Lisdexamfetamine Dimesylate Effects on Binge Eating Behaviour and Obsessive-Compulsive and Impulsive Features in Adults with Binge Eating Disorder.

In a published 11-week, placebo-controlled trial, 50 and 70 mg/d lisdexamfetamine dimesylate (LDX), but not 30 mg/d LDX, significantly reduced binge eating days (primary endpoint) in adults with binge eating disorder (BED). This report provides descriptions of LDX effects on secondary endpoints (Binge Eating Scale [BES]; Three-Factor Eating Questionnaire [TFEQ]; Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE]; and the Barratt Impulsiveness Scale, version 11 [BIS-11]) from that study. Week 11 least squares mean treatment differences favoured all LDX doses over placebo on the BES (p ≤ 0.03), TFEQ Disinhibition and Hunger subscales (all p < 0.05), and Y-BOCS-BE total, obsessive, and compulsive scales (all p ≤ 0.02) and on BIS-11 total score at 70 mg/d LDX (p = 0.015) and the TFEQ Cognitive Restraint subscale at 30 and 70 mg/d LDX (both p < 0.05). These findings indicate that LDX decreased global binge eating severity and obsessive-compulsive and impulsive features of BED in addition to binge eating days.

A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide.

Background: Despite the prevalence of Major Depressive Disorder (MDD) and the propensity of affected individuals to eventually die by suicide, there is no therapeutic approved specifically for suicidal ideation and behavior (SI/B) in MDD. The NMDA receptor antagonist ketamine has been investigated for the treatment of depression and shown to have a rapid effect on symptoms. Spravato® (esketamine) is approved by the FDA for use in treatment-resistant depression and Major Depressive Episodes with Suicidal Ideation based on studies conducted in adults also taking standard antidepressants. While esketamine was associated with a large reduction in suicidality indicators, the effects did not significantly exceed those associated with placebo. Racemic ketamine, a mixture of both esketamine and arketamine, may hold greater potential for the rapid alleviation of SI/B. SLS-002 was developed as an investigational intranasal racemic ketamine for the treatment of SI/B in individuals with MDD. Methods: In part one of a two-part clinical trial, the safety, tolerability, and potential effectiveness of SLS-002 were evaluated in an open label study of 17 patients with MDD hospitalized with acute SI/B. Results: Treatment with SLS-002 was associated with a significant reduction in depression and suicidality indicators on four clinical scales: the Montgomery-Åsberg Depression Rating Scale, the Sheehan-Suicidality Tracking Scale, and the Clinical and Patient Global Impression Scales for SI/B. SLS-002 was well tolerated with an acceptable safety profile. Conclusions: The results of this open label study support the continued development of SLS-002. The randomized double-blind placebo-controlled part two of this trial was recently completed.

Intranasal Use of Prescription Stimulants Among Adults Aged 18 to 30: Results From A Crowdsourcing Platform.

OBJECTIVE: Few studies of prescription stimulant non-oral, non-medical use (NMU) (defined by use not as prescribed) have been conducted in adults beyond the college population. The purpose of this study was to characterize prescription stimulant non-oral use, specifically intranasal (IN) use (snorting) in young adults. METHOD: Amazon's MTurk platform was used to recruit participants for an online survey. Data were collected from March to April 2020. RESULTS: Thirty-two percent (n = 157) of survey respondents (N = 975), aged 18 to 30, reported IN prescription stimulant use (average of 32.1 episodes of lifetime IN use). Adderall was the most-reported prescription stimulant used intranasally (89.2%). Most IN users (82%; n = 68) reported spending no more than 5 minutes tampering with prescription stimulants. Intranasal users said they would take the medication orally if unable to tamper or manipulate medication for IN use. CONCLUSION: These data help quantify a complex public health issue of ongoing IN use of prescription stimulants and suggest a potential role for manipulation-deterrent medications.

Lisdexamfetamine Dimesylate for Adults with Moderate to Severe Binge Eating Disorder: Results of Two Pivotal Phase 3 Randomized Controlled Trials.

The efficacy and safety of lisdexamfetamine dimesylate (LDX) vs placebo in binge eating disorder (BED) was evaluated in two multicenter, double-blind, placebo-controlled trials. Adults (study 1, n=383; study 2, n=390) meeting DSM-IV-TR BED criteria were randomized (1:1) to placebo or LDX (50 or 70 mg/day) dose titration; optimized doses were maintained to the end of double-blind treatment (week 12/early termination). Change from baseline in binge eating days/week at weeks 11-12 (primary efficacy endpoint) was assessed with mixed-effects models for repeated measures. Secondary endpoints related to binge eating and medical parameters, safety, and treatment compliance were also assessed. Least squares mean (95% CI) treatment differences for change from baseline binge eating days/week at weeks 11-12 significantly favored LDX (study 1: -1.35 [-1.70, -1.01]; study 2: -1.66 [-2.04, -1.28]; both P<0.001). In both studies, treatment-emergent adverse events (TEAEs) reported by ⩾10% of LDX participants were dry mouth, insomnia, and headache. Serious TEAEs occurred in two (1.1%) placebo participants in each study and in three (1.6%) and one (0.6%) LDX participants in study 1 and study 2, respectively. Across studies, mean increases from baseline at week 12/early termination with LDX for pulse and systolic and diastolic blood pressure ranged from 4.41-6.31 b.p.m. and 0.2-1.45 and 1.06-1.83 mm Hg, respectively. LDX (50 and 70 mg/day) was superior to placebo in decreasing binge eating days/week from baseline and improving binge eating-related key secondary endpoints. Safety results appear consistent with the known safety profile of LDX.

Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial.

IMPORTANCE: Binge-eating disorder (BED), a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome, lacks approved pharmacotherapies. OBJECTIVE: To examine the efficacy and safety of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to severe BED. DESIGN, SETTING, AND PARTICIPANTS: We performed a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to-treat analyses included 259 and 255 adults with BED, respectively. INTERVENTIONS: Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2) days after the last dose. MAIN OUTCOMES AND MEASURES: We assessed the change in binge-eating (BE) behaviors measured as days per week (baseline to week 11) with a mixed-effects model using transformed log (BE days per week) + 1. Secondary measures included BE cessation for 4 weeks. Safety assessments included treatment-emergent adverse events, vital signs, and change in weight. RESULTS: At week 11, log-transformed BE days per week decreased with the 50-mg/d (least squares [LS] mean [SE] change, -1.49 [0.066]; P = .008) and 70-mg/d (LS mean [SE] change, -1.57 [0.067]; P < .001) treatment groups but not the 30-mg/d treatment group (LS mean [SE] change, -1.24 [0.067]; P = .88) compared with the placebo group. Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-, and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively. The percentage of participants achieving 4-week BE cessation was lower with the placebo group (21.3%) compared with the 50-mg/d (42.2% [P = .01]) and 70-mg/d (50.0% [P < .001]) treatment groups. The incidence of any treatment-emergent adverse events was 58.7% for the placebo group and 84.7% for the combined treatment group. In the treatment groups, 1.5% of participants had serious treatment-emergent adverse effects. Events with a frequency of at least 5% and changes in heart rate were generally consistent with the known safety profile. The mean (SD) change in body weight was -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group, the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups, respectively (P < .001 for each dose vs placebo group comparison in post hoc analysis). CONCLUSIONS AND RELEVANCE: The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement. The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder. Further investigation of lisdexamfetamine in BED is ongoing. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01291173.

A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder.

To date, no large-scale, controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75 mg/day or 150 mg/day), or paroxetine 40 mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions--Severity (CGI-S) and--Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder.

Venlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled study.

BACKGROUND: Venlafaxine extended-release (ER) has proven efficacy in the treatment of anxiety symptoms in major depression, generalised anxiety disorder and social anxiety disorder. AIMS: To evaluate the efficacy, safety and tolerability of venlafaxine ER in treating panic disorder. METHOD: Adult out-patients (n=361) with panic disorder were randomly assigned to receive venlafaxine ER (75-225 mg/day) or placebo for up to 10 weeks in a double-blind study. RESULTS: Venlafaxine ER was not associated with a greater proportion of patients free from full-symptom panic attacks at the final on-therapy evaluation, but was associated with lower mean panic attack frequency and a higher proportion free from limited-symptom panic attacks, higher response and remission rates, and improvements in anticipatory anxiety, fear and avoidance. Adverse events were comparable with those of the drug in depression and anxiety disorders. CONCLUSIONS: Venlafaxine ER seems to be effective and well tolerated in the short-term treatment of panic disorder.

Time to deterioration of the elderly, anticoagulated, minor head injury patient who presents without evidence of neurologic abnormality.

BACKGROUND: Generally accepted guidelines regarding the care of the elderly, anticoagulated minor head injury patient do not exist within the trauma literature. METHODS: Charts were reviewed on all anticoagulated, minor head injury patients older than 65 years between January 1993 and May 2000. Postinjury course was examined for neurologic changes, times, coagulation/radiographic studies, reversal, operative intervention, and outcome. RESULTS: Thirty-two patients were identified. Twenty-four patients were discharged from the Emergency Department. Three of the remaining eight patients had initial Glasgow Coma Scale scores of 15, 15, and 14 but became comatose over a mean course of 3.83 hours. A fourth patient presented comatose 6 hours postinjury, down from "acting normal." Three of these four patients died. CONCLUSION: Elderly, anticoagulated patients with minor head trauma risk neurologic deterioration within 6 hours of injury, despite an initially normal neurologic examination. Early cranial computed tomographic scanning and close observation for a minimum of 6 hours are indicated.