P.0451 Effects of SEP-363856, novel TAAR1 agonist, on negative symptoms in schizophrenia: results of a double-blind acute and 6-month extension study

IntroductionIn a recent placebo-controlled, double blind crossover trial (n = 52), we found significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) after 12 weeks memantine augmentation in patients with clozapine-refractory schizophrenia.AimsIn this open-label 1 year extension study, we report the long-term effects and tolerability of memantine add-on therapy to clozapine.MethodsCompleters of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for one year. Primary endpoints were memory and executive function using the Cambridge neuropsychological test automated battery (CANTAB), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S).ResultsOf 31 RCT completers who experienced beneficial effects from memantine, 24 received memantine for one year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50), and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects.ConclusionsIn the one-year extension phase, the favorable effect of adjunctive memantine on memory was sustained and we observed further improvement of positive, negative and overall symptoms of schizophrenia.Disclosure of interestP.F.J.S. reports personal fees from H. Lundbeck A/S, outside the submitted work and he is a board member of the Dutch Clozapine Collaboration Group. L.d.H., has received investigator-led research grants or recompense for presenting his research from Eli Lilly, Bristol-Myers Squibb, Janssen-Cilag and AstraZeneca.

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Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study

Psychological Medicine ◽

10.1017/s0033291716002476 ◽

2016 ◽

Vol 47 (2) ◽

pp. 363-375 ◽

Cited By ~ 16

Author(s):

S. R. T. Veerman ◽

P. F. J. Schulte ◽

J. B. Deijen ◽

L. de Haan

Keyword(s):

Executive Function ◽

Negative Symptoms ◽

Controlled Trial ◽

Neuropsychological Test ◽

Extension Study ◽

Favourable Effect ◽

Long Term Effects ◽

Open Label ◽

Double Blind ◽

Beneficial Effects

BackgroundIn a recent placebo-controlled, double-blind crossover trial (n = 52), significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) were found after 12 weeks of memantine augmentation in patients with clozapine-refractory schizophrenia. In this open-label 1-year extension study we report the long-term effects and tolerability of memantine add-on therapy to clozapine.MethodCompleters of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for 1 year. Primary endpoints were memory and executive function using the Cambridge Neuropsychological Test Automated Battery, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S).ResultsOf 31 randomized controlled trial completers who experienced beneficial effects from memantine, 24 received memantine for 1 year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50) and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks of memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects.ConclusionsIn the 1-year extension phase the favourable effect of adjunctive memantine on memory was sustained and we observed further improvement of negative, positive and overall symptoms in patients with clozapine-treated refractory schizophrenia.

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Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: A double-blind placebo-controlled study

Pharmacopsychiatry ◽

10.1055/s-2003-825390 ◽

2004 ◽

Vol 36 (05) ◽

Author(s):

MC Jockers-Scherübl ◽

A Bauer ◽

F Godemann ◽

FM Reischies ◽

F Selig ◽

...

Keyword(s):

Negative Symptoms ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo

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Faculty Opinions recommendation of A detailed analysis of the effect of repetitive transcranial magnetic stimulation on negative symptoms of schizophrenia: a double-blind trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718028173.793480013 ◽

2013 ◽

Author(s):

Steven Potkin ◽

Adrian Preda

Keyword(s):

Transcranial Magnetic Stimulation ◽

Detailed Analysis ◽

Magnetic Stimulation ◽

Negative Symptoms ◽

Repetitive Transcranial Magnetic Stimulation ◽

Double Blind Trial ◽

Double Blind ◽

Blind Trial

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Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

Genetics in Medicine ◽

10.1038/s41436-021-01287-7 ◽

2021 ◽

Author(s):

Ravi Savarirayan ◽

Louise Tofts ◽

Melita Irving ◽

William R. Wilcox ◽

Carlos A. Bacino ◽

...

Keyword(s):

Growth Velocity ◽

Bone Growth ◽

Growth Factor Receptor ◽

Extension Study ◽

Controlled Study ◽

Open Label ◽

Phase 3 ◽

Double Blind ◽

Pathogenic Variants ◽

Growth Promoting

Abstract Purpose Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

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Adjunctive Garcinia mangostana Linn. (Mangosteen) Pericarp for Schizophrenia: A 24-Week Double-blind, Randomized, Placebo Controlled Efficacy Trial: Péricarpe d’appoint Garcinia mangostana Linn (mangoustan) pour la schizophrénie : un essai d’efficacité de 24 semaines, à double insu, randomisé et contrôlé par placebo

The Canadian Journal of Psychiatry ◽

10.1177/0706743720982437 ◽

2020 ◽

pp. 070674372098243

Author(s):

Alyna Turner ◽

Andrea Baker ◽

Olivia M. Dean ◽

Adam J. Walker ◽

Seetal Dodd ◽

...

Keyword(s):

Quality Of Life ◽

Schizoaffective Disorder ◽

Negative Symptoms ◽

Controlled Trial ◽

Safety Data ◽

Rate Of Change ◽

Adjunctive Treatment ◽

Garcinia Mangostana ◽

Double Blind

Objectives: Garcinia mangostana Linn. (“mangosteen”) pericarp contains bioactive compounds that may target biological pathways implicated in schizophrenia. We conducted a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp, compared to placebo, in the treatment of schizophrenia. Methods: People diagnosed with schizophrenia or schizoaffective disorder ( Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), recruited across 2 sites (Brisbane and Victoria, Australia), were randomized to receive 24 weeks of adjunctive mangosteen pericarp (1,000 mg/day) or matched placebo. The primary outcome measure was the Positive and Negative Symptom Scale total score. Secondary outcomes included positive and negative symptoms, general psychopathology, clinical global severity and improvement, participant reported overall improvement, depressive symptoms, functioning, quality of life, and safety data at 24 and 28 weeks (4 weeks postdiscontinuation). Data were collected from July 2016 to February 2019. Results: Baseline assessments were conducted on 148 people (mangosteen = 74, placebo = 74); data analyses were conducted on 136 (92%) participants with postbaseline data. The treatment group had significantly higher symptom severity compared to placebo, and both groups significantly improved on all symptom, functioning, and quality of life measures over time. No between-group differences were found for the rate of change between baseline and 24 or 28 weeks. Conclusion: Despite promising preclinical and clinical work, our results do not support mangosteen pericarp extract as an adjunctive treatment for schizophrenia or schizoaffective disorder.

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