Open Label Pilot of Lorcaserin (a serotonin 2C-receptor agonist) for Cannabis Use Disorder.

Background And Objective: Cannabis Use Disorder (CUD) has no FDA approved treatment. Serotonin-2c (5HT2c) agonists have preclinical and human laboratory evidence for potential efficacy for CUD. We assessed the tolerability and effects of lorcaserin (5HT2c agonist) on CUD. Methods: In a 10-week, open label, uncontrolled trial, the tolerability of lorcaserin was tested in outpatients with CUD. Adverse events (AE) were assessed weekly. Cannabis use was assessed twice weekly by the Timeline follow-back and quantitative urine metabolites. Results: 17 participants enrolled, and 14 received medication. Participants' average age was 35 years; majority were male (N=12). The medication was well tolerated in males. There were no serious adverse events (SAE). The most common AE's were headache/migraine (N=4, all females), anorexia (N=3), and irritability (N=2). Participants decreased their frequency of cannabis use significantly (p < 0.001), adjusted for baseline use. By the end of the trial, participants decreased by 1.76 (SE=0.47) cannabis using days/week. Average daily amount of cannabis and urine THC metabolite levels did not change significantly. Conclusions: Lorcaserin was well tolerated in males but not females suggesting possible sex differences. Future trials of other 5HT2c agonists (lorcaserin was withdrawn at the request of the FDA) should consider longer dose titration phases. Trial Registration: NCT02932215.

Open label trial of lofexidine-assisted non-opioid induction onto naltrexone extended-release injection for opioid use disorder.

Background: Opioid use disorder (OUD) continues to be major public health problem in the US and innovative medication strategies are needed. The extended-release injectable formulation of naltrexone (ER-NTX), an opioid receptor antagonist, is an effective treatment for OUD, but the need for an opioid-free period during the induction phase of treatment is a barrier to treatment success, particularly in the outpatient setting. Lofexidine, an alpha-2-adrenergic agonist, is an effective treatment for opioid withdrawal.Objectives: To evaluate the feasibility, safety, and tolerability of lofexidine for facilitating induction onto ER-NTX in the management of OUD.Methods: In an open-label, uncontrolled, 10-week outpatient clinical trial, 20 adults (four women) with OUD were treated with a fixed-flexible dosing strategy (maximum 0.54 mg 4×/daily) of lofexidine for up to 10 days to manage opioid withdrawal prior to receiving ER-NTX. The COVID-19 pandemic resulted in a modification of the study methods after enrolling 10 participants who attended all visits in person. The second group of 10 participants attended most induction period visits remotely.Results: Overall, 10 of the 20 participants (50%) achieved the primary outcome by receiving the first ER-NTX injection. Rates of induction success did not differ by the presence of fentanyl or remote visit attendance, although the small sample size provided limited statistical power. Six out of 20 participants (30%) initiated on lofexidine required dose adjustments. There were no study-related serious adverse events.Conclusions: This study provides preliminary evidence supporting the feasibility of inducting individuals with OUD onto ER-NTX using lofexidine.

Open-label trial of a single-day induction onto buprenorphine extended-release injection for users of heroin and fentanyl.

BACKGROUND AND OBJECTIVES: Fentanyl and other highly potent synthetic opioids are the leading cause of opioid overdose deaths in the United States. METHODS: This study was an open-label, uncontrolled 12-week outpatient clinical trial to test the feasibility of a single-day induction onto extended-release buprenorphine (BXR) injection treatment for five adults (N = 5) with opioid use disorder using heroin-containing fentanyl. Participants were planned to receive three monthly BXR injections (300, 300, and 100 mg). RESULTS: After receiving 24 mg sublingual buprenorphine (SL-BUP), all five participants received the BXR 300 mg injection on the first day of induction. All five participants were retained for the full 3-month study period postinduction and received all three scheduled BXR injections. DISCUSSION AND CONCLUSION: This study provides preliminary evidence supporting the feasibility of inducting users of heroin-containing fentanyl onto BXR 300 mg in a single day. SCIENTIFIC SIGNIFICANCE: The ability to administer a long-acting injection of BXR that assures therapeutic serum levels for a month on the first day of treatment contact is a promising development for the treatment of OUD.

An open-label pilot study of pregabalin pharmacotherapy for alcohol use disorder.

Background: There is a need for alcohol use disorder (AUD) pharmacotherapy that can be administered to actively drinking outpatients. Pregabalin, a gabapentoid anticonvulsant, has preliminary evidence supporting effects on alcohol withdrawal and AUD.Objectives: To evaluate the safety, tolerability, and optimal dosing of pregabalin for treating AUD.Methods: In an open-label, 8-week, outpatient trial of eighteen adults (nine women) with AUD, participants were titrated to 600 mg/day (or the maximum tolerated dose) over 3 weeks and then maintained for 5 weeks.Results: The majority (11/14, 78.6%) of participants with at least one-week of medication exposure achieved a maximum dose of 600 mg/day. Mean retention was 6.8 weeks (SD = 2.6). Eighty percent (12/15) of participants with post-enrollment data reported any adverse effects during the trial; and for those reporting adverse effects the most common were drowsiness (33.3%, 4/12), and fogginess (25%, 3/12), dizziness (25%, 3/12), and insomnia (25%, 3/12). Two participants discontinued study medication due to adverse effects and one had a dose reduction. Mean Heavy Drinking Days (HDD)/week decreased significantly by 3.43 days (SD = 2.47; median (IQR) = 4.00 (1.00 to 5.50)); Wilcoxon signed rank test statistic ((S) = 49.5, p = .0006). Mean proportion of HDD significantly decreased on average by 48.7% (SD = 35.1%; median (IQR) = 57.1% (14.3% to 78.6%)). The proportion of abstinent days increased significantly on average by 36.1% (SD = 35.0%; median (IQR) = 17.9% (14.3% to 75.0%); S = 49.5, p = .0005).Conclusions: Pregabalin treatment of AUD appears to be safe and well tolerated in doses up to 600 mg per day.Trial Registration: clinicaltrials.gov identifier: NCT03256253.

Open-label pilot study of lisdexamfetamine for cocaine use disorder.

Background: Cocaine use disorder (CUD) is a substantial public health problem with no FDA-approved medication treatments. Psychostimulants have shown promise as pharmacotherapy for CUD. Lisdexamfetamine, a novel prodrug psychostimulant, is roughly 40-50% as potent as dextroamphetamine.Objectives: To evaluate the safety, tolerability, and optimal dosing of lisdexamfetamine for treating CUD.Methods: Open-label, 8-week trial of 17 CUD adults. Participants were titrated to the maximum tolerated dose of 140 mg over 2-week period and maintained for 4 weeks, followed by a two-week taper period. The primary outcome measures were the maximum daily dose achieved during the study period and tolerability as measured by medication-related study drop-out.Results: Among the 16 participants with post-enrollment data, the mean dose of lisdexamfetamine achieved was 118.1 mg (standard deviation (SD) = 40.4), mean retention was 6.5 weeks (SD = 2.0), and no participants discontinued study medication due to adverse effects. Four participants had dose reductions due to adverse effects and continued in the trial. Six participants (37.5%) were abstinent for the last 3 weeks of their study participation. Mean dollars of cocaine spent per day significantly decreased from $19.72 at baseline to $7.57 during the last 3 weeks of study participation (t15 = 3.60, p = .003). The mean percent of using days significantly decreased from 25% at baseline to 12% during the last 3 weeks of study participation (t15 = 3.33, p = .005).Conclusion: The use of lisdexamfetamine for CUD in doses ranging to 140 mg daily was safe and generally well tolerated.

Lorcaserin treatment for extended-release naltrexone induction and retention for opioid use disorder individuals: A pilot, placebo-controlled randomized trial.

BACKGROUND: Opioid Use Disorder (OUD) is a significant public health problem associated with severe morbidity and mortality. While effective pharmacotherapies are available, limitations exist with each. Induction onto extended-release naltrexone (XR-NTX) is more difficult than initiation of buprenorphine or methadone, even in inpatient settings, as it is recommended that patients remain abstinent for at least 7 days prior to initiating XR-NTX. The purpose of this trial was to determine if lorcaserin, a 5HT2c agonist, improves outpatient XR-NTX induction rates. METHODS: An 8-week trial beginning with a brief detoxification period and induction onto XR-NTX. Sixty participants with OUD were enrolled in the trial, with 49 participants at the initiation of detoxification randomized to lorcaserin or placebo for 39 days. Additionally, ancillary medications were provided. The primary outcome was the proportion of participants inducted onto the first XR-NTX injection. Secondary outcomes were withdrawal severity (measured by COWS and SOWS) prior to the first injection and the proportion of participants receiving the second XR-NTX injection. RESULTS: The proportion of participants inducted onto the first (lorcaserin: 36 %; placebo: 44 %; p = .67) and the second XR-NTX injection (lorcaserin: 27 %; placebo: 31 %; p = .77) was not significantly different between treatment arms. Prior to the first injection, withdrawal scores did not significantly differ between treatment arms over time (treatment*time interaction COWS: p = .11; SOWS: p = .39). CONCLUSIONS: Lorcaserin failed to improve outpatient XR-NTX induction rates. Although this study is small, the findings do not support the use of lorcaserin in promoting induction onto XR-NTX or in mitigating withdrawal symptoms.

Quetiapine treatment for cannabis use disorder.

BACKROUND: Pharmacotherapy for cannabis use disorder (CUD) is an important unmet public health need. METHODS: In a 12-week randomized double-blind placebo-controlled trial, the efficacy of quetiapine (300 mg nightly) for the treatment of CUD was tested in 130 outpatients. Weekly cannabis use was categorized into three groups: heavy use (5-7 days), moderate use (2-4 days) and light use (0-1 days). RESULTS: At baseline both groups were considered heavy users (using days per week: median = 7.0; interquartile range (IQR): 6.5-7.0; daily dollar value: median = $121.4; IQR: 73.8-206.3). The week-by-treatment interaction was marginally significant (χ2(2) = 5.56, P = .06). With each week, the odds of moderate compared to heavy use significantly increased in the quetiapine group (OR=1.17, P < .0001), but not significantly in the placebo group (OR=1.05, P = .16). The odds of light versus heavy use did not significantly differ over time (P = .12). Treatment was also associated with reduced cannabis withdrawal symptoms by 10.4% each week (95% CI: 8.9-11.8). No serious adverse events occurred during the study and no evidence of development of a movement disorder was detected. Adverse effects were not significantly different between the quetiapine and placebo treatment arms. CONCLUSIONS: The use of quetiapine to treat CUD was associated with an increased likelihood of heavy frequency use transitioning to moderate use, but not light use. The clinical significance of reductions in cannabis use, short of abstinence warrants further study.

Case Series: Rapid Induction Onto Long Acting Buprenorphine Injection for High Potency Synthetic Opioid Users.

BACKGROUND AND OBJECTIVES: Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States. METHODS: In an open-label, uncontrolled trial to test the feasibility of extended-release buprenorphine (BXR) injection treatment of heroin-using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms. RESULTS: Two participants received the BXR injection on the second day of the induction and three participants on the third day. DISCUSSION AND CONCLUSION: All five participants were retained at least 1-month postinduction. SCIENTIFIC SIGNIFICANCE: It may be feasible to provide BXR treatment to HPSO-positive heroin users rapidly to achieve clinical stabilization. (Am J Addict 2020;00:00-00).

Guanfacine extended-release for cannabis use disorder: a pilot feasibility trial.

Background: Currently, there are no established pharmacotherapies for cannabis use disorders (CUDs). As a long-acting alpha-2-adrenergic receptor agonist, guanfacine extended-release (G-XR) could be useful in the treatment of CUDs by mitigating withdrawal and improving behavioral control.Objectives: To evaluate the feasibility and tolerability of G-XR as a treatment for CUDs.Methods: In an eight-week open-label outpatient pilot trial, we evaluated the safety and tolerability of G-XR in 22 cannabis dependent individuals. Using 2 different titration schedules, G-XR was gradually titrated to a dose of 4 mg or the highest dose tolerated. All participants received standard medication management.Results: Retention at week eight was 41%. Average daily amount of cannabis use (in grams: F1,86 = 8.74, p = .004; in dollars: F1,86 = 16.67, p < .0001) and cannabis using days (F1,86 = 7.67, p = .007) significantly reduced over the course of study participation. There were no significant differences between the titration schedules on emergence of side effects (Fisher exact test, p = .378) or retention (Log-Rank Test X21 = 0.021, p = .886). A total of 3 participants achieved 3 weeks or greater of total abstinence.Conclusions: G-XR is a feasible treatment for CUDs, and should be evaluated further in an efficacy trial.

ADHD Is Highly Prevalent in Patients Seeking Treatment for Cannabis Use Disorders.

Objective: To estimate the prevalence of ADHD and determine an effective screening test for ADHD in a population-seeking treatment for cannabis use disorders. Method: The Conners Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; CAADID) was used to generate sensitivity and specificity data for ADHD screening tests, which were then administered to 99 participants seeking treatment for cannabis use disorders to estimate ADHD prevalence. Results: The prevalence estimated from the Wender Utah Rating Scale (WURS) was 45% (sensitivity = 0.88, sensitivity of 0.75), from the Conners Adult ADHD Rating Scale (CAARS) 34% (sensitivity = 0.80, specificity = 0.91), from the WURS + CAARS 36% (sensitivity = 0.71, specificity = 0.95), and from the Adult ADHD Self-Report Scale (ASRS) 46% (sensitivity = 0.61, specificity = 0.86). Conclusion: The prevalence of ADHD in adults seeking treatment for cannabis use disorders is estimated to be between 34% and 46%. The WURS paired with the CAARS provides excellent sensitivity and specificity for the diagnosis of ADHD in this population.

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

BACKGROUND: Cocaine 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. METHODS: A 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. RESULTS: The 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%). CONCLUSIONS: While 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.

BACKGROUND: Attention-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. METHODS: The 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. RESULTS: The 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). CONCLUSION: When 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.

Abstinence and reduced frequency of use are associated with improvements in quality of life among treatment-seekers with cannabis use disorder.

BACKGROUND AND OBJECTIVE: Many patients with cannabis use disorder (CUD) do not achieve or do not have abstinence as a goal of treatment, rather they reduce their use. Assessing outcome measures as they relate to functioning and reductions in cannabis use is an important area of study. Quality of life (QoL) shows promise as one such measure. Past studies have demonstrated gender differences in QoL and CUD. We aim to assess (1) the relationship between cannabis use and QoL and (2) gender effects in an outpatient medication treatment study for CUD. METHODS: Data from an 11-weeks, double-blind, placebo-controlled trial of lofexidine and dronabinol for CUD (n = 62) was analyzed. Pearson's correlations between baseline QoL as measured with the Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form (QLES-Q-SF) and cannabis use assessed with modified timeline follow-back (TLFB) were examined. Multiple linear regression models of cannabis use on end of study QLES-Q-SF were analyzed, while adjusting for baseline QLES-Q-SF, study arm, and gender. Moderation effects with gender were also tested. RESULTS: No significant association between baseline cannabis use and QoL was found. End of study abstinence (F1,47 = 8.34, p = .006) and reduced proportion of using days (F1,47 = 9.48, p = .004) were each significantly associated with end of study QoL. Reduction in grams (F1,27 = 0.25, p = .62) was not associated with QoL at end of study. Gender was not a significant moderator. DISCUSSION AND CONCLUSIONS: Abstinence and lower frequency of use are associated with higher QoL, regardless of gender. SCIENTIFIC SIGNIFICANCE: This is the first time QoL has been demonstrated to change over the course of CUD medication treatment. QoL is an important outcome in CUD treatment. TRIAL REGISTRATION: NCT01020019. (Am J Addict 2018;27:101-107).

Open-label pilot study of injectable naltrexone for cannabis dependence.

BACKGROUND: There are no FDA-approved pharmacotherapies for cannabis use disorders (CUD), despite the evaluation of numerous medications. Notably, chronic dosing of oral naltrexone decreases self-administration of cannabis in human laboratory studies. OBJECTIVES: To test the feasibility of long-acting injectable naltrexone for the treatment of CUD, while obtaining preliminary safety and efficacy data. METHODS: Twelve adult participants (seven male) meeting DSM-IV-TR criteria for cannabis dependence enrolled into an 8-week, open-label pilot study conducted at an academic treatment research clinic. They received 380 mg intramuscular injections of long-acting naltrexone on study day 1 and at the start of study week 5. Outcome measures included percentages of study completers and participants who received the second injection, frequency of adverse events (AEs), and cannabis consumption measured by average daily grams, dollars, and using days per week as measured by timeline follow-back and urine oral delta-9-tetrahydrocannabinol (THC) concentrations. RESULTS: Of the 12 participants enrolled in the study, 9 completed the study and 6 received the second injection. There were no severe AEs but an unexpected AE led to the addition of supportive medications to the protocol. Number of cannabis use days per week significantly decreased over the course of the study (p = .001). Creatinine-corrected urine THC concentrations and average daily cannabis use per study week in grams and in dollars did not decrease over the course of the study. CONCLUSIONS: Long-acting injectable naltrexone is a feasible intervention for CUD worthy of further study in a placebo-controlled, double-blinded randomized clinical trial.

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).

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS: One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS: There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS: Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.

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

IMPORTANCE: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00553319.

The utility of attention-deficit/hyperactivity disorder screening instruments in individuals seeking treatment for substance use disorders.

OBJECTIVE: Several screening tools for attention-deficit/hyperactivity disorder (ADHD) have been validated in non-substance-abusing populations, but limited data are available regarding their utility in adults with current substance use disorders. The aim of this study was to determine the sensitivity, specificity, and positive and negative predictive values of 3 commonly used ADHD screening instruments in cocaine-dependent individuals. METHOD: Adults seeking treatment for cocaine dependence (N = 102) were administered 3 self-report instruments between May 2009 and April 2011: the Conners Adult ADHD Rating Scale (CAARS), the Wender Utah Rating Scale (WURS), and the Adult ADHD Self-Report Scale-Version 1.1 (ASRS-V1.1). They then met with master's-level clinicians who administered the Conners Adult ADHD Diagnostic Interview for DSM-IV (CAADID). With the CAADID serving as the gold standard, the validity of the screening instruments was determined, both singly and in combination. RESULTS: Twenty-five (25%) of the 102 patients met DSM-IV criteria for ADHD or ADHD not otherwise specified (NOS) based on the CAADID. Kappa scores determining agreement between the screening tools and the CAADID (with ADHD NOS labeled as ADHD or labeled as not ADHD) ranged from 0.37 to 0.69. Sensitivity scores for the broadest range of ADHD cases were 80.0%, 87.5%, and 60.9% for the CAARS, WURS, and ASRS-V1.1, respectively. Positive predictive value was highest for the CAARS, at 74.1%, and negative predictive value was highest for the WURS, at 95.1%. The highest sensitivity (96.0%) was found with coadministration of the WURS and CAARS. CONCLUSION: While all of the screening instruments were found to have adequate sensitivity and specificity, the CAARS outperformed the other instruments in regard to agreement with the CAADID and positive predictive values. However, the WURS, with the highest sensitivity in regard to the broadest range of ADHD cases, may be the single best instrument for preliminary screening purposes. Further, because the ASRS-V1.1 is the simplest and shortest instrument to administer, it may have advantages when a large number of patients need to be screened.