Azapirone

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Nakao Iwata - One of the best experts 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.

  • augmentation of antipsychotic drug action by Azapirone 5 ht1a receptor partial agonists a meta analysis
    The International Journal of Neuropsychopharmacology, 2013
    Co-Authors: Taro Kishi, Herbert Y Meltzer, Nakao Iwata
    Abstract:

    The aim of the study was to evaluate the evidence that serotonin1A (5-HT1A) receptor partial agonists of the Azapirone class, which are not antipsychotic, have benefits for adjunctive treatment of overall psychopathology, positive and negative symptoms for patients with schizophrenia. We carried out a systematic review of the literature available through PubMed, Cochrane Library, PsycINFO and Google Scholar during September 2012, followed by a meta-analysis of randomized placebo-controlled trials. Risk ratio (RR), 95% confidence intervals (CI) and standardized mean difference (s.m.d.) were calculated. Four studies, involving 163 patients with schizophrenia, met inclusion criteria: buspirone: three trials and 137 patients; tandospirone: one trial and 26 patients. As adjunctive therapy, 5-HT1A partial agonists were significantly superior to placebo for overall improvement in psychopathology (s.m.d. = −0.46, CI = −0.79 to −0.13, p = 0.006, N = 4, n = 149) and marginally more effective to improve positive symptoms (s.m.d. = −0.31, CI = −0.64 to 0.01, p = 0.06, N = 4, n = 149). However, 5-HT1A partial agonists were not more efficacious than placebo as adjunctive therapy for improving negative symptoms (s.m.d. = −0.09, CI = −0.60 to 0.42, p = 0.72, N = 4, n = 149). In addition, there was no significant difference in discontinuation rates between 5-HT1A partial agonists and placebo (all cause: RR = 0.98, CI = 0.49–1.98, p = 0.96, N = 4, n = 153, side-effects: RR = 1.96, CI = 0.54–7.19, p = 0.31, N = 4, n = 153). 5-HT1A partial agonists as adjunctive therapy improved overall psychopathology with a trend to improve positive symptoms in patients with schizophrenia. Because the number of studies was small, additional controlled clinical trials with larger numbers of patients are indicated.

John C. Pecknold - One of the best experts 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 - One of the best experts 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.

  • augmentation of antipsychotic drug action by Azapirone 5 ht1a receptor partial agonists a meta analysis
    The International Journal of Neuropsychopharmacology, 2013
    Co-Authors: Taro Kishi, Herbert Y Meltzer, Nakao Iwata
    Abstract:

    The aim of the study was to evaluate the evidence that serotonin1A (5-HT1A) receptor partial agonists of the Azapirone class, which are not antipsychotic, have benefits for adjunctive treatment of overall psychopathology, positive and negative symptoms for patients with schizophrenia. We carried out a systematic review of the literature available through PubMed, Cochrane Library, PsycINFO and Google Scholar during September 2012, followed by a meta-analysis of randomized placebo-controlled trials. Risk ratio (RR), 95% confidence intervals (CI) and standardized mean difference (s.m.d.) were calculated. Four studies, involving 163 patients with schizophrenia, met inclusion criteria: buspirone: three trials and 137 patients; tandospirone: one trial and 26 patients. As adjunctive therapy, 5-HT1A partial agonists were significantly superior to placebo for overall improvement in psychopathology (s.m.d. = −0.46, CI = −0.79 to −0.13, p = 0.006, N = 4, n = 149) and marginally more effective to improve positive symptoms (s.m.d. = −0.31, CI = −0.64 to 0.01, p = 0.06, N = 4, n = 149). However, 5-HT1A partial agonists were not more efficacious than placebo as adjunctive therapy for improving negative symptoms (s.m.d. = −0.09, CI = −0.60 to 0.42, p = 0.72, N = 4, n = 149). In addition, there was no significant difference in discontinuation rates between 5-HT1A partial agonists and placebo (all cause: RR = 0.98, CI = 0.49–1.98, p = 0.96, N = 4, n = 153, side-effects: RR = 1.96, CI = 0.54–7.19, p = 0.31, N = 4, n = 153). 5-HT1A partial agonists as adjunctive therapy improved overall psychopathology with a trend to improve positive symptoms in patients with schizophrenia. Because the number of studies was small, additional controlled clinical trials with larger numbers of patients are indicated.

Michael J Rowan - One of the best experts on this subject based on the ideXlab platform.

  • the Azapirone metabolite 1 2 pyrimidinyl piperazine depresses excitatory synaptic transmission in the hippocampus of the alert rat via 5 ht1a receptors
    European Journal of Pharmacology, 1995
    Co-Authors: Denise Manahanvaughan, Roger Anwyl, Michael J Rowan
    Abstract:

    Abstract The effects of acute and repeated treatment with 1-(2-pyrimidinyl)piperazine (1-PP), a metabolite of the 5-HT 1A receptor ligand Azapirones, were investigated on hippocampal excitatory synaptic transmission. Recordings of the electrically evoked field population excitatory post-synaptic potentials (e.p.s.p.s) were carried out in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert rats. Acute i.p. administration of 1-PP transiently reduced the e.p.s.p. amplitude in a dose-dependent (0.25–1 mg/kg) manner. This effect was blocked by the 5-HT 1A receptor antagonists spiroxatrine (1 mg/kg) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl methylaminoethyl]-8-azaspirol[4,5]decane-7,9-dione methyl sulphonate, 2 mg/kg). Intraphippocampal administration of 1-PP (5 μg) evoked a transient reduction of the e.p.s.p. amplitude which was similar to that obtained with 5-HT (10 μg). 1-PP (0.25 mg/kg per day) administered for 9 days produced a gradual reduction in the daily pre-injection baseline e.p.s.p. amplitude coupled with a decrease in the acute response to the drug. The chronic baseline reduction was transiently reversed by spiroxatrine and full recovery to pretreatment levels was observed 4 days after the last 1-PP dose. These findings indicate that the previously reported reduction in the e.p.s.p. produced by the Azapirone group of 5-HT 1A receptor ligands may be mediated in part by their metabolite 1-PP through activation of 5-HT 1A receptors.

Charles S. Wilcox - One of the best experts on this subject based on the ideXlab platform.

  • Serotonin 5-HT1a Receptor Agonists as Antidepressants
    CNS Drugs, 1998
    Co-Authors: Jon F. Heiser, Charles S. Wilcox
    Abstract:

    Although typically considered anxiolytics, for 20 years serotonin 5-HT1A receptor agonists have been evaluated for effectiveness in treating depressive disorders and depressive symptoms occurring in a range of diagnostic categories, including major and minor depression, mixed states of anxiety and depression, and mixed syndromes of depression and alcohol dependence. 5-HT1A agonists have also been studied as adjuncts to standard antidepressant therapy. Most of the work has been done with the widely marketed Azapirone, buspirone. A limited amount has been done with other, unmarketed Azapirones, including gepirone, ipsapirone, tandospirone and zalospirone. NonAzapirone 5-HT1A receptor agonists have also been studied, and one, flesinoxan, is continuing in clinical trials for the treatment of depression and anxiety.

  • Serotonin 5-HT_1a Receptor Agonists as Antidepressants
    CNS Drugs, 1998
    Co-Authors: Jon F. Heiser, Charles S. Wilcox
    Abstract:

    Although typically considered anxiolytics, for 20 years serotonin 5-HT_1A receptor agonists have been evaluated for effectiveness in treating depressive disorders and depressive symptoms occurring in a range of diagnostic categories, including major and minor depression, mixed states of anxiety and depression, and mixed syndromes of depression and alcohol dependence. 5-HT_1A agonists have also been studied as adjuncts to standard antidepressant therapy. Most of the work has been done with the widely marketed Azapirone, buspirone. A limited amount has been done with other, unmarketed Azapirones, including gepirone, ipsapirone, tandospirone and zalospirone. NonAzapirone 5-HT_1A receptor agonists have also been studied, and one, flesinoxan, is continuing in clinical trials for the treatment of depression and anxiety. As a whole, the results have shown antidepressant effects for all compounds, though neither consistently nor robustly. The compounds appear to be well tolerated but adverse effects such as dizziness and nausea are common, and the short half-life of these drugs makes twice or 3 times daily administration necessary. Tolerability and adverse effect problems have been attributed to a metabolite of the Azapirones, 1-pyrimidinyl-piperazine (1-PP), which is not a metabolite of the nonAzapirone flesinoxan. The short half-life issue has been addressed by extended release oral preparations and transdermal administration via a once-daily skin patch. One study was of 6 months’ duration; the remaining studies have lasted 10 weeks or less. We cannot recommend buspirone, the only currently marketed 5-HT_1A receptor agonist, as a first-line treatment for depression, but it is reasonable to consider its use as an adjunct to standard antidepressant drug therapy or in mixed states of anxiety and depression. The combined results have greatly contributed to our understanding of the role of the 5-HT_1A receptor in a range of clinical forms of depression. They have also been useful in understanding the mechanisms of actions of other antidepressants and have guided the development of new medications.