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Azapirone

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Nakao Iwata – 1st expert on this subject based on the ideXlab platform

  • Azapirones for Attention Deficit Hyperactivity Disorder: A Systematic Review
    Pharmacopsychiatry, 2016
    Co-Authors: Yuki Matsui, Shinji Matsunaga, Yuki Matsuda, Taro Kishi, Nakao Iwata

    Abstract:

    Introduction: No meta-analysis has evaluated Azapirones (serotonin 1A receptor partial agonists) as anxiolytics for attention deficit hyperactivity disorder (ADHD). Methods: Randomized controlled trials (RCTs) and single-arm trials published before October 27, 2015 were retrieved from major healthcare databases and clinical trial registries. Relative risk and 95% confidence intervals were calculated. Results: 5 RCTs (n=429) and 3 single-arm studies (n=70) were identified. 3 RCTs compared buspirone vs. methylphenidate in children/adolescents, one buspirone patches vs. placebo patches in children/adolescents, and one atomoxetine plus buspirone vs. atomoxetine vs. placebo in adults. The single-arm studies were buspirone trails in children/adolescents. All-cause discontinuation rates and adverse events did not differ between pooled buspirone and methylphenidate groups. No other meta-analyses of buspirone efficacy and safety vs. comparators were conducted due to insufficient data. 2 RCTs found no significant differences in parent and teacher ADHD-Rating Scale total scores between buspirone and methylphenidate, while one reported that methylphenidate improved parent and teacher ADHD-RS total scores vs. buspirone. Discussion: It remains unclear whether buspirone use has benefit for ADHD patients and therefore further evidence is needed for better clinical use of buspirone in patients with ADHD.

  • Azapirone 5 ht1a receptor partial agonist treatment for major depressive disorder systematic review and meta analysis
    Psychological Medicine, 2014
    Co-Authors: Taro Kishi, Yuki Matsuda, Herbert Y Meltzer, Nakao Iwata

    Abstract:

    Background
    A 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.
    Method
    We 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).
    Results
    Fifteen 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). Conclusions Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

  • Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: systematic review and meta-analysis.
    Psychological Medicine, 2013
    Co-Authors: Taro Kishi, Yuki Matsuda, Herbert Y Meltzer, Nakao Iwata

    Abstract:

    BACKGROUND: A 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. METHOD: We 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). RESULTS: Fifteen 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). CONCLUSIONS: Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

John C. Pecknold – 2nd expert on this subject based on the ideXlab platform

  • Serotonin 5-HT1A Agonists: A Comparative Review
    CNS Drugs, 2012
    Co-Authors: John C. Pecknold

    Abstract:

    In 1980, buspirone was found to have anxiolytic potential. This finding initiated the development of the Azapirones — highly serotonin 5-HT1A agonists. The balance of evidence suggests that the Azapirones act as partial agonists postsynaptically, but as full agonists presynaptically in the dorsal raphe. This review focuses mainly on agents for which there are published clinical trial data. Numerous studies have shown that buspirone, gepirone and ipsapirone are as effective as the benzodiazepines in the treatment of generalised anxiety. However, they have a slower onset of action. The Azapirones have a completely different adverse reaction profile (dizziness and gastric complaints) compared with the benzodiazepines (sedation, memory loss and withdrawal dependency). Several controlled studies have shown that the Azapirones are effective in depression, particularly of the melancholic type. They have an adverse effects profile similar to, but less severe than, the selective serotonin reuptake inhibitors and different to that of the tricyclic antidepressants. Buspirone has not yet proven to be effective in panic disorder. However, gepirone, ipsapirone and other Azapirones may be more effective in this disorder. Early studies indicate promising results for buspirone in the treatment of obsessive-compulsive disorder. Clinical trials in alcoholism are equivocal. Further studies of this class of drugs in the treatment of social phobia, post-traumatic stress disorder, premenstrual syndrome, and compulsive and aggressive disorders are in progress. A principle drawback with this class of drug is their short half-life. However, sustained release preparations are being developed.

  • Serotonin 5-HT_1A Agonists
    CNS Drugs, 1994
    Co-Authors: John C. Pecknold

    Abstract:

    In 1980, buspirone was found to have anxiolytic potential. This finding initiated the development of the Azapirones — highly serotonin 5-HT_1A agonists. The balance of evidence suggests that the Azapirones act as partial agonists postsynaptically, but as full agonists presynaptically in the dorsal raphé. This review focuses mainly on agents for which there are published clinical trial data. Numerous studies have shown that buspirone, gepirone and ipsapirone are as effective as the benzodiazepines in the treatment of generalised anxiety. However, they have a slower onset of action. The Azapirones have a completely different adverse reaction profile (dizziness and gastric complaints) compared with the benzodiazepines (sedation, memory loss and withdrawal dependency). Several controlled studies have shown that the Azapirones are effective in depression, particularly of the melancholic type. They have an adverse effects profile similar to, but less severe than, the selective serotonin reuptake inhibitors and different to that of the tricyclic antidepressants. Buspirone has not yet proven to be effective in panic disorder. However, gepirone, ipsapirone and other Azapirones may be more effective in this disorder. Early studies indicate promising results for buspirone in the treatment of obsessive-compulsive disorder. Clinical trials in alcoholism are equivocal. Further studies of this class of drugs in the treatment of social phobia, post-traumatic stress disorder, premenstrual syndrome, and compulsive and aggressive disorders are in progress. A principle drawback with this class of drug is their short half-life. However, sustained release preparations are being developed.

  • Gepirone and the treatment of panic disorder: an open study.
    Journal of Clinical Psychopharmacology, 1993
    Co-Authors: John C. Pecknold, Lorenz Luthe, Marie-h L Ne Scott-fleury, Stephen W. Jenkins

    Abstract:

    : Gepirone, an Azapirone, is a potent 5-hydroxytryptamine 1A (5-HT1A) agonist. We report an uncontrolled 6-week study in 21 patients (4 men, 17 women: mean age, 36.71 years) with a concurrent DSM-III-R diagnosis of generalized anxiety disorder and panic disorder with agoraphobia. After a 2-week medication-free period, patients were started on 2 mg of gepirone per day increasing over 3 weeks to 12 mg/day. Three patients dropped out in the first week, and one patient violated the protocol. They were therefore excluded from analysis. Two patients who dropped out at weeks 4 and 5 because they found the treatment ineffective were included. Twelve of the 17 patients (70.6%) had at least a 50% reduction in their panic attacks by week 6, and 9 of them had at least a 50% reduction by week 3. Ten patients had “0” panic attacks by week 6 (59%). On the Hamilton Anxiety Scale, 65% had a 50% or greater reduction in total score, mostly beginning in week 1. On Global Assessment, by week 6, 11 were much improved or better (65%). Adverse effects were rare and consisted of stomach upset, dizziness, or headaches. This preliminary study suggests the possible efficacy of gepirone in panic disorder.

Taro Kishi – 3rd expert on this subject based on the ideXlab platform

  • Azapirones for Attention Deficit Hyperactivity Disorder: A Systematic Review
    Pharmacopsychiatry, 2016
    Co-Authors: Yuki Matsui, Shinji Matsunaga, Yuki Matsuda, Taro Kishi, Nakao Iwata

    Abstract:

    Introduction: No meta-analysis has evaluated Azapirones (serotonin 1A receptor partial agonists) as anxiolytics for attention deficit hyperactivity disorder (ADHD). Methods: Randomized controlled trials (RCTs) and single-arm trials published before October 27, 2015 were retrieved from major healthcare databases and clinical trial registries. Relative risk and 95% confidence intervals were calculated. Results: 5 RCTs (n=429) and 3 single-arm studies (n=70) were identified. 3 RCTs compared buspirone vs. methylphenidate in children/adolescents, one buspirone patches vs. placebo patches in children/adolescents, and one atomoxetine plus buspirone vs. atomoxetine vs. placebo in adults. The single-arm studies were buspirone trails in children/adolescents. All-cause discontinuation rates and adverse events did not differ between pooled buspirone and methylphenidate groups. No other meta-analyses of buspirone efficacy and safety vs. comparators were conducted due to insufficient data. 2 RCTs found no significant differences in parent and teacher ADHD-Rating Scale total scores between buspirone and methylphenidate, while one reported that methylphenidate improved parent and teacher ADHD-RS total scores vs. buspirone. Discussion: It remains unclear whether buspirone use has benefit for ADHD patients and therefore further evidence is needed for better clinical use of buspirone in patients with ADHD.

  • Azapirone 5 ht1a receptor partial agonist treatment for major depressive disorder systematic review and meta analysis
    Psychological Medicine, 2014
    Co-Authors: Taro Kishi, Yuki Matsuda, Herbert Y Meltzer, Nakao Iwata

    Abstract:

    Background
    A 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.
    Method
    We 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).
    Results
    Fifteen 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). Conclusions Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

  • Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: systematic review and meta-analysis.
    Psychological Medicine, 2013
    Co-Authors: Taro Kishi, Yuki Matsuda, Herbert Y Meltzer, Nakao Iwata

    Abstract:

    BACKGROUND: A 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. METHOD: We 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). RESULTS: Fifteen 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). CONCLUSIONS: Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.