Paul Hammerness, MD

Mr. Z, age 42, is referred by his primary care physician with symptoms suggesting attention-deficit/hyperactivity disorder (ADHD). Mr. Z has seen his physician sporadically for 10 years and acknowledges not following dietary and exercise advice. He has had intermittent “minor” depression, is overweight, and is a smoker with a family history of cardiovascular disease and diabetes.

A salesman, Mr. Z recently was promoted to an administrative position that substantially increased his paperwork. He is having difficulty performing his job because of longstanding forgetfulness and disorganization. He says he feels “like I’m in grade school again, lost in paperwork.” He also describes a recent educational assessment for his son, age 7, who may have ADHD. Similarities between Mr. Z’s and his son’s early childhood academic struggles are striking.

Like Mr. Z, adults with ADHD commonly seek treatment when increasing stressors and demands overwhelm their cognitive-attentional abilities. Some may be “healthy” men and women without psychiatric histories, whose disorganization, forgetfulness, or impulsivity contributes to functional impairment, including nonadherence with medical advice. For others, such as those with known psychiatric disorders, ADHD may be a hidden comorbidity contributing to seemingly refractory depression or anxiety disorder.

Despite growing evidence related to adult ADHD, individualizing and maintaining treatment over time can be challenging for clinicians and patients. Fortunately, new tools and multiple stimulant and nonstimulant medications can help you screen for, assess, and treat adult ADHD.

ADHD diagnosis

To diagnose ADHD in an adult patient, first establish that symptoms have existed from childhood to adulthood. One approach is to review DSM-IV-TR criteria for ADHD with your patient and ask him or her to reflect on childhood symptoms and dysfunction. Begin with orienting questions, such as “Do you remember your first grade teacher, your school, where you lived?” ADHD symptoms might have been present even if the patient maintained acceptable grades, particularly in elementary school, as dedicated parents or teachers might have contributed to early academic success.

Next, turn to diagnostic language that captures ADHD symptoms in adults. For example, the 18-item World Health Organization Adult ADHD Self-Report Scale (ASRS-v1.1) prompts individuals to self-report DSM-IV ADHD symptoms, and a 6-item subset (Table 1) is a highly specific screener (see Related Resources). The ASRS is most reliable in adults with limited psychiatric comorbidity.¹

Adults often describe fluctuations in symptom severity over time. Symptoms may have less impact with more physically demanding work—such as sales—and greater impact with organizationally demanding work—such as administration.

Base your summary ADHD diagnosis on DSM-IV-TR criteria, including:

• lifetime persistence of symptoms, beginning before age 7
• functional impairment in ≥2 life settings, such as work, school, or home
• lack of another medical or psychiatric condition sufficient to explain the symptoms.

Table 1

Adult Self-Report Scale-v1.1 WHO 6-question screening tool for ADHD*

CASE CONTINUED: ‘All the time, every day’

Mr. Z completes the ASRS self-report symptom checklist and brings his wife to the next appointment. He rated all 6 screening symptoms and most others as occurring “often” or “very often.” He describes functional impairments “essentially all the time, basically every day” at work, home, and socially. His wife confirms these symptoms and the frustrations and conflicts they have caused.

Mr. Z describes ADHD symptoms from early elementary school to college. He was held back in kindergarten for being “immature,” his academic performance was inconsistent, and he “just got by…by cramming” in high school and college. His school performance pattern does not suggest a learning disability; he did not need special help in 1 subject more than others, and under pressure he could achieve average grades.

Medical review excludes explanations other than ADHD for his inattention, restlessness, and impulsivity. You conclude that Mr. Z meets criteria for ADHD, combined subtype, and discuss medication treatment.

FDA-approved medications

Medication for ADHD is appropriate only if symptoms are impairing. Five effective and generally well-tolerated medications are FDA-approved for adults with ADHD (Table 2):

• extended-release mixed amphetamine (Adderall XR)
• extended-release OROS methylphenidate (Concerta)
• extended-release dexmethylphenidate (Focalin XR)
• atomoxetine (Strattera)
• lisdexamfetamine (Vyvanse).

Efficacy. A meta-analysis of 29 pediatric ADHD trials across 30 years demonstrated greater effect size for stimulant class medications (immediate- and long-acting), compared with nonstimulant medications (including bupropion, atomoxetine, and modafinil).² This finding is consistent with the American Academy of Child and Adolescent Psychiatry’s recommendation of stimulant medications as first-line agents for pediatric ADHD.³ A similar meta-analysis of 6 controlled studies of methylphenidate-class medications in adults found a large mean effect size (0.9), with greater effects associated with higher doses.⁴

Atomoxetine, a norepinephrine reuptake inhibitor, is the only nonstimulant medication FDA-approved for ADHD in adults. More than 6,000 children, adolescents, and adults have taken atomoxetine in clinical trials for ADHD (Lilly, prescribing information), with 4 years of open treatment data showing benefit being maintained over time.⁵

Tolerability. Although ADHD medications are generally well-tolerated by healthy adults, assess for a history of potential contraindications:

• unstable medical condition, hyperthyroidism, glaucoma
• treatment with a monoamine oxidase inhibitor or other pressor agents because of possible effects on blood pressure and heart rate
• use of cytochrome P450 2D6 inhibitors, which may increase atomoxetine steady-state plasma concentrations
• cardiovascular disease or family history of early cardiac disease (Box 1)^6,7
• history of or active substance use disorder, such as alcohol dependence, cocaine or heroin abuse
• history of psychosis, bipolar disorder, or an active clinically significant psychiatric comorbidity (major depression, agitated state, suicidality).

Clinically, some patients appear to tolerate 1 class of stimulant (such as methylphenidate or amphetamine) over another. Consider switching to an alternate stimulant if your patient has bothersome side effects—mild low appetite, insomnia, tension, or jitteriness—or has received limited or partial benefit during an initial stimulant trial.

Box 1

Extended-release formulations. Early adult studies demonstrated the efficacy of immediate-release stimulants, but adults with ADHD’s inherent deficits in organization and memory may have higher adherence rates and greater success with once-daily, extended-release formulations.^8-11 Unless your patient wants to begin with small, short-acting dosages (5 to 10 mg) or desires to target treatment to specific times of day (such as in the morning for administrative work only), many appreciate once-daily formulations. Extended-release formulations also may be the simplest stimulants with which to begin ADHD treatment.

Over time, patients may benefit from an immediate-release form:

• added for certain times of day—such as in late afternoon, when the morning extended-release dose has worn off (Box 2)^12,13
• to use as an alternative to extended-release formulations when more or less flexibly is desired, such as on weekends.

Table 2

Administering medications approved for adult ADHD

CASE CONTINUED: Feeling ‘calm, less frenetic’

During the next 6 months, you start Mr. Z on stimulant treatment at robust dosing consistent with his weight (90 kg). He complains that extended-duration methylphenidate (MPH)—titrated to 90 mg/d—doesn’t last into the late afternoon, and he feels mildly tense with a low appetite. Because of an apparent partial response and relatively mild adverse effects, you discontinue MPH and try an extended-duration amphetamine, titrated to 60 mg.

Mr. Z’s blood pressure and heart rate remain stable. He begins to exercise regularly and reduce his use of tobacco and caffeine drinks, as you recommend. He says he feels “calm, less frenetic.” He reports no tension on this medication and only mild reduced appetite. With a plan to continue taking the stimulant medication with regular monitoring, he then disappears from treatment.

Promoting adherence

Treatment nonadherence is an issue throughout medicine, and individuals with disorganization, forgetfulness, and impulsivity may be at higher-than-usual risk of not following through on medication regimens.

Box 2

In addition, restrictions on stimulant-class medications do not permit multiple-month prescribing (refills), as is allowed with non-scheduled medications such as atomoxetine. Discuss with patients how they will obtain stimulant medications on a regular, monthly or bimonthly basis. In our experience, the practical challenges of remaining in treatment at times may limit patients’ adherence to ADHD medications more than a lack of response or tolerability concerns.

Explain to patients early in treatment that they might need to try several different medications before settling on 1 that is optimally tolerated and efficacious. Because stimulants are generally quite effective for ADHD symptoms, set your goal to identify adverse effects and aim for a patient response of “this works well, and I don’t feel any different on it.”

CASE CONTINUED: Ready to try again

Three years later, Mr. Z returns and reports gradually discontinuing the stimulant because he “wanted to go it on my own.” He functioned relatively well at first, but errors and conflicts at his job led to his dismissal.

Since then, he has been unemployed. He is increasingly depressed and reports drinking and smoking “more heavily than in college.” He asks about resuming ADHD treatment.

Mr. Z does not meet DSM-IV-TR criteria for major depressive disorder or alcohol abuse/dependence. His depressed mood appears to be linked to his marked ADHD symptoms. Mr. Z agrees to a new treatment plan that includes starting atomoxetine at 25 mg to allow for flexible titration and psychotherapy to monitor his mood and achieve sobriety.

ADHD and substance abuse

Clinical judgment determines whether an adult with ADHD and a history of substance use disorders may safely benefit from treatment with a stimulant. The relationship between ADHD and substance use disorders is of clinical concern, but ADHD medications have not been shown to increase risk for later substance use disorders in children.¹⁴ Conversely, effective ADHD treatment appears to reduce later cigarette and substance use.¹⁵

Consider using a nonstimulant-class medication in adults with ADHD and active substance use disorders. In a 12-week, double-blind, controlled trial, atomoxetine improved ADHD symptoms significantly more than placebo in adults meeting DS-MIV-TR criteria for comorbid alcohol use disorders. After 4 to 30 days of alcohol abstinence, 72 patients were randomly assigned to atomoxetine, 25 to 100 mg/d (mean final dose 90 mg/d), and 75 patients to placebo. Although estimated times to initial relapse to heavy drinking did not differ:

• atomoxetine-treated subjects had 26% fewer cumulative heavy drinking days than placebo-treated subjects (P=0.023)
• the difference in cumulative heavy drinking days between the atomoxetine and placebo groups became statistically significant after 55 days of treatment.¹⁶

Related resources

• World Health Organization Adult Self-Report Scale (ASRS) 18-item instrument and 6-item screener. www.med.nyu.edu/psych/psychiatrist/adhd.html.
• Volkow ND, Swanson JM. Does childhood treatment of ADHD with stimulant medication affect substance abuse in adulthood? Am J Psychiatry 2008;165:553-5.
• Adler LA, Spencer TJ, Levine LR, et al. Functional outcomes in the treatment of adults with ADHD. J Atten Disord 2008; 11:720-7.

Drug brand names

• Atomoxetine • Strattera
• Bupropion • Wellbutrin
• Extended-release mixed amphetamine • Adderall XR
• Extended duration OROS methylphenidate • Concerta
• Extended-release dexmethylphenidate • Focalin XR
• Lisdexamfetamine • Vyvanse
• Modafinil • Provigil

Disclosure

Dr. Hammerness has received research support from and is on the speakers bureau for Shire Pharmaceuticals. He has received support for CME activities and talks from Shire Pharmaceuticals, Ortho-McNeil, and Abbott Laboratories.

Dr. Surman receives research support and/or is a speaker for Abbott Laboratories, Cephalon, Eli Lilly and Company, Janssen, Ortho-McNeil, Merck, New River Pharmaceuticals, Novartis, Pfizer Inc., Shire Pharmaceuticals, and Takeda Pharmaceutical Company.

Dr. Sassi reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

Clinical research assistant Katherine Miller, BA, contributed to the literature review for this article and assisted in preparing the manuscript.

Mr. Z, age 42, is referred by his primary care physician with symptoms suggesting attention-deficit/hyperactivity disorder (ADHD). Mr. Z has seen his physician sporadically for 10 years and acknowledges not following dietary and exercise advice. He has had intermittent “minor” depression, is overweight, and is a smoker with a family history of cardiovascular disease and diabetes.

A salesman, Mr. Z recently was promoted to an administrative position that substantially increased his paperwork. He is having difficulty performing his job because of longstanding forgetfulness and disorganization. He says he feels “like I’m in grade school again, lost in paperwork.” He also describes a recent educational assessment for his son, age 7, who may have ADHD. Similarities between Mr. Z’s and his son’s early childhood academic struggles are striking.

Like Mr. Z, adults with ADHD commonly seek treatment when increasing stressors and demands overwhelm their cognitive-attentional abilities. Some may be “healthy” men and women without psychiatric histories, whose disorganization, forgetfulness, or impulsivity contributes to functional impairment, including nonadherence with medical advice. For others, such as those with known psychiatric disorders, ADHD may be a hidden comorbidity contributing to seemingly refractory depression or anxiety disorder.

Despite growing evidence related to adult ADHD, individualizing and maintaining treatment over time can be challenging for clinicians and patients. Fortunately, new tools and multiple stimulant and nonstimulant medications can help you screen for, assess, and treat adult ADHD.

ADHD diagnosis

To diagnose ADHD in an adult patient, first establish that symptoms have existed from childhood to adulthood. One approach is to review DSM-IV-TR criteria for ADHD with your patient and ask him or her to reflect on childhood symptoms and dysfunction. Begin with orienting questions, such as “Do you remember your first grade teacher, your school, where you lived?” ADHD symptoms might have been present even if the patient maintained acceptable grades, particularly in elementary school, as dedicated parents or teachers might have contributed to early academic success.

Next, turn to diagnostic language that captures ADHD symptoms in adults. For example, the 18-item World Health Organization Adult ADHD Self-Report Scale (ASRS-v1.1) prompts individuals to self-report DSM-IV ADHD symptoms, and a 6-item subset (Table 1) is a highly specific screener (see Related Resources). The ASRS is most reliable in adults with limited psychiatric comorbidity.¹

Adults often describe fluctuations in symptom severity over time. Symptoms may have less impact with more physically demanding work—such as sales—and greater impact with organizationally demanding work—such as administration.

Base your summary ADHD diagnosis on DSM-IV-TR criteria, including:

• lifetime persistence of symptoms, beginning before age 7
• functional impairment in ≥2 life settings, such as work, school, or home
• lack of another medical or psychiatric condition sufficient to explain the symptoms.

Table 1

Adult Self-Report Scale-v1.1 WHO 6-question screening tool for ADHD*

CASE CONTINUED: ‘All the time, every day’

Mr. Z completes the ASRS self-report symptom checklist and brings his wife to the next appointment. He rated all 6 screening symptoms and most others as occurring “often” or “very often.” He describes functional impairments “essentially all the time, basically every day” at work, home, and socially. His wife confirms these symptoms and the frustrations and conflicts they have caused.

Mr. Z describes ADHD symptoms from early elementary school to college. He was held back in kindergarten for being “immature,” his academic performance was inconsistent, and he “just got by…by cramming” in high school and college. His school performance pattern does not suggest a learning disability; he did not need special help in 1 subject more than others, and under pressure he could achieve average grades.

Medical review excludes explanations other than ADHD for his inattention, restlessness, and impulsivity. You conclude that Mr. Z meets criteria for ADHD, combined subtype, and discuss medication treatment.

FDA-approved medications

Medication for ADHD is appropriate only if symptoms are impairing. Five effective and generally well-tolerated medications are FDA-approved for adults with ADHD (Table 2):

• extended-release mixed amphetamine (Adderall XR)
• extended-release OROS methylphenidate (Concerta)
• extended-release dexmethylphenidate (Focalin XR)
• atomoxetine (Strattera)
• lisdexamfetamine (Vyvanse).

Efficacy. A meta-analysis of 29 pediatric ADHD trials across 30 years demonstrated greater effect size for stimulant class medications (immediate- and long-acting), compared with nonstimulant medications (including bupropion, atomoxetine, and modafinil).² This finding is consistent with the American Academy of Child and Adolescent Psychiatry’s recommendation of stimulant medications as first-line agents for pediatric ADHD.³ A similar meta-analysis of 6 controlled studies of methylphenidate-class medications in adults found a large mean effect size (0.9), with greater effects associated with higher doses.⁴

Atomoxetine, a norepinephrine reuptake inhibitor, is the only nonstimulant medication FDA-approved for ADHD in adults. More than 6,000 children, adolescents, and adults have taken atomoxetine in clinical trials for ADHD (Lilly, prescribing information), with 4 years of open treatment data showing benefit being maintained over time.⁵

Tolerability. Although ADHD medications are generally well-tolerated by healthy adults, assess for a history of potential contraindications:

• unstable medical condition, hyperthyroidism, glaucoma
• treatment with a monoamine oxidase inhibitor or other pressor agents because of possible effects on blood pressure and heart rate
• use of cytochrome P450 2D6 inhibitors, which may increase atomoxetine steady-state plasma concentrations
• cardiovascular disease or family history of early cardiac disease (Box 1)^6,7
• history of or active substance use disorder, such as alcohol dependence, cocaine or heroin abuse
• history of psychosis, bipolar disorder, or an active clinically significant psychiatric comorbidity (major depression, agitated state, suicidality).

Clinically, some patients appear to tolerate 1 class of stimulant (such as methylphenidate or amphetamine) over another. Consider switching to an alternate stimulant if your patient has bothersome side effects—mild low appetite, insomnia, tension, or jitteriness—or has received limited or partial benefit during an initial stimulant trial.

Box 1

Extended-release formulations. Early adult studies demonstrated the efficacy of immediate-release stimulants, but adults with ADHD’s inherent deficits in organization and memory may have higher adherence rates and greater success with once-daily, extended-release formulations.^8-11 Unless your patient wants to begin with small, short-acting dosages (5 to 10 mg) or desires to target treatment to specific times of day (such as in the morning for administrative work only), many appreciate once-daily formulations. Extended-release formulations also may be the simplest stimulants with which to begin ADHD treatment.

Over time, patients may benefit from an immediate-release form:

• added for certain times of day—such as in late afternoon, when the morning extended-release dose has worn off (Box 2)^12,13
• to use as an alternative to extended-release formulations when more or less flexibly is desired, such as on weekends.

Table 2

Administering medications approved for adult ADHD

CASE CONTINUED: Feeling ‘calm, less frenetic’

During the next 6 months, you start Mr. Z on stimulant treatment at robust dosing consistent with his weight (90 kg). He complains that extended-duration methylphenidate (MPH)—titrated to 90 mg/d—doesn’t last into the late afternoon, and he feels mildly tense with a low appetite. Because of an apparent partial response and relatively mild adverse effects, you discontinue MPH and try an extended-duration amphetamine, titrated to 60 mg.

Mr. Z’s blood pressure and heart rate remain stable. He begins to exercise regularly and reduce his use of tobacco and caffeine drinks, as you recommend. He says he feels “calm, less frenetic.” He reports no tension on this medication and only mild reduced appetite. With a plan to continue taking the stimulant medication with regular monitoring, he then disappears from treatment.

Promoting adherence

Treatment nonadherence is an issue throughout medicine, and individuals with disorganization, forgetfulness, and impulsivity may be at higher-than-usual risk of not following through on medication regimens.

Box 2

In addition, restrictions on stimulant-class medications do not permit multiple-month prescribing (refills), as is allowed with non-scheduled medications such as atomoxetine. Discuss with patients how they will obtain stimulant medications on a regular, monthly or bimonthly basis. In our experience, the practical challenges of remaining in treatment at times may limit patients’ adherence to ADHD medications more than a lack of response or tolerability concerns.

Explain to patients early in treatment that they might need to try several different medications before settling on 1 that is optimally tolerated and efficacious. Because stimulants are generally quite effective for ADHD symptoms, set your goal to identify adverse effects and aim for a patient response of “this works well, and I don’t feel any different on it.”

CASE CONTINUED: Ready to try again

Three years later, Mr. Z returns and reports gradually discontinuing the stimulant because he “wanted to go it on my own.” He functioned relatively well at first, but errors and conflicts at his job led to his dismissal.

Since then, he has been unemployed. He is increasingly depressed and reports drinking and smoking “more heavily than in college.” He asks about resuming ADHD treatment.

Mr. Z does not meet DSM-IV-TR criteria for major depressive disorder or alcohol abuse/dependence. His depressed mood appears to be linked to his marked ADHD symptoms. Mr. Z agrees to a new treatment plan that includes starting atomoxetine at 25 mg to allow for flexible titration and psychotherapy to monitor his mood and achieve sobriety.

ADHD and substance abuse

Clinical judgment determines whether an adult with ADHD and a history of substance use disorders may safely benefit from treatment with a stimulant. The relationship between ADHD and substance use disorders is of clinical concern, but ADHD medications have not been shown to increase risk for later substance use disorders in children.¹⁴ Conversely, effective ADHD treatment appears to reduce later cigarette and substance use.¹⁵

Consider using a nonstimulant-class medication in adults with ADHD and active substance use disorders. In a 12-week, double-blind, controlled trial, atomoxetine improved ADHD symptoms significantly more than placebo in adults meeting DS-MIV-TR criteria for comorbid alcohol use disorders. After 4 to 30 days of alcohol abstinence, 72 patients were randomly assigned to atomoxetine, 25 to 100 mg/d (mean final dose 90 mg/d), and 75 patients to placebo. Although estimated times to initial relapse to heavy drinking did not differ:

• atomoxetine-treated subjects had 26% fewer cumulative heavy drinking days than placebo-treated subjects (P=0.023)
• the difference in cumulative heavy drinking days between the atomoxetine and placebo groups became statistically significant after 55 days of treatment.¹⁶

Related resources

• World Health Organization Adult Self-Report Scale (ASRS) 18-item instrument and 6-item screener. www.med.nyu.edu/psych/psychiatrist/adhd.html.
• Volkow ND, Swanson JM. Does childhood treatment of ADHD with stimulant medication affect substance abuse in adulthood? Am J Psychiatry 2008;165:553-5.
• Adler LA, Spencer TJ, Levine LR, et al. Functional outcomes in the treatment of adults with ADHD. J Atten Disord 2008; 11:720-7.

Drug brand names

• Atomoxetine • Strattera
• Bupropion • Wellbutrin
• Extended-release mixed amphetamine • Adderall XR
• Extended duration OROS methylphenidate • Concerta
• Extended-release dexmethylphenidate • Focalin XR
• Lisdexamfetamine • Vyvanse
• Modafinil • Provigil

Disclosure

Dr. Hammerness has received research support from and is on the speakers bureau for Shire Pharmaceuticals. He has received support for CME activities and talks from Shire Pharmaceuticals, Ortho-McNeil, and Abbott Laboratories.

Dr. Surman receives research support and/or is a speaker for Abbott Laboratories, Cephalon, Eli Lilly and Company, Janssen, Ortho-McNeil, Merck, New River Pharmaceuticals, Novartis, Pfizer Inc., Shire Pharmaceuticals, and Takeda Pharmaceutical Company.

Dr. Sassi reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

Clinical research assistant Katherine Miller, BA, contributed to the literature review for this article and assisted in preparing the manuscript.

Mr. Z, age 42, is referred by his primary care physician with symptoms suggesting attention-deficit/hyperactivity disorder (ADHD). Mr. Z has seen his physician sporadically for 10 years and acknowledges not following dietary and exercise advice. He has had intermittent “minor” depression, is overweight, and is a smoker with a family history of cardiovascular disease and diabetes.

A salesman, Mr. Z recently was promoted to an administrative position that substantially increased his paperwork. He is having difficulty performing his job because of longstanding forgetfulness and disorganization. He says he feels “like I’m in grade school again, lost in paperwork.” He also describes a recent educational assessment for his son, age 7, who may have ADHD. Similarities between Mr. Z’s and his son’s early childhood academic struggles are striking.

Like Mr. Z, adults with ADHD commonly seek treatment when increasing stressors and demands overwhelm their cognitive-attentional abilities. Some may be “healthy” men and women without psychiatric histories, whose disorganization, forgetfulness, or impulsivity contributes to functional impairment, including nonadherence with medical advice. For others, such as those with known psychiatric disorders, ADHD may be a hidden comorbidity contributing to seemingly refractory depression or anxiety disorder.

Despite growing evidence related to adult ADHD, individualizing and maintaining treatment over time can be challenging for clinicians and patients. Fortunately, new tools and multiple stimulant and nonstimulant medications can help you screen for, assess, and treat adult ADHD.

ADHD diagnosis

To diagnose ADHD in an adult patient, first establish that symptoms have existed from childhood to adulthood. One approach is to review DSM-IV-TR criteria for ADHD with your patient and ask him or her to reflect on childhood symptoms and dysfunction. Begin with orienting questions, such as “Do you remember your first grade teacher, your school, where you lived?” ADHD symptoms might have been present even if the patient maintained acceptable grades, particularly in elementary school, as dedicated parents or teachers might have contributed to early academic success.

Next, turn to diagnostic language that captures ADHD symptoms in adults. For example, the 18-item World Health Organization Adult ADHD Self-Report Scale (ASRS-v1.1) prompts individuals to self-report DSM-IV ADHD symptoms, and a 6-item subset (Table 1) is a highly specific screener (see Related Resources). The ASRS is most reliable in adults with limited psychiatric comorbidity.¹

Adults often describe fluctuations in symptom severity over time. Symptoms may have less impact with more physically demanding work—such as sales—and greater impact with organizationally demanding work—such as administration.

Base your summary ADHD diagnosis on DSM-IV-TR criteria, including:

• lifetime persistence of symptoms, beginning before age 7
• functional impairment in ≥2 life settings, such as work, school, or home
• lack of another medical or psychiatric condition sufficient to explain the symptoms.

Table 1

Adult Self-Report Scale-v1.1 WHO 6-question screening tool for ADHD*

CASE CONTINUED: ‘All the time, every day’

Mr. Z completes the ASRS self-report symptom checklist and brings his wife to the next appointment. He rated all 6 screening symptoms and most others as occurring “often” or “very often.” He describes functional impairments “essentially all the time, basically every day” at work, home, and socially. His wife confirms these symptoms and the frustrations and conflicts they have caused.

Mr. Z describes ADHD symptoms from early elementary school to college. He was held back in kindergarten for being “immature,” his academic performance was inconsistent, and he “just got by…by cramming” in high school and college. His school performance pattern does not suggest a learning disability; he did not need special help in 1 subject more than others, and under pressure he could achieve average grades.

Medical review excludes explanations other than ADHD for his inattention, restlessness, and impulsivity. You conclude that Mr. Z meets criteria for ADHD, combined subtype, and discuss medication treatment.

FDA-approved medications

Medication for ADHD is appropriate only if symptoms are impairing. Five effective and generally well-tolerated medications are FDA-approved for adults with ADHD (Table 2):

• extended-release mixed amphetamine (Adderall XR)
• extended-release OROS methylphenidate (Concerta)
• extended-release dexmethylphenidate (Focalin XR)
• atomoxetine (Strattera)
• lisdexamfetamine (Vyvanse).

Efficacy. A meta-analysis of 29 pediatric ADHD trials across 30 years demonstrated greater effect size for stimulant class medications (immediate- and long-acting), compared with nonstimulant medications (including bupropion, atomoxetine, and modafinil).² This finding is consistent with the American Academy of Child and Adolescent Psychiatry’s recommendation of stimulant medications as first-line agents for pediatric ADHD.³ A similar meta-analysis of 6 controlled studies of methylphenidate-class medications in adults found a large mean effect size (0.9), with greater effects associated with higher doses.⁴

Atomoxetine, a norepinephrine reuptake inhibitor, is the only nonstimulant medication FDA-approved for ADHD in adults. More than 6,000 children, adolescents, and adults have taken atomoxetine in clinical trials for ADHD (Lilly, prescribing information), with 4 years of open treatment data showing benefit being maintained over time.⁵

Tolerability. Although ADHD medications are generally well-tolerated by healthy adults, assess for a history of potential contraindications:

• unstable medical condition, hyperthyroidism, glaucoma
• treatment with a monoamine oxidase inhibitor or other pressor agents because of possible effects on blood pressure and heart rate
• use of cytochrome P450 2D6 inhibitors, which may increase atomoxetine steady-state plasma concentrations
• cardiovascular disease or family history of early cardiac disease (Box 1)^6,7
• history of or active substance use disorder, such as alcohol dependence, cocaine or heroin abuse
• history of psychosis, bipolar disorder, or an active clinically significant psychiatric comorbidity (major depression, agitated state, suicidality).

Clinically, some patients appear to tolerate 1 class of stimulant (such as methylphenidate or amphetamine) over another. Consider switching to an alternate stimulant if your patient has bothersome side effects—mild low appetite, insomnia, tension, or jitteriness—or has received limited or partial benefit during an initial stimulant trial.

Box 1

Extended-release formulations. Early adult studies demonstrated the efficacy of immediate-release stimulants, but adults with ADHD’s inherent deficits in organization and memory may have higher adherence rates and greater success with once-daily, extended-release formulations.^8-11 Unless your patient wants to begin with small, short-acting dosages (5 to 10 mg) or desires to target treatment to specific times of day (such as in the morning for administrative work only), many appreciate once-daily formulations. Extended-release formulations also may be the simplest stimulants with which to begin ADHD treatment.

Over time, patients may benefit from an immediate-release form:

• added for certain times of day—such as in late afternoon, when the morning extended-release dose has worn off (Box 2)^12,13
• to use as an alternative to extended-release formulations when more or less flexibly is desired, such as on weekends.

Table 2

Administering medications approved for adult ADHD

CASE CONTINUED: Feeling ‘calm, less frenetic’

During the next 6 months, you start Mr. Z on stimulant treatment at robust dosing consistent with his weight (90 kg). He complains that extended-duration methylphenidate (MPH)—titrated to 90 mg/d—doesn’t last into the late afternoon, and he feels mildly tense with a low appetite. Because of an apparent partial response and relatively mild adverse effects, you discontinue MPH and try an extended-duration amphetamine, titrated to 60 mg.

Mr. Z’s blood pressure and heart rate remain stable. He begins to exercise regularly and reduce his use of tobacco and caffeine drinks, as you recommend. He says he feels “calm, less frenetic.” He reports no tension on this medication and only mild reduced appetite. With a plan to continue taking the stimulant medication with regular monitoring, he then disappears from treatment.

Promoting adherence

Treatment nonadherence is an issue throughout medicine, and individuals with disorganization, forgetfulness, and impulsivity may be at higher-than-usual risk of not following through on medication regimens.

Box 2

In addition, restrictions on stimulant-class medications do not permit multiple-month prescribing (refills), as is allowed with non-scheduled medications such as atomoxetine. Discuss with patients how they will obtain stimulant medications on a regular, monthly or bimonthly basis. In our experience, the practical challenges of remaining in treatment at times may limit patients’ adherence to ADHD medications more than a lack of response or tolerability concerns.

Explain to patients early in treatment that they might need to try several different medications before settling on 1 that is optimally tolerated and efficacious. Because stimulants are generally quite effective for ADHD symptoms, set your goal to identify adverse effects and aim for a patient response of “this works well, and I don’t feel any different on it.”

CASE CONTINUED: Ready to try again

Three years later, Mr. Z returns and reports gradually discontinuing the stimulant because he “wanted to go it on my own.” He functioned relatively well at first, but errors and conflicts at his job led to his dismissal.

Since then, he has been unemployed. He is increasingly depressed and reports drinking and smoking “more heavily than in college.” He asks about resuming ADHD treatment.

Mr. Z does not meet DSM-IV-TR criteria for major depressive disorder or alcohol abuse/dependence. His depressed mood appears to be linked to his marked ADHD symptoms. Mr. Z agrees to a new treatment plan that includes starting atomoxetine at 25 mg to allow for flexible titration and psychotherapy to monitor his mood and achieve sobriety.

ADHD and substance abuse

Clinical judgment determines whether an adult with ADHD and a history of substance use disorders may safely benefit from treatment with a stimulant. The relationship between ADHD and substance use disorders is of clinical concern, but ADHD medications have not been shown to increase risk for later substance use disorders in children.¹⁴ Conversely, effective ADHD treatment appears to reduce later cigarette and substance use.¹⁵

Consider using a nonstimulant-class medication in adults with ADHD and active substance use disorders. In a 12-week, double-blind, controlled trial, atomoxetine improved ADHD symptoms significantly more than placebo in adults meeting DS-MIV-TR criteria for comorbid alcohol use disorders. After 4 to 30 days of alcohol abstinence, 72 patients were randomly assigned to atomoxetine, 25 to 100 mg/d (mean final dose 90 mg/d), and 75 patients to placebo. Although estimated times to initial relapse to heavy drinking did not differ:

• atomoxetine-treated subjects had 26% fewer cumulative heavy drinking days than placebo-treated subjects (P=0.023)
• the difference in cumulative heavy drinking days between the atomoxetine and placebo groups became statistically significant after 55 days of treatment.¹⁶

Related resources

• World Health Organization Adult Self-Report Scale (ASRS) 18-item instrument and 6-item screener. www.med.nyu.edu/psych/psychiatrist/adhd.html.
• Volkow ND, Swanson JM. Does childhood treatment of ADHD with stimulant medication affect substance abuse in adulthood? Am J Psychiatry 2008;165:553-5.
• Adler LA, Spencer TJ, Levine LR, et al. Functional outcomes in the treatment of adults with ADHD. J Atten Disord 2008; 11:720-7.

Drug brand names

• Atomoxetine • Strattera
• Bupropion • Wellbutrin
• Extended-release mixed amphetamine • Adderall XR
• Extended duration OROS methylphenidate • Concerta
• Extended-release dexmethylphenidate • Focalin XR
• Lisdexamfetamine • Vyvanse
• Modafinil • Provigil

Disclosure

Dr. Hammerness has received research support from and is on the speakers bureau for Shire Pharmaceuticals. He has received support for CME activities and talks from Shire Pharmaceuticals, Ortho-McNeil, and Abbott Laboratories.

Dr. Surman receives research support and/or is a speaker for Abbott Laboratories, Cephalon, Eli Lilly and Company, Janssen, Ortho-McNeil, Merck, New River Pharmaceuticals, Novartis, Pfizer Inc., Shire Pharmaceuticals, and Takeda Pharmaceutical Company.

Dr. Sassi reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

Clinical research assistant Katherine Miller, BA, contributed to the literature review for this article and assisted in preparing the manuscript.