally, in patients with comorbid ADHD and mood disorders, the affective disorder should be given higher priority, and residual ADHD symptoms can then be assessed once the mood disorder has been addressed pharmacologically . In bipolar disorder, mood stabilization is a prerequisite for effective ADHD treatment .
Similarly, in SUD it is generally recommended that substance abuse should be stabilized first . The CADDRA (2011) guideline recommendations for treating ADHD and comorbid psychiatric disorders are summarized in Table 3.
One study hypothesized that ADHD treatment with methylphenidate or bupropion reduced cocaine use because it facilitated successful utilization of non-pharmacological interventions, or it addressed underlying deficits in dopamine function .
It has been hypothesized that the improvement in ADHD symptoms following treatment results in decreased functional impairment and increased quality of life, thereby reducing symptoms of comorbid anxiety or depression [114, 134].
ADHD is a prevalent psychiatric disorder in the adult population that is frequently unrecognized, under-diagnosed, and under-treated.
Given that it is often comorbid with other psychopathologies including mood or anxiety disorders, substance use disorders, and personality disorders, adults presenting with symptoms of ADHD should be screened for these frequently comorbid conditions, and vice versa, in order to identify patients who could potentially benefit from optimal management of ADHD and its comorbidities.
Although the clinical presentation of ADHD in adults can be variable and complex, it can often be identified using a few high-yield clinical questions, and the use of validated assessment scales in patients screening positive.
Early and optimal treatment of ADHD has the potential to change the trajectory of psychiatric morbidity later in life and to substantially improve functional outcomes across the spectrum of psychiatric comorbidities.
In general, when ADHD coexists with other psychiatric pathologies, the more severe disorder should be treated first according to evidence-based guidelines.
In the coming years, research on the genetic and neurobiological basis of ADHD should continue to uncover fruitful avenues of treatment for this debilitating disorder and ultimately improve outcomes for patients and their families.
Katzman, M. A., Bilkey, T. S., Chokka, P. R., Fallu, A., & Klassen, L. J. (2017, August 22). Adult ADHD and comorbid disorders: Clinical implications of a dimensional approach. BMC Psychiatry. BioMed Central Ltd. https://doi.org/10.1186/s12888-017-1463-3