Extended-release Mixed Amphetamine Salts Research Articles

Extended-Release Mixed Amphetamine Salts for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cannabis Use Disorder: A Pilot, Randomized Double-Blind, Placebo-Controlled Trial.

To determine if treatment of co-occurring adult ADHD and Cannabis Use Disorder (CUD) with extended-release mixed amphetamine salts (MAS-ER) would be effective at improving ADHD symptoms and promoting abstinence. A 12-week randomized, double-blind, two-arm pilot feasibility trial of adults with comorbid ADHD and CUD (n = 28) comparing MAS-ER (80 mg) to placebo. Main outcomes: ADHD: ≥30% symptom reduction, measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS). CUD: Abstinence during last 2 observed weeks of maintenance phase. Overall, medication was well-tolerated. There was no significant difference in ADHD symptom reduction (MAS-ER: 83.3%; placebo: 71.4%; p = .65) or cannabis abstinence (MAS-ER: 15.4%; placebo: 0%; p = .27). MAS-ER group showed a significant decrease in weekly cannabis use days over time compared to placebo (p < .0001). MAS-ER was generally well-tolerated. The small sample size precluded a determination of MAS-ER's superiority reducing ADHD symptoms or promoting abstinence. Notably, MAS-ER significantly reduced weekly days of use over time.

Effects of Stimulant Treatment on Changes in Brain Activation During Reward Notifications in Drug Naïve Youth With ADHD

Background: Research examining the potential effects of stimulant exposure in childhood on subsequent development of substance use disorder (SUD) have focused on differences in the brain reward system as a function of risk. Methods: 18 drug naïve children ages 7 to 12 years (11 High Risk [ADHD + ODD/CD]; 7 Low Risk [ADHD only]), underwent fMRI scans before and after treatment with mixed amphetamine salts, extended release (MAS-XR). We examined correlations between clinical ratings and fMRI activation at baseline and following treatment as a function of risk status. Results: High Risk children had higher activation than Low Risk children at baseline during both the Reward and Surprising Non-Reward conditions. Treatment produced strong differential effects on brain activation pertinent to group and reward outcome. Conclusions: Findings support the hypothesized role of reward mechanisms in SUD risk, and suggest that stimulant treatment may have differential effects on reward processing in relation to SUD risk.

31.2 Neural and Clinical Alternations in ADHD in Youth With and Without a Familial Risk for Bipolar Disorder

We used proton magnetic resonance spectroscopy (1H MRS) and structural MRI to compare baseline clinical and neural characteristics among youth who have ADHD with and without a family history of bipolar disorder (BP) and healthy comparison (HC) youth, and differences in clinical changes between youth who have ADHD with and without a family history of BP, following treatment with mixed amphetamine salts-extended release (MAS-XR).

A single-dose, comparative bioavailability study comparing amphetamine extended-release oral suspension with extended-release mixed amphetamine salts capsules.

To evaluate the relative bioavailability of a single dose of amphetamine extended-release oral suspension (AMPH EROS) compared with a single dose of extended-release mixed amphetamine salts (ER MAS) in healthy, fasted adult subjects. The study population consisted of healthy adult volunteers. The study drug used in this study was 7.5mL of 2.5mg/mL AMPH EROS equivalent to 18.8mg of amphetamine base administered after an overnight fast of at least 10hours. AMPH EROS comprises a 3.2:1 enantiomeric ratio of d-amphetamine to l-amphetamine. The reference product was one 30mg ER MAS capsule (equivalent to 18.8mg of amphetamine base). Relative bioavailability between the products was determined by a statistical comparison of the area under the curve and maximum concentration (Cmax) for d-amphetamine and l-amphetamine. PK (PK) blood samples were collected prior to dosing (0-hour) and at 1, 2, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, 14, 16, 24, 36, 48, and 60hours after drug administration, totaling 20 samples in each period. The mean subject age was 35.0 (standard deviation ±8) years, and the overall study population comprised 19 (63.3%) males and 11 (36.7%) females. The contrasts for geometric mean ratios for all assessed PK parameters (for both l- and d-amphetamine) between the test article AMPH EROS and reference product ER MAS fell within the prescribed 80% to 125% limits. The overall PK profile of single-dose AMPH EROS 7.5mL was found to be comparable with a single dose of oral ER MAS 30mg.

Improved Executive Function in Adults Diagnosed With Attention-Deficit/ Hyperactivity Disorder as Measured by the Brown Attention-Deficit Disorder Scale Following Treatment With SHP465 Mixed Amphetamine Salts Extended-Release: Post Hoc Analyses From 2 Randomized, Placebo-Controlled Studies

Objective: Assess executive function (EF) improvement with SHP465 mixed amphetamine salts (MAS) extended-release in adults with attention-deficit/hyperactivity disorder (ADHD) using responder analyses of the Brown Attention-Deficit Disorder Scale (BADDS). Methods: Post hoc analyses examined data from placebo-controlled SHP465 MAS dose-optimization (12.5–75 mg) and fixed-dose (25–75 mg) studies. Treatment response was assessed using two definitions (BADDS total score at endpoint <50 [no EF impairment] vs. ≥50 [impaired]; BADDS total score at endpoint relative to the in-treatment 90% CI range for baseline total score [below the range = improved]). Results: Response rates (SHP465 MAS vs. placebo) favored SHP465 MAS (all nominal p < .0001) in the dose-optimization (BADDS <50: 41.9% vs. 19.2%; below 90% CI range: 57.4% vs. 29.6%) and fixed-dose (BADDS <50: 51.9% vs. 16.7%; below 90% CI range: 70.6% vs. 32.3%) studies. Conclusion: Improvement in EF measured by BADDS response rates was approximately 2-fold greater with SHP465 MAS than placebo.

An adaptive clinical trial design for cocaine use disorder: Extended-release amphetamine salts for early behavioral intervention non-responders

Background/aimsCocaine use disorder (CUD) persists as a major public health problem in the United States. Response to evidence-based behavioral treatment has been shown to be predicted by dopaminergic dysfunction. Amphetamine formulations modulate dopaminergic systems and are one of the few agents with positive clinical findings but are associated with unique risks. We aimed to find a model for determining the most appropriate patients for treatment with mixed amphetamine salts-extended-release (MAS-ER) for CUD using an adaptive trial design. MethodsWe are enrolling treatment-seeking adults ages 18–60 years. All eligible participants receive bi-weekly individual counseling augmented with a computer-based intervention based on the community reinforcement approach with contingency management (CRA + CM) for 4 weeks. Participants who fail to achieve abstinence are additionally randomly assigned to 10 weeks of either MAS-ER, titrated up to 80 mg daily, or placebo. All participants complete a follow-up assessment after 12 weeks. ResultsFrequency and amount of cocaine use, cravings, retention, and quality of life will be compared between groups. The primary outcome will be having at least 3 weeks of urine toxicology-confirmed self-reported abstinence. Analyses will also be conducted to identify variables that may help identify who is more or less likely respond to the behavioral intervention during the first 4-weeks of treatment. ConclusionsThis trial more closely mimics a personalized medicine approach that is often used in clinical practice. It will help us understand who may be appropriate for psychostimulant therapy as an enhancement to evidence-based behavioral interventions, while limiting exposure to those who would respond to a psychosocial intervention alone.ClinicalTrials.gov Identifier: NCT01986075

Pharmacotherapeutic strategies for treating cocaine use disorder-what do we have to offer?

Cocaine use contines to be a significant public health problem world-wide. However, despite substantial research efforts, no pharmacotherapies are approved for the treatment of cocaine use disorder (CUD). Studies have identified positive signals for a range of medications for treating CUD. These include long-acting amphetamine formulations, modafinil, topiramate, doxazosin and combined topiramate and mixed amphetamine salts extended-release (MAS-ER). However, valid conclusions about a medication's clinical efficacy require nuanced approaches that take into account behavioural phenotypes of the target population (frequency of use, co-abuse of cocaine and other substances, genetic subgroups, psychiatric comorbidity), variables related to the medication (dose, short-/long-acting formulations, titration speed, medication adherence) and other factors that may affect treatment outcomes. Meta-analyses frequently do not account for these co-varying factors, which contributes to a somewhat nihilistic view on pharmacotherapeutic options for CUD. In addition, the predominant focus on abstinence, which is difficult for most patients to achieve, may overshadow more nuanced therapeutic signals. While there is an emphasis on finding new medications with novel mechanisms of action for treating CUD, currently available medications deserve further investigation based on the existing literature. Evaluating refined metrics of treatment success in well-defined subgroups of patients, and further exploring combination therapies and their synergy with behavioural/psychosocial interventions, are promising avenues to establishing effective therapies for CUD.

Post hoc Responder and Remission Analyses from Two Studies of SHP465 Mixed Amphetamine Salts Extended-Release Among Adults with Attention-Deficit/Hyperactivity Disorder.

Objectives: In two studies of adult attention-deficit/hyperactivity disorder (ADHD), SHP465 mixed amphetamine salts (MAS) extended-release significantly reduced ADHD-Rating Scale, 4th Edition total score (ADHD-RS-IV-TS) versus placebo (PBO). This report describes post hoc analyses of SHP465 MAS treatment response and remission rates from those studies.Methods: Adults with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision–defined ADHD were randomized to SHP465 MAS (12.5–75 mg) or PBO in a 7-week dose-optimization study and to SHP465 MAS (25, 50, or 75 mg) or PBO in a 6-week fixed-dose study. Response was examined using three definitions (definition 1: ≥30% ADHD-RS-IV-TS reduction + Clinical Global Impressions-Improvement [CGI-I] rating of 1 or 2; definition 2: ≥50% ADHD-RS-IV-TS reduction + CGI-I rating of 1 or 2; definition 3: ADHD-RS-IV-TS ≤18). Remission was defined as ADHD-RS-IV-TS ≤12. The Kaplan–Meier analyses assessed time to response or remission.Results: The intent-to-treat populations included 136 SHP465 MAS and 132 PBO participants in the dose-optimization study and 302 SHP465 MAS and 103 PBO participants in the fixed-dose study. Percentages of participants meeting response criteria (SHP465 MAS vs. PBO) at the final treatment week in the dose-optimization and fixed-dose studies, respectively, were 66.0% versus 31.6% and 72.7% versus 28.3% (definition 1); 47.9% versus 27.6% and 60.6% versus 16.7% (definition 2); and 54.3% versus 30.3% and 52.6% versus 18.3% (definition 3). The remission criterion (SHP465 MAS vs. PBO) at the final treatment week was met by 37.2% versus 19.7% of participants in the dose-optimization study and 39.7% versus 10.0% of participants in the fixed-dose study. Times to response and remission favored SHP465 MAS over PBO in both studies (all nominal log-rank p < 0.0001).Conclusion: These post hoc analyses indicate that SHP465 MAS was associated with greater response and remission rates than PBO in adults with ADHD, with times to response and remission also nominally favoring SHP465 MAS.

Impulsiveness as a moderator of amphetamine treatment response for cocaine use disorder among ADHD patients

BackgroundAmphetamines are a first-line treatment for ADHD and have shown promise for the treatment of cocaine use disorder (CUD), both alone and with comorbid ADHD. Impulsiveness is a key aspect of both ADHD and substance use disorders. We sought to understand the role of baseline impulsiveness in the treatment of comorbid CUD and ADHD. MethodsIn a post hoc analysis (N = 76) of a 14-week, double-blind, randomized, placebo-controlled trial of mixed amphetamine salts-extended release (MAS-ER) for comorbid ADHD and CUD, we examined the relationship between treatment response and participants’ baseline Barratt Impulsiveness Scale (BIS-11) score by comparing those with scores below versus above the median. In the original trial, participants received daily 60 mg MAS-ER, 80 mg MAS-ER, or placebo, in conjunction with cognitive behavioral therapy. ResultsThe odds of a cocaine-abstinent week over time were significantly greater in the high BIS group compared to the low BIS group, both when missing data was treated as missing (p = .0155; OR = 1.23, 95% CI: 1.13, 1.35 versus OR = 1.04, 95% CI: 0.95, 1.15) and when missing data was treated as cocaine-positive (p = .003; OR = 1.15, 95% CI: 1.06, 1.24 versus OR = 0.96, 95% CI: 0.88, 1.05). ConclusionsThe results show an association between higher within-group trait impulsiveness, as measured by the BIS-11, and response to MAS-ER for CUD in a cohort with comorbid ADHD. This result further demonstrates that impulsiveness is an important factor when considering treatment options for patients with CUD and that higher baseline impulsiveness may predict response to treatment with psychostimulants for CUD.

Extended release mixed amphetamine salts and topiramate for cocaine dependence: A randomized clinical replication trial with frequent users

BackgroundCocaine use disorder (CUD) remains a substantial public health problem with no clearly effective pharmacotherapy available. In a prior trial, combined amphetamine and topiramate treatment significantly reduced cocaine use among individuals demonstrating the most frequent use at baseline. This trial targeted such frequent users. MethodsA double-blind, randomized placebo-controlled trial, testing the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate or placebo over a 12-week medication phase was conducted. The two-site outpatient trial included 127 adults (96 males) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report. ResultsThe proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%). ConclusionsWhile these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable “proof of concept.”

How treatment improvement in ADHD and cocaine dependence are related to one another: A secondary analysis

BackgroundAttention-deficit hyperactivity disorder (ADHD) is overrepresented among individuals seeking treatment for substance use disorders. We previously reported that treatment with extended release mixed amphetamine salts (MAS-XR) increased abstinence, compared to placebo, among patients with co-occurring ADHD and cocaine dependence. This secondary analysis investigates the temporal relationship between ADHD improvement and cocaine abstinence in the first six weeks of the trial. MethodsThe study was a three-arm, randomized, double-blinded, placebo-controlled, 14-week trial comparing MAS-XR (60 mg or 80 mg daily) versus placebo among 126 participants with ADHD and cocaine dependence. An autoregressive cross-lagged structural equation model was fit and evaluated weekly ADHD improvement (defined as ≥30% reduction in the Adult ADHD Investigator Symptom Rating Scale) and urine-confirmed abstinence over the first six weeks. ResultsThe proportion of patients with each of the possible overall patterns of response was: ADHD improves before cocaine abstinence: 24%; Cocaine abstinence occurs before ADHD improvement: 12%; ADHD improvement and abstinence occur during the same week: 6%; ADHD improves but abstinence never achieved: 34%; Abstinence achieved but ADHD never improves: 6%; Neither ADHD improvement nor abstinence: 18%. A significant cross-lagged association was found; subjects with ADHD improvement at week 2 had significantly higher odds of cocaine abstinence at week 3 (p = .014). ConclusionWhen treating co-occurring ADHD and cocaine dependence with stimulant medication, abstinence is most likely preceded by improvement in ADHD, which tends to occur early with medication treatment. Other observed temporal patterns suggest the potential complexity of the relationship between ADHD and cocaine dependence.

Medication use in adults with attention deficit/hyperactivity disorder in a commercially-insured population in the United States

Objective: To examine real-world prescription medication usage among commercially-insured adults with attention deficit/hyperactivity disorder (ADHD) in the US.Methods: Adults with ADHD who received ≥1 ADHD medication during 2013 were identified from a large US claims database. Combination therapy was defined as an overlap of ≥30 days between the index (first treatment ≥30 days in 2013) and another medication(s). Patients were classified into six groups: long-acting (LA) monotherapy, short-acting (SA) monotherapy, LA + LA, SA + SA, LA + SA, and >2 therapies. Analyses compared baseline characteristics by regimen, ranked combination regimens, and estimated daily average consumption (DACON) for monotherapy users.Results: Of 206,443 adults with ADHD (mean age = 32.9 years; 51.6% female), 56.9% used LA monotherapy, 30.7% SA monotherapy, and 12.5% used combination therapies (LA + SA: 10.3%; LA + LA: 1.3%; SA + SA: 0.4%; >2 therapies: 0.5%). Extended-release mixed amphetamine salts (MAS-XR, 39.2%) and lisdexamfetamine (LDX, 31.5%) were the most common LA monotherapies. Nearly all SA monotherapy patients received immediate-release mixed amphetamine salts (MAS-IR; 81.7%). The top three therapies among combination categories were: (a) LA + LA: branded MAS-XR + generic MAS-XR (13.7%), LDX + generic MAS-XR (10.8%), LDX + guanfacine ER (10.7%); (b) SA + SA: generic MAS-IR + clonidine IR (33.5%), generic MAS-IR + generic MPH SA (17.9%), branded MAS-IR + generic MAS-IR (11.1%); (c) LA + SA: generic MAS-XR+/-IR (39.2%), LDX + generic MAS-IR (16.7%), LA + SA generic MPH (12.6%). Among monotherapy users, DACON was 1.2 ± 0.6 (LA) and 2.1 ± 0.9 (SA) tablets.Conclusions: There is significant treatment heterogeneity among US adults with ADHD. A sizable proportion of patients received monotherapies at above the recommended dosages or combination therapies, suggesting existing single-tablet regimens may not meet patients’ needs.

A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults

Objective: The purpose of this study was to compare the pharmacokinetics of a new extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended-release mixed amphetamine salts product, Adderall XR®. Method: In this single-dose, open-label, randomized, two-period, two-treatment crossover study, 42 healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg Adderall XR capsule in another period (both containing 18.8 mg of amphetamine base) under fasted conditions. Blood samples were analyzed for d - and l -amphetamine concentrations, and pharmacokinetic parameters Cmax, AUC0-5, AUC5-last, and AUCinf were calculated to determine bioequivalence. Safety was monitored throughout the study. Results: The 90% confidence intervals (CIs) for the log-transformed Cmax, AUC0-5, AUC5-last, and AUCinf fell within the accepted 80% to 125% range for establishing bioequivalence for d - and l -amphetamine. The most common adverse events were nausea and decreased appetite. Conclusion: AMP XR-OS is bioequivalent to Adderall XR in healthy adult participants.

Pharmacokinetics of a New Amphetamine Extended-release Oral Liquid Suspension Under Fasted and Fed Conditions in Healthy Adults: A Randomized, Open-label, Single-dose, 3-treatment Study

PurposeA new amphetamine extended-release liquid formulation (AMP XR-OS), intended for the treatment of attention-deficit/hyperactivity disorder, has been developed. This study was performed to determine if administration with food affected the rate of absorption or bioavailability of AMP XR-OS. The formulation was also compared with an equivalent dose of an extended-release mixed amphetamine salts reference product (30 mg) under fed conditions. MethodsThirty adult volunteers participated in this single-dose, open-label, randomized, 3-period, 3-treatment crossover study. Each participant received a single 15-mL dose of AMP XR-OS (equivalent to 30 mg of the reference drug) under fasted conditions, a single 15-mL dose of AMP XR-OS under fed conditions, and a single dose of the reference drug under fed conditions. A 7-day washout separated the 3 treatment periods. Blood samples were collected at predetermined time points and analyzed for d- and l-amphetamine. Pharmacokinetic parameters reported are AUC0–5, AUC0–last, AUC5–last, and AUC0–∞; Cmax; elimination t1/2; and Tmax. The geometric mean ratios and 90% CIs of Cmax, AUC0–last, and AUC0–∞were determined for the comparison of AMP XR-OS fed and fasted, and Cmax, AUC0–5, AUC5–last, and AUC0–∞ were calculated for AMP XR-OS compared with the reference drug under fed conditions. Safety was also assessed. FindingsTwenty-nine subjects completed the study. Subjects were mostly male, white, and of Hispanic/Latino ethnicity with a mean age of 35.83 years and a mean BMI of 25.36kg/m2. The 90% CIs of Cmax, AUC0–last, and AUC0–∞ for AMP XR-OS fasted versus fed were within the accepted 80% to 125% range, indicating lack of a food effect. In the comparison of AMP XR-OS fed versus the reference product, Cmax, AUC5–last, and AUC0–∞ were within the range to establish bioequivalence; however, AUC0–5 was significantly higher for AMP XR-OS compared with that of the reference drug. This difference between products was likely due to the known delay of Tmax and decreased exposure when the extended-release mixed amphetamine salts reference product is administered with food. A total of 36 mild or moderate adverse events were reported; 1 subject withdrew due to an adverse event, and no deaths occurred. These adverse events were consistent with the known pharmacodynamic effects of amphetamine. ImplicationsThe absence of a food effect may allow for AMP XR-OS to be administered with or without a meal.

Mixed-amphetamine salts increase abstinence from marijuana in patients with co-occurring attention-deficit/hyperactivity disorder and cocaine dependence.

The prevalence of ADHD is greater in substance use disorders than the general population, and ADHD and substance use disorders share neurobiological features such as dysregulation of reward circuitry. We tested the hypothesis that stimulants would decrease marijuana use in a randomized controlled trial of extended release mixed amphetamine salts (MAS-XR) for treatment of co-occurring ADHD and cocaine use disorders. Marijuana users were defined as participants reporting use in the 30 days before study initiation, collected with timeline follow-back. The original 14-week trial utilized a 3-arm randomized design, comparing placebo, MAS-XR 60 mg, and MAS-XR 80 mg. For this analysis, both MAS-XR groups were combined, leaving n = 20 in the placebo group and n = 37 in the MAS-XR group. The primary outcome was proportion of subjects reporting any marijuana use per study week. Comparisons between groups were made using a logistic mixed effects model incorporating multiple predictors and modeling time-by-treatment interactions. There were no significant baseline differences in marijuana use frequency and quantity. There was a significant decrease in the proportion of participants using marijuana over time in the MAS-XR group, but no difference in the proportion of marijuana-use days over time. Treatment of ADHD and comorbid cocaine use disorders with MAS-XR is associated with increased weekly abstinence from marijuana but not with a decrease in the proportion of marijuana using days per week. Stimulant treatment of ADHD and cocaine use disorders may diminish co-occurring cannabis use. (Am J Addict 2016;25:666-672).

A randomized crossover study to assess the pharmacokinetics of a novel amphetamine extended-release orally disintegrating tablet in healthy adults

ABSTRACTObjectives: In this pharmacokinetic (PK) study in healthy adults, we sought to: (1) compare the PK properties of a novel amphetamine extended-release orally disintegrating tablet formulation (Adzenys XR-ODT™ [AMP XR-ODT]) to a reference extended-release mixed amphetamine salts (MAS ER) formulation and (2) assess the effect of food on AMP XR-ODT.Methods: Forty-two adults were enrolled in a single-dose, open-label, 3-period, 3-treatment, randomized crossover study and received an 18.8-mg dose of AMP XR-ODT (fasted or fed) or equivalent dose (30 mg) of MAS ER (fasted). Plasma samples were analyzed for d-and l-amphetamine. Maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), elimination half-life (T1/2), area under the concentration-time curve from time zero to last quantifiable concentration (AUClast), from time zero to infinity (AUCinf), relevant partial AUCs, and weight-normalized clearance (CL/F/kg) were assessed. The PK parameters were compared across treatments using an ANOVA. Safety was also assessed.Results: A total of 39 adults completed this study. The geometric mean ratios (90% confidence interval [CI]) for AMP XR-ODT/MAS ER Cmax, AUC5-last, AUClast, and AUCinf were within 80%–125% for both d-and l-amphetamine. The 90% CIs for AUC0-5 were slightly below the 80%–125% range. When AMP XR-ODT was administered with food, there was a slight decrease in the d-and l-amphetamine Cmax and approximately a 2-hour delay in Tmax. The most common adverse events reported (>5% of participants) were dry mouth, palpitations, nausea, dizziness, headache, anxiety, and nasal congestion.Conclusions: AMP XR-ODT displayed a PK profile similar to MAS ER, and no clinically relevant food effect was observed.

Mixed-amphetamine salts increase abstinence from marijuana in patients with co-occurring attention-deficit/hyperactivity disorder and cocaine dependence

Background and Objectives The prevalence of ADHD is greater in substance use disorders than the general population, and ADHD and substance use disorders share neurobiological features such as dysregulation of reward circuitry. We tested the hypothesis that stimulants would decrease marijuana use in a randomized controlled trial of extended release mixed amphetamine salts (MAS-XR) for treatment of co-occurring ADHD and cocaine use disorders. Methods Marijuana users were defined as participants reporting use in the 30 days before study initiation, collected with timeline follow-back. The original 14-week trial utilized a 3-arm randomized design, comparing placebo, MAS-XR 60 mg, and MAS-XR 80 mg. For this analysis, both MAS-XR groups were combined, leaving n = 20 in the placebo group and n = 37 in the MAS-XR group. The primary outcome was proportion of subjects reporting any marijuana use per study week. Comparisons between groups were made using a logistic mixed effects model incorporating multiple predictors and modeling time-by-treatment interactions. Results There were no significant baseline differences in marijuana use frequency and quantity. There was a significant decrease in the proportion of participants using marijuana over time in the MAS-XR group, but no difference in the proportion of marijuana-use days over time. Discussion and Conclusions Treatment of ADHD and comorbid cocaine use disorders with MAS-XR is associated with increased weekly abstinence from marijuana but not with a decrease in the proportion of marijuana using days per week. Scientific Significance Stimulant treatment of ADHD and cocaine use disorders may diminish co-occurring cannabis use. (Am J Addict 2016;25:666–672)

Cigarette smoking trajectories among comorbid cocaine-dependent and attention deficit/hyperactivity-disorder individuals treated with extended-release mixed amphetamine salts

Cigarette smoking trajectories among comorbid cocaine-dependent and attention deficit/hyperactivity-disorder individuals treated with extended-release mixed amphetamine salts

Effects of single dose mixed amphetamine salts--extended release on processing speed in multiple sclerosis: a double blind placebo controlled study.

Multiple sclerosis (MS) commonly affects cognitive function, most frequently presenting as impaired processing speed (PS). There are currently no approved treatments for PS in this population, but previous studies suggest amphetamines may be beneficial. The objective of this study is to determine if mixed amphetamine salts, extended release (MAS-XR) has the potential to improve impaired PS in MS patients in a randomized controlled pre- and post-dose testing study. Fifty-two MS patients demonstrating PS impairment on either the Symbol Digit Modalities Test (SDMT) or Paced Auditory Serial Addition Test (PASAT) were randomized to a single dose of 5 mg MAS-XR (n = 18), 10 mg MAS-XR (n = 20), or placebo (n = 14). Subjects were evaluated a second time, after taking the blinded medication. ANOVA was used to compare the change on the SDMT and PASAT in each of the treatment groups compared to the placebo. Cohen's d was used to calculate effect size. At baseline, the mean SDMT score was 43.3 ± 7.2 and the mean PASAT was 34.8 ± 13.4, with 47 (90.4 %) and 25 (48.1 %) categorized as impaired on the SDMT and PASAT, respectively. The change in SDMT scores from baseline to post-treatment demonstrated significant improvement for the MAS-XR 10-mg dose compared to placebo, increasing by 5.2 ± 4.5 vs. 0.6 ± 4.4 points (p = 0.043), with a medium effect size of 0.47. Change on the PASAT was not significantly different in either treatment group. This study supports MAS-XR 10 mg as a potential treatment for MS patients with demonstrated PS impairment, warranting a larger longitudinal study.

Extended-Release Mixed Amphetamine Salts vs Placebo for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cocaine Use Disorder: A Randomized Clinical Trial.

Adult attention-deficit/hyperactivity disorder (ADHD) is prevalent but often unrecognized, in part because it tends to co-occur with other disorders such as substance use disorders. Cocaine use disorder is one such disorder with high co-occurrence of ADHD. To examine whether treatment of co-occurring ADHD and cocaine use disorder with extended-release mixed amphetamine salts is effective at both improving ADHD symptoms and reducing cocaine use. Thirteen-week, randomized, double-blind, 3-arm, placebo-controlled trial of participants meeting DSM-IV-TR criteria for both ADHD and cocaine use disorder conducted between December 1, 2007, and April 15, 2013, at 2 academic health center substance abuse treatment research sites. One hundred twenty-six adults diagnosed as having comorbid ADHD and cocaine use disorder were randomized to extended-release mixed amphetamine salts or placebo. Analysis was by intent-to-treat population. Participants received extended-release mixed amphetamine salts (60 or 80 mg) or placebo daily for 13 weeks and participated in weekly individual cognitive behavioral therapy. For ADHD, percentage of participants achieving at least a 30% reduction in ADHD symptom severity, measured by the Adult ADHD Investigator Symptom Rating Scale; for cocaine use, cocaine-negative weeks (by self-report of no cocaine use and weekly benzoylecgonine urine screens) during maintenance medication (weeks 2-13) and percentage of participants achieving abstinence for the last 3 weeks. More patients achieved at least a 30% reduction in ADHD symptom severity in the medication groups (60 mg: 30 of 40 participants [75.0%]; odds ratio [OR] = 5.23; 95% CI, 1.98-13.85; P < .001; and 80 mg: 25 of 43 participants [58.1%]; OR = 2.27; 95% CI, 0.94-5.49; P = .07) compared with placebo (17 of 43 participants [39.5%]). The odds of a cocaine-negative week were higher in the 80-mg group (OR = 5.46; 95% CI, 2.25-13.27; P < .001) and 60-mg group (OR = 2.92; 95% CI, 1.15-7.42; P = .02) compared with placebo. Rates of continuous abstinence in the last 3 weeks were greater for the medication groups than the placebo group: 30.2% for the 80-mg group (OR = 11.87; 95% CI, 2.25-62.62; P = .004) and 17.5% for the 60-mg group (OR = 5.85; 95% CI, 1.04-33.04; P = .04) vs 7.0% for placebo. Extended-release mixed amphetamine salts in robust doses along with cognitive behavioral therapy are effective for treatment of co-occurring ADHD and cocaine use disorder, both improving ADHD symptoms and reducing cocaine use. The data suggest the importance of screening and treatment of ADHD in adults presenting with cocaine use disorder. clinicaltrials.gov Identifier:NCT00553319.