BackgroundFew studies have examined treatment response in adolescents with schizophrenia who are ... more BackgroundFew studies have examined treatment response in adolescents with schizophrenia who are treatment-naive; and there is no placebo-controlled study that we are aware of in first episode treatment-naive patients with schizophrenia. The aim of this analysis was to evaluate the long-term efficacy of lurasidone in antipsychotic-naive adolescents with schizophrenia.MethodPatients aged 13–17 years with schizophrenia, and a PANSS total score ≥70 and <120, were randomized to 6 weeks of double-blind (DB) treatment with lurasidone (40 or 80 mg/day) or placebo. Six-week completers were eligible to enroll in a 2-year open-label extension phase receiving lurasidone flexibly dosed from 20–80 mg/day. In a post-hoc analysis, efficacy was evaluated for 2 patient groups based on treatment status prior to entering the initial 6-week DB study (treatment naïve [TN] vs. treated previously [TP]). Treatment-naïve was defined as never having received antipsychotic treatment. Efficacy measures incl...
BACKGROUND Lurasidone is approved for the treatment of bipolar depression both as monotherapy and... more BACKGROUND Lurasidone is approved for the treatment of bipolar depression both as monotherapy and adjunctive therapy with lithium or valproate (Li/VPA). The aim of these analyses was to evaluate the prevalence of treatment-emergent mania (TEM) and worsening of mania symptom severity in clinical trials of both adult and pediatric patients with bipolar depression treated with lurasidone. METHOD In these post-hoc analyses, TEM and change in manic symptom severity as measured by the Young Mania Rating Scale (YMRS) were evaluated in two double-blind (DB), 6-week studies in adults of lurasidone monotherapy, 20-60 mg/d (n=161) and 80-120 mg/d (n=162) vs. placebo (n=162), and adjunctive therapy of lurasidone 20-120 mg/d + Li/VPA (n=179) vs. placebo + Li/VPA (n=161). Prevalence of TEM was also evaluated in a 6-month, open-label (OL) extension study of adults treated with lurasidone monotherapy (n=316) or adjunctive therapy (n=497). In pediatric patients (ages 10-17) TEM and change in manic s...
Background Childhood and adolescent schizophrenia is a severe and debilitating disorder associate... more Background Childhood and adolescent schizophrenia is a severe and debilitating disorder associated with long-term impairments in functioning, poor physical health, and reduced life expectancy. Compared with adult-onset schizophrenia, childhood and adolescent schizophrenia may be a more severe disorder, negatively influencing social, cognitive and psychological development, educational achievements and life-long occupational functioning. Therefore, treatment of childhood and adolescent schizophrenia is highly important and presents a major therapeutic challenge. The aim of this systematic review and meta-analysis was to assess whether antipsychotics (APs) have different clinical benefits and harms profiles in acute treatment of childhood and adolescent schizophrenia. Methods We conducted systematic review and meta-analysis of randomized placebo-controlled trials (RCTs) assessing efficacy and adverse effects of APs in acute childhood and adolescent schizophrenia to compare clinical be...
The aim of this secondary analysis was to evaluate whether treatment with lurasidone was associat... more The aim of this secondary analysis was to evaluate whether treatment with lurasidone was associated with impairment in sexual functioning in major depressive disorder (MDD) patients with subthreshold hypomanic symptoms (mixed features). Patients meeting DSM-IV-TR criteria for MDD, who presented with 2 or 3 protocol-specified manic symptoms, were randomized to 6 weeks of double-blind treatment with flexible doses of either lurasidone 20-60 mg/d (n = 109) or placebo (n = 100). The study was conducted between September 2011 and October 2014. Change in sexual functioning was assessed utilizing the 14-item self-report Changes in Sexual Functioning Questionnaire (CSFQ-14) administered at baseline and week 6 endpoint. Change from baseline to week 6 in depression severity was assessed utilizing the Montgomery-Asberg Depression Rating Scale (MADRS) total score, the primary efficacy endpoint. Lurasidone significantly reduced mean MADRS total scores at week 6 endpoint (-20.5 vs -13.0; P < ....
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, Jan 10, 2017
To evaluate the safety and effectiveness of 6 months of treatment with lurasidone in older adults... more To evaluate the safety and effectiveness of 6 months of treatment with lurasidone in older adults with a diagnosis of bipolar I depression. Post-hoc analysis of a multicenter, 6-month, open-label extension study. Outpatient. Patients aged 55 to 75 years with a DSM-IV-TR diagnosis of bipolar I depression who had completed 6 weeks of double-blind, placebo-controlled treatment with either lurasidone monotherapy (1 study) or adjunctive therapy with lithium or valproate (2 studies). Flexible doses of lurasidone, 20 to 120 mg/day, either as monotherapy, or adjunctive with lithium or valproate. Effectiveness was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS; change from open-label-baseline to month-6, observed case analysis). A total of 141 older adults entered the extension study (monotherapy, N = 55; 39%; adjunctive therapy, N = 86; 61%). At the end of 6 months of open-label treatment with lurasidone, as monotherapy or adjunctive therapy, minimal changes were observ...
Background The objective of this post-hoc analysis was to evaluate recovery-related outcomes in p... more Background The objective of this post-hoc analysis was to evaluate recovery-related outcomes in patients with bipolar depression treated with lurasidone. Methods Subjects meeting DSM-IV-TR criteria for bipolar I depression, with or without rapid cycling, were randomized to 6 weeks of once-daily, double-blind treatment with either lurasidone 20-60 mg (LUR20-60), lurasidone 80-120 mg (LUR80-120) or placebo (PBO), followed by a 6-month, open-label, continuation study of lurasidone. Results At end of the 6-week acute phase, a significantly higher proportion of subjects met both symptomatic (MADRS total score ≤ 12) and functional (mean SDS total score ≤ 3 and all SDS domain scores ≤ 3 for mildly impairment) remission criteria in the lurasidone group (33%,N=273 pooling the LUR20-60 and LUR80-120 groups) compared to the placebo group (15%, N=143,p<0.05, NNT = 6). In the 6-month continuation study, the proportion of subjects achieving symptomatic and functional remission at both week 19 and week 32 (month 3 and month 6 of the continuation study, respectively) was 61% (85/140) in subjects who continued lurasidone treatment (LUR-LUR) and 45% (31/69) in subjects who switched from placebo to lurasidone (PBO-LUR). Multivariate logistic modeling revealed that statistically significant predictors of symptomatic and functional recovery included: lower baseline symptom severity, non-white race, and taking lurasidone (rather than placebo) during the acute phase. Discussion Our findings support the potential for attainment of remission in patients with bipolar I depression treated with lurasidone, which might lead to clinical and functional recovery.
Progress in neuro-psychopharmacology & biological psychiatry, Aug 9, 2017
Several studies have found that depressed, post-menopausal females may respond differently to ant... more Several studies have found that depressed, post-menopausal females may respond differently to antidepressants compared to pre-menopausal females. The atypical antipsychotic lurasidone, whose mechanism of action differs from SSRIs and other standard antidepressants, was shown in a 6-week randomized, flexible-dose, placebo-controlled study (n=209), to be effective in treating major depressive disorder (MDD) with mixed features (subthreshold hypomanic symptoms). This post-hoc analysis assessed the efficacy of lurasidone in this study by menopausal status. The main outcome measure for this post-hoc analysis was change in MADRS score from baseline to week 6 endpoint for two lurasidone-treated subgroups: presumptive pre-menopausal (<52years) and presumptive post-menopausal (≥52years) patients, compared to placebo treatment, using a mixed-model for repeated-measures analysis, and calculation of the effect size for each subgroup. Additional efficacy assessments included the CGI-S, HAM-A ...
ObjectiveThe aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating... more ObjectiveThe aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability.MethodsThe 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.ResultsSome 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo...
In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium... more In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium or valproate, patients with bipolar I depression were randomized to 6 weeks of double-blind treatment with lurasidone (N = 180) or placebo (N = 176), added to background treatment with lithium or valproate. All patients were treated with lithium or valproate for a minimum of 4 weeks prior to screening. This was confirmed either by prospective treatment after study enrolment (run-in cohort), or retrospectively, with blood levels of lithium and valproate at screening (non-run-in cohort). Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP-S), respectively. Treatment with lurasidone was associated with non-significant improvement at week 6 vs. placebo for the MADRS total score (-11.8 vs -10.4; P = 0.176), and ...
Depressive symptoms associated with bipolar disorder negatively impact health-related quality of ... more Depressive symptoms associated with bipolar disorder negatively impact health-related quality of life (HRQoL). The efficacy of lurasidone in reducing depressive symptoms has been previously demonstrated. The objective of this study was to examine the direct and indirect effect (mediated through improvement in depression symptoms) of lurasidone in improving patient HRQoL. A secondary analysis of data was conducted of two 6-week, double-blind, placebo-controlled trials assessing the effect of lurasidone (lurasidone monotherapy [20-60 mg/day or 80-120 mg/day]; lurasidone adjunctive to lithium or valproate [20-120 mg/day]) in patients with bipolar depression. Patient HRQoL was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q SF). Depression symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). Analysis of covariance (ANCOVA) was used to estimate the effect of lurasidone on improvement in the Q-LES-Q SF percenta...
Bipolar depression is characterized by depressive symptoms and impairment in many areas of functi... more Bipolar depression is characterized by depressive symptoms and impairment in many areas of functioning, including work, family, and social life. The objective of this study was to assess the independent, direct effect of lurasidone treatment on functioning improvement, and examine the indirect effect of lurasidone treatment on functioning improvement, mediated through improvements in depression symptoms. Data from a 6-week placebo-controlled trial assessing the effect of lurasidone monotherapy versus placebo in patients with bipolar depression was used. Patient functioning was measured using the Sheehan disability scale (SDS). Descriptive statistics were used to assess the effect of lurasidone on improvement on the SDS total and domain scores (work/school, social, and family life), as well as number of days lost and unproductive due to symptoms. Path analyses evaluated the total effect (β1), as well as the indirect effect (β2×β3) and direct effect (β4) of lurasidone treatment on SDS...
The medical information department within a pharmaceutical company functions to provide concise, ... more The medical information department within a pharmaceutical company functions to provide concise, consistent, and appropriate information and customer service to external and internal customers, while maintaining effective and quality-controlled processes. These medical information departmental goals become more challenging when two companies form a partnership, because of the complexity of additional staff members with varying goals and objectives involved in joint venture projects. The objective of this article is to review how two medical information groups function within a pharmaceutical alliance, and examine changes in the partnership that occurred in the different stages of the drug product life cycle. This is the first published article on the late-phase maintenance of a pharmaceutical alliance in medical information.
BackgroundFew studies have examined treatment response in adolescents with schizophrenia who are ... more BackgroundFew studies have examined treatment response in adolescents with schizophrenia who are treatment-naive; and there is no placebo-controlled study that we are aware of in first episode treatment-naive patients with schizophrenia. The aim of this analysis was to evaluate the long-term efficacy of lurasidone in antipsychotic-naive adolescents with schizophrenia.MethodPatients aged 13–17 years with schizophrenia, and a PANSS total score ≥70 and <120, were randomized to 6 weeks of double-blind (DB) treatment with lurasidone (40 or 80 mg/day) or placebo. Six-week completers were eligible to enroll in a 2-year open-label extension phase receiving lurasidone flexibly dosed from 20–80 mg/day. In a post-hoc analysis, efficacy was evaluated for 2 patient groups based on treatment status prior to entering the initial 6-week DB study (treatment naïve [TN] vs. treated previously [TP]). Treatment-naïve was defined as never having received antipsychotic treatment. Efficacy measures incl...
BACKGROUND Lurasidone is approved for the treatment of bipolar depression both as monotherapy and... more BACKGROUND Lurasidone is approved for the treatment of bipolar depression both as monotherapy and adjunctive therapy with lithium or valproate (Li/VPA). The aim of these analyses was to evaluate the prevalence of treatment-emergent mania (TEM) and worsening of mania symptom severity in clinical trials of both adult and pediatric patients with bipolar depression treated with lurasidone. METHOD In these post-hoc analyses, TEM and change in manic symptom severity as measured by the Young Mania Rating Scale (YMRS) were evaluated in two double-blind (DB), 6-week studies in adults of lurasidone monotherapy, 20-60 mg/d (n=161) and 80-120 mg/d (n=162) vs. placebo (n=162), and adjunctive therapy of lurasidone 20-120 mg/d + Li/VPA (n=179) vs. placebo + Li/VPA (n=161). Prevalence of TEM was also evaluated in a 6-month, open-label (OL) extension study of adults treated with lurasidone monotherapy (n=316) or adjunctive therapy (n=497). In pediatric patients (ages 10-17) TEM and change in manic s...
Background Childhood and adolescent schizophrenia is a severe and debilitating disorder associate... more Background Childhood and adolescent schizophrenia is a severe and debilitating disorder associated with long-term impairments in functioning, poor physical health, and reduced life expectancy. Compared with adult-onset schizophrenia, childhood and adolescent schizophrenia may be a more severe disorder, negatively influencing social, cognitive and psychological development, educational achievements and life-long occupational functioning. Therefore, treatment of childhood and adolescent schizophrenia is highly important and presents a major therapeutic challenge. The aim of this systematic review and meta-analysis was to assess whether antipsychotics (APs) have different clinical benefits and harms profiles in acute treatment of childhood and adolescent schizophrenia. Methods We conducted systematic review and meta-analysis of randomized placebo-controlled trials (RCTs) assessing efficacy and adverse effects of APs in acute childhood and adolescent schizophrenia to compare clinical be...
The aim of this secondary analysis was to evaluate whether treatment with lurasidone was associat... more The aim of this secondary analysis was to evaluate whether treatment with lurasidone was associated with impairment in sexual functioning in major depressive disorder (MDD) patients with subthreshold hypomanic symptoms (mixed features). Patients meeting DSM-IV-TR criteria for MDD, who presented with 2 or 3 protocol-specified manic symptoms, were randomized to 6 weeks of double-blind treatment with flexible doses of either lurasidone 20-60 mg/d (n = 109) or placebo (n = 100). The study was conducted between September 2011 and October 2014. Change in sexual functioning was assessed utilizing the 14-item self-report Changes in Sexual Functioning Questionnaire (CSFQ-14) administered at baseline and week 6 endpoint. Change from baseline to week 6 in depression severity was assessed utilizing the Montgomery-Asberg Depression Rating Scale (MADRS) total score, the primary efficacy endpoint. Lurasidone significantly reduced mean MADRS total scores at week 6 endpoint (-20.5 vs -13.0; P < ....
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, Jan 10, 2017
To evaluate the safety and effectiveness of 6 months of treatment with lurasidone in older adults... more To evaluate the safety and effectiveness of 6 months of treatment with lurasidone in older adults with a diagnosis of bipolar I depression. Post-hoc analysis of a multicenter, 6-month, open-label extension study. Outpatient. Patients aged 55 to 75 years with a DSM-IV-TR diagnosis of bipolar I depression who had completed 6 weeks of double-blind, placebo-controlled treatment with either lurasidone monotherapy (1 study) or adjunctive therapy with lithium or valproate (2 studies). Flexible doses of lurasidone, 20 to 120 mg/day, either as monotherapy, or adjunctive with lithium or valproate. Effectiveness was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS; change from open-label-baseline to month-6, observed case analysis). A total of 141 older adults entered the extension study (monotherapy, N = 55; 39%; adjunctive therapy, N = 86; 61%). At the end of 6 months of open-label treatment with lurasidone, as monotherapy or adjunctive therapy, minimal changes were observ...
Background The objective of this post-hoc analysis was to evaluate recovery-related outcomes in p... more Background The objective of this post-hoc analysis was to evaluate recovery-related outcomes in patients with bipolar depression treated with lurasidone. Methods Subjects meeting DSM-IV-TR criteria for bipolar I depression, with or without rapid cycling, were randomized to 6 weeks of once-daily, double-blind treatment with either lurasidone 20-60 mg (LUR20-60), lurasidone 80-120 mg (LUR80-120) or placebo (PBO), followed by a 6-month, open-label, continuation study of lurasidone. Results At end of the 6-week acute phase, a significantly higher proportion of subjects met both symptomatic (MADRS total score ≤ 12) and functional (mean SDS total score ≤ 3 and all SDS domain scores ≤ 3 for mildly impairment) remission criteria in the lurasidone group (33%,N=273 pooling the LUR20-60 and LUR80-120 groups) compared to the placebo group (15%, N=143,p<0.05, NNT = 6). In the 6-month continuation study, the proportion of subjects achieving symptomatic and functional remission at both week 19 and week 32 (month 3 and month 6 of the continuation study, respectively) was 61% (85/140) in subjects who continued lurasidone treatment (LUR-LUR) and 45% (31/69) in subjects who switched from placebo to lurasidone (PBO-LUR). Multivariate logistic modeling revealed that statistically significant predictors of symptomatic and functional recovery included: lower baseline symptom severity, non-white race, and taking lurasidone (rather than placebo) during the acute phase. Discussion Our findings support the potential for attainment of remission in patients with bipolar I depression treated with lurasidone, which might lead to clinical and functional recovery.
Progress in neuro-psychopharmacology & biological psychiatry, Aug 9, 2017
Several studies have found that depressed, post-menopausal females may respond differently to ant... more Several studies have found that depressed, post-menopausal females may respond differently to antidepressants compared to pre-menopausal females. The atypical antipsychotic lurasidone, whose mechanism of action differs from SSRIs and other standard antidepressants, was shown in a 6-week randomized, flexible-dose, placebo-controlled study (n=209), to be effective in treating major depressive disorder (MDD) with mixed features (subthreshold hypomanic symptoms). This post-hoc analysis assessed the efficacy of lurasidone in this study by menopausal status. The main outcome measure for this post-hoc analysis was change in MADRS score from baseline to week 6 endpoint for two lurasidone-treated subgroups: presumptive pre-menopausal (<52years) and presumptive post-menopausal (≥52years) patients, compared to placebo treatment, using a mixed-model for repeated-measures analysis, and calculation of the effect size for each subgroup. Additional efficacy assessments included the CGI-S, HAM-A ...
ObjectiveThe aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating... more ObjectiveThe aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability.MethodsThe 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.ResultsSome 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo...
In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium... more In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium or valproate, patients with bipolar I depression were randomized to 6 weeks of double-blind treatment with lurasidone (N = 180) or placebo (N = 176), added to background treatment with lithium or valproate. All patients were treated with lithium or valproate for a minimum of 4 weeks prior to screening. This was confirmed either by prospective treatment after study enrolment (run-in cohort), or retrospectively, with blood levels of lithium and valproate at screening (non-run-in cohort). Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP-S), respectively. Treatment with lurasidone was associated with non-significant improvement at week 6 vs. placebo for the MADRS total score (-11.8 vs -10.4; P = 0.176), and ...
Depressive symptoms associated with bipolar disorder negatively impact health-related quality of ... more Depressive symptoms associated with bipolar disorder negatively impact health-related quality of life (HRQoL). The efficacy of lurasidone in reducing depressive symptoms has been previously demonstrated. The objective of this study was to examine the direct and indirect effect (mediated through improvement in depression symptoms) of lurasidone in improving patient HRQoL. A secondary analysis of data was conducted of two 6-week, double-blind, placebo-controlled trials assessing the effect of lurasidone (lurasidone monotherapy [20-60 mg/day or 80-120 mg/day]; lurasidone adjunctive to lithium or valproate [20-120 mg/day]) in patients with bipolar depression. Patient HRQoL was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q SF). Depression symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). Analysis of covariance (ANCOVA) was used to estimate the effect of lurasidone on improvement in the Q-LES-Q SF percenta...
Bipolar depression is characterized by depressive symptoms and impairment in many areas of functi... more Bipolar depression is characterized by depressive symptoms and impairment in many areas of functioning, including work, family, and social life. The objective of this study was to assess the independent, direct effect of lurasidone treatment on functioning improvement, and examine the indirect effect of lurasidone treatment on functioning improvement, mediated through improvements in depression symptoms. Data from a 6-week placebo-controlled trial assessing the effect of lurasidone monotherapy versus placebo in patients with bipolar depression was used. Patient functioning was measured using the Sheehan disability scale (SDS). Descriptive statistics were used to assess the effect of lurasidone on improvement on the SDS total and domain scores (work/school, social, and family life), as well as number of days lost and unproductive due to symptoms. Path analyses evaluated the total effect (β1), as well as the indirect effect (β2×β3) and direct effect (β4) of lurasidone treatment on SDS...
The medical information department within a pharmaceutical company functions to provide concise, ... more The medical information department within a pharmaceutical company functions to provide concise, consistent, and appropriate information and customer service to external and internal customers, while maintaining effective and quality-controlled processes. These medical information departmental goals become more challenging when two companies form a partnership, because of the complexity of additional staff members with varying goals and objectives involved in joint venture projects. The objective of this article is to review how two medical information groups function within a pharmaceutical alliance, and examine changes in the partnership that occurred in the different stages of the drug product life cycle. This is the first published article on the late-phase maintenance of a pharmaceutical alliance in medical information.
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Papers by Andrei Pikalov