Long-Term Improvement in Efficacy and Safety After Switching to Ziprasidone in Stable Outpatients with Schizophrenia

ABSTRACTIntroduction:The long-term efficacy and tolerability of treatment with ziprasidone following a switch from prior antipsychotics was evaluated in outpatients with schizophrenia or schizoaffective disorder in three open-label, flexible-dose, 1-year extension studies.Methods:These studies enrolled completers of 6-week trials in which subjects were switched to ziprasidone from conventional antipsychotics, olanzapine, or risperidone. Identical study designs and the small number of patients entering the extensions supported pooling of the data.Results:Of 185 pooled subjects entering the extension studies, 72 completed 58 weeks of treatment. Median treatment duration was 34.6 weeks; median dose was 120 mg/day at endpoint. The intent-to-treat population showed significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores (−4.3 [P≤.01]), PANSS negative scores (−2.4 [P≤.0001]), and Clinical Global Impression of severity score (−0.3 [P≤.001]). Completers showed significant improvement in mean PANSS total scores (−10.2 [P<.0001]), PANSS positive scores (−2.7 [P<.0001]), PANSS negative scores (−2.7 [P<.001]), and Clinical Global Impression of severity scores (−0.6 [P<.0001]).Conclusion:Ziprasidone was well tolerated, and patients demonstrated significant improvement in metabolic parameters and in all movement disorder assessments. Insomnia and somnolence were the only adverse events with an incidence >10% in pooled subjects. No subject had a corrected QT interval ≥500 msec.

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Long-term safety and tolerability of iloperidone: results from a 25-week, open-label extension trial

CNS Spectrums ◽

10.1017/s1092852912000764 ◽

2013 ◽

Vol 18 (1) ◽

pp. 43-54 ◽

Cited By ~ 15

Author(s):

Andrew J. Cutler ◽

Amir H. Kalali ◽

Greg W. Mattingly ◽

Jelena Kunovac ◽

Xiangyi Meng

Keyword(s):

Serum Glucose ◽

Favorable Effect ◽

Controlled Clinical Trial ◽

Open Label ◽

Once Daily ◽

Syndrome Scale ◽

Open Label Extension ◽

Negative Syndrome ◽

Extension Trial

Introduction/ObjectiveLong-term use of the atypical antipsychotic iloperidone has not been investigated at doses above 16 mg/d. This article describes safety and tolerability results from the 25-week open-label extension of a 4-week placebo- and ziprasidone-controlled clinical trial of iloperidone.MethodsPatients received a dose of 24 mg/d (given as 12 mg twice daily; mean dose = 21.6 mg) that could be reduced to 12 mg/d (given once daily at bedtime) any time after day 35 at the investigator's discretion.ResultsA total of 72/173 patients (41.6%) completed the open-label extension. Treatment-emergent adverse events (TEAEs), most mild to moderate in severity, included headache (13.9%), weight increase (9.2%), dizziness (6.9%), nausea (6.4%), sedation (6.4%), and insomnia (5.2%). The only notable dose-related TEAEs were increased weight and headache. Levels of serum glucose, lipids, and prolactin were essentially unchanged or decreased during treatment. In general, akathisia and extrapyramidal symptoms (EPS) improved or were unchanged during treatment. There was no signal of worsening of efficacy based on changes from baseline in the Positive and Negative Syndrome Scale-Total.Discussion/ConclusionThis study further supports the long-term safety and tolerability of iloperidone for the treatment of schizophrenia, including iloperidone's favorable effect on metabolic laboratory parameters and low propensity to cause akathisia or EPS.

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Aripiprazole for Patients with Schizophrenia and Schizoaffective Disorder: An Open-Label, Randomized, Study Versus Haloperidol

CNS Spectrums ◽

10.1017/s1092852900000249 ◽

2009 ◽

Vol 14 (2) ◽

pp. 93-102 ◽

Cited By ~ 9

Author(s):

Irismar Reis de Oliveira ◽

Hélio Elkis ◽

Wagner Farid Gattaz ◽

Ana Cristina Chaves ◽

Eduardo Pondé de Sena ◽

...

Keyword(s):

Schizoaffective Disorder ◽

Negative Symptoms ◽

Partial Agonist ◽

Randomized Study ◽

Open Label ◽

Anticholinergic Medications ◽

Syndrome Scale ◽

Number Of Patients ◽

Negative Syndrome ◽

Haloperidol Group

Introduction: Aripiprazole, a dopamine D2 receptor partial agonist, has also partial agonist activity at serotonin (5-HT)1A receptors and antagonist activity at 5-HT2A receptors.Methods: In this 8-week, multicenter, randomized, parallel-group, open-label, flexible-dose study, patients diagnosed with schizophrenia or schizoaffective disorder were randomized to aripiprazole 15–30 mg/day or haloperidol 10–15 mg/day.Results: Patients treated with both aripiprazole and haloperidol improved from baseline in Positive and Negative Syndrome Scale total, positive, and negative scores as well as in Clinical Global Impressions scores (all P<.001). At the end of the study, the percentage of patients classified as responders—according to ≥40% reduction in the Positive and Negative Syndrome Scale negative subscale score—was significantly higher in the aripiprazole group (20%) than in the haloperidol group (0%) (P<.05). Additionally, a higher number of patients receiving haloperidol required more anticholinergic medications (P<.001) than aripiprazole-treated patients, whereas more aripiprazole (45.5%) than haloperidol-treated patients (12.9%) required benzodiazepines (P=.002). At endpoint, rates of preference of medication were higher in the aripiprazole group (63.2%) than in the haloperidol group (21.7%), as expressed by patients and caregivers (P=.001).Conclusion: Aripiprazole and haloperidol had similar efficacy in terms of reduction of overall psychopathology. Although aripiprazole has been demonstrated to be superior concerning negative symptoms and in terms of tolerability (extrapyramidal symptoms) and preferred by patients and caregivers than haloperidol, significantly more aripiprazole-treated patients required benzodiazepines.

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Blonanserin augmentation in patients with schizophrenia – who is benefited from blonanserin augmentation?: An open-label, prospective, multicenter study

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.558 ◽

2016 ◽

Vol 33 (S1) ◽

pp. s226-s226

Author(s):

Y.S. Woo ◽

J.E. Park ◽

D.H. Kim ◽

I.K. Sohn ◽

T.Y. Hwang ◽

...

Keyword(s):

Multicenter Study ◽

Atypical Antipsychotics ◽

Therapeutic Strategy ◽

Psychiatric Symptoms ◽

Open Label ◽

Prospective Multicenter Study ◽

Syndrome Scale ◽

Schizophrenic Patients ◽

Competing Interest ◽

Negative Syndrome

IntroductionEvidences for antipsychotics augmentation for schizophrenic patients with suboptimal efficacy have been lacking although it has been widespread therapeutic strategy in clinical practice.ObjectivesThe purpose of this study was to investigate the efficacy and tolerability of blonanserin augmentation with an atypical antipsychotics (AAPs) in schizophrenic patients.MethodsA total of 100 patients with schizophrenia partially or completely unresponsive to treatment with an AAP recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to existing AAPs which were maintained during the study period. Efficacy was primarily evaluated using Positive and Negative Syndrome Scale (PANSS) at baseline, week 2, 4, 8, and 12. Predictors for PANSS response (≥ 20% reduction) was investigated.ResultsThe PANSS total score was significantly decreased at 12 weeks after blonanserin augmentation (–21.0 ± 18.1, F = 105.849, P < 0.001). Response rate on PANSS at week 12 was 51.0%. Premature discontinuation was occurred in 17 patients (17.0%) and 4 patients among them discontinued the study due to adverse events. Nine patients experienced significant weight gain during the study. Response to blonanserin augmentation was associated with severe (PANSS > 85) baseline symptom (OR = 10.298, P = 0.007) and higher dose (> 600 mg/day of chlorpromazine equivalent dose) of existing AAPs (OR = 4.594, P = 0.014).ConclusionsBlonanserin augmentation improved psychiatric symptoms of schizophrenic patients in cases of partial or non-responsive to an AAP treatment with favorable tolerability. Patients with severe symptom despite treatment with higher dose of AAP were benefited from this augmentation. These results suggested that blonanserin augmentation could be an effective strategy for specific patients with schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Safety and effectiveness of lurasidone in adolescents with schizophrenia: results of a 2-year, open-label extension study

CNS Spectrums ◽

10.1017/s1092852920001893 ◽

2020 ◽

pp. 1-11

Author(s):

Christoph U. Correll ◽

Robert L. Findling ◽

Michael Tocco ◽

Andrei Pikalov ◽

Ling Deng ◽

...

Keyword(s):

Body Weight ◽

Adverse Events ◽

Rating Scales ◽

Extension Study ◽

Open Label ◽

Double Blind ◽

Syndrome Scale ◽

Open Label Extension ◽

Glycemic Indices

Abstract Background Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia. Methods Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score. Results About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104. Conclusion In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.

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Efficacy and safety of brexpiprazole in patients with schizophrenia presenting with severe symptoms: Post-hoc analysis of short- and long-term studies

Journal of Psychopharmacology ◽

10.1177/0269881120936485 ◽

2020 ◽

Vol 34 (8) ◽

pp. 829-838

Author(s):

Nicole Meade ◽

Lily Shi ◽

Stine R Meehan ◽

Catherine Weiss ◽

Zahinoor Ismail

Keyword(s):

Least Squares ◽

Social Performance ◽

Mean Difference ◽

Syndrome Scale ◽

Scale Total Score ◽

Short And Long Term ◽

Negative Syndrome ◽

Performance Scale ◽

Long Term Studies

Background: The treatment of patients with severe schizophrenia symptoms can be complicated and expensive. Aims: The purpose of this study was to evaluate the short- and long-term effects of brexpiprazole in patients with schizophrenia presenting with severe symptoms. Methods: Data were pooled from three six-week, randomized, double-blind, placebo-controlled studies and two 52-week, open-label extension studies. In the short-term studies, 1405 patients received placebo or brexpiprazole 2–4 mg/day; 412 brexpiprazole-treated patients rolled over into the long-term studies and received brexpiprazole 1–4 mg/day. More severe symptoms were defined as a Positive and Negative Syndrome Scale Total score >95 (median score at baseline). Outcomes included change in Positive and Negative Syndrome Scale Total and Personal and Social Performance scale scores. Results: Brexpiprazole improved Positive and Negative Syndrome Scale Total score over 6 weeks among more severely ill patients, with a least squares mean difference versus placebo of −6.76 (95% confidence limits: −9.80, −3.72; p<0.0001; Cohen’s d: 0.43). Brexpiprazole also improved Personal and Social Performance scale score over 6 weeks in more severely ill patients (least squares mean difference: 4.38; limits: 2.14, 6.62; p=0.0001; Cohen’s d: 0.38). Improvement of functioning was greatest in the ‘Self-care’ domain, followed by ‘Personal and social relationships’. Among less severely ill patients, brexpiprazole was superior to placebo on Positive and Negative Syndrome Scale Total and Personal and Social Performance scale at Week 6. Improvements were maintained over 58 weeks. No new safety or tolerability concerns were observed. Conclusions: Brexpiprazole is an efficacious and well-tolerated treatment for schizophrenia in patients with more severe, and less severe, symptoms.

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Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale—supportive analyses from a Phase 3 study

CNS Spectrums ◽

10.1017/s1092852917000396 ◽

2017 ◽

Vol 23 (4) ◽

pp. 284-290 ◽

Cited By ~ 5

Author(s):

Leslie Citrome ◽

Robert Risinger ◽

Andrew J. Cutler ◽

Yangchun Du ◽

Jacqueline Zummo ◽

...

Keyword(s):

Scale Score ◽

Clinical Global Impression ◽

Response Rates ◽

Fixed Dose ◽

Phase 3 ◽

General Psychopathology ◽

Syndrome Scale ◽

Long Acting ◽

Post Hoc ◽

Negative Syndrome

ObjectiveAripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints.MethodsPatients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression–Improvement (CGI-I) scale score, was also analyzed.ResultsOf 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92–94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo.ConclusionAL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.

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Severe idiopathic pulmonary fibrosis: what can be done?

European Respiratory Review ◽

10.1183/16000617.0047-2017 ◽

2017 ◽

Vol 26 (145) ◽

pp. 170047 ◽

Cited By ~ 21

Author(s):

Antonella Caminati ◽

Roberto Cassandro ◽

Olga Torre ◽

Sergio Harari

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Clinical Observation ◽

Anxiety And Depression ◽

Neoplastic Disease ◽

Therapeutic Approaches ◽

Slow Disease Progression ◽

Open Label ◽

Number Of Patients

Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to the fact that severe IPF patients are usually not enrolled in randomised, prospective, multicentre, international trials. Clinical observation experiences and preliminary results of long-term, open-label extensions of clinical trials suggest that both pirfenidone and nintedanib may also slow or decrease progression in patients with severe IPF. However, data are sparse and obtained from a relatively small number of patients. Lung transplantation should be taken into account early and discussed with patients, when indicated. Rehabilitative strategies are important and effective supportive therapies. The needs of patients with severe IPF are similar to those of patients with an advanced neoplastic disease. Palliative care and psychological support play an important role in the relief of symptoms of anxiety and depression. Accordingly, these therapeutic approaches should start early in IPF patients.

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Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial

The International Journal of Neuropsychopharmacology ◽

10.1017/s146114571200137x ◽

2013 ◽

Vol 16 (7) ◽

pp. 1661-1666 ◽

Cited By ~ 3

Author(s):

Viacheslav Terevnikov ◽

Jan-Henry Stenberg ◽

Jari Tiihonen ◽

Evgeni Chukhin ◽

Marina Joffe ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Side Effects ◽

First Generation ◽

Metabolic Effects ◽

Open Label ◽

Double Blind ◽

Cholesterol Levels ◽

Syndrome Scale ◽

Negative Syndrome

Abstract Clinical efficacy and metabolic side-effects of antipsychotics seem to correlate with each other. In this study, interrelationship of similar metabolic effects of mirtazapine and its earlier reported desirable effects on psychopathology in first-generation antipsychotics (FGAs)-treated schizophrenia were explored. Symptomatic FGAs-treated patients with schizophrenia received a 6-wk double-blind treatment with add-on mirtazapine (n = 20) or placebo (n = 16), followed by a 6-wk open-label mirtazapine treatment. Mirtazapine (but not placebo) induced an increase in body weight and cholesterol levels. The latter was associated with a clinical improvement in all (sub)scales of the Positive and Negative Syndrome Scale [PANSS; an increase of cholesterol by 1 mmol/l predicted 7 points reduction on the PANSS total score (r = 0.85, p = 0.001)]. In schizophrenia, mirtazapine-induced weight gain and increase of total cholesterol are associated with the improved efficacy of mirtazapine-FGAs combination – a novel observation with possible clinical and theoretical implications.

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Réponse thérapeutique, tolérance et sécurité d’emploi du palmitate de palipéridone à dose flexible : une étude prospective chez des patients adultes non-aigus atteints de schizophrénie, après échec d’un traitement par antipsychotiques oraux

European Psychiatry ◽

10.1016/j.eurpsy.2013.09.284 ◽

2013 ◽

Vol 28 (S2) ◽

pp. 107-107

Author(s):

P. Vidailhet ◽

A. Schreiner ◽

P. Bergmans ◽

P. Cherubin ◽

E. Rancans ◽

...

Keyword(s):

Clinical Global Impression ◽

Severity Scale ◽

Effets Indésirables ◽

Étude Prospective ◽

Clinical Global Impression Severity ◽

Syndrome Scale ◽

La Substitution ◽

Negative Syndrome

ObjectifsÉvaluer la tolérance, la sécurité d’emploi et la réponse à un traitement mensuel par palmitate de paliperidone (PP) à doses flexibles chez des patients adultes atteints de schizophrénie, non-aigus mais symptomatiques, après échec d’un traitement par antipsychotiques oraux.MéthodesAnalyse d’un groupe de patients atteints de schizophrénie, non-aigus mais symptomatiques, inclus dans une étude internationale, ouverte, prospective de six mois, évaluant la symptomatologie clinique : PANSS (Positive and Negative Syndrome Scale) et CGIS-S (Clinical Global Impression-Severity Scale), les événements indésirables (EIs) et le changement de poids.RésultatsCinq cent quatre-vingt-treize patients (population en intention de traiter) : 63,1 % d’hommes, âge moyen 38,4 ± 11,8 ans, 78,6 % souffrant de schizophrénie paranoïde. La principale raison de la substitution d’un antipsychotique oral par le PP était un manque d’efficacité (24,3 %). 74,5 % des patients ont terminé l’étude de six mois. Les raisons les plus fréquentes d’arrêt précoce étaient : le choix du patient (9,3 %), des effets indésirables (EIs) (6,1 %), les perdus de vue (3,0 %) et le manque d’efficacité (2,5 %). Le score total moyen à l’échelle PANSS a diminué de 71,5 ± 14,6 à l’inclusion à 59,7 ± 18,1 à la fin de l’étude (soit une différence de −11,7 ± 15,9 points ; 95 % IC 95 % [−13,0 ; −10,5] ; p <0,0001). 64,0 % des patients ont eu une amélioration supérieure ou égale à 20 % du score total à la PANSS et le pourcentage de patients légèrement malades ou moins (CGI-S) est passé de 31,8 à 63,2 %. Les EIs touchant plus de 5 % des patients sont : douleur au site d’injection (12,3 %), insomnie (8,6 %), anxiété (6,7 %), trouble psychotique (6,1 %) et céphalées (5,6 %). Le changement moyen de poids a été de 1,2 ± 5,0 kg (IC 95 % [0,7 ; 1,6]).ConclusionsCes résultats confirment la bonne tolérance et l’efficacité thérapeutique du PP à doses flexibles chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par antipsychotiques oraux.

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Tolerability and treatment response in patients with recently diagnosed vs. chronic schizophrenia treated with paliperidone ER

European Psychiatry ◽

10.1016/s0924-9338(11)73206-0 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1502-1502

Author(s):

A. Schreiner ◽

D. Hoeben ◽

C. Tessier ◽

M. Lahaye ◽

J. Turczynski ◽

...

Keyword(s):

Treatment Response ◽

Chronic Schizophrenia ◽

Psychotic Symptoms ◽

Chronic Patients ◽

Open Label ◽

Patient Functioning ◽

Syndrome Scale ◽

Negative Syndrome ◽

Mean Time ◽

Time Since Diagnosis

ObjectiveTo explore tolerability and treatment response in adult patients with recently diagnosed (<5 years) and chronic (>5 years) schizophrenia treated with flexible doses of paliperidone ER.MethodsInternational prospective open-label 6-month study. Endpoints were the Positive and Negative Syndrome Scale (PANSS), patient functioning and treatment-emergent adverse events (TEAEs).ResultsOf 713 recently diagnosed patients, most were male (60.9%), mean age was 33.6 ± 11.2 years and mean time since diagnosis was 2.3 ± 1.7 years. Chronic patients (n = 1003) were predominantly male (59.2%) with a mean age of 43.8 ± 11.4 and mean time since diagnosis of 15.6 ± 9.2 years. 70.4% and 71.7% of patients completed the study, respectively. Mean mode doses of paliperidone ER were similar between recently diagnosed and chronic patients (7.0 ± 2.9 mg/day and 7.2 ± 2.9 mg/day). 63.1% of recently diagnosed and 60.8% of chronic patients switching due to lack of efficacy with their previous antipsychotic had a >20% improvement in PANSS total score at endpoint, and improvement with other switching reasons was consistently numerically higher in recently diagnosed patients. The rate of patients with mild or no functional impairment increased from 17.7% to 39.8% in recently diagnosed and from 14.4% to 32.9% in chronic patients. TEAEs reported in >5% were insomnia (10.7% and 8.1%), anxiety (8.6% and 6.0%) and somnolence (5.8% and 3.4%), respectively.ConclusionThese data suggest that both recently diagnosed and chronic patients previously unsuccessfully treated with other oral antipsychotics may benefit from paliperidone ER, with a tendency for recently diagnosed patients showing some higher treatment response in psychotic symptoms and patient functioning.

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