Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib in Humans

Background Numerous experimental and clinical studies suggest that brief opioid exposure can enhance pain sensitivity. It is suggested that spinal cyclooxygenase activity may contribute to the development and expression of opioid tolerance. The aim of the investigation was to determine analgesic and antihyperalgesic properties of the cyclooxygenase-2 inhibitor parecoxib on remifentanil-induced hypersensitivity in humans. Methods Fifteen healthy male volunteers were enrolled in this randomized, double-blind, placebo-controlled study in a crossover design. Transcutaneous electrical stimulation at high current densities was used to induce spontaneous acute pain (numeric rating scale 6 of 10) and stable areas of pinprick hyperalgesia. Pain intensities and areas of hyperalgesia were assessed before, during, and after a 30-min intravenous infusion of remifentanil (0.1 microg x kg x min) or placebo (saline). Parecoxib (40 mg) was administered intravenously either with onset of electrical stimulation (preventive) or in parallel to the remifentanil infusion. Results Remifentanil reduced pain and mechanical hyperalgesia during the infusion, but upon withdrawal, pain and hyperalgesia increased significantly above control level. Preventive administration of parecoxib led to an amplification of remifentanil-induced antinociceptive effects during the infusion (71.3 +/- 7 vs. 46.4 +/- 17% of control) and significantly diminished the hyperalgesic response after withdrawal. In contrast, parallel administration of parecoxib did not show any modulatory effects on remifentanil-induced hyperalgesia. Conclusion The results confirm clinically relevant interaction of mu opioids and prostaglandins in humans. Adequate timing seems to be of particular importance for the antihyperalgesic effect of cyclooxygenase-2 inhibitors.

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Effect of Nefopam-Based Patient-Controlled Analgesia with and without Fentanyl on Postoperative Pain Intensity in Patients Following Laparoscopic Cholecystectomy: A Prospective, Randomized, Controlled, Double-Blind Non-Inferiority Trial

Medicina ◽

10.3390/medicina57040316 ◽

2021 ◽

Vol 57 (4) ◽

pp. 316

Author(s):

Ki Tae Jung ◽

Keum Young So ◽

Seung Chul Kim ◽

Sang Hun Kim

Keyword(s):

Laparoscopic Cholecystectomy ◽

Adverse Effects ◽

Rating Scale ◽

Analgesic Efficacy ◽

Numeric Rating Scale ◽

Controlled Study ◽

Patient Controlled Analgesia ◽

Double Blind ◽

Randomized Controlled ◽

Lockout Interval

Background and Objectives: We investigated the non-inferiority of patient-controlled analgesia (PCA), using either nefopam alone or combined nefopam-fentanyl for postoperative analgesia in patients undergoing laparoscopic cholecystectomy. Materials and Methods: In this prospective, randomized, controlled study, 78 patients were allocated to receive nefopam 240 mg (Group N240) or nefopam 120 mg with fentanyl 600 μg (Group NF), equivalent to fentanyl 1200 μg, with a total PCA volume of 120 mL. Patients were given a loading dose (0.1 mL/kg) from the PCA device along with ramosetron (0.3 mg) and connected to a PCA device with a background infusion rate of 2 mL/h, bolus dose amount set at 2 mL, and lockout interval set at 15 min. Pain scores were obtained using the numeric rating scale (NRS) at 30 min after recovery room (RR) admission, as well as 8 and 24 h postoperatively. The primary outcome was analgesic efficacy evaluated using NRS-rated 8 h postoperatively. Other evaluated outcomes included the incidence rate of bolus demand, rescue analgesic and antiemetic requirements, and postoperative adverse effects. Results: NRS scores were not significantly different between the groups throughout the postoperative period (p = 0.539). NRS scores of group N240 were not inferior to those of group NF at 30 min after RR admission, or at 8 and 24 h postoperatively (mean difference [95% CI], −0.05 [−0.73 to 0.63], 0.10 [−0.29 to 0.50], and 0.28 [−0.06 to 0.62], respectively). Postoperative adverse effects were not significantly different between the two groups (p = 1.000) and other outcomes were also not significantly different between the two groups (p ≥ 0.225). Conclusions: PCA using nefopam alone has a non-inferior and effective analgesic efficacy and produces a lower incidence of postoperative adverse effects compared to a combination of fentanyl and nefopam after laparoscopic cholecystectomy.

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A Double-Blind, Randomized, Active-Controlled Study for Post-Hemorrhoidectomy Pain Management with Liposome Bupivacaine, a Novel Local Analgesic Formulation

The American Surgeon ◽

10.1177/000313481207800540 ◽

2012 ◽

Vol 78 (5) ◽

pp. 574-581 ◽

Cited By ~ 73

Author(s):

Eric Haas ◽

Erol Onel ◽

Howard Miller ◽

Madhu Ragupathi ◽

Paul F. White

Keyword(s):

Rating Scale ◽

Area Under The Curve ◽

Numeric Rating Scale ◽

Controlled Study ◽

Opioid Use ◽

Double Blind ◽

Local Infiltration ◽

Pain Scores ◽

Liposome Bupivacaine ◽

Post Hoc

This randomized, active-controlled study evaluated the extent and duration of analgesia after administration of liposome bupivacaine (LB), a novel formulation of bupivacaine, compared with bupivacaine HCl given via local infiltration in excisional hemorrhoidectomy. One hundred patients were randomly assigned to receive a single dose of bupivacaine HCl 75 mg (0.25% with 1:200,000 epinephrine) or LB 66, 199, or 266 mg upon completion of hemorrhoidectomy. Postoperative pain intensity was assessed using a numeric rating scale at rest to calculate a cumulative pain score (area under the curve). Cumulative pain scores were significantly lower with LB at each study dose ( P < 0.05) compared with bupivacaine HCl 72 hours after surgery. Post hoc analysis showed that mean total postoperative opioid consumption was statistically significantly lower for the LB 266-mg group compared with the bupivacaine HCl group during the 12- to 72-hour postoperative period ( P = 0.019). Median time to first opioid use was 19 hours for LB 266 mg versus 8 hours for bupivacaine HCl ( P = 0.005). Incidence of opioid-related adverse events was 4 per cent for LB 266 mg compared with 35 per cent for bupivacaine HCl ( P = 0.007). Local infiltration with LB resulted in significantly reduced postsurgical pain compared with bupivacaine HCl in patients after hemorrhoidectomy surgery.

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Ultrasound-Guided Injection of Dextrose Versus Corticosteroid in Chronic Plantar Fasciitis Management: A Randomized, Double-Blind Clinical Trial

Foot & Ankle Specialist ◽

10.1177/1938640020980924 ◽

2021 ◽

pp. 193864002098092

Author(s):

Gholamreza Raissi ◽

Amin Arbabi ◽

Maryam Rafiei ◽

Bijan Forogh ◽

Arash Babaei-Ghazani ◽

...

Keyword(s):

Clinical Trial ◽

Plantar Fasciitis ◽

Rating Scale ◽

Corticosteroid Injection ◽

Treatment Options ◽

Plantar Fascia ◽

Numeric Rating Scale ◽

Therapeutic Effects ◽

Ultrasound Guided ◽

Double Blind

Design Chronic plantar fasciitis (PF) is a common cause of chronic heel pain, with different conventional treatment options. In this randomized clinical trial, the effect of ultrasound-guided injection of dextrose versus corticosteroid in chronic PF was evaluated and compared. Methods A total of 44 patients suffering from chronic PF who visited the physical medicine and rehabilitation clinic were enrolled in the study. Two table-randomized groups were formed. They received an ultrasonography-guided, single injection of either 40 mg methylprednisolone or 20% dextrose. Numeric Rating Scale (NRS), Foot and Ankle Ability Measure questionnaire with 2 subscales, Activities of Daily Living (FAAM-A) and Sports (FAAM-S), along with ultrasonographic parameters were evaluated before and at 2 and 12 weeks after the injection. Results. A total of 40 participants completed the study. Both interventions significantly improved pain and function at 2 and 12 weeks postinjection. After 2 weeks, compared with the dextrose prolotherapy, the corticosteroid group had significantly lower daytime and morning NRS scores (2.55 vs 4.1, P = .012, and 2.75 vs 4.65, P = .004), higher FAAM-S (66.84 vs 54.19; P = .047), and lower plantar fascia thickness at insertion and 1 cm distal to the insertion zone (3.89 vs 4.29 mm, P = .004, and 3.13 vs 3.48 mm, P = .002), whereas FAAM-A was similar in both groups ( P = .219). After 12 weeks, all study variables were statistically similar between corticosteroid and dextrose prolotherapy groups. No injection-related side effects were recorded in either group. Conclusion Both methods are effective. Compared with dextrose prolotherapy, our results show that corticosteroid injection may have superior therapeutic effects early after injection, accompanied by a similar outcome at 12 weeks postinjection. Levels of Evidence: Level II

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Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

International Journal of Bipolar Disorders ◽

10.1186/s40345-019-0155-y ◽

2019 ◽

Vol 7 (1) ◽

Author(s):

Maximilian Pilhatsch ◽

Thomas J Stamm ◽

Petra Stahl ◽

Ute Lewitzka ◽

Anne Berghöfer ◽

...

Keyword(s):

Bipolar Disorder ◽

Rating Scale ◽

Bipolar Depression ◽

Phenotypic Expression ◽

Anxiety Symptoms ◽

Controlled Study ◽

Double Blind ◽

Comorbid Anxiety ◽

Depressed Patients ◽

Depressive Episodes

Abstract Background Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Methods Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Results Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). Conclusions This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

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Oral paracetamol versus zolmitriptan to treat acute migraine attack in the emergency department

10.22514/sv.2021.040 ◽

2021 ◽

Keyword(s):

Emergency Department ◽

Rating Scale ◽

Rescue Therapy ◽

Tertiary Care ◽

Numeric Rating Scale ◽

Controlled Study ◽

Care Hospital ◽

Acute Migraine ◽

Pain Scores ◽

Significant Difference

Background: Treatment provided in an emergency department is aimed at alleviating pain immediately with minimized adverse effects as well as warding off further migraine attacks. The primary aim of this article is to compare the effectiveness of oral paracetamol versus zolmitriptan in treating acute migraine attacks. Methods: This prospective, randomized, and controlled study was carried out at a tertiary care hospital visited by 95,000 patients annually. The study recruited 200 participants who were randomized into two groups. One group received 1000 mg paracetamol while the other group received 2.5 mg zolmitriptan orally. Baseline pain scores were recorded using the Visual Analogue Scale (VAS) and Numeric Rating Scale (NRS) at 15, 30 and at 60 min following administration of the study drugs. Patients requiring further treatment were provided fentanyl at a dosage of 1 µg/kg as a rescue therapy. Results: A significant decrease was evident in VAS and NRS scores following the administration of the study drugs in both groups (P < 0.001). The change in VAS pain scores after 15, 30 and 60 min was calculated as 17.0 ± 13.9, 41.2 ± 16.3 and 61.2 ± 17.5 mm, respectively, in the paracetamol group and 14.2 ± 11.7, 39.2 ± 17.9 and 59.2± 19.3 mm, respectively, in the zolmitriptan group, which did not indicate significant differences (P = 0.103, P = 0.425, P = 0.483, respectively). Likewise, NRS pain scores showed a downward trend in line with VAS pain scores and did not yield a significant difference (P = 0.422). No significant difference concerning rescue therapy was noted between the two groups (P = 0.596). Conclusion: Oral paracetamol and zolmitriptan prove to be similarly effective and have low incidence of acute side effects in treating acute migraine cases without aura.

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Assessment of Acupuncture and Moxibustion Effects on the Electrophysiological Properties of the Ulnar Nerve: A Nerve Conduction Study

Integrative Medicine International ◽

10.1159/000490176 ◽

2018 ◽

Vol 4 (3-4) ◽

pp. 198-207 ◽

Cited By ~ 2

Author(s):

Sónia Chan ◽

Sérgio Ferreira ◽

Bruno Ramos ◽

Maria João Santos ◽

Luís Carlos Matos ◽

...

Keyword(s):

Electrical Stimulation ◽

Ulnar Nerve ◽

Rating Scale ◽

Intervention Group ◽

Maximum Amplitude ◽

Numeric Rating Scale ◽

Control Group ◽

Reaction Velocity ◽

Electrophysiological Properties ◽

Acupuncture And Moxibustion

Background/Aims: Acupuncture and moxibustion, when used together, have act mechanically and thermally on treated reflexological areas. The main goal of this work was to evaluate the effects of acupuncture and moxibustion on the electrophysiological properties of the ulnar nerve. Methods: Electrical stimulation was applied to the ulnar nerve above the epicondyle of 28 volunteers. A 20-V potential was applied, and after each 10 impulses it was increased by 10 V, up to a maximum of 80 V. At 20 and 80 V, the participants were asked to rate the discomfort from 0 to 10 on a Numeric Rating Scale for pain. After the first stimulation and data collection, the control group rested for 6 min, while the intervention group was submitted to acupuncture and moxibustion on Lingdao (HT 4). Following this period of time, a second electrical stimulation was performed on both groups. Results: The discomfort was greater in the intervention group during the second stimulation. The stimulus required to achieve the maximum amplitude decreased, but the changes were only statistically significant in the intervention group (p = 0.006). An increase in latency and a decrease in reaction velocity were noticed between the first and the second stimulation for both groups; however, only the control group presented statistically significant differences (p = 0.018 and p = 0.022, respectively). Conclusions: Acupuncture and moxibustion on HT 4 increased the electrical sensitivity, decreased the stimulus intensity to achieve the maximum amplitude, and avoided a significant increase in latency and decrease in reaction velocity in two consecutive electrical stimulations.

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Perioperative pregabalin for reducing pain, analgesic consumption, and anxiety and enhancing sleep quality in elective neurosurgical patients: a prospective, randomized, double-blind, and controlled clinical study

Journal of Neurosurgery ◽

10.3171/2015.10.jns151516 ◽

2016 ◽

Vol 125 (6) ◽

pp. 1513-1522 ◽

Cited By ~ 22

Author(s):

Nir Shimony ◽

Uri Amit ◽

Bella Minz ◽

Rachel Grossman ◽

Marc A. Dany ◽

...

Keyword(s):

Postoperative Pain ◽

Sleep Quality ◽

Rating Scale ◽

Preoperative Anxiety ◽

Controlled Study ◽

Double Blind ◽

Analgesic Consumption ◽

Pain Scores ◽

Neurosurgical Patients ◽

Duration Of Surgery

OBJECTIVE The aim of this study was to assess in-hospital (immediate) postoperative pain scores and analgesic consumption (primary goals) and preoperative anxiety and sleep quality (secondary goals) in patients who underwent craniotomy and were treated with pregabalin (PGL). Whenever possible, out-of-hospital pain scores and analgesics usage data were obtained as well. METHODS This prospective, randomized, double-blind and controlled study was conducted in consenting patients who underwent elective craniotomy for brain tumor resection at Tel Aviv Medical Center between 2012 and 2014. Patients received either 150 mg PGL (n = 50) or 500 mg starch (placebo; n = 50) on the evening before surgery, 1.5 hours before surgery, and twice daily for 72 hours following surgery. All patients spent the night before surgery in the hospital, and no other premedication was administered. Opioids and nonsteroidal antiinflammatory drugs were used for pain, which was self-rated by means of a numerical rating scale (score range 0–10). RESULTS Eighty-eight patients completed the study. Data on the American Society of Anesthesiologists class, age, body weight, duration of surgery, and intraoperative drugs were similar for both groups. The pain scores during postoperative Days 0 to 2 were significantly lower in the PGL group than in the placebo group (p < 0.01). Analgesic consumption was also lower in the PGL group, both immediately and 1 month after surgery. There were fewer requests for antiemetics in the PGL group, and the rate of postoperative nausea and vomiting was lower. The preoperative anxiety level and the quality of sleep were significantly better in the PGL group (p < 0.01). There were no PGL-associated major adverse events. CONCLUSIONS Perioperative use of twice-daily 150 mg pregabalin attenuates preoperative anxiety, improves sleep quality, and reduces postoperative pain scores and analgesic usage without increasing the rate of adverse effects. Clinical trial registration no.: NCT01612832 (clinicaltrials.gov)

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A double-blind randomized placebo-controlled study of low dose mirtazapine once daily in patients of major depressive disorders on escitalopram

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20191602 ◽

2019 ◽

Vol 8 (5) ◽

pp. 1067

Author(s):

Mallikarjuna Rao I. ◽

Usha Kiran Prayaga ◽

Dharma Rao Uppada ◽

Ramachandra Rao E. ◽

B. L. Kudagi

Keyword(s):

Depressive Disorders ◽

Low Dose ◽

Rating Scale ◽

Controlled Study ◽

P Value ◽

Chi Square ◽

Double Blind ◽

Increased Risk ◽

Significant Difference ◽

Chi Square Test

Background: The SSRIs being used as 1st line therapy in treatment of depression have delayed therapeutic effect which makes the patient vulnerable to an increased risk of suicide and decreased adherence to the treatment and will prematurely discontinue the therapy. The present study was conducted to evaluate if low dose mirtazapine-escitalopram combination therapy has any add on benefit over monotherapy with escitalopram.Methods: In a single-centered, comparative study involving patients with depression attending the out-patient after screening and exclusion, 60 eligible patients were randomly assigned to receive tablet mirtazapine 7.5 mg plus tablet escitalopram 10 mg intervention or tablet escitalopram 10 mg plus placebo intervention in a double-blind 6-week treatment phase. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline. Participants were evaluated at baseline, 1st, 2nd,4th and 6th week. Results were analyzed using Chi-Square test for adverse effects and independent t-test analysis for efficacy parameter.Results: In the analysis of results at 6th week the numbers of patients achieved remission in mirtazapine group are more with a p-value of 0.018 which is significant and the numbers of responders in mirtazapine group are also more which is statistically significant on chi-square test. There is no significant difference was observed between the two groups with reference to occurrence of adverse effect.Conclusions: Adding low dose mirtazapine has an added benefit in terms of efficacy and getting remission early with more number of responders in the treatment of major depression.

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Baseline endometriosis-associated pain burden: Data from 1600+ women enrolled in elagolix clinical trials

Journal of Endometriosis and Pelvic Pain Disorders ◽

10.1177/2284026519864232 ◽

2019 ◽

Vol 11 (3) ◽

pp. 117-125 ◽

Cited By ~ 1

Author(s):

Nicholas Leyland ◽

Stephanie J Estes ◽

Samantha Eichner ◽

Ahmed M Soliman ◽

Yabing Mai ◽

...

Keyword(s):

Clinical Trials ◽

Pelvic Pain ◽

Rating Scale ◽

Numeric Rating Scale ◽

Phase 3 ◽

Double Blind ◽

Scale Range ◽

Study Participants ◽

Numeric Rating Scale Score ◽

Numeric Rating

Background: The daily pain burden experienced by women with endometriosis has not been well studied. Objective: To characterize baseline pain among women with moderate-to-severe endometriosis-associated pain enrolled in phase 3 studies of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist. Study design: Data were pooled from the screening phase of two randomized, double-blind, placebo-controlled clinical trials. After cessation of endometriosis medications, patients entered the screening phase during which symptoms (dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia) and rescue medication use were recorded daily in electronic diaries. Endometriosis-associated pain was also scored using the Numeric Rating Scale (range 0–10). Baseline was defined as the last 35 days during the screening period. Results: Endometriosis-associated pain was reported by the 1686 study participants on most days during the baseline interval. Pain was often moderate or severe, with a mean Numeric Rating Scale score of 5.6 ± 1.7. Women reported dysmenorrhea an average of 8.1 ± 3.0 days (97.9% ± 7.0% of menstruating days), nonmenstrual pelvic pain on 20.5 ± 5.4 days (90.3% ± 15.8% of nonmenstruating days), and dyspareunia on 8.7 ± 8.0 days (81.7% ± 29.7% of sexually active days). When they occurred, dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia were frequently moderate or severe in intensity. Women were free of pelvic pain for an average of 2.4 ± 3.9 days during the 35-day evaluation interval. Conclusion: Among women with untreated moderate-to-severe endometriosis pain, the daily burden of pain was extensive, both during menstruation and on nonmenstruating days.

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111 Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (P301) Assessing Efficacy and Safety of Extended-Release Viloxazine in Children with ADHD

CNS Spectrums ◽

10.1017/s1092852920000292 ◽

2020 ◽

Vol 25 (2) ◽

pp. 272-272 ◽

Cited By ~ 1

Author(s):

Azmi Nasser ◽

Joseph T. Hull ◽

Fatima A. Chowdhry ◽

Toyin Adewole ◽

Tesfaye Liranso ◽

...

Keyword(s):

Clinical Global Impression ◽

Extended Release ◽

Rating Scale ◽

Controlled Study ◽

Average Score ◽

Efficacy And Safety ◽

Phase 3 ◽

Double Blind ◽

T Score ◽

Total Average

Abstract:Study Objective:SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P301) evaluated the efficacy and safety of once-daily SPN-812 at doses of 100 and 200 mg compared to placebo in children ages 6-11yrs with ADHD.Method:Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, a Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=477) were randomized 1:1:1 to placebo:100 mg SPN-812:200 mg SPN-812. The 6-week treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=460; placebo=155, 100 mg=147, 200 mg=158). The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and in Weiss Functional Impairment Rating Scale-Parent Version (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale.Results:Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 100 mg and 200 mg SPN-812 treatment groups beginning at week 1 (p=0.0004, p=0.0244; respectively) through EOS (p=0.0004, p<0.0001; respectively). Significant improvement at EOS for both 100 mg and 200 mg SPN-812 compared to placebo was also observed in CGI-I score (p=0.0020, p<0.0001; respectively), Connors 3-PS Composite T-score (p=0.0003, p=0.0002; respectively), and in WFIRS-P total average score (p=0.0019, p=0.0002, respectively). The most common (≥5%) treatment-related AEs reported were somnolence, decreased appetite, and headache.Conclusions:In this study, SPN-812 at 100 mg and 200 mg doses met the primary and secondary objectives with statistical significance. AE-related dropouts were ≤5%, indicating SPN-812 treatment was well tolerated.This study is an encore of a poster presentation at the 2019 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).Funding Acknowledgements:This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.

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