Changes in physical function and physical activity in patients up to 5 years after bariatric surgery.

BACKGROUND: Bariatric surgery is effective for patients with severe obesity, but relatively little is known about long-term functional outcomes. OBJECTIVE: To describe physical fitness and activity changes among bariatric surgery patients in a clinical trial of physical activity interventions through 5 years postoperatively. SETTING: Large bariatric center in the midwestern United States. METHODS: Preoperatively, 6 months, and 5 years after surgery, 42 bariatric surgery patients wore an accelerometer to track activity and completed strength and cardiovascular endurance testing via treadmill, where estimated metabolic equivalents (METs) and ratings of perceived exertion (RPEs) were obtained. RESULTS: Preoperatively, 25% of patients reported exertion of <3 METs (equivalent to walking 2.5 mi/hr) as an RPE of 16 ("hard to very hard"). This decreased significantly to approximately 5% of patients 6 months and 5 years after surgery. Before surgery, 7.5% achieved ≥6 METs (vigorous activity) at an RPE of 16. This increased significantly to 36.6% at 6 months and 42.1% at 5 years after surgery. Body mass index and age, but no physical activity measure, predicted functional ability over time. The steps/d and exercise bout min/wk increased significantly from before surgery to 6 months postoperatively (4886.5 to 5948.5 steps and 23.8 to 66.6 bout min), but increases were not maintained at 5 years (5677.7 steps and 41.4 bout min). Conversely, moderate to vigorous min/ d increased progressively from before surgery (17.4) to 6 months (32.3) and 5 years (48.1) postoperatively. CONCLUSIONS: Functional abilities of bariatric surgery patients increased postoperatively and were maintained over 5 years. However, treadmill testing suggests that most patients are still unable to perform sustained activities of 6 METs (vigorous) or greater. Research is needed on bariatric patients' long-term function- and intervention- optimizing outcomes.

Long-term Engagement in Physical Activity Among Bariatric Surgery Patients: Associations with Treatment Outcomes at 5-Year Follow-up.

PURPOSE: Physical activity studies involving bariatric surgery patients tend to be short-term or cross-sectional investigations. Longer-term studies are limited and typically consist of relatively brief objective measurement periods used to generalize activity patterns. Very little research combines objective measurements with structured interviews to determine both the patterns and related factors of long-term physical activity among patients undergoing bariatric surgery. MATERIALS AND METHODS: Previous volunteers in a perioperative physical activity study were invited to participate in a mixed methods study investigating physical activity among bariatric patients over a 5-year postoperative period. Fifty-one patients (Mage = 45.4 years; 76.5% female, 90.2% White; 86.3% Roux-en-Y procedure) provided interview, survey, accelerometer, and anthropometric data. RESULTS: Participants were divided into four exercise quartiles, based on self-report of their length of regular exercise involvement from 1 year before through 5 years after surgery. Those reporting the most periods of regular exercise took the most measured steps per day, had greater moderate-to-vigorous physical activity and more bout-related activity, experienced the largest decrease in BMI, and reported the most adherence to nutritional guidelines. Participants reporting the most and least physical activity found the measurement periods to be most similar to their normal activity patterns. While physical activity increased significantly after surgery, measured physical activity did not reach recommended levels for steps or exercise bout minutes. CONCLUSIONS: Measured physical activity and self-reported physical activity show congruent trends among patients undergoing bariatric surgery. More research is needed to determine optimal long-term monitoring and promotion of physical activity among patients.

Revision Gastrojejunostomy Versus Suturing With and Without Omental Patch for Perforated Marginal Ulcer Treatment After Roux-en-Y Gastric Bypass.

BACKGROUND: Ulceration at the gastrojejunostomy is a late bariatric surgery complication in 0.6-16% of Roux-en-Y gastric bypass (RYGB) patients. As there is no general consensus on management of acute ulcer perforations, we compare two methods of surgical repair: the most commonly performed procedure, suturing of ulcer with or without omental patch versus revision gastrojejunostomy (RG). METHODS: A retrospective chart review of cases at a single large, Midwestern US high-volume bariatric center from November 2, 2006 through March 11, 2021 identified 144 RYGB patients undergoing surgical repair for a perforated ulcer: 72 treated by SGP and 72 by RG. Outcomes, including length of stay, leaks, readmissions, and reoperations, were compared. Categorical variables were compared by Chi-square tests and continuous variables by ANOVA. RESULTS: Patients were primarily female (77.1%) and Caucasian (97.2%), 49.7 ± 12.5 years old, and 90.6 ± 26.6 kg. Most had laparoscopic RYGBs (98.6%). There were no demographic differences between groups. Of the RG patients, 11.4% experienced ulcer recurrence versus 41.7% of SGP patients (p < .001), and 2.8% of RG versus 11.1% of SGP patients required a reversal (p < .05). No significant differences between groups occurred in time to perforation (3.2 vs. 2.5 years for RG and SGP groups, respectively), length of stay (5.0 vs. 6.8 days), leaks (1.4% vs. 2.8%), readmissions (4.2% vs. 4.2%), or reoperations (2.8% vs 5.6%). CONCLUSIONS: Patients developing perforated marginal ulcers after RYGB can be safely and effectively treated by revision gastrojejunostomy with a lower likelihood of ulcer recurrence. Short-term morbidity was comparable to suturing with or without an omental patch.

Spiritual practices are associated with improved weight management following bariatric surgery.

BACKGROUND: Research shows that spirituality and religiosity may positively impact various health outcomes, but little is known about their role in supporting weight management efforts, particularly in the context of bariatric surgery. OBJECTIVE: This study examined spiritual practices and health-related behaviors of bariatric surgery patients 1-2 years postoperatively. SETTING: Large bariatric center in the Midwest of the United States. METHODS: Patients (n = 152) completed questionnaires 1-2 years postoperatively examining weight, physical activity, eating behaviors, and spiritual practices and experiences related to bariatric surgery. RESULTS: Participants were primarily married (59.2%), Caucasian (81.6%), and female (84.2%) who had undergone Roux-en-Y gastric bypass (64.5%) or sleeve gastrectomy (32.9%) 17.3 months previously. Most participants (71%) believed their spirituality did or could impact weight loss after surgery. Practices including connecting with nature, art and music, meditation, yoga, and attending spiritual or religious-based activities were positively correlated with weight loss, healthy eating, or exercise participation. CONCLUSION: Findings provide preliminary evidence for the benefits of spirituality in bariatric patients making lifestyle changes after surgery.

Safety and Efficacy of Bariatric Surgery in Cirrhosis Patients With Extreme Obesity.

OBJECTIVE: To assess the safety and efficacy of bariatric surgery in patients with cirrhosis. SUMMARY BACKGROUND DATA: Bariatric surgery may be a viable option for patients with cirrhosis and extreme obesity. However, the risk of liver decompensation after surgery is not thoroughly investigated. METHODS: We conducted a case-controlled study with 106 obese patients with cirrhosis (cases) and 317 age, sex, body mass index-, and type of surgery-matched obese patients without cirrhosis (controls) who underwent bariatric surgery. RESULTS: Patients with cirrhosis were predominantly Child-Pugh class A (97%) with the diagnosis established prior to surgery in only 46%. In the cirrhosis group, there was no death in the first 30 days compared with 1 patient in the control group. At 90 days there was 1 death in the cirrhosis group but no additional deaths in the control group. In total, 12 months after the surgery, there were 3 deaths in the cirrhosis group and 1 in the control group (2.8% vs 0.6%, P = 0.056). The surgery-related length of stay was significantly longer in patients with cirrhosis (3.7 ±â€Š4.0 vs 2.6 ±â€Š2.4 d, P = 0.001), but the 30-day readmission rate was lower (7.5% vs 11.9%, P = 0.001). The percent of total weight loss at 30 and 90-days was not significantly different between the groups and remained that way even at 1 year (29.1 ±â€Š10.9 vs 31.2 ±â€Š9.4%, P = 0.096). CONCLUSIONS: Bariatric surgery in obese cirrhotic patients is not associated with excessive mortality compared with noncirrhotic obese patients.

Psychosocial and behavioral correlates of weight loss 12 to 15 years after bariatric surgery.

While significant weight loss occurs post-bariatric surgery, partial weight regain is common. Psychological and dispositional variables have been examined as predictors of weight change, but most studies have focused on the relationship of preoperative constructs to shorter-term postoperative outcomes. The goal of the current study was to examine associations between weight loss and postoperative psychosocial and behavioral factors up to an average of 13.7 years after surgery. The current study was conducted at a large bariatric center in a Midwestern U.S. city. The sample was comprised of 125 adult patients who participated in the second wave of a long-term bariatric surgery outcome study, examining weight history, physical activity, and psychological health and functioning. Correlations between percent total weight loss (%TWL) and psychosocial and behavioral variables were examined. The variables that had significant correlations with %TWL were used in stepwise linear regressions to determine their contribution to %TWL. These same variables were tested to determine differences among those in the highest and lowest weight loss quartiles. Life satisfaction, conscientiousness, positive affect, and regular exercise were positively associated with weight loss in the entire sample and were significantly higher among those in the highest versus the lowest weight-loss quartile. Experiencing a stressful event and food addiction symptoms were negatively associated with weight loss. Positive affect, fewer food addiction symptoms, and regular exercise significantly predicted weight loss, accounting for 23% of the variance in %TWL. Long-term weight loss maintenance after bariatric surgery may be related to positive affect, conscientiousness, regular physical activity, and an addictive-type relationship with food. Future studies should explore these relationships and develop approaches to deal with the interaction between dispositional tendencies and lifestyle factors.

Factor Structure and Measurement Invariance of the Attitudes Toward Persons with Obesity (ATOP) Scale in a Preoperative and Postoperative Bariatric Surgery Sample.

BACKGROUND: The Attitudes Toward Persons with Obesity (ATOP) scale is widely used to assess stigmatization toward persons with obesity. The measure has previously been suggested to assess three facets-self-esteem, personality, and social difficulties-however, psychometric support for this has been inconsistent and warrants further study if the measure intends to be scored this way. OBJECTIVES: Explore and confirm the factor structure of the ATOP in people assessed prior to bariatric surgery and reassessed 1 year postoperatively SETTING: Midwestern hospital in the USA. MATERIALS AND METHODS: Three-hundred sixteen people who were seeking bariatric surgery were assessed preoperatively, and 161 of those people were reassessed 1 year after surgery with a battery of measures including the ATOP. Exploratory factor analysis (EFA) was performed on ATOP data from a random split-half of people before surgery, and confirmatory factor analysis (CFA) was performed on the second randomly selected half. With the postoperative sample, a CFA was performed, testing the best-fitting model from the preoperative CFA findings. RESULTS: The EFA suggested a two-factor structure interpreted as self-esteem and personality/social difficulties. This structure was supported by CFA performed on the second randomly selected half of people at preoperative assessment and by CFA performed on people 1 year following surgery. Tests of measurement invariance suggested that the two-factor structure was similar at both time points. CONCLUSIONS: Only two factors for the ATOP were empirically supported in the current sample (self-esteem and personality/social difficulties), which is slightly different from the three factors that were originally proposed when the measure was developed. This factor structure is supported both prior to bariatric surgery and 1 year after bariatric surgery.

Psychological Functioning and Health Behaviors Associated with Weight Loss Patterns up to 13.7 Years After Weight Loss Surgery.

Weight loss surgery produces dramatic health improvements immediately after surgery, including rapid declines in diabetes. However, less is known about its long-term effects. 124 St. Vincent Bariatric Center patients completed questionnaires on weight and psychological functioning a mean of 7.7 and 13.7 years post-surgery (T1 and T2, respectively). Because mean weight data may mask differing weight trajectories, participants were categorized based on weight over time. Most participants underwent Roux-En-Y gastric bypass (90.3%) and were Caucasian (96%), female (81.5%), and married (69.1%). Mean age at T2 was 64; mean %EWL was 64.9%. Most patients fit into one of three weight change patterns, reaching weight nadir, and regaining by T1 and then, by T2, experiencing (1) Weight Loss (n = 36), (2) Weight Maintenance (n = 37), or (3) Continued Weight Gain (n = 39). Groups differed significantly on body satisfaction, weighing frequency, and conscientiousness, with Weight Gainers significantly lower than other groups on conscientiousness and body satisfaction, and Weight Losers reporting higher frequency of weighing than Maintainers. Bariatric patients can maintain substantial weight loss and positive psychological functioning for many years post-surgery, although weight regain is associated with less body satisfaction. Conscientiousness may signify medical adherence, whereas frequent weighing may be a behavior that promotes ongoing weight loss.

Examining Weight Bias and Loss-of-Control Eating among Individuals Seeking Bariatric Surgery.

OBJECTIVE: Externalized weight bias (EWB), directed towards others, and internalized weight bias (IWB), directed towards the self, are thought to exacerbate obesity and disordered eating and may be important factors to assess and understand among individuals seeking bariatric surgery. This study examined clinical correlates (pre-surgical BMI, depressive symptoms, weight self-efficacy, and shape/weight overvaluation) of both EWB and IWB among individuals presenting for bariatric surgery with and without regular loss-of-control eating (LOC eating). METHODS: A total of 316 adults presenting for bariatric surgery completed established self-report measures to assess EWB, IWB, depressive symptoms, weight self-efficacy, and core symptoms of disordered eating including LOC eating and overvaluation of shape/weight. RESULTS: IWB and EWB were not associated with pre-surgical BMI, age, or sex, but were both significantly higher among White than non-White participants. Adjusting for race, IWB and EWB were significantly associated with greater eating disorder psychopathology and depressive symptoms and with less weight-related self-efficacy. Participants who endorsed regular LOC eating (53.5% of the sample) endorsed significantly lower weight self-efficacy and higher IWB, EWB, depressive symptoms, and overvaluation of shape/weight. CONCLUSIONS: Findings suggest that regular LOC eating is common among individuals seeking bariatric surgery and associated with a range of heightened eating disorder and psychosocial concerns including both IWB and EWB. Future research exploring the longitudinal significance of the relationship between these two forms of weight bias and LOC eating is indicated.

Exercise Testing Reveals Everyday Physical Challenges of Bariatric Surgery Candidates.

BACKGROUND: Few studies have quantified cardiorespiratory fitness among individuals seeking bariatric surgery. Treadmill testing allows researchers to determine exercise capacity through metabolic equivalents. These findings can assist clinicians in understanding patients' capabilities to carry out various activities of daily living. The purpose of this study was to determine exercise tolerance and the variables associated with fitness, among individuals seeking bariatric surgery. METHODS: Bariatric surgery candidates completed submaximal treadmill testing and provided ratings of perceived exertion. Each participant also completed questionnaires related to history of exercise, mood, and perceived barriers/benefits of exercise. RESULTS: Over half of participants reported that exercise was "hard to very hard" before reaching 70% of heart rate reserve, and one-third of participants reported that exercise was "moderately hard" at less than 3 metabolic equivalents (light activity). Body mass index and age accounted for the majority of the variance in exercise tolerance, but athletic history, employment status, and perceived health benefits also contributed. Perceived benefit scores were higher than barrier scores. CONCLUSION: Categories commonly used to describe moderate-intensity exercise (3-6 metabolic equivalents) do not coincide with perceptions of intensity among many bariatric surgery candidates, especially those with a body mass index of 50 or more.

A randomized trial comparing two interventions to increase physical activity among patients undergoing bariatric surgery.

OBJECTIVE: To test the effectiveness of two levels of physical activity interventions before and up to 6½ months after bariatric surgery. METHODS: Before surgery, individuals completed submaximal exercise testing on a treadmill. After random assignment to standard care, pedometer use, or exercise counseling plus pedometer, participants wore an accelerometer for approximately 2 weeks and returned it to the bariatric center before surgery and 2, 4, and 6 months postoperatively. RESULTS: Individuals in exercise counseling plus pedometer had higher steps per day and bout minutes of exercise per week than standard care and pedometer use over the course of the study. There were no group differences related to exercise tolerance; however, all groups made significant improvement. There was no statistically significant change in sedentary or light activity nor was there a difference between groups. CONCLUSIONS: Exercise counseling using pedometers increases physical activity from the perioperative period to 6½ months after surgery, but providing pedometers without professional feedback may not be more effective than standard bariatric surgery treatments. Rapid weight loss increases exercise tolerance and may mask the fitness improvements achieved through a modest physical activity intervention during the first 6 months after bariatric surgery.

Predictors of Lowest Weight and Long-Term Weight Regain Among Roux-en-Y Gastric Bypass Patients.

BACKGROUND: Weight loss surgery (WLS) outcomes are poorly understood. This study aimed to evaluate the relationship of well-documented (e.g., health, diet, physical activity) and theoretically relevant variables (e.g., substance use and "food addiction") with both weight nadir and weight regain (WR) following WLS. METHODS: A sample of 97 Roux-en-Y gastric bypass patients (M time since surgery = 8.86 years) were surveyed about pre- and post-WLS weight, health, self-management behaviors, alcohol problems, and clinical symptoms. RESULTS: Patients lost a mean of 42 % (SD = 10.71 %) of total weight at weight nadir, but 26 % (SD = 19.66 %) of the lost weight was regained by the time of the survey. Correlates of lower weight nadir and WR differed considerably, with minor overlap. Weight nadir was associated with pre-WLS drug use and post-WLS medical comorbidities. WR, on the other hand, was associated with post-WLS adherence to dietary and physical activity modification. Post-WLS nocturnal eating, depression, and problematic alcohol use were also associated with WR. With all associated variables in regression models, number of post-WLS medical comorbidities (ß = -.313, p < 0.01) and post-WLS depression (ß = 0.325, p < 0.01) accounted for the most variance and remained as significant predictors of weight nadir and WR, respectively. CONCLUSIONS: While weight nadir was associated with relatively few and largely nonmodifiable variables, WR was significantly associated with adherence-related behaviors, mood symptoms, and pathological patterns of food and alcohol use, all of which are potentially modifiable. These findings underscore the importance of long-term behavioral and psychosocial monitoring after surgery.

Associations between relationship stability, relationship quality, and weight loss outcomes among bariatric surgery patients.

After weight loss surgery (WLS), psychosocial functioning, including the quality of social relationships, generally improves, but for a minority, relationships worsen. We examined how changes in relationship stability and quality from pre- to post-WLS relate to long-term weight loss outcomes. Postoperative patients (N=361) completed surveys which queried relationship changes and weight loss. The sample was 95.9% Caucasian, 80.1% female, averaged 7.7years post-WLS, with a mean age at surgery of 47.7years (range 21-72); 87.3% had a Roux-en-Y gastric bypass. Four relationship status groups were created: Not in a relationship at surgery or follow-up (No-Rel, n=66; 18.2%); Post-WLS relationship only (New-Rel, n=23; 6%); Pre-WLS relationship only (Lost-Rel, n=17; 5%); and Pre-Post Relationship (Maintainer, n=255; 70.6%). Current BMI was 34.5 for No-Rel; 40.5 for New-Rel; 37.4 for Lost-Rel; 33.3 for Maintainers (p<.05 for Maintainers and No-Rel vs. New-Rel). These same group differences were significant for weight loss, which was not associated with gender, time since surgery, or age at time of surgery, but was associated with pre-WLS BMI (lower pre-WLS BMI was associated with greater %EWL). Analyses were repeated with pre-WLS BMI as a covariate; group differences remained significant [F (3, 355)=3.09, p=.03], as did pre-WLS BMI, [F (1, 355)=9.12, p=.003]. Among Maintainers, relationship quality was associated with weight loss outcomes: those with improved relationships post-WLS had significantly greater %EWL [F (2, 234)=15.82, p<0.000; p<.05 for Improved>(Stayed Same=Got Worse)]. Findings support the importance of assessing relationship stability and quality in pre-WLS candidates, as healthy and stable relationships may support improved long-term outcomes. Interventions to improve relationships pre-and post-WLS may increase both quality of life and weight loss outcomes.

New-onset substance use disorder after gastric bypass surgery: rates and associated characteristics.

BACKGROUND: Substance use disorder (SUD) may develop de novo for a subgroup of weight loss surgery patients, particularly those who have had the Roux-en-Y gastric bypass (RYGB) procedure. The present study examined the rate of SUD in a broad sample of RYGB patients and identified associated behavioral and psychological factors. METHODS: Participants included 143 RYGB patients; the majority were women (n = 120; 83.9 %) and white (n = 135; 94.4 %). Participants completed a web-based survey assessing retrospective accounts of presurgical substance use, eating pathology, family history, and traumatic history, postsurgical substance use, life stressors, and global trait-like measures (emotion dysregulation, impulsivity, sensation-seeking, and coping skills). RESULTS: A subgroup (n = 28, 19.6 %) of post-RYGB patients met criteria for probable SUD; however, the majority of those who met SUD criteria postsurgery (n = 19, 68 %) did not report a pre-RYGB SUD history. Family history of substance abuse, poor coping skills, and potential life stressors were related to post-RYGB SUD, particularly for the new-onset group. Additionally, the majority of those who met criteria for pre-RYGB SUD (n = 21, 70 %) did not continue to meet SUD criteria following RYGB. CONCLUSIONS: Findings highlight a subgroup of post-RYGB patients reporting new-onset SUD, which is unexpected among middle-aged women. Importantly, findings also indicate that many patients with presurgical SUD did not relapse postsurgery. Assessing for family history of SUD and coping skills at the presurgical evaluation is recommended. Future research should identify psychological and physiological risk factors for SUD postsurgery and examine protective factors of those who discontinue substance use postsurgery.

Substance misuse following Roux-en-Y gastric bypass surgery.

Post-bariatric surgery patients are overrepresented in substance abuse treatment, particularly those who have had the Roux-en-Y gastric bypass (RYGB) procedure. The severity of the substance use disorder (SUD; i.e., warranting inpatient treatment) and related consequences necessitate a better understanding of the variables associated with post-RYGB SUDs. This investigation assessed factors associated with post-RYGB substance misuse. Post-RYGB patients (N = 141; at least 24 months postsurgery) completed an online survey assessing variables hypothesized to contribute to post-RYGB SUDs. Fourteen percent of participants met criteria for postoperative substance misuse. Those with a lower percent total weight loss (%TWL) were more likely to endorse substance misuse. Family history of substance misuse was strongly associated with postoperative substance misuse. Eating-related variables including presurgical food addiction and postsurgical nocturnal eating, subjective hunger, and environmental responsiveness to food cues were also associated with a probable postoperative SUD. These findings have clinical utility in that family history of substance misuse can be easily assessed, and at-risk patients can be advised accordingly. In addition, those who endorse post-RYGB substance misuse appear to have stronger cognitive and behavioral responses to food, providing some support for the theory of behavioral substitution (or "addiction transfer").

A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder.

RATIONALE: Treatment of attention-deficit/hyperactivity disorder (ADHD) has for many years relied on psychostimulants, particularly various formulations of amphetamines and methylphenidate. These are central nervous system stimulants and are scheduled because of their abuse potential. Atomoxetine (atomoxetine hydrochloride; Strattera®) was approved in 2002 for treatment of ADHD, and was the first nonstimulant medication approved for this disorder. It was classified as an unscheduled medication indicating a low potential for abuse. However, the abuse potential of atomoxetine has not been reviewed. OBJECTIVES: In this article, we review the evidence regarding abuse potential of atomoxetine, a selective inhibitor of the presynaptic norepinephrine transporter, which is unscheduled/unrestricted in all countries where it is approved. METHODS: Results from receptor binding, in vitro electrophysiology, in vivo microdialysis, preclinical behavioral, and human laboratory studies have been reviewed. RESULTS: Atomoxetine has no appreciable affinity for, or action at, central receptors through which drugs of abuse typically act, i.e., dopamine transporters, GABA(A) receptors, and opioid µ receptors. In behavioral experiments in rodents, atomoxetine does not increase locomotor activity, and in drug discrimination studies, its profile is similar to that of drugs without abuse potential. Atomoxetine does not serve as a reinforcer in monkey self-administration studies, and human laboratory studies suggest that atomoxetine does not induce subjective effects indicative of abuse. CONCLUSION: Neurochemical, preclinical, and early clinical studies predicted and supported a lack of abuse potential of atomoxetine, which is consistent with the clinical trial and postmarketing spontaneous event data in the past 10 years.

Atomoxetine treatment outcomes in adolescents and young adults with attention-deficit/hyperactivity disorder: results from a post hoc, pooled analysis.

BACKGROUND: Many children with attention-deficit/hyperactivity disorder (ADHD) continue to experience this disorder as adults, which may, in part, be due to the discontinuity of health care that often occurs during the transition period between late adolescence and young adulthood. Although atomoxetine is reported to be efficacious in both adolescents and young adults, no longitudinal studies have been designed to assess directly the effects of atomoxetine treatment during this transition period. As a first step, we present the results of a post hoc, pooled analysis that compared the efficacy and safety profile of atomoxetine in these 2 patient populations. OBJECTIVE: The aim of the present study was to assess the efficacy and safety profile of atomoxetine treatment in adolescents and young adults with ADHD. METHODS: A post hoc, pooled analysis was conducted by combining data from 6 double-blind trials (6-9 weeks in duration) that studied adolescents (12-17 years of age; atomoxetine, n = 154; placebo, n = 88; mean final dose = 1.38 mg/kg) and 3 trials (10 weeks in duration) that studied young adults (18-30 years of age; atomoxetine, n = 117; placebo, n = 125; mean final dose = 1.21 mg/kg). Efficacy measures used in these analyses were ADHD Rating Scale (ADHDRS) for adolescents, Conners' Adult ADHD Rating Scale (CAARS) for young adults, and Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) for both age groups. Treatment response was defined as ≥30% reduction from baseline in total ADHD symptom score. RESULTS: In adolescents (mean age, 13.4 years), atomoxetine improved ADHD significantly compared with placebo (ADHDRS total score change, -12.9 vs -7.5; P < 0.001). In young adults (mean age, 24.7 years), atomoxetine improved ADHD significantly (CAARS total score change, -13.6 vs -7.7; P < 0.001; CGI-ADHD-S change, -1.1 vs -0.6; P < 0.001). No significant treatment-by-age subgroup interaction was observed. Tolerability was similar for both age subgroups, except for treatment-emergent nausea, which occurred significantly more frequently with atomoxetine than with placebo in young adults (13.7% vs 4.8%, respectively; P = 0.024); in adolescents no statistically significant differences were observed in frequency of nausea between atomoxetine and placebo treatment (4.5% vs 10.2%, respectively; P = 0.108). CONCLUSIONS: Results from this post hoc, pooled analysis suggest that acute treatment with atomoxetine was efficacious in both adolescent and young adult patients with ADHD. The safety profile findings from this study were consistent with the previously reported atomoxetine safety and tolerability profiles, suggesting that it may be continued during the transition from adolescence to young adulthood.

Retrospective safety analysis of atomoxetine in adult ADHD patients with or without comorbid alcohol abuse and dependence.

This post hoc analysis compared the safety of atomoxetine treatment of ADHD in adults with or without comorbid alcohol abuse/dependence. Study completion rates in patients receiving atomoxetine were comparable between heavy drinkers (60.9%) and patients with no alcohol-use disorder (71.0%) but lower in nonheavy drinkers (35.7%); however, there was no significant difference in discontinuation rates due to adverse events or lack of efficacy among these groups. Alcohol-use disorder patients, especially heavy drinkers, generally experienced the greatest frequency of treatment-emergent adverse events in both the atomoxetine and placebo groups. Vital signs and measures of hepatic function were not significantly different among the 3 drinking status groups taking atomoxetine.

Characteristics of placebo responders in pediatric clinical trials of attention-deficit/hyperactivity disorder.

OBJECTIVE: Understanding placebo response is a prerequisite to improving clinical trial methodology. Data from placebo-controlled trials of atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were analyzed to identify demographic and clinical characteristics that might predict placebo response in future clinical trials. METHOD: Data were pooled across 731 placebo-treated pediatric patients who participated in 10 acute, randomized, placebo-controlled trials. Responder status was based on empirically derived thresholds of change on the total score of the ADHD Rating Scale with minimal and robust response defined as 25% or greater and 40% or greater decrease, respectively. Study design characteristics, including randomization ratio, dose, and titration strategy, and patient demographic and clinical characteristics were examined as potential predictors of placebo response. RESULTS: Inattentive subtype, lack of previous stimulant treatment, presence of comorbid tics and nonwhite ethnicity were associated with robust placebo response. A subset analysis of patients completing 6 weeks of treatment (to eliminate the effects of early dropout) identified inattentive subtype and lack of previous stimulant experience as significant predictors of robust placebo response. CONCLUSIONS: Placebo response is less likely in subjects with combined-subtype ADHD who are not stimulant-naive. Limiting ADHD clinical trials to this more restricted subject group is likely to maximize treatment differences. However, because this is not always possible or desirable, identifying other methods of mitigating placebo response is essential.

Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders.

OBJECTIVE: Adults with attention-deficit/hyperactivity disorder (ADHD) have higher rates of alcohol and drug use disorders than adults without ADHD. The study aim was to determine if atomoxetine was superior to placebo in improving ADHD and alcohol use in recently abstinent adults with ADHD and comorbid alcohol use disorder. METHODS: Adults with DSM-IV diagnoses of ADHD and alcohol abuse and/or dependence were abstinent from alcohol at least 4 days (maximum 30 days) before study randomization. Participants received atomoxetine (25-100mg daily) or placebo for 12 weeks. ADHD symptoms were assessed using ADHD Investigator Symptom Rating Scale (AISRS) total score. Time-to-relapse to heavy alcohol use was analyzed using a 2-sided log-rank test based on Kaplan-Meier estimates and cumulative heavy drinking events over time were evaluated post hoc with recurrent-event analysis. RESULTS: Subjects received atomoxetine (n=72) or placebo (n=75) and 80 subjects completed the 12-week double-blind period (n=32 and 48, respectively). ADHD symptoms were significantly improved in the atomoxetine cohort compared to placebo (AISRS total score mean [S.D.], atomoxetine: -13.63 [11.35], P<.001; placebo: -8.31 [11.44], P<.001, difference: P=.007; effect size=0.48). No significant differences between treatment groups occurred in time-to-relapse of heavy drinking (P=.93). However, cumulative heavy drinking days were reduced 26% in atomoxetine-treated subjects versus placebo (event ratio=0.74, P=.023). There were no serious adverse events or specific drug-drug reactions related to current alcohol use. CONCLUSIONS: This 3-month, double-blind, placebo-controlled study of atomoxetine in adults with ADHD and comorbid alcohol use disorder demonstrates clinically significant ADHD improvement, and inconsistent effects on drinking behavior.