Carla Canuso - Academia.edu (original) (raw)

Papers by Carla Canuso

Biological Psychiatry, 2017

Current Medical Research and Opinion, 2011

The aim of this post-hoc analysis was to describe change in employment status over time in patien... more The aim of this post-hoc analysis was to describe change in employment status over time in patients with schizophrenia. Data were from three 52-week open-label extensions of the double-blind pivotal trials of paliperidone extended-release (ER) (trial numbers NCT00650793, NCT00210769 and NCT00668837). Employment status prior to trial entry was recorded at baseline of the open-label phase and change was measured at 4-week intervals. Patients were included if they were in the open-label, intent-to-treat analysis set (i.e., received at least one dose of the study medication and had a baseline and at least one post-baseline efficacy measurement) and had valid dates in the productivity data. Employment categories included full-time, part-time, casual, sheltered work, unemployed but seeking work, unemployed and not seeking work, retired, not employed outside the home and student. Change in employment status from baseline to post-baseline (last visit) was assessed using McNemar's test. Of the 1077 patients enrolled in the open-label extensions, 1012 (94.0%) met inclusion criteria. The average age was 37.7 years (SD 10.9) and 59.1% were male. At baseline, the largest percentage of patients was unemployed and not seeking work (56.8%), followed by retired (14.9%) and unemployed but seeking work (11.7%). Five different definitions of employment were created. Employment rates increased according to all five definitions (p < 0.0001), ranging from a 43% increase according to the definition most similar to that used by the US Bureau of Labor Statistics to an increase of 114% when only part-time and full-time employment were considered. In this uncontrolled population of patients with schizophrenia who were treated with paliperidone ER, the percentage of patients who were employed increased over time. By using multiple measures of employment, researchers can identify the nature of the employment status change.

Annals of internal medicine

Major depressive disorder has high prevalence, morbidity, and mortality. Inadequate results with ... more Major depressive disorder has high prevalence, morbidity, and mortality. Inadequate results with antidepressants have prompts addition of a nonstandard treatment (augmentation therapy). To assess whether augmentation therapy with risperidone reduces symptoms and increases response to antidepressant therapy and remission of depression in adults. Multicenter, double-blind, placebo-controlled, randomized trial conducted from 19 October 2004 to 17 November 2005. 75 primary care and psychiatric centers. 274 outpatient adults with major depressive disorder that was suboptimally responsive to antidepressant therapy. After a 4-week run-in period to ensure insufficient response to standard antidepressants, patients were randomly assigned to receive risperidone, 1 mg/d, or placebo for 6 weeks. After 4 weeks, the dosage of risperidone was increased to 2 mg/d in some cases. Symptoms were measured by using the 17-item Hamilton Rating Scale for Depression (HRSD-17). Other outcomes were response to therapy, remission of depression, and various clinician- and patient-rated assessments. Of the intention-to-treat population (268 patients), 81% (111 of 137) who received risperidone and 87.8% (115 of 131) who received placebo completed 6 weeks of double-blind treatment. Mean (+/-SE) HRSD-17 scores improved more in the risperidone augmentation group than in the placebo group (13.4 +/- 0.54 vs. 16.2 +/- 0.53; difference, -2.8 +/- 0.72 [95% CI, -4.2 to -1.4]; P <0.001). More risperidone recipients than placebo recipients experienced remission of depression (24.5% [26 of 106] vs. 10.7% [12 of 112]; P = 0.004) and had a response (46.2% [49 of 106] vs. 29.5% [33 of 112]; P = 0.004). Headache (8.8% of risperidone recipients vs. 14.5% of placebo recipients), somnolence (5.1% vs. 1.5%), and dry mouth (5.1% vs. 0.8%) were the most frequently reported adverse events. Patients were receiving many different antidepressants, and the duration of augmentation therapy was limited. Risperidone augmentation produced a statistically significant mean reduction in depression symptoms, substantially increased remission and response, and improved other patient- and clinician-rated measures. ClinicalTrials.gov registration number: NCT00095134.

Psychopharmacology bulletin

What are the important gender differences seen in men and women with schizophrenia? Although schi... more What are the important gender differences seen in men and women with schizophrenia? Although schizophrenia affects men and women with equal frequency, the illness is expressed differently between the sexes. Women with schizophrenia tend to have better premorbid functioning, a later age at onset, a distinct symptom profile and better course of illness, and different structural brain abnormalities and cognitive deficits. Additionally, premenopausal women appear to have a superior response to typical antipsychotics compared to men and postmenopausal women. These gender differences are thought to arise from the interplay between hormonal and psychosocial factors. It has been hypothesized that estrogen, with effects on both neurodevelopment and neurotransmission, may play a protective role in women with schizophrenia and account for some of the gender differences observed in the disorder. Despite the potential benefit of estrogen in this population, women with schizophrenia appear to be ...

Psychopharmacology bulletin

Residual symptoms despite treatment are common in generalized anxiety disorders (GAD). The Patien... more Residual symptoms despite treatment are common in generalized anxiety disorders (GAD). The Patient-Rated Troubling Symptoms for Anxiety (PaRTS-A) is a newly created and validated instrument that measures the symptoms most troublesome to each individual patient and was used to test the hypothesis that adjunctive risperidone improves residual GAD symptoms. Primary care and psychiatry clinicians enrolled adults (n = 417) with GAD and a Clinical Global Impressions of Severity rating ≥ 4 despite ≥ 8 weeks of anxiolytic treatment. Subjects were randomized to adjunctive risperidone or placebo. The primary endpoint was change from baseline to week 4 endpoint in PaRTS-A. Improvement from baseline to week 4 endpoint in PaRTS-A total score (mean +/-SE) was similar between treatment groups (-8.54 [0.63] and -7.61 [0.64] for adjunctive risperidone and placebo, respectively; P = .265). Patients in each treatment group exhibited significant improvements from baseline in nearly all patient- and cli...

Psychopharmacology bulletin, 2007

What are the important gender differences seen in men and women with schizophrenia? Although schi... more What are the important gender differences seen in men and women with schizophrenia? Although schizophrenia affects men and women with equal frequency, the illness is expressed differently between the sexes. Women with schizophrenia tend to have better premorbid functioning, a later age at onset, a distinct symptom profile and better course of illness, and different structural brain abnormalities and cognitive deficits. Additionally, premenopausal women appear to have a superior response to typical antipsychotics compared to men and postmenopausal women. These gender differences are thought to arise from the interplay between hormonal and psychosocial factors. It has been hypothesized that estrogen, with effects on both neurodevelopment and neurotransmission, may play a protective role in women with schizophrenia and account for some of the gender differences observed in the disorder. Despite the potential benefit of estrogen in this population, women with schizophrenia appear to be ...

Psychiatry Research, 2002

Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinem... more Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic with prolactin-elevating potential (five with typical antipsychotics and three with risperidone) and eight treated with an antipsychotic with prolactin-sparing potential (seven with olanzapine and one with clozapine), were studied for eight weeks. Data were collected on menstrual functioning and on serum prolactin, estradiol, and progesterone levels, and were compared between subjects who received an antipsychotic with prolactinelevating potential and an antipsychotic with prolactin-sparing potential, and between subjects with hyperprolactinemia (Ns6) and normoprolactinemia (Ns10). Additionally, peak ovarian hormone levels were compared to normal values. While mean prolactin levels of subjects who received an antipsychotic with prolactin-elevating potential were significantly greater than those of subjects who received an antipsychotic with prolactin-sparing potential, there were no differences in rates of menstrual dysfunction or in ovarian hormone values between the two groups. Additionally, similar rates of menstrual dysfunction and ovarian hormone values were observed between the hyperprolactinemic and normoprolactinemic subjects. Moreover, irrespective of medication type or prolactin status, most subjects had peak estradiol levels below normal reference values for the periovulatory phase of the menstrual cycle. While our (C.M. Canuso).

The Journal of Clinical Psychiatry, 2014

Schizoaffective disorder is a complex illness for which optimal treatment is not well established... more Schizoaffective disorder is a complex illness for which optimal treatment is not well established. Results of the first controlled, relapse-prevention study of paliperidone palmitate once-monthly injectable (paliperidone monthly) in schizoaffective disorder are presented. The study was conducted between September 20, 2010, and October 22, 2013. Patients with schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and randomly assigned (1:1) to paliperidone monthly or placebo in a 15-month, double-blind, relapse-prevention phase. Randomization was stratified by administration as monotherapy or adjunctive therapy and by study center. The primary endpoint was time to relapse. 334 patients were evaluated. Paliperidone monthly significantly delayed time to relapse for psychotic, depressive, and manic symptoms compared with placebo (P < .001, log-rank test). Relapse risk was 2.49 times greater for placebo (hazard ratio = 2.49; 95% CI, 1.55 to 3.99; P < .001, Cox proportional hazards model). Overall relapse rates were 33.5% for placebo and 15.2% for paliperidone monthly. For monotherapy, relapse risk was 3.38 times greater with placebo (P = .002), and for adjunctive treatment it was 2.03 times greater with placebo (P = .021). Paliperidone monthly was superior to placebo in maintaining functioning as measured by the Personal and Social Performance scale (P = .014, mixed-model repeated-measures analysis). The most common adverse events (placebo, paliperidone monthly) were increased weight (4.7%, 8.5%), insomnia (7.1%, 4.9%), schizoaffective disorder (5.9%, 3.0%), headache (3.5%, 5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related adverse event was 7.1% for placebo and 8.5% for paliperidone monthly. Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic, depressive, and/or manic relapses; reduced their risk; and better maintained functioning in patients with schizoaffective disorder. Results support the value of maintenance treatment with paliperidone monthly in schizoaffective disorder. ClinicalTrials.gov identifier: NCT01193153.

Schizophrenia Research, 2010

Schizophrenia Research, 2008

Innovations in clinical neuroscience, 2012

The Clinical Global Impression for Schizoaffective Disorder scale is a new rating scale adapted f... more The Clinical Global Impression for Schizoaffective Disorder scale is a new rating scale adapted from the Clinical Global Impression scale for use in patients with schizoaffective disorder. The psychometric characteristics of the Clinical Global Impression for Schizoaffective Disorder are described. Content validity was assessed using an investigator questionnaire. Inter-rater reliability was determined with 12 sets of videotaped interviews rated independently by two trained individuals. Test-retest reliability was assessed using 30 randomly selected raters from clinical trials who evaluated the same videos on separate occasions two weeks apart. Convergent and divergent validity and effect size were evaluated by comparing scores between the Clinical Global Impression for Schizoaffective Disorder and the Positive and Negative Syndrome Scale, 21-item Hamilton Rating Scale for Depression, and Young Mania Rating Scale scales using pooled patient data from two clinical trials. Clinical Gl...

Schizophrenia Research, 2008

toms segregate into psychopathological dimensions. However, it is still unclear how these dimensi... more toms segregate into psychopathological dimensions. However, it is still unclear how these dimensions are associated with other clinical, neurobiological or sociodemographic variables. We investigated underlying psychopathological dimensions in a large epidemiological sample of patients with first onset psychosis and examined the association of these dimensions with other variables. Methods: We recruited 536 patients as part of a multicenter, population based, incidence study of psychosis. A Principal Axis Factor analysis was performed on symptom scores, using Varimax rotation. The relationship between dimension scores and different variables was then examined. Results: Factor analysis yielded pentagonal solution of manic, reality distortion, negative, depressive, and disorganization symptom dimensions, accounting for 47% of total variance. Manic dimension was associated with the most variables: female gender, acute onset, shorter duration of untreated psychosis, higher education and cannabis use. A number of variables were associated with the presence of negative symptoms: male gender, unemployment, ethnicity and lower education. Reality distortion was related to lower education, Black African ethnicity and unemployment. Finally, disorganization and depressive dimensions were associated with two variables each: disorganization with further education and being in a stable relationship whereas depressive symptoms were positively associated with being in a stable relationship, and inversely with unemployment Conclusions: The pattern of item segregation indicates that a dimensional structure previously reported in patients with chronic psychosis emerges even at the time of first onset. Furthermore, these dimensions show significant associations with validating variables, providing further support for a dimensional model of psychosis.

Schizophrenia Research, 2010

The Medication Satisfaction Questionnaire (MSQ) is a single-item questionnaire which evaluates sa... more The Medication Satisfaction Questionnaire (MSQ) is a single-item questionnaire which evaluates satisfaction with antipsychotic medication in schizophrenia patients. This study evaluated the reliability and validity for its use in research and clinical settings. Data pooled across treatment groups (control vs. Paliperidone ER) from a randomized 6-week study were used to conduct four psychometric assessments of the MSQ: (1) test-retest reliability, (2) convergent validity, (3) known-groups validity, and (4) minimally important difference (MID). This analysis included 191 randomized subjects. Test-retest reliability was evaluated for patients with no change in satisfaction from weeks 2 to 4 and weeks 4 to 6 (ICC=0.80; 0.83, respectively). Convergent validity was demonstrated through large correlations with Treatment Satisfaction Questionnaire for Medication (TSQM) global score (r=0.72-0.77), and through small correlations with variables measuring clinical symptoms and functioning (e.g., Positive and Negative Syndrome Scale (PANSS) total score [r=-0.30 to -0.17], CGI-S [r=-0.35 to -0.27], SF-36 Physical Functioning Score [r=0.18] and side effects and extrapiramidal measures (including UKU, ESRS-A, SAS). Mean MSQ scores were significantly different between those who completed and discontinued the study, and between different satisfaction groups based on TSQM, demonstrating good known-groups validity. MID estimates for the MSQ ranged from 0.47 (standard error of measurement) to 0.58 (anchor-based method). Results suggest that the MSQ has acceptable reliability and validity, making this single-item questionnaire appropriate and easy to use in clinical research and potentially in clinical practice. A 1-point change on the MSQ may be considered clinically meaningful.

Schizophrenia Research, 2008

Schizophrenia Research, 2009

Most patients with schizophrenia exhibit negative symptoms, even during acute episodes. These dif... more Most patients with schizophrenia exhibit negative symptoms, even during acute episodes. These difficult-to-treat symptoms are often associated with poor functioning and outcomes. A post-hoc analysis of pooled data from three 6-week double-blind studies included patients in an acute episode of schizophrenia who received paliperidone extended-release (ER) (3, 6, 9, or 12 mg) or placebo. Based on criteria developed by the authors, patients were stratified by the presence or absence of predominant negative symptoms at baseline (>or=40% of the maximum negative factor score and <40% of the maximum positive factor score on the Positive and Negative Syndrome Scale [PANSS]). Although these studies were not designed to examine patients with predominant negative symptoms, the criteria identified 23% of acutely ill patients (270/1193). The mean (SD) baseline PANSS negative symptoms factor score, 27.4 (3.3), was 49% of the maximum; the positive symptoms factor score, 23.7 (2.8), was 33% of the maximum. Completion rates with paliperidone ER (n=195) and placebo (n=75) were 64.6% and 44.0%, respectively. Greater improvements occurred with paliperidone ER vs placebo on PANSS (total, negative and other factors), Clinical Global Impressions-Severity and Personal and Social Performance scores at endpoint (all P values <0.05). Adverse events reported in >or=10% of patients were (paliperidone ER vs placebo): headache (14.4% vs 6.7%), insomnia (13.8% vs 21.3%) and sinus tachycardia (10.3% vs 1.3%). Paliperidone ER treatment was associated with a similar response profile in patients without predominant negative symptoms (paliperidone ER, n=647; placebo, n=276). Schizophrenia patients with predominant negative symptoms were identified in a population of acutely ill patients. Findings of this post-hoc analysis suggest that acutely ill patients with or without predominant negative symptoms respond similarly to treatment with paliperidone ER. No unexpected tolerability findings were observed.

Schizophrenia Research, 1997

Neurocognition and clinical symptomotology were evaluated in 27 OSM-IV diagnosed patients with sc... more Neurocognition and clinical symptomotology were evaluated in 27 OSM-IV diagnosed patients with schizophrenia during a double-blind, placebo-controlled, crossover study involving clozapine, an atypical antipsychotic agent, and haloperidol, a conventional, standard neuroleptic. Patients were assessed five to six weeks following initiation of each phase. Clinical symptomatology, based upon BPRS total score ratings, markedly improved following treatment with both haloperidol and clozapine (p= .0001). The beneficial effects of clozapine were statistically significantlygreater than those from the haloperidol treatment (p=.04). Positive and negative symptoms were also assessed with the BPRS index for positive symptoms and the SANS, respectively. Clozapine significantly decreased positive symptoms from placebo levels (p = .01), and both clozapine and haloperidol were effectiveat reducing negative symptomotology (p -=.004and p= .0004,respectively). Both agents proved efficacious in improving performance on nearly aU measures compared to placebo. Clozapine significantlyimproved performance on Trails B, verbal fluency, and measures of delayed verbal memory (p=.04; p=.02, and p=.OI, respectively), and tended to increase performance on most measures compared to haloperidol. Additional analyses indicated that the improvement on neurocognitive measures was not due to symptom amelioration; rather, neurocognitive deficits appear to be an intrinsic, enduring feature of schizophrenia. The superiority of clozapine over haloperidol may be related to clozapine's unique psychopharmacological profile. the VA CSHSH17 Study Group

Psychiatric Clinics of North America, 2003

Approximately half of patients with schizophrenia have at least one comorbid psychiatric or medic... more Approximately half of patients with schizophrenia have at least one comorbid psychiatric or medical condition, worsening prognosis and contributing to the high rate of morbidity and mortality. Depression is associated with suicide, the leading cause of premature death in patients with schizophrenia; obsessive-compulsive symptoms may worsen prognosis; alcohol and substance use disorders are associated with a poor outcome; and comorbid medical conditions, including cardiac and pulmonary disease, infectious diseases, diabetes, hyperlipidemia, hypogonadism, and osteoporosis, are often underrecognized and undertreated. The new generation of antipsychotic medications has improved the potential outcome of patients with schizophrenia. Providing optimal treatment for patients and fully realizing the potential of these new agents require focused attention on detection, recognition, and treatment of comorbid psychiatric and medical conditions in patients with schizophrenia.

Neuropsychopharmacology, 1994

High dosages of neuroleptics do not appear to have additional benefits in psychiatric patients an... more High dosages of neuroleptics do not appear to have additional benefits in psychiatric patients and are associated with higher prevalence and more severe side effects. However, they continue to be used by clinicians. The medication of all (N=360) psychiatric inpatients admitted in a long-term hospital was reviewed. A substantial number of patients (19%) were taking high dosages of neuroleptics (>1000

Neuropsychopharmacology, 2006

Approximately one-third of persons with depression do not respond to antidepressant monotherapy. ... more Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in-and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with o50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17p7 or CGI-Sp2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had o50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (o25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p ¼ 0.05); relapse rates were 56.1 and 64.1%, respectively (pp0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.

Biological Psychiatry, 2017

Current Medical Research and Opinion, 2011

The aim of this post-hoc analysis was to describe change in employment status over time in patien... more The aim of this post-hoc analysis was to describe change in employment status over time in patients with schizophrenia. Data were from three 52-week open-label extensions of the double-blind pivotal trials of paliperidone extended-release (ER) (trial numbers NCT00650793, NCT00210769 and NCT00668837). Employment status prior to trial entry was recorded at baseline of the open-label phase and change was measured at 4-week intervals. Patients were included if they were in the open-label, intent-to-treat analysis set (i.e., received at least one dose of the study medication and had a baseline and at least one post-baseline efficacy measurement) and had valid dates in the productivity data. Employment categories included full-time, part-time, casual, sheltered work, unemployed but seeking work, unemployed and not seeking work, retired, not employed outside the home and student. Change in employment status from baseline to post-baseline (last visit) was assessed using McNemar's test. Of the 1077 patients enrolled in the open-label extensions, 1012 (94.0%) met inclusion criteria. The average age was 37.7 years (SD 10.9) and 59.1% were male. At baseline, the largest percentage of patients was unemployed and not seeking work (56.8%), followed by retired (14.9%) and unemployed but seeking work (11.7%). Five different definitions of employment were created. Employment rates increased according to all five definitions (p < 0.0001), ranging from a 43% increase according to the definition most similar to that used by the US Bureau of Labor Statistics to an increase of 114% when only part-time and full-time employment were considered. In this uncontrolled population of patients with schizophrenia who were treated with paliperidone ER, the percentage of patients who were employed increased over time. By using multiple measures of employment, researchers can identify the nature of the employment status change.

Annals of internal medicine

Major depressive disorder has high prevalence, morbidity, and mortality. Inadequate results with ... more Major depressive disorder has high prevalence, morbidity, and mortality. Inadequate results with antidepressants have prompts addition of a nonstandard treatment (augmentation therapy). To assess whether augmentation therapy with risperidone reduces symptoms and increases response to antidepressant therapy and remission of depression in adults. Multicenter, double-blind, placebo-controlled, randomized trial conducted from 19 October 2004 to 17 November 2005. 75 primary care and psychiatric centers. 274 outpatient adults with major depressive disorder that was suboptimally responsive to antidepressant therapy. After a 4-week run-in period to ensure insufficient response to standard antidepressants, patients were randomly assigned to receive risperidone, 1 mg/d, or placebo for 6 weeks. After 4 weeks, the dosage of risperidone was increased to 2 mg/d in some cases. Symptoms were measured by using the 17-item Hamilton Rating Scale for Depression (HRSD-17). Other outcomes were response to therapy, remission of depression, and various clinician- and patient-rated assessments. Of the intention-to-treat population (268 patients), 81% (111 of 137) who received risperidone and 87.8% (115 of 131) who received placebo completed 6 weeks of double-blind treatment. Mean (+/-SE) HRSD-17 scores improved more in the risperidone augmentation group than in the placebo group (13.4 +/- 0.54 vs. 16.2 +/- 0.53; difference, -2.8 +/- 0.72 [95% CI, -4.2 to -1.4]; P <0.001). More risperidone recipients than placebo recipients experienced remission of depression (24.5% [26 of 106] vs. 10.7% [12 of 112]; P = 0.004) and had a response (46.2% [49 of 106] vs. 29.5% [33 of 112]; P = 0.004). Headache (8.8% of risperidone recipients vs. 14.5% of placebo recipients), somnolence (5.1% vs. 1.5%), and dry mouth (5.1% vs. 0.8%) were the most frequently reported adverse events. Patients were receiving many different antidepressants, and the duration of augmentation therapy was limited. Risperidone augmentation produced a statistically significant mean reduction in depression symptoms, substantially increased remission and response, and improved other patient- and clinician-rated measures. ClinicalTrials.gov registration number: NCT00095134.

Psychopharmacology bulletin

What are the important gender differences seen in men and women with schizophrenia? Although schi... more What are the important gender differences seen in men and women with schizophrenia? Although schizophrenia affects men and women with equal frequency, the illness is expressed differently between the sexes. Women with schizophrenia tend to have better premorbid functioning, a later age at onset, a distinct symptom profile and better course of illness, and different structural brain abnormalities and cognitive deficits. Additionally, premenopausal women appear to have a superior response to typical antipsychotics compared to men and postmenopausal women. These gender differences are thought to arise from the interplay between hormonal and psychosocial factors. It has been hypothesized that estrogen, with effects on both neurodevelopment and neurotransmission, may play a protective role in women with schizophrenia and account for some of the gender differences observed in the disorder. Despite the potential benefit of estrogen in this population, women with schizophrenia appear to be ...

Psychopharmacology bulletin

Residual symptoms despite treatment are common in generalized anxiety disorders (GAD). The Patien... more Residual symptoms despite treatment are common in generalized anxiety disorders (GAD). The Patient-Rated Troubling Symptoms for Anxiety (PaRTS-A) is a newly created and validated instrument that measures the symptoms most troublesome to each individual patient and was used to test the hypothesis that adjunctive risperidone improves residual GAD symptoms. Primary care and psychiatry clinicians enrolled adults (n = 417) with GAD and a Clinical Global Impressions of Severity rating ≥ 4 despite ≥ 8 weeks of anxiolytic treatment. Subjects were randomized to adjunctive risperidone or placebo. The primary endpoint was change from baseline to week 4 endpoint in PaRTS-A. Improvement from baseline to week 4 endpoint in PaRTS-A total score (mean +/-SE) was similar between treatment groups (-8.54 [0.63] and -7.61 [0.64] for adjunctive risperidone and placebo, respectively; P = .265). Patients in each treatment group exhibited significant improvements from baseline in nearly all patient- and cli...

Psychopharmacology bulletin, 2007

What are the important gender differences seen in men and women with schizophrenia? Although schi... more What are the important gender differences seen in men and women with schizophrenia? Although schizophrenia affects men and women with equal frequency, the illness is expressed differently between the sexes. Women with schizophrenia tend to have better premorbid functioning, a later age at onset, a distinct symptom profile and better course of illness, and different structural brain abnormalities and cognitive deficits. Additionally, premenopausal women appear to have a superior response to typical antipsychotics compared to men and postmenopausal women. These gender differences are thought to arise from the interplay between hormonal and psychosocial factors. It has been hypothesized that estrogen, with effects on both neurodevelopment and neurotransmission, may play a protective role in women with schizophrenia and account for some of the gender differences observed in the disorder. Despite the potential benefit of estrogen in this population, women with schizophrenia appear to be ...

Psychiatry Research, 2002

Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinem... more Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic with prolactin-elevating potential (five with typical antipsychotics and three with risperidone) and eight treated with an antipsychotic with prolactin-sparing potential (seven with olanzapine and one with clozapine), were studied for eight weeks. Data were collected on menstrual functioning and on serum prolactin, estradiol, and progesterone levels, and were compared between subjects who received an antipsychotic with prolactinelevating potential and an antipsychotic with prolactin-sparing potential, and between subjects with hyperprolactinemia (Ns6) and normoprolactinemia (Ns10). Additionally, peak ovarian hormone levels were compared to normal values. While mean prolactin levels of subjects who received an antipsychotic with prolactin-elevating potential were significantly greater than those of subjects who received an antipsychotic with prolactin-sparing potential, there were no differences in rates of menstrual dysfunction or in ovarian hormone values between the two groups. Additionally, similar rates of menstrual dysfunction and ovarian hormone values were observed between the hyperprolactinemic and normoprolactinemic subjects. Moreover, irrespective of medication type or prolactin status, most subjects had peak estradiol levels below normal reference values for the periovulatory phase of the menstrual cycle. While our (C.M. Canuso).

The Journal of Clinical Psychiatry, 2014

Schizoaffective disorder is a complex illness for which optimal treatment is not well established... more Schizoaffective disorder is a complex illness for which optimal treatment is not well established. Results of the first controlled, relapse-prevention study of paliperidone palmitate once-monthly injectable (paliperidone monthly) in schizoaffective disorder are presented. The study was conducted between September 20, 2010, and October 22, 2013. Patients with schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and randomly assigned (1:1) to paliperidone monthly or placebo in a 15-month, double-blind, relapse-prevention phase. Randomization was stratified by administration as monotherapy or adjunctive therapy and by study center. The primary endpoint was time to relapse. 334 patients were evaluated. Paliperidone monthly significantly delayed time to relapse for psychotic, depressive, and manic symptoms compared with placebo (P < .001, log-rank test). Relapse risk was 2.49 times greater for placebo (hazard ratio = 2.49; 95% CI, 1.55 to 3.99; P < .001, Cox proportional hazards model). Overall relapse rates were 33.5% for placebo and 15.2% for paliperidone monthly. For monotherapy, relapse risk was 3.38 times greater with placebo (P = .002), and for adjunctive treatment it was 2.03 times greater with placebo (P = .021). Paliperidone monthly was superior to placebo in maintaining functioning as measured by the Personal and Social Performance scale (P = .014, mixed-model repeated-measures analysis). The most common adverse events (placebo, paliperidone monthly) were increased weight (4.7%, 8.5%), insomnia (7.1%, 4.9%), schizoaffective disorder (5.9%, 3.0%), headache (3.5%, 5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related adverse event was 7.1% for placebo and 8.5% for paliperidone monthly. Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic, depressive, and/or manic relapses; reduced their risk; and better maintained functioning in patients with schizoaffective disorder. Results support the value of maintenance treatment with paliperidone monthly in schizoaffective disorder. ClinicalTrials.gov identifier: NCT01193153.

Schizophrenia Research, 2010

Schizophrenia Research, 2008

Innovations in clinical neuroscience, 2012

The Clinical Global Impression for Schizoaffective Disorder scale is a new rating scale adapted f... more The Clinical Global Impression for Schizoaffective Disorder scale is a new rating scale adapted from the Clinical Global Impression scale for use in patients with schizoaffective disorder. The psychometric characteristics of the Clinical Global Impression for Schizoaffective Disorder are described. Content validity was assessed using an investigator questionnaire. Inter-rater reliability was determined with 12 sets of videotaped interviews rated independently by two trained individuals. Test-retest reliability was assessed using 30 randomly selected raters from clinical trials who evaluated the same videos on separate occasions two weeks apart. Convergent and divergent validity and effect size were evaluated by comparing scores between the Clinical Global Impression for Schizoaffective Disorder and the Positive and Negative Syndrome Scale, 21-item Hamilton Rating Scale for Depression, and Young Mania Rating Scale scales using pooled patient data from two clinical trials. Clinical Gl...

Schizophrenia Research, 2008

toms segregate into psychopathological dimensions. However, it is still unclear how these dimensi... more toms segregate into psychopathological dimensions. However, it is still unclear how these dimensions are associated with other clinical, neurobiological or sociodemographic variables. We investigated underlying psychopathological dimensions in a large epidemiological sample of patients with first onset psychosis and examined the association of these dimensions with other variables. Methods: We recruited 536 patients as part of a multicenter, population based, incidence study of psychosis. A Principal Axis Factor analysis was performed on symptom scores, using Varimax rotation. The relationship between dimension scores and different variables was then examined. Results: Factor analysis yielded pentagonal solution of manic, reality distortion, negative, depressive, and disorganization symptom dimensions, accounting for 47% of total variance. Manic dimension was associated with the most variables: female gender, acute onset, shorter duration of untreated psychosis, higher education and cannabis use. A number of variables were associated with the presence of negative symptoms: male gender, unemployment, ethnicity and lower education. Reality distortion was related to lower education, Black African ethnicity and unemployment. Finally, disorganization and depressive dimensions were associated with two variables each: disorganization with further education and being in a stable relationship whereas depressive symptoms were positively associated with being in a stable relationship, and inversely with unemployment Conclusions: The pattern of item segregation indicates that a dimensional structure previously reported in patients with chronic psychosis emerges even at the time of first onset. Furthermore, these dimensions show significant associations with validating variables, providing further support for a dimensional model of psychosis.

Schizophrenia Research, 2010

The Medication Satisfaction Questionnaire (MSQ) is a single-item questionnaire which evaluates sa... more The Medication Satisfaction Questionnaire (MSQ) is a single-item questionnaire which evaluates satisfaction with antipsychotic medication in schizophrenia patients. This study evaluated the reliability and validity for its use in research and clinical settings. Data pooled across treatment groups (control vs. Paliperidone ER) from a randomized 6-week study were used to conduct four psychometric assessments of the MSQ: (1) test-retest reliability, (2) convergent validity, (3) known-groups validity, and (4) minimally important difference (MID). This analysis included 191 randomized subjects. Test-retest reliability was evaluated for patients with no change in satisfaction from weeks 2 to 4 and weeks 4 to 6 (ICC=0.80; 0.83, respectively). Convergent validity was demonstrated through large correlations with Treatment Satisfaction Questionnaire for Medication (TSQM) global score (r=0.72-0.77), and through small correlations with variables measuring clinical symptoms and functioning (e.g., Positive and Negative Syndrome Scale (PANSS) total score [r=-0.30 to -0.17], CGI-S [r=-0.35 to -0.27], SF-36 Physical Functioning Score [r=0.18] and side effects and extrapiramidal measures (including UKU, ESRS-A, SAS). Mean MSQ scores were significantly different between those who completed and discontinued the study, and between different satisfaction groups based on TSQM, demonstrating good known-groups validity. MID estimates for the MSQ ranged from 0.47 (standard error of measurement) to 0.58 (anchor-based method). Results suggest that the MSQ has acceptable reliability and validity, making this single-item questionnaire appropriate and easy to use in clinical research and potentially in clinical practice. A 1-point change on the MSQ may be considered clinically meaningful.

Schizophrenia Research, 2008

Schizophrenia Research, 2009

Most patients with schizophrenia exhibit negative symptoms, even during acute episodes. These dif... more Most patients with schizophrenia exhibit negative symptoms, even during acute episodes. These difficult-to-treat symptoms are often associated with poor functioning and outcomes. A post-hoc analysis of pooled data from three 6-week double-blind studies included patients in an acute episode of schizophrenia who received paliperidone extended-release (ER) (3, 6, 9, or 12 mg) or placebo. Based on criteria developed by the authors, patients were stratified by the presence or absence of predominant negative symptoms at baseline (>or=40% of the maximum negative factor score and <40% of the maximum positive factor score on the Positive and Negative Syndrome Scale [PANSS]). Although these studies were not designed to examine patients with predominant negative symptoms, the criteria identified 23% of acutely ill patients (270/1193). The mean (SD) baseline PANSS negative symptoms factor score, 27.4 (3.3), was 49% of the maximum; the positive symptoms factor score, 23.7 (2.8), was 33% of the maximum. Completion rates with paliperidone ER (n=195) and placebo (n=75) were 64.6% and 44.0%, respectively. Greater improvements occurred with paliperidone ER vs placebo on PANSS (total, negative and other factors), Clinical Global Impressions-Severity and Personal and Social Performance scores at endpoint (all P values <0.05). Adverse events reported in >or=10% of patients were (paliperidone ER vs placebo): headache (14.4% vs 6.7%), insomnia (13.8% vs 21.3%) and sinus tachycardia (10.3% vs 1.3%). Paliperidone ER treatment was associated with a similar response profile in patients without predominant negative symptoms (paliperidone ER, n=647; placebo, n=276). Schizophrenia patients with predominant negative symptoms were identified in a population of acutely ill patients. Findings of this post-hoc analysis suggest that acutely ill patients with or without predominant negative symptoms respond similarly to treatment with paliperidone ER. No unexpected tolerability findings were observed.

Schizophrenia Research, 1997

Neurocognition and clinical symptomotology were evaluated in 27 OSM-IV diagnosed patients with sc... more Neurocognition and clinical symptomotology were evaluated in 27 OSM-IV diagnosed patients with schizophrenia during a double-blind, placebo-controlled, crossover study involving clozapine, an atypical antipsychotic agent, and haloperidol, a conventional, standard neuroleptic. Patients were assessed five to six weeks following initiation of each phase. Clinical symptomatology, based upon BPRS total score ratings, markedly improved following treatment with both haloperidol and clozapine (p= .0001). The beneficial effects of clozapine were statistically significantlygreater than those from the haloperidol treatment (p=.04). Positive and negative symptoms were also assessed with the BPRS index for positive symptoms and the SANS, respectively. Clozapine significantly decreased positive symptoms from placebo levels (p = .01), and both clozapine and haloperidol were effectiveat reducing negative symptomotology (p -=.004and p= .0004,respectively). Both agents proved efficacious in improving performance on nearly aU measures compared to placebo. Clozapine significantlyimproved performance on Trails B, verbal fluency, and measures of delayed verbal memory (p=.04; p=.02, and p=.OI, respectively), and tended to increase performance on most measures compared to haloperidol. Additional analyses indicated that the improvement on neurocognitive measures was not due to symptom amelioration; rather, neurocognitive deficits appear to be an intrinsic, enduring feature of schizophrenia. The superiority of clozapine over haloperidol may be related to clozapine's unique psychopharmacological profile. the VA CSHSH17 Study Group

Psychiatric Clinics of North America, 2003

Approximately half of patients with schizophrenia have at least one comorbid psychiatric or medic... more Approximately half of patients with schizophrenia have at least one comorbid psychiatric or medical condition, worsening prognosis and contributing to the high rate of morbidity and mortality. Depression is associated with suicide, the leading cause of premature death in patients with schizophrenia; obsessive-compulsive symptoms may worsen prognosis; alcohol and substance use disorders are associated with a poor outcome; and comorbid medical conditions, including cardiac and pulmonary disease, infectious diseases, diabetes, hyperlipidemia, hypogonadism, and osteoporosis, are often underrecognized and undertreated. The new generation of antipsychotic medications has improved the potential outcome of patients with schizophrenia. Providing optimal treatment for patients and fully realizing the potential of these new agents require focused attention on detection, recognition, and treatment of comorbid psychiatric and medical conditions in patients with schizophrenia.

Neuropsychopharmacology, 1994

High dosages of neuroleptics do not appear to have additional benefits in psychiatric patients an... more High dosages of neuroleptics do not appear to have additional benefits in psychiatric patients and are associated with higher prevalence and more severe side effects. However, they continue to be used by clinicians. The medication of all (N=360) psychiatric inpatients admitted in a long-term hospital was reviewed. A substantial number of patients (19%) were taking high dosages of neuroleptics (>1000

Neuropsychopharmacology, 2006

Approximately one-third of persons with depression do not respond to antidepressant monotherapy. ... more Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in-and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with o50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17p7 or CGI-Sp2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had o50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (o25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p ¼ 0.05); relapse rates were 56.1 and 64.1%, respectively (pp0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.