It isIt illegal to post this copyrighted PDF on any website. Park Ave, 8th Fl, New York, NY 10016 NY York, New ([email protected]) Fl, Ave, 8th Park Stephen V. Faraone, PhD York, New York New York, J ClinPsychiatry 82:4,July/August 2021 For [email protected]. reprints orpermissions, contact ♦ e d c b a © Copyright 2021Physicians Postgraduate Press, Inc. To https://doi.org/10.4088/JCP.20m13687 share: Psychiatry JClin ADHD. adult in the treatmentlisdexamfetamine of sluggish comorbid cognitive tempo and cite: To 2021;82(4):20m13687 J ClinPsychiatry Trial Registration: ClinicalTrials.gov NCT02635035 identifier: ADHD. to show stimulant improvement therapy after inadultswith inSCT impairment. deficits, andfunctional function This isthe firststudy improvement LDX after vs placebo inratings ofSCT, ADHD, executive hadsignificantConclusions: Adults withADHD andcomorbid SCT race, were andethnicity seen. Executive Function—Adult Version. Nomoderating effectsofsex, age, of Inventory Behavior Rating Global Executivethe Complex score of without order effects;nosite differences were seenexcept onthe ADHD, executive impairmentratings, deficit, andfunctional function the second. Significant effectswere alsoseenfor LDX over placebo in firsttreatment epochintothe in block1owing to effectsof carryover size ratings inbothtreatmentplacebo (block1effect periods onSCT Results: There were moderately large treatment effectsofLDX vs outcome subscalewere measures. coprimary SCT Scale-IV the otherarm. Adult ADHDRating andBarkley Scale The ADHDRating (mean LDX (30–70 mg/d;mean treatment. witheither treatment Participants received 4weeks of during impairmentatdeficits, baselineandweekly andfunctional centers andassessedfor symptoms ofADHD, SCT, executive function were recruitedDiagnostic v1.2)andSCT Scale at 2academicmedical 2018,38adultswithDSM-5ADHD(viatheAdultApril ADHDClinical arandomized 2016– In crossoverMethods: January conducted trial disorderadults withattention-deficit/hyperactivity (ADHD) andSCT. in placebo onbehavioral attributes ofsluggish cognitive tempo (SCT) Objective: (LDX)Tolisdexamfetamine versus of examine theefficacy Adler, MD A. Lenard and Adult ADHD in theTreatment of Tempo Comorbid Sluggish Cognitive TrialA Placebo-Controlled of Lisdexamfetamine Research Original University, Syracuse, New York New Syracuse, University, Medicine, New York, New York New York, New Medicine, * New York New ABSTRACT Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New New Sinai, Mount at Medicine of School Icahn Psychiatry, of Department Department of Psychiatry, NYU Grossman School of Medicine, New York, York, New Medicine, of School Grossman NYU Psychiatry, of Department Department of Psychology, University, Pennsylvania Drexel Philadelphia, Department Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical Medical Upstate SUNY Sciences, Behavioral and Psychiatry of Department Department of Child and Adolescent Psychiatry, NYU Grossman School of of School Grossman NYU Psychiatry, Adolescent and Child of Department Corresponding author:
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14.8 mg/d)orma week washout before switching to eached significance only tching placebo a ; Taylor Sardoff, BA M. . a,e ; and Jeffrey H. Newcorn, MD H. ; andJeffrey S social, occupational,social, and educational). and in15domains of impairment (including home, ADHD and SCT was significantly more impaired overall impairment with ADHD, seen such that cohort the with had ADHD. Additionally, having to SCTadded the subgroupthis was 5.8%,approximately of half whom the Barkley SCTScale). Barkley the Adult ADHD Rating Scale-IV: (BAARS-IV; Self-Report often on 9-item the from SCTsubscale Barkley the had atif they least 5of 9symptoms rated often or very individuals identified (ADHD), Barkley as having SCT and without attention-deficit/hyperactivity disorder between SCTandbetween quality of life, likely an effect mediated Furthermore, studies have found anegative correlation uniquely associated with learning/organization problems. drowsiness) dimensions, with behavioral the dimension cognitive (ie, daydreaming) and behavioral (ie, slowness, SCT sy quickly/accurately. slowbeing moving; and (9)not processing information underactive/havingbeing than less others; energy (8) afog;spacey/in (6)frequently feeling lethargic; (7) bored; easily (4)being confused; easily being (5)feeling trouble staying alert/awake inboring situations; (3) (2) prone to daydreaming, instead of concentrating; (1) has 9cardinal identified Barkley symptoms of SCT: and undermotivated often seem and underaroused. moving, hypoactive, have initiating difficulty tasks, et al, to individuals with ADHD. In ameta-analysis by Becker community sample, but SCTis not necessarily restricted impairing inalarge subgroup of adults with ADHD ina studythis suggest that SCTmay present be and highly SCT inchildren with ADHD-combined type. and adults. studies Other have found elevated levels of hyperactive-impulsive symptoms children (HI),inboth with inattentive the (IA) symptoms of ADHD than the 19,000 participants, SCTwas more strongly associated they werethey found also innon-ADHD groups. clinical greatest in youth with ADHD inattentive though type, or learning problems and found that SCT symptoms were children and adolescents for behavioral, emotional, and/ and coworkers evaluated parent and teacher reports in322 © 2021Copyright Physicians Postgraduate Press, Inc. individuals are who “dreamy,” “spacey,” slow luggish cognitive tempo (SCT)describes a 3 ; Beth Krone, PhD ; Beth considering 23 independent studies including mptoms have thought been to separate into 1 In astudy of 1,249individuals with c c ; 2 The prevalence of SCT in 2 The results of 4,5 Garner e1 6 You are prohibited from making this PDF publicly available. influence changes in SCTscores. controlling for changes inADHD scores didnot significantly study (Froehlich etal Adler etal the responsethe for core ADHD symptoms. found that response the for SCTbehaviors was lower than of methylphenidatetrial inchildren with ADHD and SCT for effective be symptoms of inattention to linked SCT. One of youth with ADHD-IA and didnot medication the find to children with ADHD, dyslexia, and ADHD norepinephrine reuptake inhibitor, versus in placebo methylphenidate response in teacher ratings of ADHD. children (n month of open-label methylphenidate treatment response in pretreatment ADHD among severity other variables on 1 e2 For [email protected]. reprints orpermissions, contact ♦ (EF). by adverse the consequences of SCTon executive function treatment response. to ADHD, with distinct underlying pathophysiology and SCT might aclinically meaningfulcondition be not restricted absenceSCT inthe of ADHD, current the is that thinking community samples of adults and children have found high and SCTsymptoms were unrelated to EF. As recent studies in with EFdeficits inbehavioral regulation, ADHD-IA while ratings of EF. ADHD-HI symptoms were strongly associated ADHD and SCTsymptoms were correlated highly with ratings for 52 adolescents with ADHD and found that et al to date have on children, focused rather than adults. Milich forneed appropriate identification and treatment. inquired about evaluation,clinical in the highlighting the not driver of aprimary treatment clinical and is often not prevalent and associated with substantial impairment, it is not. Finally, Firat etal methylphenidate nonresponse, daydreaming while was attributes—eg, sluggish and sleepy—were associated with from that of SCTbehavioral ADHD subtype. Certain moderating of SCTon effect medication response is distinct long methylphenidate acting and, specifically, the whether attributes rated by teachers moderate response dose the to ylxa group. ADHD +dyslexia groups,in all with most the significant change inthe found that atomoxetine reduced SCT behavioral attributes al, response ratings. in both results the Like of Froehlich et age positively methylphenidate-SCT the affected treatment ADHD-HI and SCTscores after decreased treatment. Older It isIt illegal to post this copyrighted PDF on any website. ■ ■ 12 A study of atomoxetine, anonstimulant selective The few treatment studies of SCT in patients with ADHD ■ ■ increased SCTscores were associated with decreased 10 treatment optionfor adultswithADHDandSCT. Clinicians could consider lisdexamfetamine asapotential accepted treatments. inadultswithADHDiscomplex, andthere are no (SCT) Recognizing thesymptoms ofsluggish cognitive tempo
7
investigated of use the methylphenidate for treatment Becker and Becker Langberg = 185); they found185); they that parent- and teacher-rated Clinical PointsClinical 1,4,9 12 ) examined SCTbehavioral whether 13 Ofnote, although SCTis highly 14 assessed the effects of SCTand effects the assessed Post analyses that hoc revealed 8 assessed parent assessed and teacher 11 Amore recent + dyslexia with ADHD. class to have largest the of treatments all effect for adults recent meta-analysis showed amphetamine the stimulant with SCTand ADHD. This important is particularly as a no treatment of amphetamines trials inchildren or adults treatment of SCT in adults with ADHD, and there have been in executive Impairment function. was by determined a T with SCTmust have had clinically significant impairment symptom score of 26 or higher. Additionally, group the rated clinically significantSCT Scale and atotal SCT SCT was required to have 5 or more items on Barkley the Functional Impairment (BFIS). The subgroup Scale with Barkley impairment,the on norms the based determined of (ACDS)Scale v1.2;and (3)demonstrated significant AdultADHD via as diagnosed Diagnostic ADHD Clinical for diagnosis of a primary inattentive or combined type ages the between of 18 and 60years; (2)met DSM-5 criteria andExclusionInclusion Criteria treatmentthe period. end of wasweek maintained highestdose 3, the effective until the to aminimum of 30mg/d and maximum of 70mg/d. After or during decreased weeks 2and 3by 20-mg/d increments responseclinical and were adverse doses effects, increased ofstarting dose on 30mg/d. weekly Based assessments of week of atreatment LDX period, or was placebo given at a over during second the treatment phase. first the During receive either oral LDX or matching before placebo crossing firstthe treatment subjects were period, randomized to intervening 2-week single-blind washout. placebo During blind treatment consisting periods of 4weeks eachand an Study Design SCT behavioral indicators inadults with ADHD and SCT. of LDX on nature the and of severity ADHD symptoms and study is tothis determine placebo.efficacy the The of goal phase were recruited into crossover this of LDX trial versus Sinai ADHD had who both and phenotypic SCTinthe ofSchool Medicine and Icahn of School Medicine at Mount study—the treatment phase. Subjects at NYUGrossman of inattentive symptoms and impairment. ADHD, versus adults with ADHD alone, have levels higher above in children and adults, individuals SCT andwith both inthatseen study found that, similar to prior studies noted were SCTnegative. hadwho ADHD and SCTversus had who ADHD and those characterized SCT, ADHD, and EFsymptoms insubjects ofSchool Medicine at Mount Sinai). The phenotypic phase centers (NYU Grossman of School Medicine and Icahn treatment) examination of SCTand ADHD at 2academic METHODS No treatment have conducted trials been investigating Inclusion criteria were as follows: (1)man or woman This was a10-week crossover with 2double- trial, We are now reportingthis data from second the phase of The current study of is apart a2-phase (phenotypic and © 2021Copyright Physicians Postgraduate Press, Inc. 15,16 17 An interim J ClinPsychiatry 82:4,July/August 2021 17 report of the NYUcohort the report of
You are prohibited from making this PDF publicly available. changes insymptom and severity impairment. functional SCT,Barkley and were BFIS scales repeated to assess overall At end the of eachtreatment ADHD-RS, BRIEF-A, period, clinician judgment regarding symptoms and adverse events. Any adjustment to medication dosage using was decided on aweekly basis with ADHD-RS and SCTscales. Barkley treatment During S) scale. symptoms periods, were rated BFIS,the and Global Impression-Severity Clinical the (CGI- and impairment functional was measured BRIEF-A, the via symptom SCTscale, Barkley the via was assessed severity ADHD-RS the via withassessed adult prompts, baselineSCT 2-week washout, placebo measures baseline of ADHD were self-reported. and psychiatric histories, as well as demographics, were Columbia-Suicidevia Medical Rating Scale. Severity disorders MINIv7.0;suicidality the was via assessed at ACDS the via baseline v1.2,and comorbid psychiatric Assessments was conductedThe trial January 2016through April 2018. registered at ClinicalTrials.gov NCT02635035 ). (identifier: Medicine and Icahn of School Medicine at Mount Sinai and ofBoards New York University Grossman of School LDX for ADHD. participant’s and (8)had previously safety; treated been with person from participating study in the or compromise the investigator,that,the opinion in the of would prevent the contextual issues (including of ahistory disorders) sleep toxicology screen at (7)had baseline; any other or clinical planning to become pregnant; (6)had apositive drug urine MINI;(5)were the as per pregnant, breast-feeding, or bipolar disorder or anylifetime of history psychotic disorder ideationsuicidal or of a history suicide attempts; (4) had a that required pharmacotherapy treatment; (3)had current International Neuropsychiatric Interview(MINI)v7.0, other current psychiatric disorder, Mini the via determined ACDS the ADHD via astype diagnosed v1.2;(2)had any hyperactive-impulsivecriteria for diagnosis of aprimary BRIEF-A. than 65 on Metacognition less the the T score Index of of with atotal symptom than 26,inadditionless to a score of than 5clinically significant items SCTScale on Barkley the executive The function. subgroup without SCThad fewer Adult Version (BRIEF-A), aself-reported rating of scale Behavior Rating Inventorythe of of Executive Function— score of 65 or on higher Metacognition the Index subscale J ClinPsychiatry 82:4,July/August 2021 For [email protected]. reprints orpermissions, contact ♦ in adultused ADHD studies. ACDS v1.2, widely a semistructured diagnostic interview in adult ADHD studies. to widely evaluatehas used been psychiatric comorbidity to assess used DSM-5interview psychiatric disorders and It isIt illegal to post this copyrighted PDF on any website. MINI v7.0. Prior to first treatment the the and at period end the of Study participants’ ADHD were diagnoses confirmed The study was approved by Institutional the Review Participants (1)met DSM-5 they were excluded if ACDS v1.2.ADHD diagnosis was evaluated with the The MINIv7.0 20,21 22,23 18,19 The clinical interview The interview clinical is astructured clinical
ADHD Rating Scale below). (see alongtrial, with total the score onSCTscale Barkley the total score, is which coprimaryoutcome the measure inthis IA and are HIsubscales to added obtain ADHD-RS the reported as hyperactive-impulsive the The (HI)subscale. hyperactive-impulsive symptoms are summed and also and reported as inattentive the (IA), subscale and 9 the 3 be calculated to calculated quantifybe impairment. using (0 a4-point scale Likert to ensure adequate probing of symptoms; items are rated lastthe rating). Adult prompts interview were incorporated to 2weeks during (and treatment the trial inthis phase, since to measureinterview ADHD symptom last inthe 1 severity written for EFDand the EDitems. DSM-5 items, developmentally relevant prompts have been lability, irritability, and emotional overreactivity. As with the (ED; 4items). EDincludes behavioral descriptors of mood deficitsfunction (EFDs; 9items) and emotional dyscontrol additional prompts 16clinical intended to assess executive as 3(moderate), 1(never),severity 2(mild), or 4(severe). on participant responses, clinician the rates symptom the ADHD present as they and adulthood. inchildhood Based stem questions to designed capture DSM includesThe scale developmentally relevant prompts and year) symptoms, including DSM-5 all ADHD and probes then an of expanded set recent (past with anbegins assessment symptoms of childhood of Function—Adult Version study criterion requiring atotal score of at least 26. more items rated “often” often,” or “very with an additional item).each Subjects with SCTwere required to have 5or latterthe two cutoff the being for for significance clinical rarely,”2 =“sometimes,” 3 =“often,” often,” 4 =“very with and symptoms scored on a 4-point rating (1 scale interactions) using a10-point scale. Likert different major life completing (eg, activities chores, social measures self-perceived,Scale current impairment in15 function. significantclinically behavioral impairment inexecutive severity.describe AT havesubscales standardized, been and Tscores are to used of executive The GEC,BRI, function. MI,and individual Complex as (GEC)score. ageneral measure The GECserves 2 indices, combined, when Executive Global yield the emotionalshift, control, and self-monitor The subscales. Behavioralthe Regulation Index (BRI) is sum the of inhibit, task monitor, and organization of material and subscales, initiate,the working is sum the memory, of plan/organize, deficits of executive function. The Metacognition Index (MI) to designed measure subscales clinical various and aspects = The SCT subscale of the Barkley Adult Barkley the of SCTscale. The SCTsubscale Barkley ADHD-RS. The ACDS expanded to include v1.2has been an BRIEF-A. The Behavior Rating Inventory of Executive The Barkley FunctionalBFIS. The Barkley Impairment Rating severe). The 9inattentive and symptoms are summed Lisdexamfetamine for Sluggish Cognitive Tempo andADHD © 2021Copyright Physicians Postgraduate Press, Inc. ADHD-RS 1 is a9-item of self-report SCTbehavioral score of ≥ 25 23,24 is aself-report composed of 9 = is clinical asemistructured none, 1 65 is considered to represent A1 and A2 symptoms. = mild, 2 26 Mean scores can symptoms of symptoms = = moderate, “never or
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You are prohibited from making this PDF publicly available. (GAD; n psychiatric included diagnoses generalized anxiety disorder 34% were and male 66%were female. Comorbid current written informed consent prior to participation. anxiety disorderGAD and (n social Adler etal e4 For [email protected]. reprints orpermissions, contact ♦ (Pearson χ except for proportion a higher of Latino subjects at NYU were no significant demographic differences sites, between ADHD, 66%had combined the while presentation. There subjects had inattentivefourthe percent of presentation of and Icahn of School Medicine at Mount Sinai (n New York University Grossman of School Medicine (n Participants were drawn from centers, medical 2academic subjects were included Figure analyses in the (see 1). violations with treatment on multiple visits; data on 38 1 subject were excluded to significant adherence secondary SCT were recruited to participate study. in this Ratings for Participants (1 ADHD impairmentglobal that a7-point uses rating Likert clinician-rated awidely used scale, CGI-S measure of Abbreviations: NYU age of 34.6 It isIt illegal to post this copyrighted PDF on any website. Figure 1.Study Participant Disposition SCT = Thirty-nine participantsThirty-nine with comorbid ADHD and impairment Overall CGI-S. by assessed was also the normal, 7
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sluggish cognitive tempo. xcluded n 111 Completed SCT assessment Completed SCT otmeetingtreatment phase SCT n 4 phenotype = nr ll en ll ll ca i n clinician discretion n 2 intreatment,participate phase only declinedto inclusion n 44 2 3), obsessive-compulsive disorder (n nal sis ± =6.6087, 10.1 years, and 53%(n = among most the severely patients). ill
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= Didnotreceive allocated eceived allocated Allocated to n intervention .010). Participants had amean inconsistent n 1 reporting xcluded from analysis Analy ed n 8 termination y patient n Discontinued early intervention n 1 Lost to follo up death infamily intervention n 0 intervention n intervention eligi ility n 1 1 eligi ility n 120 Assessed for = = 20) were Caucasian; 1). All subjects gave1). All andomi ed andomi ed n = 15). Thirty- = 1), and 27 = 23) for continuous variables and Pearson χ Data Analysis χ drug effect: χ effect: drug disorder, ADHD =attention-deficit/hyperactivity Abbreviations: a functional impairment ratings P (all for LDX over for placebo total ADHD symptoms, EF, and as LDX Table (see vsplacebo 1).Significant were effects seen and results from 2blocks the were combined and presented For other all measures, no significant order were effects seen, presented separately for 2 treatment the blocks (Figure 2). ratings didnot return to therefore, baseline; SCTresults are LDX and treatment placebo following block 1such that SCT in block 1.Thereboth were significant of carryover effects ES =0.61, 2 block (Figure d] =0.68, size[ES;Cohen 2)(block 1effect of LDX over on placebo SCT ratings treatment in both epochs (15.4) mg/d (P was significantly than higher mean the LDX by dose 7.5 ofdose was placebo 66.6(9.1)mg/d. The mean dose placebo LDX was 59.1(14.8)mg/d, mean the overall while titrated than (n placebo reduced by 1step (20 mg) during treatment with LDX (n 2blocks,the with slightly more subjects having dose their correlations visits. between equations with robust standard errors to account for limited to positive integers. We generalized estimating used our wasmodel chosen because outcome measures were equations and robust standard errors. Anegative binomial negative binomial regression with generalized estimating outcomesvariables. trial Clinical data were analyzed with of the ADHD-RS (IA:the χ sequence effect: of forwere seen LDX also over on placebo IA and HIsubscales RESULTS Sequence effect:χ Figure During Ratings 2.SCT Treatment 2 drug effect block2:χ sluggish cognitive tempo. cognitive =sluggish SCT 1 =1.15, Demographic data were analyzed using regression logistic
Titration patterns of LDX and were placebo similar in ar ley Adult ADHD ating Scale
2 0 20 © 2021Copyright Physicians Postgraduate Press, Inc. 1 P
= 2 2 .28; drug effect: χ effect: .28; drug 1 =9.54, 2 = 1 = loc 1 =7.6, .0037). There were moderately large effects 2). The mean (SD) overall titrated of dose 2 P 1 =2.7, = P P .10), which reached.10), which only significance ≤ J ClinPsychiatry 82:4,July/August 2021
≤ .006; drugeffect block1:χ P 4 Place o ≤ .0001; ES: 0.92; HI: sequence effect: .0001; ES:0.92;HI:sequence effect: .10; effectsize: block1:0.68;2:0.61. Study isit 2 1 =5.32, 1
≤
.05). Significant effects effects Significant .05). 2 Drug 2 a P tests for categorical
≤ loc 2 2 .02; ES: 0.53). No 1 2 =1.04, 1 =7.3, 4 P <.008; P =.008; P =.31; = 5) 5)
You are prohibited from making this PDF publicly available. lost (t significance changes the between intotal ADHD and SCTsymptoms was mediated by changes in BRIEF GECsymptoms. univariate association ADHD between and SCTsymptoms attention-deficit/hyperactivity disorder. ADHD =attention-deficit/hyperactivity Abbreviation: J ClinPsychiatry 82:4,July/August 2021 For [email protected]. reprints orpermissions, contact ♦ significant (t associationthe BRIEF GECand between SCTremained from changes the intotal ADHD and BRIEF GECsymptoms, regression analysis predicting change in SCT symptoms change inSCTsymptoms was 0.49(P change the between inADHD total symptoms and the 2 symptom for sets; LDX the treated group, correlation the and SCTsymptoms, we examined correlations the between block 2:0.91,P =.007). in each blockplacebo (ES—Cohen Figure 3(by block); are significant for effects seen LDX over ADHD-RS total scores are shown for LDX and in placebo moderating of age, effects sex, race, and ethnicity were seen. site differences were except seen on BRIEF the GEC.No a It isIt illegal to post this copyrighted PDF on any website. Sequence effect:χ Figure During 3.ADHDRatings Treatment drug effect block2:χ 0.91.
To examine relationship the changes between inADHD To examine ADHD total symptoms by treatment block, ADHD ating Scale
40 20 0 1 2 33 2 =2.6, 1 =1.6, loc 1 2 1 33 =7.33, =2.6, P P =
= .21; drugeffectblock1:χ 4 P Place o .01). In contrast, association the = P P value Abbreviations: ADHD-RS Lisdexamfetamine Placebo χ Study isit .007; effectsize block1:0.97;2: Treatment (EOT) Table 1.Mean 2 = CGI-S Scale, BRIEF-A Metacognition Index. MI =Metacognition 1 EOT Baseline EOT Baseline .01), which suggests.01), which that the n n n n 1 = Clinical GlobalImpression-Severity, GEC d: block 1: 0.97, 2 = Drug = .003). In amultiple Behavior Rating Inventory ofExecutive Inventory Behavior Rating Function—Adult Version, a ± loc 2
SD Rating Scale Scores Scale SD Rating at andEndof Baseline 2 1 18.5 36.1 29.1 34.4 =6.26, ADHD-RS ≤ = 19.9 .0001 36 38 33 35 ± ± ± ± ADHD Rating Scale, BFIS ADHD Rating 12.8 11.9 14.7 10.2 4 P =.01; P =.01; BRIEF-A (MI) 66.3 79.2 73.6 76.9 ≤ 7.7 .006 36 38 33 35 ± ± ± ± 17.7 11.5 16.7 15.6 commonly reported with stimulants. (LDX: adverse 2.52%).These 4.20%; placebo: events are (LDX: 0.84%),and 7.56%; placebo: anxiety/jitteriness or asleep mouth falling (LDX: 3.36%),dry 10.08%; placebo: headache (LDX: 7.56%),trouble 10.08%;placebo: sleeping were appetite decreased (LDX: 0.00%), 10.92%;placebo: adverse events during LDX both and/or treatments placebo gone through LDX the phase. The most commonly reported subject withdrew during treatment, placebo having already iswhich commonly reported during LDX treatment. This participant withdrew due to an adverse event—anxiety, discontinuation was due to adverse events. Only 1 treatment early during LDX the phase, although neither to moderate in severity. Two participants discontinued events were reported. Adverse events reported were mild Safety SCT ratings tofailed return to for baseline treatments both block 1.In addition, there were and carryover effects, also in block 1than block 2that limited statistical to significance however, an order with larger was seen effects effect placebo present treatment inboth with epochs, amoderately large ES; treatedwhen with LDX vsplacebo. The SCTfindings were improved in ratings of SCT, ADHD, EF, and impairment pulse: χ BP: χ BP: −2.2bpmplacebo: (11.4). (Changes over treatment: systolic Hg (9.8).Mean changes for pulsewere LDX: 6.7bpm (11.6); diastolic BP were LDX: 4.3mmHg −6.6 mm (8.5);placebo: Hg −5mmHg (13.8);placebo: (12.8).Mean changes for treatment) for systolicof BP (SD) were LDX: −1.2mm throughout study. the The mean changes to (baseline end pulse (beats/min [bpm]) LDX inthe and groups placebo in systolic and diastolic pressure blood (BP) (mmHg) and study.the There were minor, insignificant clinically changes no reporting of suicidality or ideation suicidal throughout DISCUSSION = Overall, LDXOverall, was well tolerated, and no serious adverse Adults with comorbid ADHD and SCTsignificantly = Global Executive Complex, BRIEF-A (GEC) Lisdexamfetamine for Sluggish Cognitive Tempo andADHD Barkley Functional Barkley Impairment 62.9 76.5 70.7 75.4 2 © 2021Copyright Physicians Postgraduate Press, Inc. ≤ 1 =3.93, 7.9 2 .005 36 38 33 35 ± ± ± ± 1 =11.91, 18.1 12.4 16.6 13.3 P BFIS (MI) 3.9 5.7 4.8 5.4
≤ ≤ P ≤.001.) 5.8 .016 36 37 33 35 .05; diastolic BP: χ ± ± ± ± 2.3 1.6 2.1 1.6 3.1 4.6 4.3 4.6 ≤ CGI-S 15.1 .0001 36 38 33 35 ± ± ± ± 1.2 1 1.1 0.7 28 Moreover, there was 2 1 =13.78, P ≤.001;
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You are prohibited from making this PDF publicly available. Adler etal e6 For [email protected]. reprints orpermissions, contact ♦ continuing education and/or support, research expenses, travel income, potential income, and Dr materials. training Faraone scales ADHD adult of license for NYU from 2004 since (as inventor) payments royalty received has and Baseball; League Major and League, Football SUNY, National the Pharmaceuticals, Otsuka Pharmaceuticals, Shire/Takeda Pharmaceuticals, Sunovion Bracket, to aconsultant as served has and Lundbeck; Pharmaceuticals, Otsuka, Shire/Takeda Enzymotec, Pharmaceuticals, Sunovion from support grant/research received has Adler Dr interest: of conflicts Potential Published online: 15, 2021. Submitted: However, examine to it fully potential is difficult moderating two constructs. the distinctivenesssuggesting partial of potentially accounted be for by changes inADHD ratings— of LDX effect the onthat SCTratings one-fourth can of be methylphenidate or atomoxetine. As noted above, we found on SCTbehavioral attributes inchildren treated with moderating of effects ADHD symptoms, or lack thereof, inprior of seen LDX trials like those inadult ADHD. pulse, along with other the adverse events were we observed, butsmall nonsignificant pressure increases inblood and to up-titrationled higher group. placebo inthe Finally, the titrateclinically and dose, the response smaller the to placebo of versus placebo LDX is not surprising, as clinicians could inpatientsspecifically with ADHD and EFD. to that inother studies seen of LDX inadult ADHD, and in adults trial within this ADHD and SCT is quite similar ratings only reached inblock 1. significance in block 2.Consequently, group differences inADHD with ADHD and SCT. treatment strategy to optimize symptom reduction in adults such whether acombinationseen an would be effective also pharmacotherapy inadults with ADHD, it remains to be to cognitive behavioral therapy incombination with treatment. As EFDs have shown been responsive to be response of ADHD, SCT, and EFD symptoms throughout patients with ADHD, and monitor to also potential the assessing for presence the of SCTand EFDat in baseline medications. findings importance highlight the These of response of ADHD and SCTsymptoms to LDX and other mechanisms (such as EFD)may moderate or mediate the possibility that different patient characteristics and/or not simply another measure of ADHD and suggests the in EFDscores. This provides that evidence SCTis further ADHDbetween and SCTscores may driven be by changes analysis presented above suggests that relationship the correlated, variance; regression the their sharing 24% of change scores for of two the ratings types were only modestly ADHD symptoms and SCTratings, to baseline endpoint the SCT. Although we found moderate to large ESs for both of LDXextends efficacy the to subjects with ADHD and It isIt illegal to post this copyrighted PDF on any website. Several studies described above studies have described Several examined potential The finding of but asmall dose significantly final higher The magnitude of of LDX effects on ADHD symptoms
September 11, March September 2020; accepted June 29, 2021. June 29,30 has received received has Takeda, and Supernus. He was a data and safety safety and adata was He Supernus. Takeda, and Shire/ Rhodes, OnDosis, NLS, Neuroscience, Eisai, Myriad Ironshore, Medice, Therapeutics, Cingulate Arbor, Interactive, Akili Therapeutics, Adlon for consultant and/or advisor an been has www.adhdinadults.com of Director Pharmacologic Interventions. ADHD: Non- Elsevier: and Facts; The Schizophrenia: Your Child’s Mental Health Talk Straight about Press: Guilford by published books from royalties receives also He ADHD. of hydrogen exchange inhibitors in the treatment US20130217707patent sodium- A1 of use the for US has he institution, his With Vallon. Tris, and Rhodes, Shire/Takeda, Sunovion, Supernus, Arbor, Genomind, Ironshore, Ondosis, Otsuka, fromsupport Akili Interactive Laboratories, 17 This study 31 ; Oxford University Press: Press: University ; Oxford He is also Program Program also is He effects. versus mixed amphetamine salts didnot such carryover see or SCT. However, a prior crossover study design of LDX crossover and are trial of design to ADHD not trials specific of note. Such are carryover effects apotential liability of any not is return 1drug fully to after baseline block washout of LDXboth and treated placebo subjects such that ratings did symptoms. Furthermore, finding the of an order in effect inadditionSCT scale to standard the threshold of symptoms by requiring atotal score of BRIEF, and toward also having more significant SCT requirementthe for having a significant MI cutoff on the weightedspecifically our sample toward having EFD with treatments remains apotential line of investigation. in other conditions or as stand-alone disorder to ADHD for Additionally, carryover effect. responsiveness the of SCT conductedbe with designs parallel to mitigate any potential mitigating of EFDsymptoms effects on response and should ADHD and SCT. Future should examine trials potential of stimulants on SCTbehavioral attributes inadults with issues may fociof the future investigations. conducting study, this may have results. the affected These or receiving treatment center, at atertiary such as those to enrollmentwhich in prior adult ADHD treatment trials SCT and EFDsymptoms. Nor could we evaluate extent the samplethe with enrichment of the to of potential effects were as large twice as on HIsymptoms, might which due be treatment however, effect; treatment on effects IA symptoms of ADHDeffects subtype or symptom subsets on LDX the was not large enough examine to fully potential differential for LDX over treatment inboth placebo sample Our epochs. diagnosis (dyslexia) (McBurnett etal control group (Firat and coworkers (teacher/parent/SCT (4) absence of scale), a placebo (3) differences rating inthe instrument or raters used the of amphetamine versus methylphenidate or atomoxetine, duebe to (1)our studying adults, (2)our studying effects examined potential moderating factors in children could Differences study infindings inthis from studies those that our as all subjects had inour ADHD trial andeffects SCT. McBurnett and colleagues Several additional caveatsSeveral should noted. be We In summary, is first this the study to treatment find effects . Dr Newcorn © 2021Copyright Physicians Postgraduate Press, Inc. 32 Nevertheless, moderate to large were effects seen
presented in part as a poster at the Annual Annual the at aposter as part in presented Previous presentation: data. of analysis and collection the for paid sponsor:the Role of investigator) Shire/Takeda from Pharmaceuticals. investigator-initiated grant (Dr Adler, principal Funding/support: article. this of subject the to relevant interest of conflicts Dr Krone National Football League. Mss Leon US the for aconsultant as served and presentations disease-state for Shire/Takeda from fees speaker received has also He Supernus. and Shire/Takeda, Otsuka, Adlon, from funds research received and monitoring board member for Pfizer and Sunovion J ClinPsychiatry 82:4,July/August 2021 14 ) and (5)inclusion of a comorbid , and Mr Silverstein Supported in part by an an by part in Supported 13 Shire/Takeda Pharmaceuticals and SCTcohort the in 14 The data were previously previously were data The ). ≥ 26 on the Barkley 26 on Barkley the report no potential potential no report and Sardoff ≥ 5/9 ,
You are prohibited from making this PDF publicly available. 10 J ClinPsychiatry 82:4,July/August 2021 For [email protected]. reprints orpermissions, contact ♦ 9. 8. 7. 6. 5. 4. 3 2. 1. declare. to interests of conflict no have Jiang Mr and Kahan and Chan Mss York. New York, New Medicine, of School Grossman NYU from all manuscript, the of preparation the in and data the of examination the in assistance their for Chan, BS; Joshua Jiang, BA; and Tamara BA, Kahan, Acknowledgments: Washington, DC. 17–19, January Disorders; 2020; Related and ADHD of Society Professional American the of Meeting REFERENCES It isIt illegal to post this copyrighted PDF on any website. . .
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