Vasomotor symptoms (hot flashes) are the most common symptom of menopause, affecting about 75% of menopausal women and about 40% of perimenopausal women. PH80, an investigational neuroactive nasal spray, is hypothesized to be a potential treatment for moderate to severe hot flashes due to menopause given that it rapidly activates olfactory to limbic-hypothalamic neural circuits that control autonomic activity, including body temperature and sweating. The primary objective of this Phase 2A clinical study was to explore the efficacy, safety, and tolerability of intranasal administration of PH80 for the acute management of hot flashes due to menopause.

The study was a randomized, double-blind, placebo-controlled, exploratory Phase 2A clinical study. PH80 nasal spray containing epoxyestrenolone 0.8 μg per 50 μL was self-administered intranasally; two sprays in each nostril (total dose = 3.2 μg) up to four times daily as needed for 4 consecutive weeks. One additional dose was allowed at night if subjects were awakened by hot flashes. During the study period, subjects recorded the number and severity of hot flashes, disruption in function, and sweating related to hot flashes. Patient global impression of change (PGI-C) and clinician global impression of severity (CGI-S) were also assessed.

At baseline, subjects reported a daily mean of 7.7 hot flashes in the PH80 group (n = 18) and 8.0 in the placebo group (n = 18). After 1 week of treatment, the number of hot flashes dropped to 2.8 for PH80 and 6.4 for placebo (P <.001), and after 4 weeks of treatment, the number of hot flashes dropped to 1.5 for PH80 and 5.1 for placebo (P <.001). Treatment with PH80 significantly reduced the severity, disruption in function, and sweating associated with hot flashes during the treatment period as compared with subjects in the placebo group. There was a significant improvement in PGI-C for PH80 vs placebo at endpoint (P = .015) and a strong trend for improvement on CGI-S (P = .053). PH80 was well-tolerated with no serious adverse events (AEs); the AE profiles of PH80 and placebo were comparable. All 36 subjects completed 4 weeks of treatment and with no study discontinuations due to AEs.

The rapid onset, significant reduction in symptoms, and improved function induced by intranasal PH80 in menopausal women with hot flashes compared with placebo, observed as early as the end of week 1 of treatment, provide a strong signal for continued development of PH80 for the acute treatment of hot flashes due to menopause. The safety data further suggest that, if approved, PH80 will provide a substantial safety benefit over all currently available agents.

Vistagen Therapeutics, Inc. Editorial assistance was provided by Peloton Advantage, an OPEN Health company, funded by Vistagen Therapeutics, Inc.

The d-ATS patch was developed as an alternative to oral amphetamine formulations for attention-deficit hyperactivity disorder (ADHD). The US Food & Drug Administration (FDA) recommends evaluating irritation of transdermal patches under intended (rotating application sites) and exaggerated use (repeated application to one site). These studies assessed irritation after d-ATS application.

Intended Use: In Study 1, adults with ADHD, d-ATS was applied daily (9-hour application) for 4 weeks rotated between 5 sites (left/right: hip, flank, chest, upper arm, upper back), with irritation assessed on Days 1, 7, 14, 27, and 28. In Study 2, children and adolescents with ADHD, d-ATS was applied daily (9 hours) for 5 weeks to the hip (left or right), with irritation assessed daily.

Exaggerated Use: In Study 3, adults with ADHD, d-ATS was applied daily (9 hours) to the hip (repeated application to one site) for 4 weeks, with irritation assessed daily. In Study 4, healthy adults, 1 d-ATS and 1 placebo patch were applied daily (24 hours) for 21 days to the back (repeated application to 1 site), with irritation assessed daily.

Irritation was assessed by a trained evaluator 30-60 min after patch removal using Berger and Bowman Dermal Response (0-7, with 7 being the worst reaction) and Other Effects (0-3, with 3 being the worst reaction) scores. Dermal Response and Other Effects scores were added together for the combined score. A combined score of ≥3 was considered clinically meaningful irritation.

Intended Use: In Study 1 (N=15), meaningful irritation after patch removal was reported in 9/15 subjects (60%). The mean (SD) combined score was 1.05 (0.21), with no treatment-emergent adverse events at the application site. In Study 2 (N=110), all combined irritation scores were ≤3 for d-ATS, with a combined score of 3 reported by 2% of patients. There were no discontinuations due to dermal reactions in either study.

Exaggerated Use: In Study 3 (N=20), meaningful irritation was reported in 19/20 subjects (95%). The mean (SD) combined score was 1.63 (0.78). In Study 4, mean (SD) combined scores were 2.1 (0.73) for d-ATS and 1.3 (0.69) for placebo (N=206 for both), with no discontinuations due to dermal reactions.

These results support previous findings that d-ATS is safe and well tolerated for ADHD. After intended use, irritation was minimal and did not cause study discontinuations.

Noven Pharmaceuticals, Inc.

This post hoc analysis investigated efficacy and tolerability of adjunctive cariprazine (CAR) in patients with major depressive disorder (MDD) using evidence-based medicine metrics of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

Data sources were five completed Phase II/III, 6-8 week, randomized, double-blind, placebo-controlled studies. Efficacy outcomes included acute response (≥50% decrease from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS] total score). Tolerability outcomes included commonly occurring adverse events (AEs) and rates of discontinuation because of an AE, with data pooled across all studies for the CAR 1-2 mg/day plus 1.5 mg/day dose groups, 2-4.5 mg/day plus 3 mg/day dose groups, and for all groups where CAR dose was ≥1 mg/day. NNT and NNH were calculated for adjunctive CAR vs. adjunctive placebo.

MADRS response rates at Week 8 for CAR 2-4.5 mg/day vs. placebo were 134/271 (49.4%) vs. 101/264 (38.3%), resulting in a NNT of 9 (95% CI 6-36). In study NCT03738215, MADRS response rates at Week 6 for CAR 1.5 mg/day vs. placebo were 110/250 (44.0%) vs. 87/249 (34.9%), resulting in a NNT of 11 (95% CI 6-193). For the pooled CAR ≥1 mg/day group, MADRS response rates at Week 6 were 765/1887 (40.5%) for CAR vs. 354/1101 (32.2%) for placebo, resulting in a NNT of 12 (95% CI 9-21). For the pooled CAR ≥1 mg/day group, rates of akathisia vs. placebo were 209/1893 (11.0%) vs. 25/1108 (2.3%) for placebo, resulting in a NNH of 12 (95% CI 10-14). This appears dose related as the NNH for akathisia vs. placebo was 24 (95% CI 17-43) for the 1-2 mg/day plus 1.5 mg/day dose groups, and 9 (95% CI 7-11) for the 2-4.5 mg/day plus 3 mg/day dose groups. For the pooled CAR ≥1 mg/day group, rates of discontinuation because of an AE vs. placebo were 122/1893 (6.4%) vs. 26/1108 (2.3%) for placebo, resulting in a NNH of 25 (95% CI 19-38). This appears dose related as the NNH for discontinuation because of an AE vs. placebo was 94 (ns) for the 1-2 mg/day plus 1.5 mg/day dose groups, and 17 (95% CI 13-28) for the 2-4.5 mg/day plus 3 mg/day dose groups. For the pooled CAR ≥1 mg/d group, rates of weight gain ≥7% from baseline vs. placebo were 35/1893 (1.8%) vs. 12/1108 (1.1%) for placebo, resulting in a NNH of 131 (ns). LHH comparing MADRS response vs. discontinuation because of an AE is >1, and >>1 for the lower dose range. Indirect comparisons of the above results with that of the effect sizes seen in positive studies of other adjunctive antipsychotic treatments vs. adjunctive placebo in MDD demonstrate similar values for NNT for response, and when the lower dose range of CAR is used, a more favorable NNH regarding discontinuation because of an AE.

The benefit-risk profile of CAR is favorable for adjunctive treatment of MDD.

AbbVie

Anhedonia, a multidimensional domain including the reduced ability to experience pleasure, is a core diagnostic symptom of major depressive disorder (MDD) and a common residual symptom. In patients with MDD, anhedonia has been associated with poor treatment outcomes, suicide and reduced functioning and quality of life. This post-hoc analysis of data from a phase 3 trial (NCT03738215) evaluated the efficacy of adjunctive cariprazine (CAR) treatment on anhedonia symptoms in patients with MDD.

Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to CAR 1.5 mg/d + ADT, CAR 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analyses evaluated the change from baseline to Week 6 in Montgomery–Åsberg Depression Rating Scale (MADRS) total score, MADRS anhedonia subscale score (items: 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]), and MADRS anhedonia item 8 in the overall modified intent-to-treat (mITT) population and in subgroups of patients with baseline MADRS anhedonia item 8 score of ≥4 or baseline anhedonia subscale score of ≥18. Least square (LS) mean change from baseline to Week 6 was analyzed using a mixed-effects model for repeated measures.

There were 751 patients in the mITT population (CAR + ADT: 1.5 mg/d=250, 3 mg/d=252; placebo + ADT=249). At baseline, 508 (67.6%) patients had MADRS anhedonia item 8 scores ≥4, and 584 (77.8%) had MADRS anhedonia subscale scores ≥18. In the overall mITT population, LS mean change from baseline to Week 6 in anhedonia subscale score was significantly greater for CAR 1.5 mg/d + ADT (-8.4) and CAR 3 mg/d + ADT (-7.9) than for placebo + ADT (-6.8; both P<.05). The LS mean change from baseline in MADRS individual item 8 was also significantly greater for CAR 1.5 mg/d + ADT (-1.7) vs placebo + ADT (-1.3; P=.0085). In both subgroups of patients with baseline anhedonia, CAR 1.5 mg/d + ADT was associated with significantly greater reduction in MADRS total score, MADRS anhedonia subscale score, and MADRS item 8 score compared with placebo + ADT (all P<.05). In the CAR 3 mg/d + ADT group, significantly greater reductions vs placebo + ADT were observed for MADRS total score and MADRS anhedonia subscale score in the subgroup of patients with baseline anhedonia subscale scores ≥18 (both P<.05).

Adjunctive treatment with CAR was associated with a reduction in symptoms of anhedonia relative to adjunctive placebo in patients with MDD and inadequate response to ADT alone. In subgroups of patients with moderate-to-severe anhedonia at baseline, CAR + ADT demonstrated greater improvements than placebo + ADT in overall depressive symptoms and symptoms of anhedonia. These results suggest that adjunctive CAR treatment may be effective for improving symptoms of anhedonia in patients with MDD who have symptoms of anhedonia.

AbbVie

Akathisia is a common adverse effect associated with use of dopamine receptor blocking agents.1,2 Symptoms of akathisia, in severe cases, may lead to discontinuation of treatment. Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist approved to treat schizophrenia and acute manic, mixed, and depressive episodes of bipolar 1 disorder. Cariprazine is well tolerated in patients across its indications, but is associated with a higher incidence of akathisia compared with placebo.3,4 This pooled post hoc analysis of data from phase 3 clinical trials of adjunctive cariprazine aimed to characterize the incidence, severity, and management of akathisia and other extrapyramidal symptoms (EPS) in adult patients with MDD.

Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to cariprazine 1.5 mg/d + ADT, cariprazine 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analysis evaluated incidence, severity, and time to resolution of akathisia, restlessness, and other EPS; use of rescue medications; and the rate of discontinuation due to these treatment-emergent adverse events (TEAEs).

A total of 1508 patients (cariprazine + ADT: 1.5 mg/d, n=502, 3 mg/d, n=503; placebo + ADT, n=503) were included in these 2 studies. The incidence of akathisia was greater with cariprazine 3 mg/d + ADT (9.7%) than with cariprazine 1.5 mg/d + ADT (6.4%) and placebo + ADT (2.0%). Most patients treated with cariprazine + ADT (94%) experienced only mild or moderate akathisia. The incidence of restlessness was 3.8% for patients treated with cariprazine 3 mg/d + ADT, 3.6% for cariprazine 1.5 mg/d + ADT, and 1.8% for placebo + ADT. The incidence of EPS excluding akathisia and restlessness was 4.4% for patients treated with cariprazine 3 mg/d + ADT, 4.6% for cariprazine 1.5 mg/d + ADT, and 3.2% for placebo + ADT. For patients treated with cariprazine + ADT and placebo + ADT, respectively, EPS-related study discontinuations were 1.4% and 0.4% due to akathisia, 0.2% and 0.0% due to restlessness, and 0.1% and 0.4% due to EPS excluding akathisia and restlessness. Rescue medications were used to treat EPS-related TEAEs during the double-blind treatment period in 3% of cariprazine-treated patients and 0.4% of placebo-treated patients. The mean time to resolution of akathisia during treatment was slightly shorter in cariprazine-treated patients (15.6 days) versus placebo-treated patients (19.5 days).

Incidence of akathisia was higher for cariprazine than placebo, with a lower incidence observed for patients treated with cariprazine 1.5 + ADT than with cariprazine 3 mg/d + ADT, suggestive of a dose related effect. Most patients experienced mild or moderate akathisia. Rates of study discontinuation and rescue medication use due to akathisia were low, suggesting that akathisia was tolerated by most patients.

This data was previously presented at the CINP World Congress; Montreal, Canada; May 7-10, 2023.

AbbVie

Patients with major depressive disorder (MDD) commonly experience comorbid anxiety and somatization, which can complicate treatment. Adjunctive therapy with atypical antipsychotics can be an effective treatment option for patients with MDD who had inadequate responses to antidepressant therapy (ADT) alone. Cariprazine is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist that is approved as an adjunctive treatment for MDD. This post hoc analysis examined the effect of adjunctive cariprazine therapy on anxiety and somatization symptoms in patients with MDD.

A post hoc analysis was conducted using data from a phase 3, double-blind, placebo-controlled, fixed-dose study of patients with MDD who had inadequate responses to ADT alone. Patients were randomized (1:1:1) to receive ADT plus cariprazine 1.5 mg/d, 3 mg/d, or placebo for 6 weeks. The least squares (LS) mean change from baseline to week 6 in Hamilton Rating Scale for Depression (HAM-D) Anxiety/Somatization subscale was measured. The Anxiety/Somatization subscale includes six HAM-D items: anxiety-psychic, anxiety-somatic, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. The modified intent to treat population included 751 patients (placebo=249; cariprazine 1.5 mg/d=250; cariprazine 3 mg/d=252).

The LS mean change from baseline in HAM-D Anxiety/Somatization subscale at week 6 was significantly greater than placebo + ADT for both cariprazine + ADT dose groups (placebo: -3.22; cariprazine 1.5 mg/d: -4.00, P<.001; 3 mg/d: -3.75, P<.05). LS mean change from baseline in the cariprazine 1.5 mg/d + ADT group was also significantly greater than placebo + ADT on the anxiety-psychic (placebo: -0.88; cariprazine 1.5 mg/d: -1.08, P<.01) and anxiety-somatic (placebo: -0.78; cariprazine 1.5 mg/d: -0.96, P<.05) items. In patients treated with cariprazine 3 mg/d + ADT, LS mean changes from baseline on anxiety-psychic and anxiety-somatic items were numerically larger than placebo + ADT but not statistically significant. Both cariprazine + ADT dose groups had significantly larger LS mean changes compared with placebo + ADT on the gastrointestinal somatic symptoms item (placebo: -0.51; cariprazine 1.5 mg/d: -0.66, P<.01; cariprazine 3 mg/d: -0.68, P<.01). General somatic symptoms, hypochondriasis, and insight items showed no significant difference between placebo + ADT and cariprazine + ADT groups.

Patients treated with adjunctive cariprazine demonstrated greater improvements than patients treated with adjunctive placebo on HAM-D Anxiety/Somatization subscale scores, as shown by reduced scores on anxiety-psychic, anxiety-somatic, and gastrointestinal items. These findings suggest adjunctive cariprazine therapy may be effective in reducing anxiety and somatization symptoms in patients with MDD.

AbbVie

Study Registration Number: NCT03738215

Esketamine nasal spray is an NMDA receptor antagonist which is FDA approved, in conjunction with an oral antidepressant, for treatment- resistant depression (TRD) in adults. Dissociation is a well-known side effect to treatment and can be measured using the CADSS (Clinician Administered Dissociative States Scale). To date, patient specific factors that may contribute to the severity of dissociation have not been described.

This case series describes two patients receiving treatment with 84-mg esketamine nasal spray twice weekly in an outpatient clinic for TRD who experienced an episode of significant dissociation several months into their treatments. History obtained prior to esketamine treatment included an assessment for any recent stressors. CADSS score was assessed posttreatment.

Case 1 was a 55-year-old female who had been receiving esketamine for over two months who presented to the clinic complaining of recent sleep-deprivation while caring for her newborn grandchild. Patient experienced extreme dissociation following administration of esketamine, verbalizing that she felt “very big” and began twitching, grimacing, moaning, and repeating nonsensical statements. CADSS score after treatment was 27. Case 2 involves a 59-year-old female with a remote history of sexual trauma who was four months into esketamine treatments when she presented to the clinic feeling sad after listening to another sexual assault victim’s testimony on social media prior to treatment. Shortly after receiving esketamine, she began experiencing a flashback to previous trauma and screaming loudly. CADSS score after treatment was 21. Although both patients reported a history of dissociation with esketamine treatments in the past, they both reported that the level of dissociation they experienced during the above sessions was far more severe.

Severe episodes of dissociation during treatment with esketamine in patients with TRD may be associated with patient specific factors. Assessing patients for the presence of recent stressors or changes to their routine prior to each treatment session may help healthcare professionals predict the risk of severe dissociation and allow providers to better prepare to support patients during these experiences.

No Funding

Valbenazine and deutetrabenazine (vesicular monoamine transporter 2 inhibitors) are approved for tardive dyskinesia (TD) treatment in adults. To prevent potential drug-drug interactions (DDIs), valbenazine labeling recommends doses 40 mg/day when taking strong CYP3A4 or CYP2D6 inhibitors and avoidance of strong CYP3A4 inducers and monoamine oxidase inhibitors (MAOIs). Deutetrabenazine labeling recommends doses ≤36-mg/day when taking strong CYP2D6 inhibitors and avoidance of MAOIs. This study estimated proportions of patients with TD at risk of DDIs with valbenazine/deutetrabenazine in real-world practice.

Patients aged ≥18 years with TD and ≥1 antipsychotic claim(s) and no valbenazine/ deutetrabenazine claims ≥3 months prior and ≥12 months after diagnosis were identified in the Symphony Health Sciences database (US-based medical, hospital, and pharmacy claims database). Proportions of patients meeting valbenazine/deutetrabenazine concomitant medication labeling restrictions were summarized descriptively.

14,264/66,046 patients with TD met inclusion criteria. Proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.2%) and >36 mg/day (21%) versus valbenazine 40 mg/day (4.4%; 22-times difference) and >40 mg/day (28%; 1.3-times difference). Across age groups, underlying conditions (major depressive, mood, and bipolar disorders; schizophrenia), and payer types, proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.0%– 0.5%) and >36 mg/day (14%– 30%) versus valbenazine 40 mg/day (3%– 5%; 8.0- to >40.0times difference) and >40 mg/day (22%– 35%; 1.2- to >1.5-times difference).

Estimated proportions of patients with TD at potential risk of DDIs was lower with deutetrabenazine versus valbenazine overall and across age, underlying conditions, and payer types.

Teva Branded Pharmaceutical Products R&D, Inc.

Tardive dyskinesia (TD) is associated with antipsychotic (AP) use and management includes antipsychotic (AP) dose modification/discontinuation, often leaving underlying psychiatric conditions undertreated. Deutetrabenazine (DTBZ) is a vesicular monoamine transporter type 2 inhibitor (VMAT2i) approved to treat TD and Huntington disease– associated chorea. AP and VMAT2i treatment patterns post-TD diagnosis are unclear.

Patients aged ≥18 years, newly diagnosed with TD (July 2019– June 2022), with ≥1 AP and no VMAT2i claims pre-index were identified from the Symphony Health Solutions Integrated Dataverse (medical, hospital, and prescription claims across all US payer types). Patients were grouped into DTBZ (≥1 DTBZ claim within ≤6 months post-diagnosis) and non-VMAT2i groups, and further by stable DTBZ dose (for ≥60 days). The index date was the first DTBZ claim (DTBZ group) or the difference between TD diagnosis and first DTBZ claim (of the matched patient) added to TD diagnosis (non-VMAT2i group).

Among 18,375 patients meeting inclusion criteria, 587 (3%) received DTBZ (292 stable-dose DTBZ), 676 (4%) received a different VMAT2i, and 17,112 (93%) had no VMAT2i claims. Among propensity score-matched patients with ≥1 AP claim pre- and post-index (326 DTBZ, 627 non-VMAT2i), pre-index mean AP proportions of days covered (PDCs) were similar between DTBZ (86%), stable-dose DTBZ (86%), and non-VMAT2i (83%) groups. Mean PDCs decreased post-index for DTBZ (86% to 85%) and non-VMAT2i (83% to 81%) groups, but increased for the stable-dose DTBZ group (86% to 88%). While these changes were small, post-index mean PDCs were significantly greater (versus non-VMAT2i) in the DTBZ (5% difference; P=.030) and stable-dose DTBZ (9%; P=.001) groups. Similar proportions of patients in the DTBZ (20%) and non-VMAT2i (20%) groups discontinued APs (ie, no AP claims within ≤6 months post-index). Proportions of patients with AP restarts (7%– 8%) and dose decreases (13%– 17%) were also similar between DTBZ, stable-dose DTBZ, and non-VMAT2i groups. Proportions of patients (16%– 18%) with AP dose increases were similar between DTBZ and non-VMAT2i groups, but significantly greater in the stable-dose DTBZ group (21%) vs non-VAMT2i (P=.02).

AP adherence was significantly, though not substantially, greater for DTBZ versus non-VMAT2i groups. These results suggest that DTBZ, when titrated to a stable/optimal dose, allows flexibility in treating underlying psychiatric conditions.

Teva Branded Pharmaceutical Products R&D, Inc.

Esketamine (ESK) nasal spray and interventional therapies including electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are indicated for patients with treatment resistant depression (TRD). Little is known about healthcare resource use and associated costs of Medicaid beneficiaries, a population with a high burden of mental health disorders, initiating ESK, ECT or TMS. This study aimed to bridge this gap in knowledge.

Medicaid-insured adults with evidence of TRD (≥2 unique antidepressants of adequate dose and duration) were selected from Merative™ MarketScan® Multi-State Medicaid Database (01/2016-06/2022). Based on therapy initiated on or after 03/05/2019 (ESK approval date for TRD), patients were classified into three cohorts: ESK, ECT, and TMS. Before treatment initiation (index date), patients had ≥12 months of continuous insurance eligibility (baseline period). Mental health (MH)-related resource use and payer costs (USD 2022) were reported per-patient-per-month (PPPM) during the follow-up period, which spanned the index date until the earliest continuous insurance eligibility or data end.

ESK cohort included 151 patients (mean age: 40.6 years; female: 70.2%), ECT cohort included 198 patients (mean age: 43.0 years; female: 60.6%), and TMS cohort included 140 patients (mean age: 39.5 years; female: 65.0%).

During the follow-up period, the mean number of MH-related inpatient (IP) days trended lower in ESK cohort (0.09) relative to the ECT (3.72) and TMS (0.31) cohorts. Similarly, the mean number of MH-related emergency department (ED) visits trended lower in ESK cohort (0.07) relative to ECT (0.12) and TMS (0.26) cohorts. The mean number of MH-related outpatient (OP) visits in ESK cohort (4.83) trended higher than in ECT cohort (4.37) but lower than in TMS cohort (6.41). Mean MH-related acute care costs during the follow-up period trended lower in ESK cohort (IP: $76; ED: $29) relative to ECT (IP: $1,547; ED: $45) and TMS cohorts (IP: $238; ED: $123). Outpatient costs in ESK cohort ($1,632) exceeded OP costs in ECT ($1,023) and TMS ($1,051) cohorts.

In this descriptive analysis, a trend towards lower use and costs of acute MH-related care was observed after the initiation of ESK relative to the initiation of ECT and TMS. This finding should be interpreted with caution, given potential differences in patient profiles, clinical history and setting of administration.

Janssen Scientific Affairs, LLC. Analysis Group is a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study.

The dextroamphetamine transdermal system (d-ATS) was developed as an alternative to current oral formulations of amphetamine, which is a first-line treatment for ADHD. In a randomized controlled trial of d-ATS in children and adolescents with ADHD, the primary endpoint (SKAMP total score) and secondary endpoints were met. This analysis evaluated the efficacy of d-ATS using SKAMP total score by optimized dose, gender, age group, ADHD type, and baseline ADHD severity.

This study comprised a 5-week, open-label dose-optimization period (DOP) followed by a 2-week, randomized, cross-over double-blind treatment period (DBP). All eligible patients received d-ATS 5 mg/9hr, with weekly evaluation for dose increase to 10 mg/9hr, 15 mg/9hr, and 20 mg/9hr. Once reached, the optimal dose was maintained for the DOP and used during the DBP. Preplanned subgroup analyses of mean SKAMP total score by optimized dose, gender, age group, ADHD type, and baseline ADHD severity were conducted. Efficacy was assessed by difference (d-ATS vs placebo) in least-squares (LS) mean SKAMP total score from a mixed-model repeated-measures (MMRM) analysis and is reported throughout as LS mean (95% confidence interval [CI]).

In total, 110 patients were enrolled in the DOP, and 106 patients were randomized in the DBP. During the DOP, three patients reported 3 TEAEs that led to study discontinuation (irritability, appetite loss, abdominal pain). The difference (d-ATS vs placebo) in LS mean SKAMP total score was -5.9 (-6.8, -5.0), with differences in attention, deportment, and quality of work sub-scores of -1.4 (-1.7, -1.1), -1.9 (-2.2, -1.5), and -1.3 (-1.5, -1.0), respectively. Patients receiving d-ATS at each optimized dose demonstrated improvements vs placebo in LS mean SKAMP total score (-7.3 [-10.8, -3.7], -4.5 [-6.0, -3.0], -5.9 [-7.4, -4.5], -7.6 [-9.6, -5.6] at 5, 10, 15, and 20 mg/9hr, respectively). Both male and female patients experienced improvements vs placebo in SKAMP total score. The observed difference was greater in males (-6.3 [-7.3, -5.2]) vs females (-5.0 [-6.6, -3.4]). Similarly, improvements vs placebo were seen in patients with combined type ADHD and in those with predominantly inattentive type ADHD, with an observed LS mean difference of -8.0 (-9.2, -6.8) for the combined type and -3.3 (-4.6, -2.1) for the inattentive type. In addition, patients demonstrated improvement during the DBP regardless of baseline ADHD severity. The difference in LS mean SKAMP total score was -4.5 (-5.9, -3.1) for patients with a baseline SKAMP total score of 0-36 and -6.7 (-7.9, -5.6) for those with a baseline SKAMP score of 37-54.

d-ATS was effective and generally well-tolerated in treating ADHD in children and adolescents regardless of optimized dose, gender, age group, ADHD type, or baseline ADHD severity.

Noven Pharmaceuticals, Inc.

Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness (EDS), among other symptoms. Previous studies of narcolepsy have largely relied on quantitative methods, providing limited insight into the patient experience. This study used qualitative interviews to better understand this rare condition.

Patients with narcolepsy (types 1 [NT1] and 2 [NT2]) were recruited using convenience and snowball sampling. Trained qualitative researchers conducted hour-long, individual interviews. Interview transcripts were coded and thematically analyzed using inductive and deductive approaches.

Twenty-two adults with narcolepsy (NT1=12; NT2=10) participated (average age: NT1=35; NT2=44). Most were female (NT1=83%; NT2=70%) and white (NT1=75%; NT2=60%). Average times since diagnosis were 7 years (NT1) and 11 years (NT2).

At disease onset, symptoms experienced included EDS (NT1=83%; NT2=80%)—sometimes involving sleep attacks (NT1=35%; NT2=50%)—fatigue (NT1=42%; NT2=30%), oversleeping (NT1=33%; NT2=20%), and cataplexy (NT1=42%). Participants sought a diagnosis from healthcare professionals including sleep specialists, neurologists, pulmonologists, psychiatrists, and primary care physicians. Many participants reported receiving a narcolepsy diagnosis >10 years after symptom onset (NT1=50%; NT2=60%). During that time, patients reported misdiagnoses, including depression, sleep apnea, and attention-deficit/hyperactivity disorder.

Common symptoms included EDS (NT1=100%; NT2=90%), cognitive impairment (NT1=92%; NT2=100%), and fatigue (NT1=75%; NT2=90%). All participants with NT1 reported cataplexy. Participants rated these symptoms as among the most bothersome.

Study results provide descriptions of narcolepsy symptoms and the often challenging journey toward seeking a diagnosis. By using patient-centered, qualitative methods, this study fills a gap by providing additional insights into the patient experience of narcolepsy.

Alkermes, Inc.

Schizophrenia is one of the top 15 causes of disability worldwide and among the most expensive mental disorders to treat. Relapse, commonly associated with healthcare utilization including hospitalization, is prevalent and progressive in schizophrenia. Electronic health record (EHR) data could be used for timely identification of those at highest risk for relapse. This study utilized a large sample of Midwestern healthcare patients (pts) diagnosed with schizophrenia and schizoaffective disorders to identify demographic, clinical, and utilization characteristics that predicted relapse.

This retrospective study includes EHR data from all pts between Oct 15, 2016, and Dec 31, 2021, who had at least 1 y of encounters. Patients’ first encounter with a schizophrenia or schizoaffective disorder diagnosis (ICD-10 F20 or F25) in this timeframe was defined as their index date, and all encounters up to 3 y post-index date (PID) were explored. Patient-level variables within the first 6 mo of follow-up (FU) were assessed as potential relapse predictors, and first relapse at or after 6 mo of FU within the system was explored as the outcome. Relapse was defined as occurrence of any behavioral health-related emergency room or inpatient encounter after 6 mo of FU within the system. Potential variables assessed include pt characteristics at index date, comorbidities diagnosed, healthcare encounter settings utilized, medication classes prescribed, and disorder-related outcomes experienced.

The study sample included 8119 pts with 325,745 total FU encounters, with an average of 28.0 mo of FU data PID. Among all pts, 30.5% experienced relapse by this study’s definition. Analyses revealed differences in insurance type, race/ethnicity, and age, and differences across a breadth of comorbid diagnoses, healthcare encounter settings utilized, disorder-related outcomes experienced, and medical classes prescribed. Adjusted analysis revealed pts who relapsed were more likely to be younger (RR=0.99[0.99,0.99]; p<0.0001); identify as Hispanic or Latino (RR=1.15[1.03,1.28]; p=0.0121) or Non-Hispanic (NH) Pacific Islander (RR=1.83[1.16,2.89]; p=0.0090) vs. NH White; have Medicare (RR=1.22[1.08,1.39]; p=0.0018) or Medicaid (RR=1.33[1.17,1.51]; p<0.0001) vs. Private insurance; have diagnoses of substance use (RR=1.33[1.24,1.43]; p<0.0001) and EPS (RR=1.78[1.65,1.92]; p<0.0001); utilize more ER (RR=1.02[1.01,1.02]; p<0.0001) and BH inpatient (RR=1.10[1.06,1.14]; p<0.0001) encounters; experience more prior relapse (RR=1.05;[1.03,1.06]; p<0.0001), and receive more LAI prescriptions (RR=1.01[1.00,1.02]; p=0.0349).

An algorithm of these variables could conceivably be used to proactively assess relapse risk among pts with schizophrenia to ultimately decide on and implement appropriate relapse prevention plans. Further exploration may be required to better understand underlying modifiable factors that put pts at increased risk of poor outcomes.

Sumitomo Pharma America, Inc. and Otsuka Pharmaceuticals Development & Commercialization, Inc.

The 21st Century Cures Act mandated that new medication research include patient focused drug development initiatives. The act also recognized CPSSs as integral members of the healthcare team. Inclusion of CPSSs within care teams is associated with reduced hospitalization, increased treatment engagement, and a renewed focus on patient desired outcomes. CPSSs are people with lived experience in navigating complex mental health systems and whose unique perspective helps guide peers on their journey to wellness. In the same manner that CPSS knowledge has improved clinical outcomes, partnering with CPSSs during CNS drug development may provide wellness outcomes in clinical trials that are more meaningful for people with lived experience. To this end, a CPSS Ambassador program was initiated.

Of 85 peer support specialists identified by internet searches, Linked-In, and peer support specialists’ registries, 7 CPSSs met our criteria (i.e., having lived experience of psychosis and being a member of a treatment team) and agreed to be part of our ambassador program. Interactions included 6 monthly virtual meetings and a live roundtable meeting. The objectives of the program were to: 1) understand unmet needs in people with lived experience and identify impediments to effective treatment, 2) learn best practices for discussing medication use to support wellness, 3) identify resources that can help educate people and families with lived experience, and 4) highlight the importance of CPSSs within healthcare teams to optimize treatment outcomes.

This CPSS ambassador program emphasized the need for shared decision making and partnership to forge a positive treatment team alliance. As such, treatment goals should be tailored to patients’ needs (“nothing about me without me”). A major obstacle to effective treatment is the presence of bias or stigma among health care practitioners. Specifically, certain language used by clinicians has the potential to ostracize patients and negatively impact treatment. Medications should be discussed as one pillar of a larger treatment plan and not as a “fix” for symptoms. Educational resources written in layman’s terms are needed to explain treatment algorithms and medication side effects. And finally, CPSSs make a significant contribution to person-focused positive outcomes and are an essential part of the treatment team. CPSSs are a conduit of lived experience and advocate for the individual

The following key outcomes were illuminated because of this work together: CPSS’s are liaisons that facilitate the intersection between the treatment team and people utilizing mental health systems. CPSS’s are critical to successful navigation of the mental health care system and reaching desired outcomes. Best practices for treatment teams are about effective, person-based and stigma free partnerships for positive and patient focused outcomes.

Sumitomo Pharma America (formerly Sunovion Pharmaceuticals Inc)

Typical and atypical antipsychotics (AAPs) are the main treatment options among patients with schizophrenia. However, AAPs have been associated with several side effects and comorbid conditions. To manage side effects, often patients are prescribed concomitant medications to manage their condition, increasing polypharmacy. Though common in practice, the prevalence of concomitant medication use in patients with schizophrenia is not well established. This study evaluated the annual prevalence of concomitant medications among patients with schizophrenia who were prescribed AAPs.

This retrospective study was conducted using the PharMetrics database (01/2019 – 12/2021). Patients were included in the analyses if they had a diagnosis of schizophrenia, were continuously enrolled in pharmacy and medical claims for the full year and were prescribed AAPs. A sensitivity analysis was also conducted among patients who demonstrated ≥50% adherence to their prescribed AAPs (with a grace period of 30 days). For both the main and sensitivity analyses patient populations, the concomitant drugs prescribed were labeled at the drug class (GPI2) and generic drug level. Prevalence for drug class and each drug was calculated as a percentage of patients who were prescribed ≥1 of the agent among those who met the inclusion and exclusion criteria within the given year.

For the year 2019, 2020 and 2021, 12,360; 13,242 and 14,780 patients met the inclusion and exclusion criteria, respectively. The mean age of the cohort ranged from 43.5 - 45.4 years. Patients were predominantly male and commercially insured. Antidepressants were the most prevalent concomitant medication prescribed (2019: 61.2%, 2020: 61.2%, 2021: 62.0%). Other highly prevalent drug classes identified were - anticonvulsants (2019: 44.2%, 2020: 44.5%, 2021: 45.0%), antianxiety agents (2019: 36.3%, 2020: 37.6%, 2021: 38.9%), antihyperlipidemics (2019: 26.3%, 2020: 28.1%, 2021: 30.7%), antihypertensives (2019: 25.7%, 2020: 27.2%, 2021: 28.1%), antiparkinson agents (2019: 61.2%, 2020: 61.2%, 2021: 62.0%), anticholinergics (2019: 61.2%, 2020: 61.2%, 2021: 62.0%) and analgesics (2019: 61.2%, 2020: 61.2%, 2021: 62.0%). At the individual drug level, benzotropine mesylate (2019: 19.5%, 2020: 18.7%, 2021: 18.8%), atorvastatin (2019: 14.5%, 2020: 16.7%, 2021: 18.4%), lorazepam (2019: 14.1%, 2020: 14.7%, 2021: 14.3%), gabapentin (2019: 13.7%, 2020: 13.9%, 2021: 14.8%), and metformin (2019: 13.2%, 2020: 13.7%, 2021: 15.4%) were the most prevalent prescribed concomitant medications. There was no difference when similar analyses were conducted in the adherent patient population.

These results indicate a high prevalence of concomitant antidepressants, antihyperlipidemics, antihypertensives and anticholinergics among patients with schizophrenia who are prescribed AAPs.

Sumitomo Pharma America Inc.

Schizophrenia is a chronic neurodevelopmental disorder characterized by positive, negative, and cognitive symptoms. While current antipsychotic (AP) medications are generally effective in treating positive symptoms, they don’t effectively manage the negative symptoms of schizophrenia (NSS). This study examined the healthcare resource utilization (HCRU) and cost among patients with NSS in the United States.

This retrospective longitudinal observational study utilized de-identified administrative claims data from STATinMED RWD Insights (01/01/2016-09/30/2022). Study sample included patients with schizophrenia identified using ICD-10-CM: F20.XX, diagnosed with NSS (cases; ICD-10-CM: F20.5; index=first NSS diagnosis) or not (controls; random date assigned as index); identification period: 01/01/2017-09/30/2021. Patients were 13 years or older at index, had 12-month of continuous capture data pre-(baseline) and post-(follow-up) index date, and had evidence of AP use at baseline. Outcomes were prevalence of NSS, mental health (MH)-related, schizophrenia-related, and all-cause HCRU and costs per patient per year (PPPY). Patients’ demographic, clinical characteristics, and other psychiatry and neurodevelopmental comorbidities were assessed at baseline. Unadjusted and Inverse Proportional Treatment Weighted (IPTW) comparison were conducted for baseline characteristics and outcomes followed by Generalized Linear Models (GLMs) for HCRU and costs.

The final study sample had 5,691 NSS and 236,895 non-NSS patients. Prevalence rate of NSS was estimated at 24.66 per 1000 patients of Schizophrenia. Patients with NSS were significantly older (mean: 50 vs 48 years), less commercially insured (10% vs 15%), and had greater comorbidities including alcohol abuse (12% vs 8%), depression (30% vs 24%), diabetes without chronic complications (22% vs 17%), drug abuse (21% vs 16%), uncomplicated hypertension (41% vs 32%), and psychoses (80% vs 58%); all p-values<0.001. After controlling for baseline characteristics, patients with NSS had significantly higher all-cause inpatient admissions (mean: 5.2 vs 4.2), outpatient emergency room (ER) visits (mean: 2.8 vs 2.0), inpatient stay costs ($23,830 vs $20,669), outpatient ER visit costs ($1,738 vs $1,167.20) and less prescriptions (mean: 49.2 vs 51.4); all p-values<0.05. GLM analysis also showed patients with NSS had significantly higher all-cause inpatient admissions (mean: 4.8 vs 3.7), number of outpatient visits (mean: 14.3 vs 13.8), and inpatient stay costs ($20,853 vs $17,809); all p-values<0.05. MH- and schizophrenia-related HCRU and costs PPPY were consistent with all-cause HCRU and cost results.

Patients with predominant NSS had higher HCRU and healthcare costs compared to patients without predominant NSS. New therapies that improve negative symptoms may reduce the burden of schizophrenia.

Sumitomo Pharma America (formerly Sunovion Pharmaceuticals Inc).

Since COVID-19, mental healthcare telehealth services have increased. A 2021 online survey (TeleSCOPE 1.0 [T1]) identified challenges evaluating, diagnosing, and monitoring DIMDs with telehealth (via video or phone). TeleSCOPE 2.0 (T2) was conducted to understand the telehealth impact post-COVID restrictions.

T2 was fielded (5/18-6/9/2023) to neurologists (neuro), psychiatrists (psych), and nurse practitioners (NP)/physician assistants (PA) affiliated with neuro/psych practices who prescribed vesicular monoamine transporter 2 inhibitors or benztropine for DIMD in the past 6 months and saw ≥15% of patients via telehealth at peak and post-COVID.

100 neuros, 100 psychs, and 105 NP/PAs responded. More patients were seen in-person post-COVID (12-27% vs 31-53%), but percentage seen by video remained largely unchanged (54-62% vs 37-53%). Issues influencing appointment setting in T2 remained access to care, technology, and digital literacy although T2 clinicians reported less patients had issues connecting for a video visit. In T2, clinicians used multiple telehealth methods to evaluate DIMDs including personal phone videos (48-66%), telemedicine apps (36-45%), health/fitness trackers (6-13%), and other (2-5%). Common T2 diagnostic telehealth issues included determining signs of difficulty with gait, falls, walking, and standing; difficulty writing, using phone, computer; and painful movements. In patients evaluated for DIMD, more received an eventual diagnosis in T2 vs T1 both in-person (34-53% vs 26-46%) and video (32-51% vs 29-44%) but, on average, neuros and psychs required 1 more telehealth visit to confirm a DIMD diagnosis vs in-person. Over half of clinicians on average recommended patients come in-person to confirm a DIMD diagnosis. Most clinicians reported ongoing difficultly diagnosing patients via phone. Neuros were less comfortable than psychs/NP/PAs with telehealth visits due to risk of misdiagnosis and liability. While all clinicians saw telehealth advantages, neuros expect to see more of their patients in person post-COVID. However, in T2, the number of clinicians who found it difficult to manage DIMDs cases by video had significantly decreased (T1 52-54%; T2 28-36%). Half of clinicians reported the non-presence of a caregiver as a significant barrier to diagnosis and treatment via telehealth. Clear guidelines and provider education were the most feasible strategies to implement to improve telehealth quality of care.

T2 clinicians are more comfortable managing DIMDs via telehealth but require ˜1 more visit to confirm a diagnosis vs in-person. Significant barriers to telehealth remain including digital literacy, inconsistent caregiver presence, and lack of clear diagnosis guidelines. Clinicians see value in telehealth but it is still not as effective as in-person. Significantly more clinicians are in-office post-COVID and >50% recommend patients come in-person to confirm a DIMD diagnosis.

Neurocrine Biosciences, Inc.

This study examined whether curriculum based continuing medical education (CME) interventions can improve provider knowledge, competence, and confidence related to the assessment and treatment of patients with major depressive disorder (MDD).

The online CME curriculum consisted of 2 online activities, which used repeated pairs pre-/post-assessment study design and McNemar’s test (P <.05 is considered significant) to assess educational effect. Clinicians who completed questions both pre- and post-assessment were aggregated across activities, stratified by 2 learning themes.

Significant improvements (n=31-756, P<0.05-0.001) were seen for knowledge/competence across all providers (psychiatrists, psychiatry NPs, psychiatry PAs, PCPs, primary care NPs, and primary care PAs) for both learning themes – “Appropriate depression medication selection and modification” and “Evaluating residual symptoms in patients with MDD”. Notable improvements:

• • There was a 48% relative improvement among PCPs, 26% relative improvement among primary care NPs, 42% relative improvement among primary care PAs, 19% relative improvement among psychiatrists, 23% relative improvement among psychiatry NPs, and 24% relative improvement among psychiatry PAs (P<0.001) related to appropriate depression medication selection and modification.

• • There was a 47% relative improvement among PCPs (P<0.01), 41% relative improvement among NPs (P<0.01), 18% relative improvement among psychiatrists, 33% relative improvement among psychiatry NPs, and 52% among psychiatry PAs (P<0.001) related to evaluating residual symptoms in patients with MDD.

Participation in CME interventions significantly improved knowledge/competence and confidence among psychiatric and primary care providers. This study identified persistent gaps in clinician knowledge and competence related to MDD care that may guide future education.

Medscape Education, Takeda Pharmaceuticals

Schizophrenia is a severe chronic illness that affects approximately 1% of the population worldwide and is estimated to affect at least 3.5 million people in the United States. Although a range of antipsychotic medications exists for treating schizophrenia, outcomes have historically been poor, and evidence confirms that clinicians remain challenged to individualize treatment for patients living with schizophrenia.

This study was designed to understand the clinical practice gaps and perspectives of clinicians related to managing schizophrenia and help inform the development of education and tools to improve clinician knowledge, competence and confidence.

A survey instrument containing 24 multiple choice, knowledge and case-based questions was used to assess participants’ knowledge, attitudes, and confidence in the management of Schizophrenia. The survey was available online to US and global physicians without monetary compensation or charge. Respondent confidentiality was maintained, and the responses were de-identified and aggregated prior to analyses. Questions were grouped into clinical themes and analyzed. Data were collected from 8/11/2022 to 12/14/2022.

In total, 560 psychiatrists, and 94 Primary Care Physicians answered all questions in the assessment. Physicians demonstrated gaps in the following areas:

This educational research on assessment of clinical practices revealed important knowledge and competence gaps amongst psychiatrists and PCPs who manage patients with Schizophrenia. Addressing these gaps is critical to improving the management of patients.

Medscape Education, Cerevel Therapeutics

Centanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI) in development for ADHD. In 2 pivotal adult ADHD trials, CTN sustained-release (SR) 200 mg/d and 400 mg/d, administered twice daily (BID), significantly reduced Adult ADHD Investigator Symptom Rating Scale (AISRS) total score vs placebo, with favorable safety and tolerability. Long-term effects of CTN SR 400 mg/d in adult ADHD are reported here.

Adults meeting DSM-5 criteria for ADHD who completed a pivotal trial or enrolled de novo were eligible for the 52-week, phase 3, open-label trial. Uncontrolled comorbid psychiatric disorder, undifferentiated diagnosis of ADHD, prohibited medicines, or positive alcohol or drug screen were exclusionary. All patients (pts) received CTN SR BID, titrated to 400 mg/d by day 8, and fixed thereafter. Safety was primarily assessed by adverse events (AEs); laboratory results, physical examinations, vital signs, ECG, Study Medication Withdrawal Questionnaire (SMWQ), and Columbia-Suicide Severity Rating Scale (C-SSRS) were also assessed. Efficacy was assessed by AISRS, Clinical Global Impression-Severity (CGI-S) and ADHD Impact Module-Adult (AIM-A). Analyses were based on observed results using descriptive statistics. Baseline was relative to the first CTN dose in the open-label trial.

Of 662 pts enrolled (mean [SD] age 36.7 [10.1] years; 51.1% female; 82.9% White), 653 received CTN SR; 345 pts completed the trial. Common discontinuation reasons were pt withdrawal (119; 18%), AEs (81; 12.2%), and lost to follow-up (41; 6.2%); 22 (3.4%) pts discontinued for lack of efficacy. Treatment-emergent AEs (TEAEs) occurred in 401 pts (61.4%); 16 (2.5%) had severe TEAEs. Common TEAEs were insomnia (8.0%), nausea (7.7%), diarrhea, and headache (7.0% each). Serious TEAEs occurred in 12 pts (1.8%); none were CTN related. AEs of special interest (n=18; 2.8%) included rash (n=5; 1 severe), papule, rash erythematous, rash maculopapular, rash papular, and urticaria (n=1 each); 3 discontinued. Abuse potential–related AEs occurred in 31 pts (4.7%). No deaths occurred. SMWQ scores were low throughout. Suicidal ideation/behavior occurred in 13 pts (2.0%) per C-SSRS. There were no trends in laboratory, vital sign, or ECG changes. Baseline mean (SD) AISRS Total, Inattentive, and Hyperactive-Impulsive scores were 34.4 [10.3], 19.2 [5.6], and 15.2 [6.0], respectively; mean (SD) changes at week 52 were −20.4 (11.9), −11.2 (6.6), and −9.2 (6.2). Baseline mean (SD) CGI-S score was 4.2 (0.9); mean (SD) change at week 52 was −1.5 (1.1). Baseline mean (SD) AIM-A score was 6.5 (1.8); mean change at week 52 was 1.23 (2.0).

Safety, tolerability, and exploratory efficacy results from this trial demonstrate that CTN SR 400 mg is a safe and effective long-term treatment for ADHD in adults.

Study Registration: NCT03605849

Previous presentation: APA Annual Meeting, May 20–24, 2023, San Francisco, CA

Otsuka