Psychiatric Comorbidities in Adult ADHD

Release Date: January 10, 2018
Expiration Date: January 10, 2019

Faculty Author

Ann Childress, MD
Adjunct Professor of Medicine
Department of Child and Adolescent Psychiatry
Touro University of Nevada
Center for Psychiatry and Behavioral Medicine, Inc.
Las Vegas, Nevada

Learning Objective

Upon completion of this educational activity, participants should be able to:

  • Identify psychiatric comorbidities that are frequently associated with ADHD and describe an approach to management

Introduction

ADHD is a disorder characterized by frequent and sometimes severe levels of inattention, impulsivity, and hyperactivity.(1-4) Traditionally, it was regarded as a neurodevelopmental condition that emerged during childhood and usually resolved by young adulthood.(3,5) However, subsequent investigations employing genetic approaches and long-term follow-up of children with ADHD have shown that the condition often persists well into adulthood, and continues to exert a pervasive negative impact across multiple life domains.(3,6,7) Indeed, a wide body of evidence has demonstrated a strong link between adult ADHD and poor outcomes related to social function, education, criminality, alcohol use, substance use/abuse, and occupational status.(8,9)

Over the past several years, there has been growing recognition of the frequent association between ADHD and comorbid psychiatric disorders in adult patients. Many of these disorders are identifiable relatively early on in life in the pivotal Multi-Modal Treatment Study of ADHD. Investigators found that nearly 30% of the children with ADHD evaluated exhibited oppositional defiant disorder and/or conduct disorder, 14% had anxiety or depression, and 25% had all three disorders. In fact, only approximately one-third of the children in the study were found to have ADHD alone.

For many 18-22 year old patients with ADHD, the presence of psychiatric comorbidities appears persistent throughout the lifespan. In a large-scale, multisite longitudinal study of college-aged men (n=214) and women (n=229), comprehensive multimethod evaluation combined with expert panel review revealed higher rates of overall comorbidity among college students with well-defined ADHD.(10) Specifically, the results indicated that 55.0% had ≥1 comorbid diagnosis and 31.8% had ≥2, relative to peers without ADHD (11.2% and 4.0%, respectively).(10) Further evaluation revealed the differences in comorbidity rates to be largely attributable to the increased presence of depressive and anxiety disorders, particularly major depressive disorder (active or in partial remission) and generalized anxiety disorder.(10)

Likewise, other studies have reported similar trends among broader populations of adults with ADHD. A national survey published in 2006 found that among adult respondents with ADHD, 47.1% had an anxiety disorder, 38.3% had a mood disorder, and 15.2% had a substance abuse disorder vs 19.5%, 11.1%, and 5.6%, respectively, among respondents without ADHD. Similarly, a separate investigation also found a high prevalence of depression in adults with ADHD compared with non-ADHD controls (14.0% vs 3.2%; P≤.0001). The next 2 most commonly observed psychiatric comorbidities in patients with ADHD, anxiety and bipolar disorder, were observed 3 to 6 times more frequently than in patients without ADHD (P≤.0001). Although less well-characterized in the context of ADHD, personality disorders such as antisocial and borderline personality disorder have also been found to be more frequently expressed in ADHD patients.(11)

In addition, ADHD has also been found to be a significant risk factor for substance use disorder (SUD) among adult patients. A recent exploration of this relationship among twins (N=18,167; 20-45 years of age) found that ADHD symptoms were significantly associated with an increased risk for all SUD types reported (ie, alcohol, illicit drugs, and nicotine).(12) Odds ratios ranged between 1.33 for regular nicotine (95% confidence interval [CI]=[1.12, 1.59]); 2.54 for multiple drug use (95% CI=[2.00, 3.23]), and 3.58 for alcohol dependence (95% CI=[2.86, 4.49]).(12) Additionally, evidence also indicates that ADHD contributes to a faster progression from initial substance use to abuse, and a more aggressive course of abuse.(13)

Psychiatric Comorbidities in Adults with ADHD: Implications for Diagnosis

The frequent presence of psychiatric comorbidities has important implications for the evaluation of adult patients suspected of having ADHD. Manifestations of ADHD tend to be less obvious in adults than in children, often making it difficult to recognize ADHD-specific symptoms against a backdrop of those related to co-occurring conditions. Conversely, symptoms of ADHD can also mask symptoms of other psychiatric disorders. As part of a patient evaluation, establishing the presence of symptoms during childhood may be helpful in distinguishing ADHD from other possible causes of inattention, with the absence of a lifelong pattern prompting consideration of other diagnoses.(4) Risk factor evaluation, likewise, may help inform the diagnosis. However, frequently co-occurring conditions (eg, depression) often share common environmental risk factors with ADHD, and thus may have only limited value in differentiating between different conditions.(14) Many of the psychiatric disorders that are commonly associated with ADHD share similar features and can therefore significantly obscure the diagnostic process (Table 1).

 

Table 1. Overlapping Symptoms of ADHD and Other Psychiatric Disorders15,16

Diagnosis Feature(s) Shared with ADHD
Mood Disorders 
Major depression Trouble concentrating; trouble initiating and completing tasks
Dysthymia Trouble concentrating; trouble initiating and completing tasks
Depression NOS Trouble concentrating; trouble initiating and completing tasks
Bipolar disorder Distractibility, hyperactive behavior
Cyclothymia Distractibility, hyperactive behavior
Anxiety Disorders
Generalized anxiety disorder Inattention, distractibility
Social anxiety disorder Performance anxiety, task avoidance (especially in front of others), unsatisfying social interaction
Obsessive-compulsive disorder Repetitious activity
Anxiety disorder NOS Inattention, distractibility
Substance-Use Disorders
Nicotine dependence Poor job performance and socialization
Alcohol abuse or dependence Poor job performance and socialization
Cannabis abuse or dependence Poor job performance and socialization
Impulse-Control Disorders
Intermittent explosive disorder Impulsivity, aggression
Impulse control disorder NOS Impulsivity, trouble with task completion
Learning Disorders
Learning disorder NOS History of poor school and job performance
Early onset dementia Poor attention, forgetfulness
Mild MR Trouble with learning, reading, attention
Personality Disorders
Borderline personality disorder Impulsivity, aggression
Antisocial personality disorder Impulsivity, aggression, history of poor school and job performance
NOS, not otherwise specified.

  

One, in particular, that has been the subject of increased attention in the context of ADHD is anxiety disorder.(17,18) Indeed, a significant symptom overlap between the two conditions has been consistently observed. Among the symptoms common to both that may complicate diagnosis are restlessness/psychomotor agitation, concentration difficulties, decreased attention, increased distractibility, mood swings, and anger outbursts.(19) In a recent attempt to gain further insight into the implications of this symptom overlap, an investigation into the validity of two widely used ADHD and anxiety rating scales, the Conners Adult ADHD Rating Scale (CAARS) and State Trait Anxiety Inventory scales (STAI), was conducted. The authors of the study found that the CAARS and STAI had limited sensitivity and specificity in patients with comorbid ADHD and anxiety, and concluded that their application may be inadequate to differentially diagnose patients affected by both conditions. Based on their findings, the authors go on to propose that modifications to the two scales might be made to improve their sensitivity and specificity. However, further investigations will be required to determine the diagnostic impact of such modifications.

Like anxiety, bipolar disorder also shares significant symptom overlap with ADHD in adults. Indeed, several studies have noted that symptoms of ADHD are often mistakenly assumed to be part of bipolar disorder in individuals who are affected by both conditions.(20) Overlapping symptoms include distractibility, impulsivity, increased talkativeness, increased motor activity, physical restlessness, and deficiency in expected degree of social inhibitions.(21) However, symptoms reflective of mood dysregulation in bipolar disorder are more likely to be episodic and cyclic in nature.(21) Because comorbid ADHD and bipolar disorder presentation is generally associated with a greater severity of mood disorder symptoms, a more severe disease course, and lower functional scores, failing to render an accurate and complete diagnosis can have an exponential negative impact on patient outcomes over the long-term.(22)

Treatment of Adults with ADHD and Comorbid Psychiatric Conditions

Recognition of comorbid conditions among patients with ADHD is crucial for informing subsequent treatment decisions. An important question that arises in the selection of an appropriate treatment regimen relates to whether treatment efficacy is adversely influenced by the presence of comorbidity. In a review of controlled clinical trials evaluating a range of psychiatric comorbidities (including bipolar disorder, major depressive disorder, oppositional defiant disorder, conduct disorder, and SUD) and its impact on treatment efficacy in adults with ADHD, it was determined that the presence of comorbidity does not substantially alter the safety and efficacy of ADHD pharmacotherapies.(23) Furthermore, the results of the review suggested that treatment of ADHD may actually improve symptoms of the comorbid disorder in conjunction with those of ADHD.(23)

At the same time, it is also important to bear in mind that the choice of therapy requires consideration of the specific type of comorbidity. For example, formulations or specific agents associated with a lower risk of abuse should be prioritized when choosing a treatment for patients demonstrating comorbid drug abuse or who might be suspected of trying to simulate or exaggerate ADHD symptoms in order to obtain stimulants for diversion or abuse.(24) Although methylphenidate (MPH) is currently considered a first-choice medication for symptoms of ADHD, its use with comorbid SUD has historically been challenging due to the potential for abuse of the treatment and because of the possible impact on SUD. Choosing a sustained-release rather than immediate-release formulation, may be one strategy for addressing these concerns, as the subjective effects of MPH are highly dependent on pharmacokinetics.(25) As a general approach, it is recommended that the response to treatment in adults with comorbid ADHD and SUD should be closely observed, with individualized consideration of side effects.(25) As an alternative to MPH, a nonstimulant may be selected. In a 3-month, double-blind, placebo-controlled study of atomoxetine in adults with ADHD and comorbid alcohol use disorder, subjects demonstrated clinically significant improvements in symptoms of ADHD. (Although brief abstinence from alcohol were also observed in the study, the effects on drinking behavior were inconsistent.) For patients with ADHD and bipolar disorder who are at risk for mood destabilization, atomoxetine may also be an appropriate choice, being associated with only a modestly increased risk of manic/hypomanic switches when utilized in combination with mood stabilizers.(24)

In addition to tailoring pharmacologic treatment to accommodate the presence of comorbidities, a multimodal approach that includes cognitive interventions is also recommended. There is general agreement that a multimodal approach is likely to be most effective for the management of ADHD alone, and in recent work, this has been shown to also be true, in the context of ADHD management in the presence of comorbid conditions, with differential but positive effects of a cognitive intervention being observed over time for ADHD symptoms and comorbid problems.(26,27)

Summary

The diagnosis and management of ADHD in adult patients is highly challenging because of the frequent comorbidity of other psychiatric disorders, many of which share overlapping symptoms with those of ADHD. In addition to creating diagnostic challenges, the presence of psychiatric comorbidities also has the potential to significantly influence treatment outcomes. As a result, it is of critical importance that healthcare providers involved in the care of adult patients with ADHD (confirmed or suspected) maintain awareness of commonly occurring psychiatric comorbidities and familiarity with symptom overlap patterns in order to render an accurate and complete diagnosis. This, in turn, will enable them to make appropriate recommendations for treatment and ultimately improved patient health outcomes over the long-term.

Clinical Pearls

  • In addition to applying current guideline criteria for the diagnosis of ADHD in adult patients, clinicians should also perform a thorough evaluation to detect the presence of any psychiatric comorbidities
  • To optimize ADHD management and overall patient outcomes, clinicians should provide pharmacologic and nonpharmacologic intervention that addresses not only ADHD but also any psychiatric comorbidities

References

  1. Surman CB, Goodman DW. Is ADHD a valid diagnosis in older adults? Atten Defic Hyperact Disord. 2017.
  2. Fields SA, Johnson WM, Hassig MB. Adult ADHD: Addressing a unique set of challenges. J Fam Pract. 2017;66(2):68-74.
  3. Bonvicini C, Faraone SV, Scassellati C. Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies. Mol Psychiatry. 2016.
  4. Surman CB. Clinical Assessment of ADHD in Adults. In: Surman CB, ed. ADHD in Adults: A Practical Guide to Evaluation and Management: Humana Press; 2013:19-44.
  5. Hill JC, Schoener EP. Age-dependent decline of attention deficit hyperactivity disorder. Am J Psychiatry. 1996;153(9):1143-1146.
  6. McGough JJ, Barkley RA. Diagnostic controversies in adult attention deficit hyperactivity disorder. Am J Psychiatry. 2004;161(11):1948-1956.
  7. Faraone SV, Biederman J, Spencer T, et al. Diagnosing adult attention deficit hyperactivity disorder: are late onset and subthreshold diagnoses valid? Am J Psychiatry. 2006;163(10):1720-1729; quiz 1859.
  8. Arnold LE, Hodgkins P, Caci H, Kahle J, Young S. Effect of Treatment Modality on Long-Term Outcomes in Attention-Deficit/Hyperactivity Disorder: A Systematic Review. PLoS ONE. 2015;10(2):e0116407.
  9. Zalsman G, Shilton T. Adult ADHD: A new disease? Int J Psychiatry Clin Pract. 2016;20(2):70-76.
  10. Anastopoulos AD, DuPaul GJ, Weyandt LL, et al. Rates and Patterns of Comorbidity Among First-Year College Students With ADHD. J Clin Child Adolesc Psychol. 2016:1-12.
  11. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006;163(4):716-723.
  12. Capusan AJ, Bendtsen P, Marteinsdottir I, Larsson H. Comorbidity of Adult ADHD and Its Subtypes With Substance Use Disorder in a Large Population-Based Epidemiological Study. J Atten Disord. 2016.
  13. Wilens TE, Biederman J, Mick E. Does ADHD Affect the Course of Substance Abuse?: Findings From a Sample of Adults With and Without ADHD. The American Journal on Addictions. 1998;7(2):156-163.
  14. Katzman MA, Bilkey TS, Chokka PR, Fallu A, Klassen LJ. Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. BMC Psychiatry. 2017;17(1):302.
  15. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
  16. Tesar GE, Seballos RJ. Attention-Deficit/Hyperactivity Disorder in Adults. 2010. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/psychiatry-psychology/attention-deficit-hyperactivity-disorder-in-adults/.
  17. Grogan K, Gormley CI, Rooney B, et al. Differential diagnosis and comorbidity of ADHD and anxiety in adults. Br J Clin Psychol. 2017.
  18. Grogan K, Bramham J. Demographic, developmental and psychosocial predictors of the development of anxiety in adults with ADHD. Atten Defic Hyperact Disord. 2016;8(1):35-44.
  19. Kooij JJ, Huss M, Asherson P, et al. Distinguishing comorbidity and successful management of adult ADHD. J Atten Disord. 2012;16(5 suppl):3s-19s.
  20. Youngstrom EA, Arnold LE, Frazier TW. Bipolar and ADHD Comorbidity: Both Artifact and Outgrowth of Shared Mechanisms. Clinical psychology : a publication of the Division of Clinical Psychology of the American Psychological Association. 2010;17(4):350-359.
  21. Duffy A. The nature of the association between childhood ADHD and the development of bipolar disorder: a review of prospective high-risk studies. Am J Psychiatry. 2012;169(12):1247-1255.
  22. Klassen LJ, Katzman MA, Chokka P. Adult ADHD and its comorbidities, with a focus on bipolar disorder. J Affect Disord. 2010;124(1-2):1-8.
  23. Babcock T, Ornstein CS. Comorbidity and its impact in adult patients with attention-deficit/hyperactivity disorder: a primary care perspective. Postgrad Med. 2009;121(3):73-82.
  24. Perugi G, Vannucchi G. The use of stimulants and atomoxetine in adults with comorbid ADHD and bipolar disorder. Expert Opin Pharmacother. 2015;16(14):2193-2204.
  25. Simon N, Rolland B, Karila L. Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder and Substance Use Disorders. Curr Pharm Des. 2015;21(23):3359-3366.
  26. Reimherr FW, Williams ED, Strong RE, Mestas R, Soni P, Marchant BK. A double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder. J Clin Psychiatry. 2007;68(1):93-101.
  27. Young S, Khondoker M, Emilsson B, et al. Cognitive–behavioural therapy in medication-treated adults with attention-deficit/hyperactivity disorder and co-morbid psychopathology: a randomized controlled trial using multi-level analysis. Psychological Medicine. 2015;45(13):2793-2804.

Target Audience

This educational initiative has been designed for primary care clinicians involved in the management of adult patients with ADHD.

Directions to Learner

There are no fees for participating and receiving CME credit for this enduring activity. During the period of January 10, 2018 through January 10, 2019, participants must:

  • Read the learning objective and faculty disclosures
  • Study the educational activity
  • Complete the posttest and the evaluation form

A statement of credit will be issued upon receipt of a completed activity evaluation form and a completed posttest with a score of 100%.

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Integrity Continuing Education, Inc. designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Integrity Continuing Education, Inc. requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent COI they may have as related to the content of this activity. All identified COI are thoroughly vetted by Integrity Continuing Education, Inc. for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

The following faculty/planners reported their financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity:

Ann Childress, MD,
Consultant: Arbor, Ironshore, Neos, Neurovance, Noven, Rhodes, Shire, Sunovion, Tris
Speakers’ Bureaus: Neos, Pfizer, Shire, Tris
Research: Alcobra, Arbor, Forest, Ironshore, Lilly, Lundbeck, Otsuka, Pearson, Pfizer, Purdue, Rhodes, Shire, Sunovion, Tris

Patima Tanapat, PhD, has no real or apparent conflicts of interest to disclose.

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