scholarly journals Scale-Up Synthesis and Identification of GLYX-13, a NMDAR Glycine-Site Partial Agonist for the Treatment of Major Depressive Disorder

Molecules ◽  
2018 ◽  
Vol 23 (5) ◽  
pp. 996 ◽  
Author(s):  
Wenchao Li ◽  
Jingjian Liu ◽  
Minghua Fan ◽  
Zhongtang Li ◽  
Yin Chen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Partial Agonist ◽  
Scale Up ◽  
Glycine Site ◽  
Major Depressive

scholarly journals Brexpiprazole: A review of a new treatment option for schizophrenia and major depressive disorder

2017 ◽  
Vol 7 (5) ◽  
pp. 207-212 ◽  
Author(s):  
Lauren A. Diefenderfer ◽  
Courtney Iuppa
Keyword(s):  
Clinical Trials ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Partial Agonist ◽  
Adjunctive Treatment ◽  
Inadequate Response ◽  
Major Depressive ◽  
Two Phase ◽  
New Treatment

Abstract Brexpiprazole is an atypical antipsychotic that works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. It has US Food and Drug Administration approval for monotherapy treatment of schizophrenia and adjunctive treatment to antidepressants for major depressive disorder. Two phase-3 clinical trials demonstrated efficacy and relatively fair tolerability with regard to adverse effects for each indication. Akathisia was frequently reported in the major depressive disorder trials but less so in the schizophrenia trials. Significant increases in body weight and triglycerides were seen across all studies. Brexpiprazole appears to be a viable option for treating an acute exacerbation of schizophrenia requiring hospitalization or adjunctive treatment of major depressive disorder in patients who showed an inadequate response to 1 to 3 antidepressants. Further clinical trials are warranted to determine the long-term efficacy of brexpiprazole, and comparison trials would be beneficial to establish its place in therapy.

Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: systematic review and meta-analysis

2013 ◽  
Vol 44 (11) ◽  
pp. 2255-2269 ◽  
Author(s):  
T. Kishi ◽  
H. Y. Meltzer ◽  
Y. Matsuda ◽  
N. Iwata
Keyword(s):  
Systematic Review ◽  
Major Depressive Disorder ◽  
Side Effects ◽  
Depressive Disorder ◽  
Partial Agonist ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Cochrane Library ◽  
Number Needed To Treat ◽  
Major Depressive

BackgroundA meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported.MethodWe carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95% confidence intervals (CIs).ResultsFifteen RCTs comparing 5-HT1A agonists with placebo (total n = 2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95% CI 0.65–083, p < 0.00001, NNT = 6, 12 trials, n = 1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p = 0.02, NNH = 16, p = 0.03, 10 trials, n = 1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p < 0.0001, NNH = 17, p = 0.001, 13 trials, n = 2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p = 0.85, 14 trials, n = 2402). Four 5-HT1A agonist augmentation studies were identified (total n = 365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p = 0.85, four trials, n = 341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p < 0.00001 to p = 0.03).ConclusionsOur results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

scholarly journals Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine

2021 ◽  
Vol 12 ◽  
Author(s):  
Borjanka Batinic ◽  
Ivan Ristic ◽  
Milica Zugic ◽  
David S. Baldwin
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Negative Symptoms ◽  
Partial Agonist ◽  
Major Depressive ◽  
Drug Of Choice ◽  
Randomized Controlled Studies ◽  
Therapeutic Uses ◽  
Mixed Features ◽  
Frequent Relapses

Cariprazine is currently approved for the treatment of patients with schizophrenia (USA and EU), and for manic, depressive, and episodes with mixed features in bipolar I disorder (USA): several randomized controlled studies have also explored its efficacy in patients with major depressive disorder. This review summarizes its current therapeutic uses and potential advantages for treating the main symptoms of schizophrenia, bipolar I and major depressive disorder, considering its pharmacodynamic properties, efficacy, and tolerability. Its predominantly D3 receptor preferring affinity, with functional selectivity according to the prevailing neuronal environment, contributes to its efficacy across a wide array of psychopathological symptoms (including reality distortion, disorganized thought, negative symptoms, mood disturbance, anhedonia, and cognitive impairment), and to a favorable side effect profile. Cariprazine may be a “drug of choice” in patients with predominant negative and cognitive symptoms of schizophrenia, as well as those with metabolic syndrome. Further investigation of its relative efficacy when compared to aripiprazole or other active comparators is warranted. Its effectiveness in the treatment of bipolar mania, bipolar I depression and bipolar I episodes with mixed features, with minimal accompanying metabolic changes is well-established. The longer half-life and delayed time to relapse in patients diagnosed with schizophrenia when compared to other second-generation antipsychotics represent other advantages, given the high rates of non-adherence and frequent relapses seen in clinical practice. Its efficacy in overlapping symptom domains in other major psychiatric disorders appears promising.

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