The elevated prevalence of metabolic syndrome (MetS) in patients with depression has been associated with increased mortality. This post hoc analysis assessed the effect of treatment with lurasidone on risk of MetS in patients with bipolar depression.

Data used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (N = 1192), consisting of 1 monotherapy, and 2 adjunctive trials (lithium or valproate). Also analyzed was a 6-month open-label (OL) extension study (monotherapy, N = 316; adjunctive therapy, N = 497); and a 5-month, OL, stabilization phase followed by randomization to a 28-week DB, placebo-controlled, adjunctive therapy study with lurasidone (N = 490). MetS was defined based on NCEP ATP III criteria (2005 revision).

The proportion of patients with new-onset MetS was similar for lurasidone vs placebo in the short-term studies (monotherapy, 13.9% vs 15.3%; adjunctive therapy, 13.6% vs 11.0%); and remained stable during both the 6-month extension phase study (monotherapy, 15.2%; adjunctive therapy, 16.9%), and the 5-month stabilization study (adjunctive therapy, 12.2%). After 28 weeks of DB treatment (following 5-month treatment in the stabilization study), new onset MetS was observed at endpoint (OC) in 26.2% of the lurasidone group, and 30.8% of the placebo group.

This post hoc analysis found that both short and long-term treatment with lurasidone was associated with a relatively low risk for the development of MetS in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.

Lurasidone is an atypical antipsychotic used in the treatment of schizophrenia and bipolar depression. Both indications are approved by the FDA nowadays, whereas in Europe it is only approved for schizophrenia. Lurasidone has been barely studied for the treatment of acute mania, nonetheless it is sometimes used off-label.

A case of a patient with a manic episode treated with lurasidone is presented, in order to provide further evidence on this topic.

The patient is a 43 year-old-woman with diagnosis of type I bipolar disorder, personality disorder and borderline intellectual functioning, resident in our Hospital’s long-stay psychiatric rehabilitation unit. She was previously under treatment with venlafaxine 75 mg/day, valproate 1500 mg/day and levomepromazine 25 mg on demand; remaining stable for months. The patient presented an episode consisting on agitation, irritability, verbiage, tachyphase, verbal aggressiveness and behavioral disturbances. Psysical restraint was needed for one day long and zuclopenthixol acetate 50 mg IM was administered twice within 5 days for the acute agitation. Venlafaxine was immediately withdrawn and lurasidone was progressively introduced up to 111 mg daily.

Approximately 3 weeks after the treatment adjustment, the patient reached the psychopatological stabilty.

Antidepressive withdrawal and introduction of Lurasidone were effective to treat the acute manic episode in this patient. It has been previosuly suggested that lurasidone caused improvement in emergent manic symptoms in patients with bipolar depression, and in subsyndromal hypomanic symptoms in patients with mixed features of depression. However, no studies have been made yet to evaluate the efficacy of lurasidone in acute mania.

I received financing from Angelini Pharma, Casen Recordati, Janssen, Exeltis and Otsuka.

Lurasidone is a second-generation antipsychotic shown to have a lower risk of weight gain and a lower incidence of metabolic adverse events compared with some medications in the same class.

To describe treatment patterns, clinical outcomes and adverse drug reactions (ADRs) over 12 months following lurasidone initiation in patients with schizophrenia.

This was a multi-centre observational study involving data collection from patients’ medical records, conducted in seven mental health centres in the United Kingdom (UK) and Switzerland. The study included patients aged ≥18 years who initiated lurasidone after 1 January 2016 for the treatment of schizophrenia. Data were collected from medical records both retrospectively and prospectively using a standardised data collection form. Data collected included patient characteristics, treatment history, lurasidone regimens, clinical outcomes and ADRs.

Forty-eight patients participated in the study. The median (interquartile range [IQR]) age at lurasidone initiation was 33.5 (25.5-50.3) years and 31 (65%) patients were male. The median (range) lurasidone starting dose was 37 mg daily (9.3–148 mg). Thirty-eight (79%) patients continued lurasidone for the entire 12-month follow-up period. Among the 14 (29%) patients with documented relapse, the median (IQR) time to relapse was 3.4 (1.5–7.9) months. Five ADRs were recorded in patient notes judged as related to lurasidone: agitation, nausea, akathisia, somnolence and vomiting (one patient each).

In this real-world study of patients with schizophrenia in the UK and Switzerland, 79% of patients continued lurasidone for at least 12 months, and ADRs were reported rarely in patient notes.

This study was sponsored by CNX Therapeutics Ltd (formerly Sunovion Pharmaceuticals Europe Ltd). AJ is an employee of CNX Therapeutics. MA is an employee of OPEN HEALTH who was contracted by CNX Therapeutics for data analysis and medical writing.

Obsessive-Compulsive Disorder (OCD) is characterized by the presence of intrusive thought (obsessions) and ritualistic behaviour (compulsions). First-choice psychopharmacological treatment is based on serotonin reuptake inhibitors (SRIs). However, about half of OCD do not or partially respond to SRIs (TR-OCD) and need an augmentation strategy with second-generation antipsychotics (SGAs).

We report a case of severe OCD with comorbid anorexia nervosa, restrictive type (AN-r) treated with fluoxetine (up to 40 mg daily) and lurasidone (37 mg daily bedtime) augmentation.

At baseline and monthly 4-months-follow-up were administered Y-BOCS-II (Yale-Brown Obsessive Compulsive Scale), CGI-S (Clinical Global Impression-Severity), SCL-90 (Symptom Checklist-90 items) and EDI-3 (Eating Disorder Inventory-3).

Compared to the baseline, a clinically significant clinical response was observed on OC at Y-BOCS-II (≥35% Y-BOCS reduction) and eating symptomatology at EDI-3 after 1 month of augmentation treatment, while a full remission after 3 months (Y-BOCS scoring ≤ 14)(p<0.01). We also noticed, throughout clinical follow up interviews, improvement in patient’s social skills and life satisfaction.

Further longitudinal and real-world effectiveness studies are needed to confirm these preliminary findings and investigate the potential of lurasidone augmentation strategy in attenuating OC symptomatology in TR-OCD and whereas a comorbid AN-r is present.

No significant relationships.

Schizophrenia is a chronic neuropsychiatric disorder which affects over 20 million people worldwide. Atypical antipsychotics are the first-line choice for the treatment of schizophrenia due to improved tolerability and diminished risk of extrapyramidal symptoms. Lurasidone is an atypical antipsychotic approved in Spain for the treatment of schizophrenia in September 2019. An RWD-based picture of lurasidone use is necessary to better understand its impact in routine clinical practice.

To set up a methodology based on Natural Language Processing (NLP) and machine learning for the analysis of the free-text information contained in the EHRs of patients treated with lurasidone in Spain.

A multicenter, retrospective study based on RWD collected in EHRs of lurasidone users will be conducted in hospitals from the Spanish National Healthcare System. Information extracted from the free text in EHRs using NLP will be treated and analyzed as big data.

A study database for lurasidone-treated patients in Spain has been instituted using the EHRead® technology (Figure 1), which applies machine learning and deep learning to extract, analyze, and interpret the free-text information written in their de-identified EHRs. Sociodemographic and clinical variables in EHRs from September 2019 until the most recent data available are being collected to describe the target patient population and address treatment-related outcomes.

NLP of free text in EHRs of lurasidone-treated patients renders a real-world picture of lurasidone usage in Spain. Studies using artificial intelligence techniques represent a novel source of information regarding psychiatric disorders and their clinical management.

I. Gabarda is employee at Angelini Pharma España, S.L.U. and C. de la Pinta is employee at Medsavana.

Lurasidone is an atypical antipsychotic agent with potential antidepressant effects through its antagonist activity at the 5-HT7 receptor. Although treatment-emergent affective switch (TEAS) induced by second-generation antipsychotics are not frequent, several cases have been reported. To our knowledge, there is no evidence of lurasidone-induced TEAS.

To describe a case of lurasidone-induced mania.

We describe a clinical case of a patient admitted to our psychiatric outpatient unit who developed a manic episode, presumably induced by the introduction of lurasidone. We also conduct a review of the literature on this subject.

A 37-year-old man diagnosed with obsessive-compulsive disorder (OCD) and an alcohol use disorder was hospitalized due to OCD decompensation with depressive symptomatology and suicidal thoughts, and for alcohol detoxification process. Since he had a previous history of clomipramine-induced TEAS, he was started on lurasidone up to 111mg to avoid the use of antidepressants, showing a progressive improvement of depressive symptoms. Thus, the patient was discharged when alcohol detoxification process was completed. Eight days after discharge, the patient began to show manic symptoms, so he had to be readmitted. Lurasidone was discontinued and valproic acid up to 1000mg/day as mood stabilizer was added, presenting a positive remission of manic symptoms.

According to our experience, lurasidone may have induced an affective switch in this patient. Based on our findings, patients and psychiatrists should monitor possible lurasidone-induced mood switching. However, further research is needed in order to back-up this one case report findings.

No significant relationships.

To evaluate the efficacy of short-term lurasidone in antipsychotic treatment-naïve (TN) adolescents with schizophrenia versus those treated previously (TP) with antipsychotics.

Patients aged 13–17 with schizophrenia, and a Positive and Negative Symptom Scale (PANSS) score ≥ 70 and < 120, were randomized to 6 weeks of double-blind treatment with lurasidone (40 or 80 mg/day) or placebo. In a post-hoc, pooled-dose analysis, efficacy was evaluated for TN (criteria: never received antipsychotic treatment) versus TP at the time of the study. Treatment response criteria: ≥20% reduction in PANSS total score.

Altogether, 57 TN and 269 TP patients enrolled in the 6-week DB study. Mean endpoint change in PANSS total score was significantly greater for lurasidone versus placebo in both the TN group (−25.0 vs. -14.4; p < 0.02; effect size = 0.75), and in the TP group (−17.3 vs. -10.0; p < 0.001; effect size = 0.45); and responder rates were higher for lurasidone versus placebo in both the TN group 84.6% versus 38.9%; number needed to treat [NNT] = 3 and in the TP group (60% vs. 42%; NNT = 6). Rates of treatment-emergent adverse events, and mean changes in body weight and metabolic parameters were similar for the TN and TP groups.

In a 6-week, placebo-controlled trial, lurasidone demonstrated significant efficacy in adolescents with schizophrenia regardless of previous antipsychotic therapy status; however, the effect size was notably larger in the TN patient group. In both the TN and TP groups, minimal effects were noted on weight, metabolic parameters, or prolactin.

Onset of schizophrenia commonly occurs during late adolescence or early adulthood and is often characterized by greater symptom severity and impairment.

To evaluate the efficacy and safety of lurasidone in the treatment of acute schizophrenia in adolescents and young adults.

The 4 studies in this pooled analysis used similar study designs. Patients (ages 13-25 years) were randomized to 6 weeks of double-blind, placebo-controlled treatment with once-daily lurasidone (37 mg, 74 mg, 111 mg, 148 mg). The primary outcome was endpoint change in the Positive and Negative Syndrome Scale (PANSS) total score; secondary measures included the Clinical Global Impression, Severity scale (CGI-S).

The safety population consisted of 537 patients; 79.1% completed the studies. Treatment with lurasidone was significant (P<0.001) at Week 6 endpoint for change in the PANSS total score, with higher effect sizes (ES) at higher doses (37 mg, 0.53; 74 mg, 0.57; 111 mg, 0.67; 148 mg, 1.35); significance was also observed for change in the CGI-S (37 mg, 0.51; 74 mg, 0.49; 111 mg, 0.57; 148 mg, 1.75). For lurasidone (combined doses), 3 adverse events occurred with a frequency ≥5% (nausea, 13.5%; somnolence, 12.1%; akathisia, 10.1%); 4.8% of patients discontinued due to an adverse event. At LOCF-endpoint, 3.6% of patients had weight gain ≥7%, and 1.5% had weight loss ≥7%. Minimal median changes were observed at endpoint in metabolic lab values.

In adolescents and young adults with schizophrenia, treatment with lurasidone in doses of 37-148 mg/d was a safe, well-tolerated, and effective treatment.

Presenter is an employee of Sunovion Pharmaceuticals Inc. The study summarized in this Abstract was supported by Funding from Sunovion Pharmaceuticals Inc.

Compared with adult onset, early onset schizophrenia is typically characterized by greater illness severity and less favorable prognosis.

To evaluate the proportion of adolescent patients with schizophrenia who achieved sustained remission and recovery during 2 years of treatment with lurasidone.

Patients aged 13-17 years with a DSM-IV-TR diagnosis of schizophrenia, and a Positive and Negative Symptom Scale (PANSS) total score ≥70 and <120, were randomized to 6 weeks of double-blind (DB), fixed-dose treatment with lurasidone (37 or 74 mg/d) or placebo. Patients who completed 6 weeks of DB treatment were eligible to enroll in a 2-year, open-label (OL), flexible dose extension study of lurasidone (18.5-74 mg/d). Criteria for sustained remission, were the 6-month consensus criteria summarized by Andreasen (Am J Psych 2005;162:441-9). Criteria for sustained recovery consisted of meeting sustained remission criteria with a Children’s Global Assessment Scale (CGAS) score ≥70 for at least 6-months indicating no clinically significant functional impairment.

A total of 271 patients completed the 6-week DB study and entered the extension study, and 186 (68.6%) and 156 (57.6%) completed 52 weeks and 104 weeks of treatment, respectively. During OL treatment with lurasidone, 52.8% met sustained remission criteria, with a Kaplan-Meier (KM) estimate of 64.1 weeks for median time to sustained remission; and 28.8% met sustained recovery criteria, KM estimate of 104.6 weeks for median time to sustained recovery.

For adolescents with schizophrenia, treatment with lurasidone was associated with high rates of sustained remission and sustained recovery over a two-year period.

Employee of Sunovion Pharmaceuticals Inc. The study summarized in this Abstract was supported by funding from Sunovion Pharmaceuticals Inc

Psychosis itself may be associated with an increased risk of atrial fibrillation. Moreover, antipscyhotic treatment increases this risk. Recently D’Urso et al. reported aripiprazole-induced atrial fibrillation in a patient with concomitant risk factors.

To the best of author’s knowledge no data has been published about the safety and the efficacy of lurasidone treatment in psychotic patient with comorbid atrial fibrillation.

A 68 years old patient with persistent atrial fibrillation and hypertension in treatment with amiodarone 100 mg/day, lurasidone 25 mg/day, rivaroxaban 15 mg/day, clopidogrel 75 mg/day, bisoprolol 1,25 mg/day, tamsulosin 0,4 mg/day presented delusional ideas of jealousy for not real betrayal by his wife, social withdrawal, reduced sleep. Blood pressure 130/80 mmHg, heart rate 70 bpm, Qtc 420 msec. The patient was drug-naïve for any psychotropic treatment. The authors decided to start lurasidone treatment at the dosage of 18,5 mg/day.

After the first administration of lurasidone treatment sleep was resolved. After two weeks delusional ideas and social withdrawal were markedly improved. After one month of treatment, blood pressure, heart rate and Qtc remained almost stable. The authors decided not to increase the dosage of lurasidone because of the age of the patient and the comorbid cardiovascular pathologies.

Lurasidone has showed safety and efficacy in the treatment of this patient with delusional disorder and comorbid atrial fibrillation. This is a preliminary data that requires follow up and further studies to confirm the usefulness of lurasidone in psychotic patients with atrial fibrillation and cardiovascular risks.

No significant relationships.

Lurasidone is an atypical antipsychotic approved for the treatment of patients with schizophrenia. We report on a meta-analysis focusing on both the efficacy and safety/tolerability of lurasidone in the treatment of patients with schizophrenia.

To obtain pooled estimates from placebo-controlled clinical trials on the efficacy and safety/tolerability of lurasidone in schizophrenia.

We selected acute, randomized placebo-controlled trials of lurasidone for schizophrenia. Primary outcome for efficacy was the Positive and Negative Syndrome Scale (PANSS) change and for “acceptability” was all-cause discontinuation. Secondary outcomes included specific adverse events, body weight change, ≥7% weight gain, and glucose and lipid parameter change.

Across 10 RCTs (n=3,963, age=40.5±2.3 years, males=64.7 %, trial duration=6.0 weeks), lurasidone outperformed placebo regarding the PANSS total score (N=10, n=3,354, SMD=-0.34, 95% CI: -0.47−-0.21, p<0.001). Stratifying the analysis by dose, lurasidone significantly outperformed placebo at doses 40-160 mg/day. Lurasidone was associated with significantly lower all-cause discontinuation than placebo (N=10, n=3,410, RR=0.87, 95% CI: 0.78−0.97, p=0.014). Lurasidone had significantly higher body weight change compared with placebo (N=10, n=3,359, SMD=0.17, 95% CI: 0.09−0.24, p<0.001), but without significant differences regarding ≥7% body weight gain (N=9, n=3,186, p=0.112). Lurasidone did not differ from placebo in total cholesterol (N=10, n=3,140, p=0.439), LDL-cholesterol (N=7, n=2,414, p=0.849), triglycerides (N=10, n=3,140, p=0.238), and fasting glucose change (N=10, n=3,112, p=0.633).

In short-term trials, lurasidone was efficacious, acceptable and safe, having minimal effect on body weight gain and glucose and lipid metabolism.

K. Hagi is a full time employee of Sumitomo Dainippon Phrma Co., Ltd.

The aim of this pooled analysis was to evaluate the efficacy and safety of lurasidone in the treatment of an acute exacerbation of schizophrenia in adolescents and young adults.

The six pooled studies in this analysis used similar study designs and outcome measures. Patients (aged 13–25 years) were randomized to 6 weeks of double-blind, placebo-controlled treatment with lurasidone in fixed doses of 40, 80, 120, or 160 mg. The primary efficacy endpoint was Week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score; secondary efficacy endpoints included Week 6 change in the Clinical Global Impression–Severity scale.

The safety population consisted of 537 patients (mean age: 18.1 years); 82.6% of patients completed the studies. Treatment with lurasidone was significantly better than placebo at all doses (p < 0.001) for change in the PANSS total score at Week 6. Placebo-adjusted PANSS scores ranged from −9.4 to −16.1 (effect sizes: 0.53–0.90), with effect sizes increasing at higher doses. For lurasidone (combined doses), three adverse events occurred with a frequency of ≥5% (nausea: 13.5%; somnolence: 12.1%; akathisia: 10.1%). At last observation carried forward (LOCF)-endpoint weight gain of ≥7% was similar for lurasidone versus placebo (3.6 vs. 4.7%). Minimal median changes were observed at endpoint in cholesterol, −2.0 mg/dL; triglycerides, 0.0 mg/dL; and glucose, 0.0 mg/dL.

In adolescents and young adults with schizophrenia, treatment with lurasidone in doses of 40–160 mg/d was a safe, well-tolerated, and effective treatment. Short-term treatment with lurasidone was associated with minimal effects on weight and metabolic parameters.

Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia.

Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score.

About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104.

In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.

To assess the effects of treatment with lurasidone on risk for metabolic syndrome (MetS) in patients with schizophrenia.

Rates of metabolic syndrome during treatment with lurasidone (40-160 mg/d) were analyzed using pooled, short-term data from three randomized, double-blind, placebo-controlled studies (vs olanzapine and quetiapine XR); long-term data from two active-comparator-controlled studies (vs risperidone and quetiapine XR); and data from two open-label studies in which patients were switched from olanzapine or risperidone to lurasidone.

MetS was defined based on the National Cholesterol Education Program criteria. In short-term studies, the odds of meeting criteria for MetS at week 6 LOCF (adjusted for baseline metabolic syndrome status) was similar for the lurasidone and placebo groups (OR = 1.18; [95% CI, 0.81-1.71]; P = .39), but the odds (vs placebo) were significantly greater for olanzapine (OR = 2.81; [95% CI, 1.53-5.15]; P < .001) and quetiapine (OR = 3.49; [95% CI, 1.93-6.29]; P < .0001). No dose effect was observed for lurasidone across the dose range of 40-160 mg/d. In long-term studies, the odds of MetS after 12 months of treatment was significantly higher for risperidone compared with lurasidone (OR = 2.12; 95% CI, 1.15-3.90; P = .016) and for quetiapine XR compared with lurasidone (OR = 3.92; 95% CI, 1.15-13.40; P = .029). In open-label extension studies, the rate of MetS decreased in patients switched to lurasidone after 6 weeks of treatment with olanzapine or 12 months of treatment with risperidone.

In this analysis of lurasidone clinical trials, the odds of developing metabolic syndrome were minimal during short- and long-term treatment with lurasidone (40-160 mg/d).

To evaluate the efficacy of lurasidone for schizophrenia using an established five-factor model of the Positive and Negative Syndrome Scale (PANSS).

Patient-level data were pooled from five randomized, double-blind, placebo-controlled, 6-week studies of lurasidone (fixed doses, 40–160 mg/d) for patients with an acute exacerbation of schizophrenia. Changes in five established PANSS factors were assessed using mixed-model repeated measures analysis.

Compared with placebo (n = 496), lurasidone (n = 1029, dose groups pooled) significantly improved the PANSS total score at Week 6 (−22.6 vs. −12.8; P < 0.001; effect size, 0.45), as well as all factor scores (P < 0.001 for each): positive symptoms (−8.4 vs. −6.0; effect size, 0.43), negative symptoms (−5.2 vs. −3.3; effect size, 0.33), disorganized thought (−4.9 vs. −2.8; effect size, 0.42), hostility/excitement (−2.7 vs. −1.6; effect size, 0.31), and depression/anxiety (−3.2 vs. −2.3; effect size, 0.31). Separation from placebo occurred at Week 1 for the positive symptoms, disorganized thought, and hostility/excitement factors and at Week 2 for the other factors.

In this pooled analysis of short-term studies in patients with acute schizophrenia, lurasidone demonstrated significant improvement for each of the five PANSS factor scores, indicating effectiveness across the spectrum of schizophrenia symptoms.

Aberrations in reward and penalty processing are implicated in depression and putatively reflect altered dopamine signalling. This study exploits the advantages of a placebo-controlled design to examine how a novel D2 antagonist with adjunctive antidepressant properties modifies activity in the brain's reward network in depression.

We recruited 43 medication-naïve subjects across the range of depression severity (Beck's Depression Inventory-II score range: 0–43), including healthy volunteers, as well as people meeting full-criteria for major depressive disorder. In a double-blind placebo-controlled cross-over design, all subjects received either placebo or lurasidone (20 mg) across two visits separated by 1 week. Functional magnetic resonance imaging with the Monetary Incentive Delay (MID) task assessed reward functions via neural responses during anticipation and receipt of gains and losses. Arterial spin labelling measured cerebral blood flow (CBF) at rest.

Lurasidone altered fronto-striatal activity during anticipation and outcome phases of the MID task. A significant three-way Medication-by-Depression severity-by-Outcome interaction emerged in the anterior cingulate cortex (ACC) after correction for multiple comparisons. Follow-up analyses revealed significantly higher ACC activation to losses in high- v. low depression participants in the placebo condition, with a normalisation by lurasidone. This effect could not be accounted for by shifts in resting CBF.

Lurasidone acutely normalises reward processing signals in individuals with depressive symptoms. Lurasidone's antidepressant effects may arise from reducing responses to penalty outcomes in individuals with depressive symptoms.

The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety.

The data in this analysis were derived from a study of patients meeting the DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/day (n=109) or placebo (n=100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM–A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM–A≤14) and moderate-to-severe anxiety (HAM–A≥15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures.

Treatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (–18.4 vs. –12.8, p<0.01, effect size [ES]=0.59) and moderate-to-severe anxiety (–22.0 vs. –13.0, p<0.001, ES=0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM–A total score for patients with both mild anxiety (–7.6 vs. –4.0, p<0.01, ES=0.62), and moderate-to-severe anxiety (–11.4 vs. –6.1, p<0.0001, ES=0.91).

In this post-hoc analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.

The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability.

The data in this analysis were derived from a study of patients meeting DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/d (n=109) or placebo (n=100). We defined “irritability” as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability.

Some 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (–22.6 vs. –9.5, p<0.0001, effect size [ES]=1.4) and without (–19.9 vs. –13.8, p<0.0001, ES=0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (–1.4 vs. –0.3, p=0.0012, ES=1.0) and the YMRS disruptive-aggressive item (–1.0 vs. –0.3, p=0.0002, ES=1.2).

In our post-hoc analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.

This post-hoc analysis assessed rates of symptomatic and functional remission, as well as recovery (combination of symptomatic and functional remission), in patients treated with lurasidone for major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features).

Patients with MDD plus two or three manic symptoms (defined as per the DSM–5 mixed-features specifier) were randomly assigned to flexible-dose lurasidone 20–60 mg/day (n=109) or placebo (n=100) for 6 weeks, followed by a 3-month open-label, flexible-dose extension study for U.S. sites only (n=48). Cross-sectional recovery was defined as the presence of both symptomatic remission (Montgomery–Åsberg Depression Rating Scale score ≤ 12) and functional remission (all Sheehan Disability Scale [SDS] domain scores ≤3) at week 6, and at both months 1 and 3 of the extension study (“sustained recovery”).

A significantly higher proportion of lurasidone-treated patients (31.3%) achieved recovery (assessed cross-sectionally) compared to placebo (12.2%, p=0.002) at week 6. The number of manic symptoms at baseline moderated the effect size for attaining cross-sectional recovery for lurasidone treatment (vs. placebo) (p=0.028). Sustained recovery rates were higher in patients initially treated with lurasidone (20.8%) versus placebo (12.5%).

In this post-hoc analysis of a placebo-controlled study with open-label extension that involved patients with MDD and mixed features, lurasidone was found to significantly improve the rate of recovery at 6 weeks (vs. placebo) that was sustained at month 3 of the extension study. The presence of two (as opposed to three) manic symptoms moderated recovery at the acute study endpoint.