lisdexamfetamine-dimesylate and Depressive-Disorder--Major

To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.. We conducted two researches on the PubMed, Scopus and Embase using the keywords ("elderly") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine") and then ("Alzheimer" OR "dementia") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine").. Twenty-nine papers met all the eligibility criteria. The results are encouraging as 81.5% of the studies showed clinical improvement of the investigated condition.. Amphetamines and methylphenidate are probably effective strategies for different conditions in the elderly population. However, further studies are needed to provide more robust evidence on efficacy, dosage and safety for this population.

Topics: Aged; Amphetamine; Dementia; Depressive Disorder, Major; Humans; Lisdexamfetamine Dimesylate; Methylphenidate

Psychostimulants have been used in the treatment of depression, with mixed results. This meta-analysis examines the efficacy and tolerability of the stimulant Lisdexamfetamine (LDX) as an add-on strategy in those with MDD who have failed to respond to an antidepressant.. Randomized control trials were identified and extracted from Pubmed; Web of Science; PsychINFO; and Cochrane Library. The efficacy of LDX was evaluated using Hedges' g and Odds Ratio, whereas Risk Difference was used to assess the safety and tolerability of LDX.. Four studies met inclusion criteria. LDX did not demonstrate superiority in efficacy relative to placebo as indicated by a Hedges' g score of 0.126 (95% CI -0.040-0.291; p = 0.136) for mean change in Montgomery-Asberg Depression Rating Scale. Odds ratios of 1.206 (95% CI 0.745-1.954; p = 0.446) and 1.244 (95% CI 0.959-1.614; p = 0.1) were found for remission and response rates respectively. Risk differences of -0.1 (95% CI -0.155-(-0.045); p < 0.001) indicated a 10% increase chance of developing treatment-emergent adverse events (TEAE) in the LDX group. There was no significant difference in risk for developing serious or severe TEAE and discontinuing treatment due to TEAE.. The number of included studies was small and only one metric was available for analysis of antidepressant efficacy of LDX.. LDX when used as antidepressant augmentation produced a small effect in improving depressive symptoms that approached trend-level significance and demonstrated comparable tolerability to placebo. Further studies are needed to determine the optimal clinical subset of depressive symptoms responsive to LDX augmentation.

Topics: Antidepressive Agents; Central Nervous System Stimulants; Depressive Disorder, Major; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic; Treatment Outcome

This randomized, double-blind, placebo-controlled study evaluated dose-response relationships of lisdexamfetamine dimesylate when used as augmentation for major depressive disorder in individuals exhibiting inadequate responses to antidepressant monotherapy.. Eligible adults (18-65 years) were assigned to antidepressant monotherapy (escitalopram or venlafaxine extended-release) plus lisdexamfetamine dimesylate-matching placebo during an eight-week single-blind lead-in phase. Participants meeting randomization criteria were randomized (1:1:1:1:1) to eight weeks of lisdexamfetamine dimesylate (10, 30, 50, or 70 mg) or placebo while maintaining antidepressant therapy. Dose-responses for changes from augmentation baseline to week 16/early termination for Montgomery-Åsberg Depression Rating Scale total score (primary efficacy endpoint) and vital signs (systolic and diastolic blood pressure and pulse) were assessed using multiple comparisons procedures with modeling.. For Montgomery-Åsberg Depression Rating Scale total score change, no significant dose-responses were observed for any candidate dose-response curve (all p>0.10). In the dose-response evaluable population, least squares mean (90% confidence interval) treatment differences versus placebo for Montgomery-Åsberg Depression Rating Scale total score change at week 16 were -1.4 (-3.9, 1.2), 0.1 (-2.5, 2.7), -0.7 (-3.4, 2.0), and -0.9 (-3.5, 1.6) with 10, 30, 50, and 70 mg lisdexamfetamine dimesylate, respectively. For all vital sign parameters, lisdexamfetamine dimesylate exhibited significant dose-responses for all candidate dose-response curves (all p<0.10), with increases observed as lisdexamfetamine dimesylate dose increased; a linear relationship provided the best fit. Mean±standard deviation changes from augmentation baseline for systolic and diastolic blood pressure and pulse at week 16/early termination were -0.7±9.90 and -0.3±7.24 mm Hg and 0.2±10.57 bpm with placebo and were 1.9±9.47 and 0.8±7.40 mm Hg and 3.6±9.74 bpm with lisdexamfetamine dimesylate (all doses combined). The safety and tolerability profile of lisdexamfetamine dimesylate was consistent with previous studies.. Lisdexamfetamine dimesylate augmentation did not provide benefit over placebo in adults with inadequate responses to antidepressant monotherapy based on the assessed efficacy measures.

Topics: Adult; Antidepressive Agents; Blood Pressure; Citalopram; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Venlafaxine Hydrochloride

The efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy in adults with major depressive disorder (MDD) from two phase 3 studies are reported.. Across study 1 (placebo, n=201; LDX, n=201) and study 2 (placebo, n=213; LDX, n=211), most participants (placebo and LDX) in the safety analysis set were female (study 1: 66.2% and 64.2%; study 2: 67.1% and 66.8%); mean±SD ages were 41.8±12.04 with placebo and 42.2±12.32 with LDX in study 1 and 42.6±11.41 with placebo and 42.0±11.63 with LDX in study 2. Participants (18-65 y) had DSM-IV-TR-diagnosed MDD and lead-in baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores ≥24. Eight-week antidepressant lead-in phases prospectively assessed antidepressant response. Then, 8 weeks of randomized (1:1), double-blind treatment with dose-optimized LDX (20-70mg) or placebo in participants exhibiting inadequate antidepressant monotherapy responses (augmentation baseline MADRS total scores ≥18 and <50% MADRS total score reductions from lead-in baseline to augmentation baseline) was initiated. The primary endpoint was MADRS total score change from augmentation baseline to week 16. Safety and tolerability measures included the occurrence of treatment-emergent adverse events (TEAEs).. Least squares mean (95% CI) treatment differences (LDX-placebo) for MADRS total score changes from augmentation baseline to week 16 were not statistically significant in study 1 (0.1 [-1.7, 2.0], P=0.883) or study 2 (-0.5 [-2.3, 1.3], P=0.583). The only TEAE reported by >5% of LDX participants at twice the placebo rate in both studies was dry mouth.. Limitations include the exclusion of participants with psychiatric comorbidities/active medical disorders, the inability to assess specific MDD symptom domains (eg, anhedonia, cognition) or subtypes, the use of telephone-based depression assessments, and the potential influence of placebo response.. Contrary to expectations, LDX augmentation was not superior to placebo in reducing depressive symptoms in individuals with MDD exhibiting inadequate responses to antidepressant monotherapy.

Topics: Adult; Antidepressive Agents; Citalopram; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dopamine Uptake Inhibitors; Double-Blind Method; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; Humans; Least-Squares Analysis; Lisdexamfetamine Dimesylate; Male; Middle Aged; Sertraline; Treatment Outcome; Venlafaxine Hydrochloride

Evaluate lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy for executive dysfunction in partially or fully remitted major depressive disorder (MDD). This randomized, placebo-controlled study (NCT00985725) enrolled 143 adults (18-55 years) with mild MDD (Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤ 18) and executive dysfunction (Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report Global Executive Composite (GEC) T score ≥ 60) on stable antidepressant monotherapy for ≥ 8 weeks. After 2 weeks of screening, participants were randomized to 9 weeks of double-blind LDX (20-70 mg/day) or placebo augmentation, followed by 2 weeks of single-blind placebo. The primary end point was change from baseline to week 9/end of study (EOS) in BRIEF-A Self-Report GEC T score; secondary assessments included the BRIEF-A Informant Report, MADRS, and treatment-emergent adverse events (TEAEs). Of 143 randomized participants, 119 completed double-blind treatment (placebo, n=59; LDX, n=60). Mean ± standard deviation (SD) BRIEF-A GEC T scores decreased from baseline (placebo, 74.2 ± 8.88; LDX, 76.8 ± 9.66) to week 9/EOS (placebo, 61.4 ± 14.61; LDX, 55.2 ± 16.15); the LS mean (95% CI) treatment difference significantly favored LDX (-8.0 (-12.7, -3.3); P=0.0009). The LS mean (95% CI) treatment difference for MADRS total score also significantly favored LDX (-1.9 (-3.7, 0.0); P=0.0465). TEAE rates were 73.6% with placebo and 78.9% with LDX; serious TEAE rates were 4.2 and 2.8%. In this trial, LDX augmentation significantly improved executive dysfunction and depressive symptoms in participants with mild MDD. The safety profile of LDX was consistent with prior studies in adults with attention-deficit/hyperactivity disorder.

Topics: Adult; Antidepressive Agents; Cognition Disorders; Depressive Disorder, Major; Dextroamphetamine; Double-Blind Method; Drug Therapy, Combination; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Psychotropic Drugs; Remission Induction; Single-Blind Method; Treatment Outcome

Evaluate the efficacy and safety of lisdexamfetamine dimesylate augmentation for major depressive disorder (MDD) in escitalopram nonremitters.. In this proof-of-concept study (conducted from July 2009-August 2010) with a prespecified critical α = .10, adults with nonpsychotic MDD (DSM-IV-TR criteria) and residual depressive symptoms (17-item Hamilton Depression Rating Scale score ≥ 4) after 8 weeks of open-label escitalopram were randomized to 6 weeks of lisdexamfetamine dimesylate (20-50 mg/d) or placebo augmentation. The primary endpoint, Montgomery-Asberg Depression Rating Scale (MADRS) total score change in escitalopram nonremitters (MADRS total score > 10) from week 8 (augmentation baseline) to week 14/end of study, was assessed using analysis of covariance, with last observation carried forward.. For nonremitters (placebo, n = 64; lisdexamfetamine dimesylate, n = 65), the least squares (LS) mean (90% CI) treatment difference for MADRS total score reduction at week 14/end of study (-2.3 [-4.5 to -0.1]; P = .0902) met the prespecified criterion for lisdexamfetamine dimesylate superiority (adjusted effect size, -0.3); the number needed to treat for MADRS remission (MADRS total score ≤ 10) was 6.7. The LS mean treatment difference in remitters was not statistically significant (1.2 [-1.6 to 4.0]; P = .4726). Among randomized participants, 49.4% (42/85) receiving placebo and 60.2% (53/88) receiving lisdexamfetamine dimesylate had ≥ 1 treatment-emergent adverse event, the most frequent with lisdexamfetamine dimesylate being dry mouth and headache (both 11.4%). Mean (SD) vital sign and electrocardiogram changes (placebo vs lisdexamfetamine dimesylate) were 0.5 (8.98) versus 2.3 (9.04) mm Hg (systolic blood pressure), -1.0 (7.19) versus 0.9 (6.61) mm Hg (diastolic blood pressure), -0.4 (7.39) versus 4.8 (8.64) beats per minute (heart rate), and -1.6 (11.23) versus -4.9 (11.84) milliseconds (Fridericia-adjusted QTc).. Lisdexamfetamine dimesylate augmentation reduced depressive symptoms in participants with inadequate escitalopram response.. ClinicalTrials.gov identifier: NCT00905424.

Topics: Adolescent; Adult; Antidepressive Agents, Second-Generation; Central Nervous System Stimulants; Citalopram; Depressive Disorder, Major; Dextroamphetamine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Personality Inventory; Psychometrics; Young Adult

In the Canadian healthcare setting, there is limited understanding of the pathways to diagnosis and treatment for patients with binge eating disorder (BED).. This retrospective chart review examined the clinical characteristics, diagnostic pathways, and treatment history of adult patients diagnosed with BED.. Overall, 202 charts from 57 healthcare providers (HCPs) were reviewed. Most patients were women (69%) and white (78%). Mean ± SD patient age was 37 ± 12.1 years. Comorbidities identified in > 20% of patients included obesity (50%), anxiety (49%), depression and/or major depressive disorder (46%), and dyslipidemia (26%). Discussions regarding a diagnosis of BED were typically initiated more often by HCPs than patients. Most patients (64%) received a diagnosis of BED ≥ 3 years after symptom onset. A numerically greater percentage of patients received (past or current) nonpharmacotherapy than pharmacotherapy (84% vs. 67%). The mean ± SD number of binge eating episodes/week numerically decreased from pretreatment to follow-up with lisdexamfetamine (5.4 ± 2.8 vs. 1.7 ± 1.2), off-label pharmacotherapy (4.7 ± 3.9 vs. 2.0 ± 1.13), and nonpharmacotherapy (6.3 ± 4.8 vs. 3.5 ±  6.0) Across pharmacotherapies and nonpharmacotherapies, most patients reported improvement in symptoms of BED (84-97%) and in overall well-being (80-96%).. These findings highlight the importance of timely diagnosis and treatment of BED. Although HCPs are initiating discussions about BED, earlier identification of BED symptoms is required. Furthermore, these data indicate that pharmacologic and nonpharmacologic treatment for BED is associated with decreased binge eating and improvements in overall well-being.. IV, chart review.

Topics: Adult; Binge-Eating Disorder; Canada; Depressive Disorder, Major; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Retrospective Studies; Young Adult

Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms and common comorbidities. A better understanding of the medications used to manage comorbid conditions in this growing population is critical; however, most previous efforts have been limited in size, duration, and lack of broad representation.. To use a nationally representative database to uncover trends in the prevalence of co-occurring conditions and medication use in the management of symptoms and comorbidities over time among US individuals with ASD.. This retrospective, population-based cohort study mined a nationwide, managed health plan claims database containing more than 86 million unique members. Data from January 1, 2014, to December 31, 2019, were used to analyze prescription frequency and diagnoses of comorbidities. A total of 26 722 individuals with ASD who had been prescribed at least 1 of 24 medications most commonly prescribed to treat ASD symptoms or comorbidities during the 6-year study period were included in the analysis.. Diagnosis codes for ASD based on International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.. Quantitative estimates of prescription frequency for the 24 most commonly prescribed medications among the study cohort and the most common comorbidities associated with each medication in this population.. Among the 26 722 individuals with ASD included in the analysis (77.7% male; mean [SD] age, 14.45 [9.40] years), polypharmacy was common, ranging from 28.6% to 31.5%. Individuals' prescription regimens changed frequently within medication classes, rather than between classes. The prescription frequency of a specific medication varied considerably, depending on the coexisting diagnosis of a given comorbidity. Of the 24 medications assessed, 15 were associated with at least a 15% prevalence of a mood disorder, and 11 were associated with at least a 15% prevalence of attention-deficit/hyperactivity disorder. For patients taking antipsychotics, the 2 most common comorbidities were combined type attention-deficit/hyperactivity disorder (11.6%-17.8%) and anxiety disorder (13.1%-30.1%).. This study demonstrated considerable variability and transiency in the use of prescription medications by US clinicians to manage symptoms and comorbidities associated with ASD. These findings support the importance of early and ongoing surveillance of patients with ASD and co-occurring conditions and offer clinicians insight on the targeted therapies most commonly used to manage co-occurring conditions. Future research and policy efforts are critical to assess the extent to which pharmacological management of comorbidities affects quality of life and functioning in patients with ASD while continuing to optimize clinical guidelines, to ensure effective care for this growing population.

Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bupropion; Child; Child, Preschool; Cohort Studies; Comorbidity; Data Mining; Depressive Disorder, Major; Dexmethylphenidate Hydrochloride; Dextroamphetamine; Female; Health Services Accessibility; Humans; Insurance; Lisdexamfetamine Dimesylate; Male; Managed Care Programs; Prevalence; Retrospective Studies

Psychostimulant augmentation is considered a potential treatment strategy for individuals with major depressive disorder who do not adequately respond to antidepressant monotherapy. The primary objective of this 12-month open-label extension study was to evaluate the safety and tolerability of lisdexamfetamine dimesylate (LDX) as augmentation therapy to an antidepressant in adults with major depressive disorder.. Eligible adults who completed 1 of 3 short-term antecedent LDX augmentation of antidepressant monotherapy studies were treated with dose-optimized LDX (20-70 mg) for up to 52 weeks while continuing on the index antidepressant (escitalopram, sertraline, venlafaxine extended-release, or duloxetine) assigned during the antecedent short-term studies. Safety and tolerability assessments included the occurrence of treatment-emergent adverse events and vital sign changes.. All 3 antecedent studies failed to meet the prespecified primary efficacy endpoint, so this open-label study was terminated early. Headache (15.5% [241/1559]), dry mouth (13.6% [212/1559]), insomnia (13.1% [204/1559]), and decreased appetite (12.1% [189/1559]) were the most frequently reported treatment-emergent adverse events. The greatest mean ± SD increases observed for systolic and diastolic blood pressure and for pulse were 2.6 ± 10.85 and 1.7 ± 7.94 mm Hg and 6.9 ± 10.27 bpm, respectively. Monitoring determined that less than 1% of participants experienced potentially clinically important changes in systolic blood pressure (10 [0.6%]), diastolic blood pressure (8 [0.5%]), or pulse (6 [0.4%]).. The overall safety and tolerability of long-term LDX augmentation of antidepressant monotherapy was consistent with the profiles of the short-term antecedent studies, with no evidence of new safety signals.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Central Nervous System Stimulants; Depressive Disorder, Major; Drug Therapy, Combination; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Young Adult

The brain reward system consists of extensive neural pathways that mediate reward behavior such as pleasure and motivation. These pathways may be involved in the development of symptoms such as apathy, anhedonia, and cognitive dysfunction seen in patients with major depression. These pathways are served primarily, although not exclusively, by the chemical neurotransmitter dopamine, which has suggested a therapeutic role for drugs that influence dopamine activity. A small number of clinical trials using various dopaminergic and stimulant drugs for the treatment of major depression and bipolar depression have demonstrated some benefit when combined with standard antidepressant drugs. Based on this work, several ongoing trials are investigating the use of the stimulant drug lisdexamfetamine (Vyvanse®) as an adjunctive treatment for depression.

Topics: Amphetamines; Antidepressive Agents; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Brain; Central Nervous System Stimulants; Depressive Disorder, Major; Dextroamphetamine; Dopamine; Dopamine Agents; Drug Therapy, Combination; Epinephrine; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Modafinil; Norepinephrine; Propylamines