Faculty Bibliography

OBJECTIVE: The purpose of this 10-week, open-label trial was to evaluate the potential utility of atomoxetine for improving attention-deficit hyperactivity disorder (ADHD) and substance craving in abstinent adults with ADHD who were being treated at a residential treatment facility. METHODS: Eighteen adults were treated with atomoxetine (25-120 mg/day) for up to 10 weeks. Researchers assessed ADHD symptoms with the Adult ADHD Investigator Symptom Rating Scale (AISRS) and substance cravings with the Brief Substance Craving Scale (BSCS). Paired t-tests were used to assess changes in symptoms and craving. RESULTS: Among the 12 participants who completed at least 2 weeks of treatment, mean total AISRS scores improved (43.2 SD 7.4 to 25.8 SD 14.4, t = 5.0, p.001). Participants also reported improvement in some measures of cravings. CONCLUSIONS: These data provide preliminarily support for the utility of atomoxetine in abstinent adults with co-occurring ADHD and substance use disorder.

OBJECTIVE: To evaluate the short-term impact of lisdexamfetamine dimesylate on cardiovascular parameters in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Medically healthy adults (18-55 years of age) with DSM-IV-TR-defined ADHD were randomly assigned to placebo or 30, 50, or 70 mg/d of lisdexamfetamine dimesylate for 4 weeks between May and November 2006. Electrocardiograms, systolic and diastolic blood pressure, and pulse were assessed pretreatment and weekly thereafter. RESULTS: There were no significant differences for mean systolic or diastolic blood pressure in any lisdexamfetamine dimesylate dose group versus placebo. Changes in pulse from baseline to endpoint were 0.0, 2.8, 4.2, and 5.2 bpm in the placebo and lisdexamfetamine dimesylate 30, 50, and 70 mg/d groups, respectively (P < .05, all lisdexamfetamine dimesylate groups vs placebo). Post hoc pulse outliers (pulse > or = 100 bpm; any 1 event) ranged from 3.3% to 8.5% of subjects in the lisdexamfetamine dimesylate groups, and no subjects in the placebo group were pulse outliers (P < .05 for lisdexamfetamine dimesylate 50 mg vs placebo only). There were no clinically meaningful electrocardiogram abnormalities. Overall, 8.3% (35/420; safety population) of subjects had treatment-emergent cardiovascular adverse events, and 1.7% (7/420) withdrew from the study because of cardiovascular complaints. Cardiovascular adverse events with lisdexamfetamine dimesylate in these medically healthy adults were generally mild to moderate in severity. CONCLUSIONS: Lisdexamfetamine dimesylate had limited short-term effects on heart rate, blood pressure, and electrocardiogram parameters that were of minimal clinical concern. These findings support the relative safety of lisdexamfetamine dimesylate. However, considering the potential of outliers, it is advisable to monitor cardiovascular parameters in stimulant-treated patients. Interpretation of these findings is limited to patients with no preexisting cardiac conditions who are taking their medication as prescribed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00334880

OBJECTIVE: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score. RESULTS: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P < .0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P < .0001). CONCLUSIONS: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months

BACKGROUND: Although attention deficit/hyperactive disorder (ADHD) is a common comorbidity in individuals who are diagnosed with substance use disorder (SUD), little data currently exist on the utility of screening tools in large samples of adults with SUD in inpatient treatment and the prevalence of ADHD in this population. The aims of this study were to assess the screen positive rate on the Adult ADHD Self Report Scale (ASRS) v.1.1 Screener in a large sample of adults being treated for SUD in a residential treatment facility (RTF) and to establish the imputed prevalence of adult ADHD. METHODS: Adults with SUD who were either newly admitted (abstinent for < 1 week) or in treatment in the RTF (abstinent < 3 months) were administered the ASRS v.1.1 Screener. Adults who screened positive on the ASRS v1.1 Screener (>or= 4/6 significant items) were then administered the Adult Clinician Diagnostic Scale (ACDS) v.1.2 to establish a diagnosis of ADHD and the positive predictive value (PPV) in this population. The imputed prevalence of adult ADHD was calculated based on the known rate of ADHD in the screened positive cohort and a calculated rate of ADHD in the screened negative sample based on prior studies of the ASRS v1.1 Screener in community-based and managed care samples. RESULTS: 1064 adults were screened via the ASRS v.1.1 Screener, with 92 screening positive (8.6% had >or= 4 significant items present). Fifty-three of those who screened positive were diagnosed as having adult ADHD (PPV = 57.6%). The imputed prevalence of adult ADHD in this population was 7.5%. CONCLUSIONS: The PPV for the ASRS v1.1 Screener for adult ADHD in this sample of adults with SUD was similar to that observed in a prior study of a managed care sample, but was somewhat less than that observed in the community-based sample. The imputed prevalence rate for comorbid ADHD in this study of adults with SUD in a RTF was similar to, but slightly lower than the prevalence rate of ADHD in patients with any SUD observed in the community-based sample

ABSTRACT: BACKGROUND: Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD). This analysis aimed to evaluate the impact of lisdexamfetamine dimesylate (LDX) on sleep quality in adults with ADHD. METHODS: This 4-week, phase 3, double-blind, forced-dose escalation study of adults aged 18 to 55 years with ADHD randomized participants to receive placebo (n = 62), or 30 (n = 119), 50 (n = 117), or 70 (n = 122) mg/d LDX, taken once a day in the morning. The self-rated Pittsburgh Sleep Quality Index (PSQI) was administered at baseline and at week 4 to assess sleep quality. The PSQI global score assesses 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) each scored from 0 (no difficulty) to 3 (severe difficulty). RESULTS: The mean baseline PSQI global score was 5.8 for LDX and 6.3 for placebo (P = .19) indicating poor overall sleep quality. At endpoint, least squares (LS) mean change from baseline was -0.8 for LDX vs -0.5 for placebo (P = .33). The daytime functioning component showed significant improvement in LS mean change at endpoint for LDX compared with placebo (LDX -0.4 vs placebo 0.0, P = .0001). LS mean changes for the other 6 PSQI components did not significantly differ from placebo. Sleep-related treatment-emergent adverse events with an incidence >/=2% in the active treatment and placebo groups, respectively, were insomnia (19.3% and 4.8%), initial insomnia (5.0% and 3.2%), middle insomnia (3.6% and 0%), sleep disorder (0.6% and 3.2%), somnolence (0.3% and 3.2%), and fatigue (4.7% and 4.8%), and were generally mild or moderate in severity. CONCLUSION: For most subjects, LDX was not associated with an overall worsening of sleep quality and significantly improved daytime functioning in adults with ADHD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00334880

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

OBJECTIVE: To assess the efficacy and safety of OROS methylphenidate (Concerta; McNeil Pediatrics Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc, Titusville, NJ) in the management of attention-deficit/hyperactivity disorder (ADHD) in adults. METHODS: A randomized, 7-week, double-blind, placebo-controlled, dose-escalation, parallel-group study of OROS methylphenidate 36, 54, 72, 90, or 108 mg/d versus placebo was conducted in adults with ADHD. The primary end point was the Adult ADHD Investigator Symptom Report Scale. Other assessments included the Clinical Global Impressions-Improvement scale, a post hoc responder analysis, adverse events, and vital signs. RESULTS: Two hundred twenty-six subjects (56.2% male; mean age, 39.0 years; range, 18-65 years) were included in the intention-to-treat population (110 subjects on OROS methylphenidate; 116 subjects on placebo). OROS methylphenidate resulted in greater ADHD symptom improvement than placebo as demonstrated by a statistically significantly lower least squares mean change from baseline in Adult ADHD Investigator Symptom Report Scale total score at the final visit (last observation carried forward [LOCF]; P = 0.012). Subjects on OROS methylphenidate also had a significantly lower least squares mean Clinical Global Impressions-Improvement score at the final visit (LOCF; P = 0.008). A significantly greater proportion of subjects on OROS methylphenidate (36.9%, 38/103 subjects) were responders at the final visit (LOCF) compared with placebo (20.9%, 24/115 subjects; P = 0.009). OROS methylphenidate was well tolerated. Adverse events were reported by 93 (84.5%) of the 110 OROS methylphenidate-treated subjects versus 74 (63.8%) of the 116 placebo-treated subjects. No serious treatment-emergent adverse events and no deaths were reported. Similar mean changes from baseline to final visit (LOCF) for systolic and diastolic blood pressures for the OROS methylphenidate and placebo groups were observed. CONCLUSIONS: In a dose escalation ranging from 36 to 108 mg/d, OROS methylphenidate is effective and well tolerated in the management of ADHD in adults

The U.S. Food and Drug Administration has approved 3 medications, atomoxetine and the extended-release formulations of amphetamine salts and dexmethylphenidate, for the treatment of adult attention-deficit hyperactivity disorder (ADHD). Different formulations of the same drugs, as well as other agents and cognitive-behavioral therapy, have been tested to determine efficacy in ADHD alone and in ADHD with comorbid substance use disorders, mood disorders, and anxiety disorders. A deficit in research exists in regard to these comorbidities in adults with ADHD

OBJECTIVE: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. METHOD: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness outcomes included change from Week 5 on ADHD Rating Scale (ADHD-RS) and proportion of responders on Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS: 103 patients completed OLE, and effectiveness was evaluable in 102 patients. d-MPH-ER was well tolerated; the most common adverse events (>15%) were headache, insomnia, and decreased appetite. Mean improvements in ADHD-RS score were -10.2 for patients switched from placebo to d-MPH-ER (n = 20) and -8.4 for those maintained on d-MPH-ER (n = 82). Respective CGI-I responder rates were 95.0% and 95.1%. CONCLUSION: Once-daily d-MPH-ER 20 to 40 mg is safe and effective for long-term treatment of adult ADHD.