Young Mania Rating Scale Items Research Articles

Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder

BackgroundHostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. MethodsData were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3–12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS–Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. ResultsMost patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [−0.93], disruptive-aggressive behavior [−0.79], combined [−1.75]; P ≤ 0.001 each), YMRS total score (−5.92, P ≤ 0.0001), and all individual YMRS items (−0.25 to −0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LimitationsPost hoc analysis. ConclusionCariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.

0642 Effect of Iloperidone on Sleep Symptoms in Bipolar Patients with Manic and Mixed Episodes: A Randomized, Placebo Controlled Study

Abstract Introduction Iloperidone, a dopamine D2 receptor and serotonin 5HT2A receptor antagonist, was evaluated for the treatment of acute manic and mixed episodes associated with bipolar I disorder in adults in a phase 3 clinical trial. A core symptom of bipolar I disorder is disturbance in sleep. During manic episodes this commonly presents as reduced need for sleep with studies finding that 69%–99% of bipolar individuals report a lessened need for sleep or difficulties in falling and/or staying asleep. Here we present a post hoc analysis evaluating iloperidone effects on the sleep component of the Young Mania Rating Scale (YMRS) in patients with bipolar I disorder which addresses both sleep and the reduced need for sleep in that component. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study of iloperidone in patients with acute manic or mixed episodes associated with bipolar I disorder. Patients received four weeks of double-blind treatment. The primary analysis demonstrating an overall improvement from baseline YMRS score in iloperidone assigned patients versus placebo assigned patients (p = 0.000008) at the end of the study (week 4). A YMRS item level analysis evaluated changes on YMRS single items including the sleep component in the intent-to-treat population (N = 392) using a mixed-effects model for repeated measures approach. Results The least squares mean difference (LSMD) in change from baseline to day 28 was statistically significant on the YMRS sleep component in favor of iloperidone versus placebo (iloperidone = -1.26, placebo = -0.95; p = 0.008). Conclusion In addition to improving overall mania symptoms as reported by the YMRS, improvements were also seen in iloperidone treated patients in the sleep component which at baseline included assessments of both decreased sleep and decreased need or denial of the need for sleep. Support (if any) This work was supported by Vanda Pharmaceuticals Inc.

Mixed Features in Bipolar Disorder: assessing symptoms profiles and their relation with DSM-5 criteria

IntroductionMixed states, the co-occurrence of manic and depressive symptoms, were recognized and described from the time of antiquity. DSM-5 first, and DSM-5-TR after, introduced the ‘’mixed features’’ specifier, defined by the presence of at least three non-overlapping opposite-pole symptoms during a syndromic depressive, hypomanic, or manic episode. Various manifestations, including irritability, distractibility, anxiety, psychomotor agitation, were excluded from the specifier, since they can occur during both depressive and hypo/manic episodes and other mental illnesses.ObjectivesThe objective of this study was to evaluate the phenomenology and prevalence of mixed states among bipolar disorder (BD) patients. We first assessed the frequency of specific features during different mood states. Then, we estimated the prevalence of mixed states by applying DSM-5 criteria, comparing it qualitatively with the one detected from psychometric questionnaires.MethodsIn a naturalistic study, 903 adult outpatients with BD participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,213 visits for 7 years. The scores at the Inventory of Depressive Symptomatology–Clinician-Rated Version (IDS-C) and at the Young Mania Rating Scale (YMRS), administered at each visit, were used to define the mood episode and to assess the frequency of specific symptoms. In addition, we applied DSM-5 criteria for “with mixed features” to our sample, to examine a DSM-5-based construct.ResultsSpecific symptomatic profiles differentiate mixed states from pure ones (Figure 1 and 2). Mainly, a higher prevalence of irritability was found during mixed episodes, both depressive and hypo/manic, compared to pure depression (0.60 vs. 1.20, p < 0,001) and hypo/mania (0.82 vs. 1.54, p < 0,001), as reported at the 6th item of IDS-C.Figure 1. Individual YMRS items scores in visits with pure depression, mixed depression, pure hypo/mania and mixed hypo/mania.Figure 2. Individual IDS-C items scores in visits with pure depression, mixed depression, pure hypo/mania and mixed hypo/mania.Image:Image 2:ConclusionsPreliminary results of the present study showed that symptoms like irritability are strongly prevalent during mixed states. Moreover, the DSM-5 diagnostic criteria for “with mixed features” specifier for any of the mood episodes detected lower rates of mixed states, hence this criteria may yield inadequate sensitivity in recognizing patients suffering from such conditions.Disclosure of InterestNone Declared

Symptoms and Characteristics of Youth Hospitalized for Depression: Subthreshold Manic Symptoms Can Help Differentiate Bipolar from Unipolar Depression.

Background: Most people who have major depressive disorder (MDD) or bipolar disorder (BD) will have their first episode of depression in adolescence. However, in the absence of significant [hypo]manic symptoms, there are no clear guidelines for distinguishing bipolar from unipolar depression, which can lead to misdiagnosis and ineffective/harmful treatment. We aimed to compare phenomenological differences among youth with MDD or BD hospitalized for an acute episode of depression. Methods: A retrospective electronic chart review of adolescents hospitalized in an acute care inpatient unit who had a discharge diagnosis of MDD, MDD with mixed or psychotic features (MDD+), BD-I-current episode depressed, or BD-II-current episode depressed, was performed. Results: Altogether, 598 patients (mean age = 15.1 ± 1.5 years, female = 71%, and White = 46%) met study inclusion criteria, i.e., BD-I: n = 39, BD-II: n = 84, MDD: n = 422, and MDD+: n = 53 patients. The admission Hamilton Depression Rating Scale (HAMD) total score was significantly higher in the BD-I (29.3 ± 9.1) and MDD+ (31.2 ± 9.3) groups versus the MDD group (24.3 ± 9.7) (p < 0.05). Although there were some group differences in the severity of individual depression symptoms, these did not line up neatly across BD and MDD groups. At admission, Young Mania Rating Scale (YMRS) total scores were significantly higher in the BD-I (14.4 ± 7.4), BD-II (13.8 ± 6.5), and MDD+ groups (14.3 ± 6.6) versus the MDD group (8.2 ± 4.6, p < 0.05). Additionally, 9 of 11 and 4 of 11 YMRS items scored significantly higher in the BD-II and BD-I groups versus the MDD group, respectively. The motor activity and hypersexuality items, in particular, were scored consistently higher in the BD groups than MDD groups. Limitations: All diagnoses were made based on a clinical interview and not a structured diagnostic interview, and some of the subgroup sample sizes were relatively modest, limiting the power for group comparisons. Conclusion: The presence of subsyndromal manic symptoms during an episode of MDD currently offers the clearest way by which to differentiate bipolar depression from unipolar depression.

Reliability, validity and psychometric properties of the Greek version of the Altman self rating mania scale

BackgroundAlthough self-rating mania scales have been developed, a lack of such instruments validated for the Greek population is noted. This study aims to examine the validity, reliability and psychometric properties of the Altman Self Rating Mania Scale (ASRM) adapted in Greek (G-ASRM). MethodsA sample of 86 consecutive inpatient and outpatient bipolar patients diagnosed by the DSM-5 criteria and 37 healthy controls were assessed by using the Young Mania Rating Scale (YMRS) and the Montgomery Asberg Depression Rating Scale (MADRS), and self-administered the G-ASRM. Factor analysis, test-retest analysis, measurement invariance tests, mean differences, Pearson's Correlation analysis and ROC analysis were used to confirm the validity of G-ASRM as a scale, test its reliability, study its psychometric properties in different subgroups and establish a cut-off value for indicating the presence of (hypo)mania in BD patients. Also, regression models were built to expose dependencies between YMRS and G-ASRM items. ResultsMonofactoriality of the scale was verified, based on Exploratory Factor Analysis (EFA). Cronbach's alpha was 0.895. G-ASRM is highly correlated with YMRS (r = 0.856, p < 0.0005) and uncorrelated with MADRS (r = −0.051, p = 0.623). Test- retest r-coefficient was calculated at 0.85. The optimal cut-off score, set at ≥6 for (hypo)mania assessment, is in agreement with the results reported for the original version. Limitations of the study are that the scale was not normed on diagnostic groups other than bipolar, nor was it administered longitudinally, so as to assess its sensitivity to symptom changes overtime. ConclusionThe G-ASRM can be validly and reliably used in the Greek population for the assessment of (hypo)mania in bipolar patients.

Prominent autistic traits and subthreshold bipolar/mixed features of depression in severe anorexia nervosa.

Objective:Autistic traits are associated with a burdensome clinical presentation of anorexia nervosa (AN), as is AN with concurrent depression. The aim of the present study was to explore the intertwined association between complex psychopathology combining autistic traits, subthreshold bipolarity, and mixed depression among people with AN.Method:Sixty patients with AN and concurrent major depressive episode (mean age, 22.2±7 years) were cross-sectionally assessed using the Autism-Spectrum Quotient test (AQ-test), the Hamilton depression scales for depression and anxiety, the Young Mania Rating Scale (YMRS), the Hypomania-Checklist-32 (HCL-32), second revision (for subthreshold bipolarity), the Brown Assessment and Beliefs Scale (BABS), the Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS), and the Eating Disorder Examination Questionnaire (EDE-Q). Cases were split into two groups depending on body mass index (BMI): severe AN (AN+) if BMI < 16, not severe (AN-) if BMI ≥ 16.Results:The “subthreshold bipolarity with prominent autistic traits” pattern correctly classified 83.6% of AN patients (AN+ = 78.1%; AN- = 91.3%, Exp(B) = 1.391). AN+ cases showed higher rates of positive scores for YMRS items 2 (increased motor activity-energy) and 5 (irritability) compared to AN- cases.Conclusions:In our sample, depressed patients with severe AN had more pronounced autistic traits and subtly mixed bipolarity. Further studies with larger samples and prospective follow-up of treatment outcomes are warranted to replicate these findings.

F95. ASSESSING MANIC SYMPTOMS IN PATIENTS WITH SCHIZOPHRENIA USING THE YOUNG MANIA RATING SCALE

BackgroundVan Os and Kapur have proposed that the discrete categorical dichotomy of schizophrenia versus bipolar disorder be changed to a dimensional conceptualization. It is also known that manic symptoms can contribute to the clinical course and prognosis of schizophrenia. Hence, a domain for mania has been included in the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). However, the psychometric properties of the Young Mania Rating Scale (YMRS) have been little studied in subjects with schizophrenia.MethodsOne hundred and sixty-six inpatients with schizophrenia (diagnosed with DSM-5,2 age ≥ 18 years and ≤ 65 years, and length of hospital stay ≥ 2 weeks) were enrolled from two mental hospitals in Korea. The Institutional Review Board approved the study protocol, and informed consent was given by all study subjects before the start of the study. The Korean version of the YMRS was used to evaluate the severity of manic symptoms. In addition, the domain for mania in the CRDPSS was used to evaluate presence or absence of manic symptoms (0–1, absence; 2–4, presence).ResultsThe average age and age-at-onset of the subjects were 46.5 (SD = 11.2) and 25.2 (SD = 13.2) years, respectively. Half were men (51.5%), and most were unmarried (79.1%), religiously affiliated (61.5%) and educated below high school graduate level (73.0%). The mean chlorpromazine equivalent dose of prescribed antipsychotics was 921.1 (SD = 952.0) mg. The mean total score on the YMRS was 7.3 (SD = 6.9) and the mean item scores were: 0.2 (SD = 0.4) for elevated mood, 0.1 (SD = 0.4) for increased motor activity, 0.1 (SD = 0.4) for sexual interest, 0.1 (SD = 0.4) for sleep, 0.4 (SD = 0.8) for irritability, 0.6 (SD = 1.2) for speech, 0.8 (SD = 1.1) for language, 2.0 (SD = 3.3) for content, 0.2 (SD = 0.7) for aggressive behavior, 1.0 (SD = 1.0) for appearance, and 1.8 (SD = 1.7) for insight. The Cronbach α for the 11 YMRS items was 0.66, which is considered an acceptable level of internal consistency. Moreover, only 4% (n = 7) of the 166 subjects had manic symptoms as assessed by the mania domain in the CRDPSS. A receiver operating characteristic curve (ROC) showed that the optimal cut-off score distinguishing schizophrenia patients with and without manic symptoms was 10 with a sensitivity of 88.3% and specificity of 75.6% (area under curve = 0.803, P = 0.012).DiscussionSince a 10 point total score on the YMRS represents a mild level of Clinical Global Impression (CGI) severity of mania, we may conclude that our threshold on the YMRS for identifying manic symptoms in patients with schizophrenia is reasonable. Hence it may be useful to investigate the evaluation of manic symptoms in patients with schizophrenia from the perspective of deconstructing psychoses.

Effects of asenapine on agitation and hostility in adults with acute manic or mixed episodes associated with bipolar I disorder.

BackgroundBipolar disorder is associated with an increased risk of aggression. However, effective management of hostility and/or agitation symptoms may prevent patients from becoming violent. This analysis investigated the efficacy of the antipsychotic asenapine on hostility and agitation in patients with bipolar I disorder.MethodsData were pooled from three randomized, double-blind, placebo-controlled, Phase III trials of asenapine in adults with manic or mixed episodes of bipolar I disorder (NCT00159744, NCT00159796, and NCT00764478). Post hoc analyses assessed the changes from baseline to day 21 on the Young Mania Rating Scale (YMRS) and the Positive and Negative Syndrome Scale (PANSS) hostility-related item scores in asenapine- or placebo-treated patients with at least minimal or mild symptom severity and on the PANSS-excited component (PANSS-EC) total score in agitated patients. Changes were adjusted for improvements in overall mania symptoms to investigate direct effects on hostility.ResultsSignificantly greater changes in favor of asenapine versus placebo were observed in YMRS hostility-related item scores (irritability: least squares mean difference [95% confidence interval] =−0.5 [−0.87, −0.22], P=0.001; disruptive–aggressive behavior: −0.7 [−0.99, −0.37], P<0.0001), PANSS hostility item score (−0.2 [−0.44, −0.04]; P=0.0181), and PANSS-EC total score (−1.4 [−2.4, −0.4]; P=0.0055). Changes in the YMRS disruptive–aggressive behavior score and the sum of the hostility-related items remained significant after adjusting for improvements in other YMRS item scores.ConclusionAsenapine significantly reduced hostility and agitation in patients with bipolar I disorder; improvement was at least partially independent of overall improvement on mania symptoms.

Changes in energy and motor activity: core symptoms of bipolar mania and depression?

Objective:To evaluate how well symptom rating scales differentiate bipolar disorder (BD) episode types.Methods:One hundred and six patients with BD were followed for 13 years. At each visit, the following clinical scales were administered: Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D) and Clinical Global Impressions scale for use in bipolar illness (CGI-BP). To perform a comparison between the affective states of BP, three time points in each patient’s follow-up period were chosen for evaluation: the most severe manic episode, the most severe depressive episode, and the euthymic period with least symptoms. Canonical discriminant analyses (CDA) were performed to identify which symptoms best discriminated episodes.Results:CDA revealed HAM-D was worse than YMRS and CGI-BP to discriminate mood states. The items evaluating increased motor activity in YMRS (2, increased motor activity/energy) and HAM-D (9, agitation) were the best to distinguish mania, depression, and euthymia. In contrast, HAM-D item 8 (retardation) and the HAM-D and YMRS items related to mood symptoms were less important and precise.Conclusion:Higher levels of energy or activity should be considered a core symptom of mania. However, our results do not confirm the association between a decrease in energy or activity and depression. HAM-D probably does not assess motor activity adequately.

Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis.

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.

An item response theory evaluation of the young mania rating scale and the montgomery-asberg depression rating scale in the systematic treatment enhancement program for bipolar disorder (STEP-BD)

BackgroundThe Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) are among the most widely used outcome measures for clinical trials of medications for Bipolar Disorder (BD). Nonetheless, very few studies have examined the measurement characteristics of the YMRS and MADRS in individuals with BD using modern psychometric methods. The present study evaluated the YMRS and MADRS in the Systematic Treatment Enhancement Program for BD (STEP-BD) study using Item Response Theory (IRT). MethodsBaseline data from 3716 STEP-BD participants were available for the present analysis. The Graded Response Model (GRM) was fit separately to YMRS and MADRS item responses. Differential item functioning (DIF) was examined by regressing a variety of clinically relevant covariates (e.g., sex, substance dependence) on all test items and on the latent symptom severity dimension, within each scale. ResultsBoth scales: 1) contained several items that provided little or no psychometric information, 2) were inefficient, in that the majority of item response categories did not provide incremental psychometric information, 3) poorly measured participants outside of a narrow band of severity, 4) evidenced DIF for nearly all items, suggesting that item responses were, in part, determined by factors other than symptom severity. LimitationsLimited to outpatients; DIF analysis only sensitive to certain forms of DIF. ConclusionsThe present study provides evidence for significant measurement problems involving the YMRS and MADRS. More work is needed to refine these measures and/or develop suitable alternative measures of BD symptomatology for clinical trials research.

Mixed Depression in Bipolar Disorder: Prevalence Rate and Clinical Correlates During Naturalistic Follow-Up in the Stanley Bipolar Network.

DSM-5 introduced the "with mixed features" specifier for major depressive episodes. The authors assessed the prevalence and phenomenology of mixed depression among bipolar disorder patients and qualitatively compared a range of diagnostic thresholds for mixed depression. In a naturalistic study, 907 adult outpatients with bipolar disorder participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,310 visits from 1995 to 2002. The Inventory of Depressive Symptomatology-Clinician-Rated Version (IDS-C) and the Young Mania Rating Scale (YMRS) were administered at each visit. Mixed depression, defined as an IDS-C score ≥15 and a YMRS score >2 and <12 at the same visit, was observed in 2,139 visits (14.9% of total visits, and 43.5% of visits with depression) by 584 patients (64.4% of all patients). Women were significantly more likely than men to experience subthreshold hypomania during visits with depression (40.7% compared with 34.4%). Patients with one or more mixed depression visits had more symptomatic visits and fewer euthymic visits compared with those with no mixed depression visits. DSM-5-based definitions of mixed depression (ranging from narrower definitions requiring ≥3 nonoverlapping YMRS items concurrent with an IDS-C score ≥15, to broader definitions requiring ≥2 nonoverlapping YMRS items) yielded lower mixed depression prevalence rates (6.3% and 10.8% of visits, respectively) but were found to have similar relationships to gender and longitudinal symptom severity. Among outpatients with bipolar disorder, concurrent hypomanic symptoms observed during visits with depression were common, particularly in women. The DSM-5 diagnostic criteria for depression with mixed features may yield inadequate sensitivity to detect patients with mixed depression.

Efficacy of lurasidone in major depression with mixed features: Pattern of improvement in depressive and manic symptoms

IntroductionEvidence indicates that manic symptoms, below the threshold for hypomania (mixed features), are common in individuals with major depressive disorder (MDD).Objectives/aimsTo evaluate the effect of lurasidone on specific depressive and manic symptoms, based on Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) items, in patients with MDD with mixed features.MethodsPatients meeting DSM-IV-TR criteria for MDD, who presented with 2–3 protocol-specified manic symptoms, were randomized to 6 weeks of double-blind treatment with lurasidone monotherapy 20–60 mg/d (n = 109) or placebo (n = 100). Change from baseline in the MADRS total, MADRS-6 core depression subscale, individual MADRS items, and total and individual items of the YMRS were analyzed by MMRM, and Cohen's d effect sizes (d) were calculated for week 6 change scores.ResultsLurasidone improved depressive symptoms at week 6 in the MADRS total score (–20.5 vs. –13.0; P &lt; 0.0001; d = 0.8) and MADRS-6 core depression score (–13.0 vs. –8.5; P &lt; 0.0001; d = 0.7). Significant improvement on lurasidone was observed at week 6 on all ten MADRS items (d = 0.36–0.78). Effect sizes for the MADRS-6 core depression subscale items ranged from 0.36 to 0.78 at week 6. Treatment with lurasidone was associated with significantly greater week 6 improvement on the YMRS (–7.0 vs. –4.9; P &lt; 0.0001). Effect sizes for the 5 YMRS items with baseline item severity ≥ 2 ranged from 0.32 to 0.48.ConclusionsIn this study of MDD with mixed features, lurasidone was effective in treating the range of depressive and manic symptoms that patients presented with.Sponsored by Sunovion Pharmaceuticals Inc.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Using the Young Mania Rating Scale for Identifying Manic Symptoms in Patients with Schizophrenia.

Dear Editor: Van Os and Kapur1 have proposed that the discrete categorical dichotomy of schizophrenia versus bipolar disorder should be changed to a dimensional conceptualization. It is also known that manic symptoms can contribute to the clinical course and prognosis of schizophrenia. Hence, a domain for mania has been included in the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5).2,3 However, the psychometric properties of the Young Mania Rating Scale (YMRS) have little been studied in subjects with schizophrenia. As described elsewhere,4 166 inpatients with schizophrenia (diagnosed with DSM-5,2 age ≥18 years and ≤65 years, and length of hospital stay ≥2 weeks) were enrolled from two mental hospitals in Korea. The Institutional Review Board of Yong-In Mental Hospital (receipt number: 2013-49) approved the study protocol, and informed consent was given by all study subjects before the start of the study. The Korean version of the YMRS was used to evaluate the severity of manic symptoms,5 and the domain for mania in the CRDPSS was used to evaluate presence or absence of manic symptoms (0–1, absence; 2–4, presence).3 The average age and age-at-onset of the subjects were 46.5 (SD=11.2) and 25.2 (SD=13.2) years, respectively. Half were men (51.5%), and most were unmarried (79.1%), religiously affiliated (61.5%) and educated below high school graduate level (73.0%). The mean chlorpromazine equivalent dose of prescribed antipsychotics was 921.1 (SD=952.0) mg. The mean total score on the YMRS was 7.3 (SD=6.9) and the mean item scores were: 0.2 (SD=0.4) for elevated mood, 0.1 (SD=0.4) for increased motor activity, 0.1 (SD=0.4) for sexual interest, 0.1 (SD=0.4) for sleep, 0.4 (SD=0.8) for irritability, 0.6 (SD=1.2) for speech, 0.8 (SD=1.1) for language, 2.0 (SD=3.3) for content, 0.2 (SD=0.7) for aggressive behavior, 1.0 (SD=1.0) for appearance, and 1.8 (SD=1.7) for insight. The Cronbach α for the 11 YMRS items was 0.66, which is considered as an acceptable level of internal consistency. Moreover, only 4% (n=7) of the 166 subjects had manic symptoms as assessed by the mania domain in the CRDPSS. As shown in Fig. 1, a receiver operating characteristic curve showed that the optimal cut-off score distinguishing schizophrenia patients with and without manic symptoms was 10 with a sensitivity of 88.3% and specificity of 75.6% (area under curve=0.803, p=0.012). Fig. 1 Receiver operating characteristic curve for total score on the Young Mania Rating Scale in schizophrenia patients with and without manic symptoms (cut-off=10, sensitivity=88.3%, specificity=75.6%) Since a 10 point total score on the YMRS represents a mild level of Clinical Global Impression severity of mania,6 we may conclude that our threshold on the YMRS for identifying manic symptoms in patients with schizophrenia is reasonable. Hence, it may be useful to evaluate manic symptoms in patients with schizophrenia from the perspective of deconstructing psychoses.

Asenapine in the Treatment of Acute Mania: A Real-World Observational Study With 6 Months Follow-Up.

Asenapine is a second-generation antipsychotic with a unique pharmacological profile that was recently approved for the treatment of moderate/severe manic episodes. Real-world data on rapidity of action in inpatient settings are lacking.The aims of the current real-world observational study were to evaluate: (i) short-term efficacy of asenapine after 7 days (T0-T1) in patients hospitalized for a manic episode in the course of bipolar I disorder or schizoaffective disorder (group A), (ii) differences in length of stay (LoS), and (iii) rehospitalization compared to a control population (group B) with a 6-month follow-up.Twenty patients were included in each group. The mean total Young Mania Rating Scale score decreased by 12.6 (SD ±10.3; t(17) = 5.2, P < 0.005), implying a mean 37.8% improvement. A statistically significant reduction was observed for all Young Mania Rating Scale items, except for "sexual interest." The mean total BPRS score decreased by 17.2 (SD ±14.9; t(17) = 4.9, P < 0.005). A statistically significant reduction was observed for several items, including "conceptual disorganization," "grandiosity," "unusual thought content," and "excitement". Length of stay was 17.9 (SD ±9.0) days for group A and 14.7 (SD ±12.7) days for group B; the result of the Kruskal-Wallis test showed no significant differences (χ = 2.199, P = 0.138). Despite a high discontinuation rate, only 17.7% of patients in group A were rehospitalized in the following 6 months compared to 41.2% of those in group B (relative risk = 0.43, 95% confidence interval, 0.13-1.39).Findings from this small, preliminary study at least partially support the results of previous trials, confirming effectiveness and tolerability in the context of comorbidity and polypsychopharmacology.

Effect of cariprazine across the symptoms of mania in bipolar I disorder: Analyses of pooled data from phase II/III trials

Bipolar I disorder is a chronic disorder characterized by episodic recurrences of mania, depression, and mixed affective states interspersed with periods of full or partial remission; subsyndromal residual symptoms between episodes are common and disabling. Cariprazine, an atypical antipsychotic, is a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. Post-hoc analyses of pooled data from 3 positive trials were conducted to evaluate the effect of cariprazine 3–12mg/d on the symptoms of mania in inpatients (18–65 years) with bipolar I disorder and a current manic episode. Analyses were based on the pooled intent-to-treat (ITT) population (placebo=429; cariprazine=608). Mean change from baseline to the end of treatment on individual Young Mania Rating Scale (YMRS) items was analysed using a mixed-effects model for repeated measures (MMRM); categorical symptom severity shifts were analysed using logistic regression. Statistically significant improvement in mean change was seen for cariprazine versus placebo on all 11 YMRS items (p<0.0001); significantly more cariprazine- versus placebo-treated patients had mild/no symptoms at the end of treatment on 11 YMRS items (p<0.0001) and concurrently on the 4 YMRS core symptoms (irritability, speech, content, and disruptive–aggressive behaviour) (p<0.0001). Significantly more cariprazine- versus placebo-treated patients shifted from a Moderate/Worse or Marked/Worse Symptoms categories to Mild/No Symptoms on all 11 (p<0.0001) and 9 of 11 YMRS items (p<0.05), respectively. Results suggest that cariprazine treatment improved mania across YMRS symptoms; a significant percentage of cariprazine- versus placebo-treated patients had mild/no symptoms at the end of treatment.

Predictors of Remission in 208 Drug-Resistant Depressive Patients Treated With Electroconvulsive Therapy

This study aimed to explore predictors of remission to electroconvulsive therapy (ECT) in a sample of depressive patients resistant to pharmacological treatments. Two hundred eight patients, 31 of whom had major depressive disorder, 101 had bipolar disorder II (BP II), and 76 had bipolar disorder I (BP I), diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were treated with bilateral ECT on a twice-a-week schedule. All patients included were undergoing a depressive episode, excluding patients with mixed and manic episodes. Patients were assessed before (baseline) and a week after the ECT course (final score) using the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Young Mania Rating Scale (YMRS), the Brief Psychiatric Rating Scale, and the Clinical Global Impression-Improvement (CGI-I). At the end of the ECT course, 56 patients (26.9%) were considered nonresponders, and 80 patients (38.4%) were considered responders (HAM-D score of at least 50% and CGI-I subscale rating of 2, "much improved") and 72 remitters (34.6%) (HAM-D scores ≤8 and a CGI-I subscale rating of 1). On backward stepwise logistic regression length of current episode, Bipolar Disorder and baseline YMRS total mean scores were statistically significant predictors of nonresponders versus remitters. Among the YMRS items at basal evaluation 8 (thought content), 10 (appearance), and 11 (insight), the mean scores were significantly lower in the remitters than in the responders and nonresponders. Major depressive disorder, short duration of the current episode, absence of psychotic symptoms, preserved insight, and adequate personal care are associated with complete remission in our sample of drug-resistant depressive patients treated with ECT.

Lithium as add-on to quetiapine XR in adult patients with acute mania: a 6-week, multicenter, double-blind, randomized, placebo-controlled study.

Quetiapine extended release (XR) and lithium are treatments with proven efficacy in acute mania. This randomized study evaluated the efficacy and safety of lithium or placebo as add-on to quetiapine XR in adult patients with manic or mixed symptoms of bipolar I disorder. In this 6-week, double-blind study (Trial D144AC00003), adult patients with DSM-IV-TR-diagnosed bipolar I disorder (current episode manic or mixed), a Young Mania Rating Scale (YMRS) total score ≥20, and score ≥4 on two of four core YMRS items were administered quetiapine XR (400 to 800 mg/day) and randomly assigned to receive add-on lithium (600 to 1,800 mg/day) or placebo. The primary efficacy end point was change in the YMRS total score from baseline to day 43, analyzed using a mixed-model for repeated measures (MMRM) approach. Secondary efficacy and safety end points were also measured. Rating scales were administered by trained staff. Three hundred fifty-six patients treated with quetiapine XR were randomized to add-on lithium (n = 173) or placebo (n = 183). Two hundred ninety-one patients (81.7%) completed the study. At day 43, least squares mean change in YMRS total score was −22.8 for add-on lithium and −20.1 for add-on placebo, a statistically significant treatment group difference of −2.69 (p < 0.001). On secondary measures, add-on lithium was associated with significant improvements in response, remission, illness severity, and overall illness versus add-on placebo (p < 0.05). The number needed to treat was 9.1 for response and 7.9 for remission for add-on lithium compared with add-on placebo. Lithium in combination with quetiapine XR was generally well tolerated, with a similar profile to quetiapine XR in combination with placebo. The addition of lithium to quetiapine XR therapy was associated with significantly greater efficacy than placebo as add-on and was generally well tolerated in patients with acute bipolar I mania. This study was registered under Clinicaltrials.gov Identifier NCT00931723.Electronic supplementary materialThe online version of this article (doi:10.1186/s40345-014-0014-9) contains supplementary material, which is available to authorized users.

The efficacy and tolerability of cariprazine in acute mania associated with bipolar I disorder: a phase II trial.

Cariprazine, an orally active and potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, is being developed for the treatment of schizophrenia and bipolar mania. This Phase II trial evaluated the efficacy, safety, and tolerability of cariprazine versus placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder. This was a multinational, randomized, double-blind, placebo-controlled, flexible-dose study of cariprazine 3-12mg/day in patients with acute manic or mixed episodes associated with bipolar I disorder. Following washout, patients received three weeks of double-blind treatment. The primary and secondary efficacy parameters were change from baseline to Week 3 in Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S) scores, respectively. Post-hoc analysis evaluated changes on YMRS single items. In each group, 118 patients received double-blind treatment; 61.9% of placebo and 63.6% of cariprazine patients completed the study. The overall mean daily dose of cariprazine was 8.8mg/day. At Week 3, cariprazine significantly reduced YMRS and CGI-S scores versus placebo, with least square mean differences of -6.1 (p<0.001) and -0.6 (p<0.001), respectively. On each YMRS item, change from baseline to Week 3 was significantly greater for cariprazine versus placebo (all, p<0.05). A significantly greater percentage of cariprazine patients than placebo patients met YMRS response (48% versus 25%; p<0.001) and remission (42% versus 23%; p=0.002) criteria at Week 3. Adverse events (AEs) led to discontinuation of 12 (10%) placebo and 17 (14%) cariprazine patients. The most common AEs (> 10% for cariprazine) were extrapyramidal disorder, headache, akathisia, constipation, nausea, and dyspepsia. Changes in metabolic parameters were similar between groups, with the exception of fasting glucose; increases in glucose were significantly greater for cariprazine versus placebo (p<0.05). Based on Barnes Akathisia Rating Scale and Simpson-Angus Scale scores, more cariprazine than placebo patients experienced treatment-emergent akathisia (cariprazine: 22%; placebo: 6%) or extrapyramidal symptoms (parkinsonism) (cariprazine: 16%; placebo: 1%). Cariprazine demonstrated superior efficacy versus placebo and was generally well tolerated in patients experiencing acute manic or mixed episodes associated with bipolar I disorder.

Efficacy of olanzapine monotherapy in the treatment of bipolar depression with mixed features

BackgroundThis analysis investigated the correlations between the efficacy of olanzapine monotherapy and the number of concurrent manic symptoms in patients treated for bipolar depression. MethodsPooled data from 2 placebo-controlled olanzapine studies in patients with bipolar I depression were analyzed (total 1214 patients; 690 olanzapine monotherapy patients and 524 placebo patients). Patients were categorized for mixed features by the number of concurrent manic symptoms at baseline (0, 1 or 2, and ≥3, respectively, as measured by a Young Mania Rating Scale item score ≥1). Efficacy was evaluated by change in Montgomery–Åsberg Depression Rating Scale (MADRS) total score from baseline to 6 weeks. ResultsLeast-squares mean differences between olanzapine and placebo in the change of MADRS total scores were −3.76 (p=0.002), −3.20 (p<0.001), and −3.44 (p=0.002) for mixed features 0, 1 or 2, and ≥3, respectively. The response rates for olanzapine versus (vs.) placebo were 52.6% vs. 39.8%, 50.3% vs. 40.0%, and 42.2% vs. 33.7% for mixed features 0, 1 or 2, and ≥3, respectively. The remission rates for olanzapine vs. placebo group were 46.1% vs. 34.3%, 39.5% vs. 32.0%, and 34.8% vs. 24.1% for mixed features 0, 1 or 2, and ≥3, respectively. No significant interaction between mixed features and treatment was seen in the MADRS changes or response and remission rates. LimitationsPost hoc analyses of the data from 2 previous randomized clinical studies. ConclusionsOlanzapine monotherapy was shown to be effective in the treatment of bipolar depression irrespective of the presence of concurrent manic symptoms.