by Rashi Agarwal, MD; Matthew Goldenberg, DO; Robert Perry, MD; and Waguih William IsHak, MD, FAPA
Dr. Agarwal is a resident at Brookdale University Hospital, Brooklyn, New York; Dr. Goldenberg is a resident at Banner Good Samaritan Medical Center, Phoenix, Arizona; and Drs. Perry and IsHak are with Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California.
Innov Clin Neurosci. 2012;9(5–6):10–21
Funding: No funding was received for the preparation of this article.
Financial Disclosures: None of the authors have a conflict of interest in the conduct and reporting of this review. Dr. IsHak has received grants in associated research areas as follows: NARSAD on quality of life in major depression and Pfizer on ziprasidone monotherapy in major depression.
Key words: Adult attention deficit hyperactivity disorder, quality of life
Abstract: Objective: Across all medical specialties, quality of life has become an important measure of outcomes in both research and clinical settings. However, to date, there has not been a systematic review of the research relevant to quality of life in populations with adult attention deficit hyperactivity disorder. We approach quality of life in adult attention deficit hyperactivity disorder by answering the following questions: 1) What specific metrics are used to assess quality of life in adult attention deficit hyperactivity disorder? 2) What is the impact of adult attention deficit hyperactivity disorder on quality of life? 3) What effects do attention deficit hyperactivity disorder treatments have on quality of life? Searches of major electronic databases were conducted, and reference lists from the identified articles were searched for additional studies, with a focus on studies that utilized quality of life measures.
Design: Thirty-six relevant studies are included in our review.
Results: There are multiple unique measures currently used to measure quality of life in adult attention deficit hyperactivity disorder, ranging from general quality of life scales to those specifically designed for use in attention deficit hyperactivity disorder. Attention deficit hyperactivity disorder was found to significantly worsen the quality of life in adults. Treatment with atomoxetine and mixed amphetamine salts has shown beneficial effects on quality of life even in cases without symptomatology improvement.
Conclusion: Pharmacological treatment and early diagnosis have a positive impact on outcomes, long-term prognosis, and quality of life in adults with attention deficit hyperactivity disorder. Having multiple unique measures of quality of life have limited the direct comparison of different classes of attention deficit hyperactivity disorder medication treatments and future research should be aimed to address this.
Introduction
Quality of life (QoL) can be described as a multidimensional construct that primarily concerns a patient’s personal evaluation of his or her life with regard to global health, handicaps or impairments, and daily living activities. An important distinction can be made between health-related QoL and overall QoL. Health-related QoL comprises disease and treatment related aspects of the individual, such as pain, limitations in motor ability, energy level, or mood. Overall QoL, however, additionally encompasses nonmedical aspects of a person’s life, such as satisfaction with social, educational, and occupational functioning. We found that QoL instruments have been developed with the specific aim of objectively measuring overall QoL in those suffering from attention deficit hyperactivity disorder (ADHD). These instruments were specifically designed to assist clinicians in identifying appropriate treatment targets, facilitate future research, and improve the well-being and functioning of adults with ADHD.[1]
We will first examine the various QoL instruments and their validity in the context of adult ADHD. We will then review studies that utilize these specific QoL measures to investigate the impact of ADHD in adults and the effects of pharmacotherapy on QoL.
Epidemiology of ADHD
The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) defines ADHD via criteria that fall under the broad categories of inattention, hyperactivity, and impulsivity. ADHD has its onset during childhood and affects approximately 3 to 7 percent of school age children.[2] There is also evidence that many adults meet the full criteria for current adult ADHD despite not having met the full childhood criteria.[3] This alludes to the difficulty in making a diagnosis of ADHD, as current criteria require evidence of symptom onset before the age of seven years and impact on activities typically undertaken by children.[4]
ADHD is often present with comorbid disorders, and this can make an accurate diagnosis even more difficult. For example, ADHD often coexists with bipolar disorder (BPD) (6–20%), and in these cases many ADHD symptoms can be mistakenly attributed to and overlooked because of BPD.5 Sentissi et al[5] have shown that impairments in QoL are a key prognostic feature for predicting the long course of BPD, and the authors raised the question as to whether there is a significant impact of comorbid ADHD on the QoL of patients with BPD. Using a sample of participants with BPD (n=73) they measured QoL using the 36-item Short Form Health Survey. It was discovered that there is, indeed, a significant impairment in the presence of comorbid ADHD in BPD patients, especially in adaptation and social functioning, by comparison, with BPD patients without ADHD. In contrast, the authors failed to detect a significant impact of substance abuse on those same functional outcomes. This impresses the large role ADHD plays in determining QoL in comorbid disorders, such as BPD, and the importance of making an accurate diagnosis of ADHD.[5]
ADHD was formerly regarded as a childhood disorder. However, it is now known as a developmental disorder persisting over the lifespan.[6] In a revealing retrospective assessment of 18- to 44-year-olds with a history of childhood ADHD (n=3,197), Kessler et al7 reported that 1 in 3 currently met DSM-IV-TR criteria for adult ADHD. A recent study conducted at the Department of Health Care Policy at Harvard Medical School (n=345) found that almost half of the respondents (45.7%) who had childhood ADHD continued to meet full DSM-IV-TR criteria for current adult ADHD.[3]
Unfortunately, it remains difficult to predict persistence of ADHD into adulthood. Kessler et al[7] found that only childhood ADHD severity and childhood treatment significantly predicted persistence. Controlling for severity and excluding treatment, none of the other variables (e.g., sociodemographics, childhood adversity, traumatic life experiences and comorbid DSM-IV-TR child-adolescent disorders [e.g., anxiety, mood, impulse-control, and substance disorders]) significantly predicted persistence, even though they were significantly associated with childhood ADHD. In a separate study, Kessler et al[3] reported adult persistence was much greater for inattention than for hyperactivity/ impulsivity. However, the authors fell short of predicting persistence within types.
Recently, there has been some genetics research linking ADHD and the latrophilin 3 (LPHN3) gene (a brain-specific member of the LPHN subfamily of G-protein-coupled receptors) that is expressed in ADHD-related regions, such as the amygdala, caudate nucleus, cerebellum, and cerebral cortex. They point at this new neuronal pathway as a common susceptibility factor for ADHD through the lifespan and a possible future source of diagnosis and treatment.[8] To date, no studies have made a direct link, and future genetics research is needed.
The diagnosis of ADHD and predicting persistence into adulthood continues to be difficult and the genetics remains unclear; however, the literature is unanimous in that ADHD negatively impacts QoL in adults. In this review, with the goal of increasing the understanding of the impact of ADHD on QoL in adults, we 1) describe the instruments used to quantify QoL in adult ADHD, 2) review studies that utilize these specific QoL scales, and 3) examine the effects of pharmacological treatments on QoL.
Design
Literature was systematically collected using the following databases: Pubmed, Medline, PsycInfo, Cochrane Database of Systematic Reviews, ACP Journal Club, DARE, CCTR, CMR, HTA, NHSEED, and EMBASE from 1969 to 2011. We focused on studies that used QoL measures. Keywords used for the search were quality of life, QOL, ADHD, ADD, attention deficit hyperactivity disorder, attention deficit disorder, adult, WHO QOL, AAQOL, AIM-A, SF-36, QLESQSF, Euro-5D, and Y-QOL-R. Thirty-six studies are included in this review, including 24 that used QoL measures to quantify the QoL in adults with ADHD.
Metrics used to assess QoL in adult ADHD
In our review of the literature, we found that a number of scales have been utilized in an attempt to measure and objectively quantify the QoL in adult ADHD (Table 1). These include ADHD Impact Module Adult Version (AIM-A), Adult ADHD Quality of Life (AAQoL), World Health Organization Quality of Life (WHO QOL), Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (QLESQ-SF), and 36-item Short Form Health Survey (SF-36). An inquiry into the accuracy and usefulness of these scales is warranted given that each of these scales proposes to accurately measure a construct that, by definition, is abstract and complex, and treatment outcomes are based on their ability to successfully and objectively measure changes in QoL. In this spirit, we have outlined the literature investigating specific scales designed to assess QoL from a generic perspective, like the WHO QoL and SF-36, to those more specifically engineered for use in adult ADHD, such as the AAQOL and AIM-A.
WHO QOL Brief Version (WHO QOL-BREF) and SF-36. WHO QOL-BREF and SF-36 are examples of generic instruments of measure for QoL. WHO QOL-BREF, the most recent 26-item version of the widely utilized 100-item WHO QOL-100 assessment, is composed of four domains: physical, psychological, social, and environmental.
WHO QOL-BREF and SF-36 were evaluated for reliability and validity in a study of patients with human immunodeficiency virus (HIV) (N=224). The scales showed high internal consistency (0.75–0.86 for WHOQOL-BREF and 0.72–0.93 for SF-36). Both also had positive correlation with happiness/self-perceived health status measures and displayed negative correlation with the number/intensity of symptoms. Subjects with fewer symptoms scored higher on all domains of WHOQOL-BREF, and the SF-36 scores also revealed an analogous relation between number of symptoms and QoL. Good correlation was seen between the physical (r=0.48) and mental (r=0.60–0.75) domains of both these scales. WHOQOL-BREF showed less floor and ceiling effect as compared to SF-36.9 The above results present clear and convincing evidence that these two scales, while not specifically designed for patients with ADHD, are valid and reliable measures of QoL.
A study utilizing the Taiwan version of these scales collected data from a national representative sample in the 2001 Taiwan National Health Interview Survey (N=11,440) (which included Taiwan versions of the SF-36 and WHO QOL-BREF).10 They used standardized effect size to compare known-group validity for health-related variables and self-reported overall QoL. They found the SF-36 and WHO QOL-BREF appeared to measure different constructs: the SF-36 measures health-related QoL, while the WHO QOL-BREF measures global QoL. The researchers concluded that clinicians and future research should carefully define research questions related to patient-reported outcomes before selecting amongst QoL measurement scales.10
In the section of this article entitled, “Mixed Amphetamine Salts,” we discuss a specific example of how the use of different QoL scales effected the conclusions that were drawn from treatment outcomes in two separate studies.
QLESQ-SF. Mick et al[11] conducted a study that investigated the validity of the psychometric properties of another generic measure of QoL, the QLESQ-SF. One hundred and fifty adults with ADHD and 134 adults without ADHD from a case-control study and 173 adults randomized to placebo or methylphenidate (MTP) were assessed with both the QLESQ-SF and the Social Adjustment Scale (SAS). Response to change was estimated by comparing change in QLESQ-SF scores in responders and nonresponders to treatment with methylphenidate. Results from this study demonstrated that adults with ADHD have significantly less life enjoyment and satisfaction compared to the non-ADHD participants (76.5±10.9) vs. (59.2±17.3) (P
AAQOL. The Adult ADHD Quality of Life (AAQoL) is an adult ADHD specific QoL scale that was designed to quantify the QoL consequences of adult ADHD. It is composed of 29 items and was developed to specifically assess health-related QoL by focusing on four domains: life productivity, psychological health, relationships, and life outlook.
A retrospective chart review using AAQoL (n=989) found good internal consistency (0.93 overall) in addition to its strong support of construct and known groups validity. Using a priori statistical analysis plan, the study concluded that the AAQoL appears to be a valid measure of QoL for adults with ADHD and can be considered for incorporation into future studies.1
While studies utilizing AAQoL to examine the effects of ADHD medications on QoL will be discussed later in this article, Matza et al[12] specifically addressed the responsiveness of AAQoL as a treatment measure of adults with ADHD started on atomoxetine (ATX). In this randomized, placebo-controlled trial, subjects (n=328) completed the AAQoL and other comparable scales (Conners’ Adult ADHD Rating Scale [CAARS], SF-36 and Endicott Work Productivity Scale [EWPS]) at Baseline and Week 8. In addition, clinicians rated symptom severity and improvement. Responsiveness was examined through effect sizes and association with change of the measures listed previously. They found all AAQoL domains reflected significant improvement from Baseline to Week 8 (P< 0.0001) and these results were significantly correlated with changes in the other scales (all P
Collectively, these studies conclude that the AAQoL yields results that are consistent with other scales of QoL and is a successful measure of QoL changes in clinical trials. Moreover, because AAQoL was designed specifically for adults with ADHD, it yields larger effect sizes than more generic measures of QoL (such as the SF-36). Larger effect sizes can aid both patients and clinicians in discriminating between treatment modalities and their outcomes.
AIM-A. Once research studies proved that condition-specific QoL measures are definitively better than generic measures, research was conducted for the purpose of developing additional scales engineered specifically for QoL in adult ADHD.
One such measure that was developed and evaluated in an open label trial (n=317) was AIM-A. This measure of QoL utilizes multi-item scales to assess both global QoL and ADHD-specific QoL in six domains. AIM-A has shown 80- to 100-percent scaling success with good internal consistency (alpha coefficients ?0.83). It was found to discriminate based upon symptom severity, subtype, and medication experience (p?0.01) and was also sensitive to change (P<0.001). It also correlated nicely with the ADHD rating scale (0.494–0.200).[14] These results strongly suggest that AIM-A is a valuable tool for objectively determining QoL in adults with ADHD. A limitation, however, is that there are no studies comparing AIM-A to the other QoL scales discussed previously. Additionally, AIM-A has been assessed in only a limited number of clinical trials measuring treatment outcomes. We hope future research will address these shortcomings in order to better assess the specific advantages and strengths of each scale in direct comparison to the others.
Minimal clinically important difference. QoL instruments gained the attention of researchers and clinicians as they continued to prove themselves as worthy measures of QoL and treatment outcomes. Once their value was established, QoL instruments were, for the first time, featured as primary outcomes in many randomized trials.[15] One of the challenges facing investigators using such measures is determining the significance of any observed differences and communicating that significance to clinicians and patients who will be applying the trial results. Jaeschke et al[15] proposed elucidating the significance of changes in scores of QoL instruments by comparing them to global ratings of change. Using this approach they established a plausible range within which the minimal clinically important difference (MCID) falls, which helps guide interpretations of questionnaire scores.[15] They cite, for example, three studies in which instruments (measuring dyspnea, fatigue, and emotional function in patients with chronic heart and lung disease) were applied using the MCID, which was represented by a mean change in score of approximately 0.5 per item (when responses were presented on a 7-point Likert scale). This affords subjective changes in scores to be given objective labels, such as “moderate” or “large” change in the domains of interest. This has been useful in both interpreting questionnaire scores and in the planning of new trials.
ADHD’s Impact On QoL
To date, a surprisingly limited number of studies have utilized these QoL measures to investigate the specific effects of ADHD on QoL in adults. A review of available studies (Table 2) shows that the ADHD population suffers greater anxiety, depression, and increased daytime sleepiness than the non-ADHD population.[16] There appears to be a consensus that patients with adult ADHD have lower QoL than non-ADHD patients. For example, a study using WHO QOL-BREF found respondents with ADHD to have lower QoL (all P?0.05), and patients with ADHD showed a below-average level of overall mental health (a component of QoL) on self-ratings measured by SF-36.[2,16] While decreased QoL scores in the adult ADHD population reflect an inferior sense of subjective well-being, they do not explain what leads to or causes adults with ADHD to feel this way. Understanding the negative impact of ADHD on QoL is important; however, if identified, these factors can serve as treatment targets and outcome measures.
In an effort to identify specific factors that decreased QoL, Gudjonsson et al17 aimed to directly associate ADHD symptoms with a negative satisfaction with life (as measured by the Satisfaction with Life Scale). As they hypothesized, they found both ADHD symptoms and associated problems to be significantly related to poorer satisfaction with life. They also found that predictors for dissatisfaction with life appear to differ between men and women with ADHD. They reported that the best predictor for decreased scores was poor social functioning in men and poor emotional control in women.[17] These specific predictors of negative satisfaction and decreased QoL are the first step in understanding how ADHD negatively affects QoL and in developing targeted treatments and outcome measures.
A study conducted by Rimmerman et al[18] also observed that differences in QoL predictors exist between men and women. They found the main predictors to be monthly income for men and level of attention deficit symptoms for women. These studies[17.18] add to the understanding that differences in QoL exist between sexes and that treatment approaches should be tailored accordingly. Further research might uncover the positive effects of other modifiable environmental factors and their differing effects on men and women.
A separate study conducted by Rimmerman et al[19] involving Israeli adults with borderline IQ (70–79) and ADHD led to a greater understanding of some of these modifiable determinants and variables. The authors measured this subset’s QoL via the QoL questionnaire by Schalock and Keith[37] and found that high scores are associated with having had inclusive education, limited medical disabilities, lower scores on the Brown ADHD Symptom Scale, high monthly income, participation in leisure activities, and having a personal friend. The authors reported the two most significant predictors of QoL as being ADHD symptomatology score and monthly income.[19] These results identify additional factors that can be addressed by clinicians seeking to improve their patients QoL, and while this study was conducted in adults with borderline IQ, the factors they identified are universal. As those subjects with lower symptomatology scores had higher QoL scores, their results also indirectly confirm that treatment of the symptoms of ADHD plays a direct role in increasing QoL. There needs to be more research targeting specifically how ADHD affects QoL in adults. The studies that have been published and are examined in this review show that there are differences between how ADHD affects the sexes and that there are modifiable factors that can be targeted in treatments and should be in the future in order to increase positive outcomes.
Treatment Affects On QoL In ADHD
In order to accurately measure pharmacological treatment impacts and compare outcomes, QoL measures have been increasingly used in both clinical settings and research. Table 3 contains a summary of the studies on the effect of treatment on QoL.
After finding that symptoms of ADHD and QoL improve simultaneously, Weiss et al[20] went so far as to conclude that satisfaction with medications is a direct measure that predicts QoL benefits. This highlights the important role that effective medication plays in shaping the QoL in adults with ADHD.
To this end, we review studies carried out with ADHD pharmacological treatments that utilized the previously discussed QoL scales as measures.
Nonstimulant medications. Atomoxetine (ATX). ATX, a norepinephrine reuptake inhibitor, was approved in November 2002 for the treatment of ADHD in children, adolescents, and adults. It is manufactured, marketed, and sold in the United States under the brand name Strattera®. Generic formulations of ATX are sold in other countries.
The effects of ATX on QoL in adults with ADHD was assessed in a series of studies by Adler et al[2,21,23,25] using SF-36 and AAQoL as measures of QoL. These studies found that ATX reduced symptomatology and also improved QoL of adult ADHD patients. Similarly, in a previously mentioned study, Adler et al[2] found significant improvement on self-ratings measured by SF-36 after six weeks of ATX treatment in adults with ADHD (P<0 .001), which correlated with improvement on the symptom scale (P<0 .001). Similar results were obtained when the AAQoL was applied to ATX-treated participants in a randomized, double-blind, placebo-controlled, six-month trial (n=501). They found ATX was statistically superior to placebo at both the 10-week and six-month time points.21 Both studies[2,21] concluded that ATX treatment not only ameliorates ADHD symptoms, but also improves perceived QoL in adults with ADHD.
An interesting distinction, with regard to treatment with ATX, was raised in a review of 13 relevant studies. In their review, Matza et al[22] point out that ATX treatment was associated with greater benefits than placebo on multiple domains, such as behavior, mental health, self esteem and social/family functioning. Subsequently, the authors concluded that there was compelling evidence that treatment of ADHD has broad positive impacts beyond pure symptom improvement. The authorse seemd to be speaking of QoL without mentioning it by name, as these data sets predated much of the research and instruments used to measure QoL in adult ADHD.[22]
Drawing a distinction between improvements in QoL and symptomatology is an important takeaway for both patients and clinicians in regards to ADHD treatment and evaluation of treatment outcomes. This topic was addressed in a six-month, double-blind trial with ATX and placebo (n=410) in adults with DSM-IV-TR-defined ADHD. In this study, Adler et al[23] found ATX-treated patients showed significantly greater improvement in QoL than placebo-treated patients on the AAQoL, after controlling for baseline severity of ADHD. Conversely, at six months, both groups had non-significantly different improvements on the EWPS total scores, a direct measure of symptom improvement. The authors concluded that while symptomatology may fail to improve, ATX-treated patients can still show significant improvement in disease-specific QoL measures.[23]
An open label study of 725 adults with ADHD found changes in attention to be a stronger mediator of ADHD-specific QoL outcomes than the more obvious changes in disruptive symptoms.[20] This impresses the importance of using QoL scales, and not solely symptomatology improvement, to assess and compare the effectiveness of treatment outcomes.
As mentioned previously, patients with ADHD have been found to have higher rates of anxiety than the non-ADHD population. We found several studies that utilized QoL measures in regard to ATX treatment and its use in adult ADHD populations with comorbid anxiety disorders.[24,25] One such study reported that the most problematic impairments in adults with ADHD are in the domain of work, followed by interpersonal (both being associated with ADHD severity); and that these impairments manifested with distress defined by anxiety and depressive symptoms.[24] ATX has been shown to decrease anxiety symptoms in a randomized, double-blind, placebo-controlled study (as measured by STAI- trait inventory) in adults with ADHD and comorbid social anxiety disorder (n=442).[25] The authors reported significant improvement of AAWoL scores at every time point. This study not only confirmed improvements in QoL of adults with ADHD treated with ATX, but also reported improvements of comorbid anxiety symptoms. Accordingly, the authors concluded that ATX treatment of ADHD is beneficial and improves the QoL in patients with comorbid anxiety symptomatology.[25]
Unfortunately, the study of how treatment of ADHD can improve the symptoms of other comorbid disorders associated with ADHD is an important data set that has yet to be fully investigated and should be the focus of future research. As in this case, understanding that ATX has beneficial effects on comorbid anxiety symptomatology can help prevent over prescribing of additional classes of medication and can improve outcomes.
Stimulant medications. Mixed amphetamine salts (MAS). MAS are another commonly prescribed class of ADHD medications. This class has been sold in the United States under the brand name Adderall® since 1996, and generic formulations are presently available in the United States. MAS formulations are collectively thought to act by increasing norepinephrine and dopamine.
Studies done by Spencer et al[26] and Spencer et al[27] monitored the effects of MAS on both symptomatology and QoL in the treatment of adult ADHD. AIM-A was utilized in both studies as a QoL measure, and the authors reported significant improvement on all six ADHD-specific AIM-A subscales. A seven-week, double-blind, placebo-controlled trial of MAS (N=274) found statistically significant improvements in global QoL (for AIM-A Question 1, P=0.0001 and for AIM-A Question 4, P=0.0006).[26] A separate randomized, double-blind, multicenter, placebo-controlled study (N=272) with MAS treatment not only found improvements in both global and ADHD-specific QoL, but also found improvements in executive functioning (EF) (as measured by BADDS) (P<0.0001).[27] The authors concluded that EF deficits play a large role in adults with ADHD, including having possible correlations to changes in QoL.[27]
Kessler et al[3] highlighted the importance of EF. The authors noted that although currently necessary for a diagnosis of ADHD, inattention is not specific to ADHD because it is strongly associated with other mental disorders. Kessler et al3 reason that EF deficits, in comparison, are more specific and, consequently, stronger predictors of adult ADHD, despite not being in the DSM-IV-TR. Supporting this hypothesis, there have been improvements in EF correlated with improvement in QoL, as assessed in two independent clinical trials in which participants received MAS for the treatment of ADHD.[28]
All of these studies[3,26–28] reported that MAS was significantly more effective than placebo in treating adult ADHD and that adverse effects were consistent with amphetamine treatment. The extended duration of action (up to 16 hours), significant improvements in EF, and both global and disease-specific QoL improvements make MAS an important treatment of adult ADHD. This also underscores that EF improvement is an area where MAS is superior to ATX in the treatment of adult ADHD. Kessler et al[3] suggests that the number of EF symptoms should be increased in the upcoming fifth edition of the DSM and the 11th edition of the International Classifications of Diseases (ICD), and that EF’s effects on QoL in the adult ADHD population should be the focus of future research.
Goodman et al,[29] who performed a 10-week analysis in a QoL, Effectiveness, Safety, and Tolerability (QU.E.S.T) trial, reported another area where MAS were found to be superior to ATX. This was an ongoing, open-label, multicenter investigation of once-daily MAS extended release (XR) in adults (n=725). After 10 weeks of treatment (on final visit mean dose 37.2mg/day), patients showed significant improvement in QoL on SF-36. ADHD symptom score also decreased for both hyperactive/impulsive and inattentive subtypes (P<0.0001), and 74.4 percent of subjects were rated as much/very much improved. In addition to improvement on vitality, social, emotional, and physical functioning, they found there was significant improvement in both mental and physical health (all P<0.0001).[29] This is in contrast to ATX results, which did not show specific physical improvement.
There are two possible explanations for the specific physical-health improvements reported with MAS, and this highlights the differences among the QoL instruments and the conclusions that can be drawn from them (as mentioned in the first section on the specific QoL scales). First, the SF-36 specifically targets physical health as one of its domains, whereas the AAQoL does not. The ATX trials used both surveys to collect data, while the MAS study by Goodman et al[29] used only the SR-36 as the authors specifically targeted physical health as one of their measures of QoL. Second, there was more discontinuation due to adverse events for ATX versus MAS, which was comparable to placebo (17.2% ATX vs. 6.9% MAS vs. 5.6% placebo).[25,29] Therefore, one could surmise that the increased adverse effects of ATX contributed to a less noticeable improvement in physical health.
To limit such ambiguities, Huang at al[10] suggested researchers should carefully define their research questions and goals before selecting a QoL instrument. Moreover, as we discuss previously, having multiple measures of QoL has limited the direct comparison of different classes of ADHD medication treatments and in this case allowed claims of superiority that may or may not be accurate. Therefore, future direct comparative clinical trials are needed to fully assess the QoL improvements of the different classes of ADHD medications.
The Impact of ADHD Treatment on Sleep Quality
We found three studies that directly investigated the impact of pharmacological interventions for ADHD on the sleep quality in adults.[30–32] These studies unfortunately did not utilize QoL instrument scales; however, actinographic studies have shown that ADHD had many effects on patients’ sleep.30,31 Those subjects with ADHD took longer to fall asleep and had lower sleep efficiency (shorter within-night periods of uninterrupted sleep).[30] These findings were consistent with subjective complaints. Similar results were reported in another study where subjects with ADHD showed increased nocturnal motor activity and also had reduced self-perceived quality of sleep.[31]
The effect of stimulant methylphenidate (MTP) on sleep quality was assessed in a double-blind, placebo controlled study that showed that stimulants reduced total sleep duration by leading to a later bedtime and later sleep onset.[30] However, nocturnal awakenings decreased and sleep efficiency increased (a measure of sleep quality), indicating more consolidated sleep. A second study also reported the beneficial effects of reduced activity level (p=0.10) and movement index (p=0.07) and improved sleep quality (p=0.05).[31] However, in contrast the authors did not find effects on sleep latency, number of awakenings, or total time in bed. A possible explanation for this disparity is the small sample size (n=8) used in the second study.[31]
The amphetamine pro-drug lisdexamfetamine (LDX) was utilized in a similar study examining its impact on sleep in ADHD treatment.[32] In the Adler et al study,[32] the authors found the mean baseline Pittsburg Sleep Quality Index (PSQI) global score was 5.8 for LDX and 6.3 for placebo (P=0.19), indicating poor overall sleep quality of subjects with ADHD in both the treatment group and the control group. Out of seven sleep components used to assess sleep quality, LDX was found to have an impact only on daytime functioning without any significant changes found in sleep quality, latency, duration and habitual sleep efficiency, sleep disturbances or use of sleep medications. The authors concluded that LDX improves daytime functioning in ADHD patients, while not disrupting sleep quality.[32]
Taken as a whole, these studies30–32 conclude that sleep problems are inherent in adults with ADHD and that ADHD medication improves the quality of sleep. However, further research is required to determine the direct effect improved sleep quality has on overall QoL.
Emerging Nonstimulant Pharmacological Treatments
The stimulant drugs commonly used for the treatment of ADHD have clinically significant side effects, such as insomnia, dry mouth, decreased appetite, and headache, in almost 1 in 5 patients.[29] Researchers are continuously investigating new classes of drugs that are more efficacious and have fewer side effects. Current nonstimulant medications include ATX, the only United States Food and Drug Administration (FDA)-approved, nonstimulant drug for adults with ADHD, which has a positive effect on QoL. Guanfancine (Intuniv®) and clonidine XR (Kapvay®), both alpha-2A adrenergic receptor agonists, were FDA-approved in the past three years for ADHD in children ages 6 to 17 years old, and has not been adequately studied in terms of its effect on QoL in adults. Three other nonstimulant formulations are undergoing clinical trials, as follows: Long-acting clonidine hydrochloride (Clonicel®) is in Phase III clinical trials with no QoL data yet. Pozanicline (ABT-089), a neuronal nicotinic receptor partial agonist, might prove to be promising, as research has shown this drug to significantly improve QoL (as measured using AAQoL), improve the core symptoms of ADHD, and also reduce the overall work impairment in the adult ADHD population. And finally, sofinicline (ABT-894), another nonstimulant agent, is in clinical trials for ADHD and no QoL data are yet available.
Discussion
While traditional treatment evaluation and outcome measures focused only on symptomatology, QoL scales expand our ability to monitor and quantify formerly subjective perceptions of physical, psychological, and social functioning. Self-esteem, body image, leisure, spirituality, safety and security, sexual relations, social supports, and home environment are clear examples of life aspects evaluated during outcome assessments of ADHD interventions with QoL instruments.33 The utilization of QoL scales permits objective evaluation of clinical samples of ADHD adults in a more ‘holistic’ sense by delving into the lesser-studied and more often neglected aspects of patients lives. This is important because there have been reports of significant improvements in QoL and positive treatment outcomes in cases without significant symptomatology improvement.[7,15] Since ADHD is a multifaceted and far-reaching disease, it is important to measure clinical course and treatment outcomes with similarly global assessments.
First-line treatment for ADHD is pharmacotherapy with stimulant drugs, such as MAS. While these medications have established efficacy in treating ADHD, they also have high abuse potential. They are currently categorized as United States Drug Enforcement Authority (DEA) schedule II controlled substances, which places MAS alongside pharmaceuticals notorious for their abuse potential, such as morphine, cocaine, and methamphetamine. While stimulant abuse is beyond the scope of this article, it was reported that patients with chemical dependency and ADHD had increased addiction severity and pathology compared to those with chemical dependency alone.[34] The potential for abuse of stimulant medications may likely influence the choices that clinicians and/or patients make regarding whether to commence therapy with the aforementioned stimulants. Therefore, there is a clear need for the utilization of nonstimulant pharmaceuticals.
With this in mind, it is important to consider that early treatment of ADHD is critical. As previously discussed, not only does early treatment simultaneously decrease symptomatology and improve QoL, but early treatment also plays a large role in adult ADHD course and prognosis, as was shown in a retrospective study of adult ADHD patients utilizing the “Index of Burden” to compare groups.[35] The index was constructed of five variables (alcohol abuse, substance abuse, criminality, global severity index of SCL-90, and the Functioning and Quality of Life questionnaire). Results from this study alert us to the clinically relevant notion that the treatment of ADHD during childhood results in higher social and psychological functioning in adults and helps reduce the burden of untreated ADHD in adulthood.[35]
A different method of calculating the burden of illness was developed for depression incorporating symptom severity, functioning, and quality of life in one measure named the Individual Burden of Illness Index (IBI-D).[36] This innovative approach, if it would to be developed for ADHD, may add significant value to outcome measurement of treatment interventions by incorporating QoL.
In summary, this review contributes to the adult ADHD literature by examining the various QoL measurement scales, ADHD’s effect on QoL in adults, and the impact of specific pharmacological interventions on QoL. Going forward we hope that when the public, patients with ADHD, and clinicians who treat these patients consider the risks and benefits of prescribing a medication or therapy for ADHD treatment, improving QoL will now be among their treatment outcome considerations. QoL research on adults with ADHD has presented a new paradigm for the evaluation of ADHD medications, showing that they do not solely alleviate symptoms and functional impairments associated with ADHD, but perhaps, more importantly, benefit the way in which an adult patient with ADHD experiences and rates his or her quality of life in general.
References
1. Brod M, Johnston J, Able S, Swindle R. Validation of the adult attention-deficit/hyperactivity disorder quality-of-life scale (AAQoL): a disease-specific quality-of-life measure. Qual Life Res. 2006 Feb;15(1):117–129.
2. Adler LA, Sutton VK, Moore RJ. Quality of life assessment in adult patients with attention-deficit/hyperactivity disorder treated with atomoxetine. J Clin Psychopharmacol. 2006;26:648–652.
3. Kessler RC, Green JG, Adler LA. Structure and diagnosis of adult attention-deficit/hyperactivity disorder: analysis of expanded symptom criteria from the Adult ADHD Clinical Diagnostic Scale. Arch Gen Psychiatry. 2010;67:1168–1178.
4. Rosler M, Casas M, Konofal E, Buitelaar J. Attention deficit hyperactivity disorder in adults. World J Biol Psychiatry. 2010;11(5):684–698.
5. Sentissi O, Navarro JC, De Oliveira H. Bipolar disorder and quality of life: impact of ADHD and substance abuse in euthymic patients. Psychiatry Res. 2008;30:36–42.
6. Schmidt S, Petermann F. Developmental psychopathology: Attention deficit hyperactivity disorder (ADHD). BMC Psychiatry. 2009;17:58.
7. Kessler RC, Adler LA, Barkley R. Patterns and predictors of attention-deficit/hyperactivity disorder persistence into adulthood: results from the national comorbidity survey replication. Biologic Psychiatry. 2005;57:1442–1451.
8. Ribases M, Ramos-Quiroga JA, Sanchez-Mora C. Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study. Genes Brain Behav. 2011;10(2):149–157.
9. Hsiung PC, Fang CT, Chang YY, et al. Comparison of WHO QOL-bREF and SF-36 in patients with HIV infection. Qual Life Res. 2005;14(1):141–150.
10. Huang IC, Wu AW, Frangakis C. Do the SF-36 and WHO QOL-BREF measure the same constructs? evidence from the Taiwan population. Qual Life Res. 2006 Feb;15(1):15-24.
11. Mick E, Faraone SV, Spencer T, Zhhang HF, Biederman J. Assessing the validity of the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form in adults with ADHD. Journal of Attention Disorders. 2008; 11: 504-509.
12. Matza LS, Johnston JA, Faries. Responsiveness of adult attention-deficit/hyperactivity disorder quality of life scale (AAQoL). Qual Life Res. 2007;16:1511–1520.
13. Matza LS, Van Brunt DL, Cates C, Murray LT. Test-retest reliability of two patient-report measures for use in adults with ADHD. J Atten Disord. 2011 Oct;15(7):557–563.
14. Landgraf JM. Monitoring quality of life in adults with ADHD: reliability and validity of a new measure. J Atten Disord. 2007;11:351–362.
15. Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials. 1989;10(4):407–415.
16. Chao CY, Gau SS, Mao. Relationship of attention-deficit-hyperactivity disorder symptoms, depressive/ anxiety symptoms, and life quality in young men. Psychiatry Clin Neurosci. 2008;62:421–426.
17. Gudjonsson GH, Sigurdsson JF, Eyjolfsdottir GA, et al. The relationship between satisfaction with life, ADHD symptoms, and associated problems among university students. J Atten Disord. 2009;12(6):507–515.
18. Rimmerman A, Yurkevich O, Birger M, Araten-Bergman T. Quality of life in men and women with borderline intelligence and attention deficit disorders living in community residencies: a comparative study. J Atten Disord. 2005;9:435–443.
19. Rimmerman A, Yurkevich O, Birger M. Quality of life of Israeli adults with borderline intelligence quotient and attention-deficit/hyperactivity disorder. Int J Rehab Res. 2007;30:55–60.
20. Weiss MD, Gibbins C, Goodman DW. Moderators and mediators of symptoms and quality of life outcomes in an open-label study of adults treated for attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2010;71(4):381–390.
21. Adler LA, Spencer T, Brown TE. Once-daily atomoxetine for adult attention-deficit/hyperactivity disorder: a 6-month, double-blind trial. J Clin Psychopharmacol. 2009;29;44–50.
22. Matza LS, Stoeckl MN, Shorr JM, Johnston JA. Impact of atomoxetine on health-related quality of life and functional status in patients with ADHD. Expert Rev Pharmacoecon Outcomes Res. 2006;6(4):379–390.
23. Adler LA, Spencer TJ, Levine LR. Functional outcomes in the treatment of adults with ADHD. J Atten Dis. 2008;11:720–727.
24. Safren SA, Sprich SE, Cooper-Vince C, et al. Life impairments in adults with medication-treated ADHD. J Atten Dis. 2010;13:524–531.
25. Adler LA, Liebowitz M, Kronenberger W, et al. Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder. Depress Anxiety. 2009;26(3):212–221.
26. Spencer TJ, Landgraf JM, Adler LA. Attention-deficit/hyperactivity disorder-specific quality of life with triple-bead mixed amphetamine salts (SPD465) in adults: results of a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2008;69:1766–1775.
27. Spencer TJ, Adler LA, Weisler RH, Youcha SH. Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: a randomized, double-blind, multicenter, placebo-controlled study. J Clin Psychiatry. 2008;69:1437–1448.
28. Brown TE, Landgraf JM. Improvements in executive function correlate with enhanced performance and functioning and health-related quality of life: evidence from 2 large, double-blind, randomized, placebo-controlled trials in ADHD. Postgrad Med. 2010;122:42–51.
29. Goodman DW, Ginsberg L, Weisler R. An interim analysis of the quality of life, effectiveness, safety, and tolerability (QU.E.S.T.) evaluation of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr. 2005;10:26–34.
30. Boonstra AM, Kooij JJ, Oosterlaan J. Hyperactive night and day? Actigraphy studies in adult ADHD: a baseline comparison and the effect of methylphenidate. Sleep. 2007;30:433–442.
31. Kooij JJ, Middelkoop HA, van Gils K, Buitelaar JK. The effect of stimulants on nocturnal motor activity and sleep quality on adults with ADHD: an open label case control study. J Clin Psychiatry. 2001;62: 952-956.
32. Adler LA, Goodman D, Weisler R. Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder. Behav Brain Funct. 2009;5:34.
33. Skevington SM, Lotfy M, O’Connell KA; WHOQOL Group. The World Health Organizations WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial: a report from the WHOQOL Group. Qual Life Res. 2004 Mar;13(2):299–310.
34. Carpentier PJ, van Gogh MT, Knapen LJ. Influence of attention deficit hyperactivity disorder and conduct disorder on opioid dependence severity and psychiatric comorbidity in chronic methadone-maintained patients. Eur Addict Res. 2011;17(1):10–20.
35. Goksøyr PK, Nøttestad JA. The burden of untreated ADHD among adults: the role of stimulant medication. Addictive Behaviors. 2007; 33: 342-346.
36. IsHak WW, Greenberg JM, Saah T, et al. Development and validation of the Individual Burden of Illness Index for Major Depressive Disorder (IBI-D). Adm Policy Ment Health. 2011 Oct 4. [Epub ahead of print].
37. Schalock RL, Keith KD. Quality of Life Questionnaire Manual. Worthington, OH: IDS Publishing Corporation; 1993.
38. Grenwald-Mayes G. Relationship between current quality of life and family of origin dynamics for college students with attention deficit hyperactivity disorder. J Atten Disord. 2002;5(4):211–222.
39. Goksøyr PK, Nøttestad JA. The burden of untreated ADHD among adults: the role of stimulant medication. Addict Behav. 2008;33(2):342–346.
