RESUMEN
N6-clyclohexyladenosine (CHA) is an adenosine A1 receptor agonist that inhibits thermogenesis. Cardiovascular side effects however, limit use of CHA as a therapeutic. We and others have shown that this can be reversed by administering 8-p-(sulfophenyl)theophylline (8-SPT), a nonspecific antagonist that does not cross the BBB. Other evidence shows that CNS actions of CHA may contribute to bradycardia through enhanced vagal tone and other mechanisms. Here we test the hypothesis that 8-SPT pretreatment alone is sufficient to prevent hypotension caused by CHA. To test this hypothesis, we pretreated rats with 8-SPT alone, and in combination with other antagonists to test the hypothesis that direct action of CHA on the heart is the primary mechanism by which CHA induces bradycardia and hypotension. Results show that pretreatment with 8-SPT alone is not sufficient to prevent CHA-induced hypotension. Pretreatment with 8-SPT or atropine alone did not prevent the fall in mean arterial pressure (MAP) and heart rate (HR), however, pretreatment with 8-SPT (25 mg/kg) and atropine (1 mg/kg) 15 min before CHA (1 mg/kg) preserves MAP and HR baseline values after CHA administration. We next asked if blood pressure was managed during the transition into a hypometabolic state, would prolong CHA-mediated inhibition of metabolism after cardiac arrest improve outcome better than anti-shivering medications meperidine and buspirone. We found that CHA-mediated hypotension can be mitigated by pretreatment with atropine and 8-SPT. This combination administered after cardiac arrest facilitated temperature management and metabolic suppression better than meperidine and buspirone, however, did not improve survival.
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Adenosina , Buspirona , Paro Cardíaco , Meperidina , Ratas Sprague-Dawley , Animales , Ratas , Adenosina/análogos & derivados , Adenosina/farmacología , Buspirona/farmacología , Buspirona/uso terapéutico , Masculino , Paro Cardíaco/tratamiento farmacológico , Meperidina/farmacología , Meperidina/análogos & derivados , Meperidina/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Teofilina/análogos & derivados , Teofilina/farmacología , Teofilina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Preclinical evidence suggests that co-administration of the 5-HT1A agonist buspirone and the 5-HT1B/1D agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone. OBJECTIVES: Assess the therapeutic potential of a fixed-dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. METHODS: Single-center, randomized, placebo-controlled, two-way crossover study (NCT02439203) of a fixed-dose buspirone/zolmitriptan regimen (10/1.25 mg three times a day) in 30 patients with PD experiencing at least moderately disabling peak-effect dyskinesia. RESULTS: Seven days of treatment with buspirone/zolmitriptan added to levodopa significantly reduced dyskinesia as assessed by Abnormal Involuntary Movement Scale scores versus placebo (mean treatment effect vs. placebo: -4.2 [-6.1, -2.3]) without significantly worsening Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON) scores (mean treatment effect vs. placebo: 0.6 [-0.1, 1.3]). No serious adverse events were reported. CONCLUSIONS: In this proof-of-concept study, addition of buspirone/zolmitriptan to the patients' PD medication regimen significantly reduced dyskinesia severity without worsening motor function. © 2024 International Parkinson and Movement Disorder Society.
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Discinesia Inducida por Medicamentos , Oxazolidinonas , Enfermedad de Parkinson , Triptaminas , Humanos , Levodopa/efectos adversos , Antiparkinsonianos/uso terapéutico , Buspirona/uso terapéutico , Estudios Cruzados , Serotonina , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Enfermedad de Parkinson/tratamiento farmacológico , Método Doble CiegoRESUMEN
Preliminary clinical findings, supported by preclinical studies employing behavioral paradigms such as marble burying, suggest that psilocybin may be effective in treating obsessive-compulsive disorder. However, the receptor mechanisms implicated in the putative anti-obsessional effect are not clear. On this background, we set out to explore (1) the role of serotonin 2A (5-HT2A) and serotonin 1A (5-HT1A) receptors in the effect of psilocybin on marble burying; (2) the effect of staggered versus bolus psilocybin administration and persistence of the effect; (3) the effect of the 5-HT1A partial agonist, buspirone, on marble-burying and the head twitch response (HTR) induced by psilocybin, a rodent correlate of psychedelic effects. Male ICR mice were administered psilocybin 4.4 mg/kg, escitalopram 5 mg/kg, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) 2 mg/kg, M100907 2 mg/kg, buspirone 5 mg/kg, WAY100635 2 mg/kg or combinations, intraperitoneally, and were tested on the marble burying test. HTR was examined in a magnetometer-based assay. The results show that (1) Psilocybin and escitalopram significantly reduced marble burying. The effect of psilocybin was not attenuated by the 5-HT2A antagonist, M100907. The 5-HT1A agonist, 8-OH-DPAT, reduced marble burying as did the 5-HT1A partial agonist, buspirone. The effect of 8-OH-DPAT was additive to that of psilocybin, but that of buspirone was not. The 5-HT1A antagonist, WAY100635, attenuated the effect of 8-OH-DPAT and buspirone but not the effect of psilocybin. (2) Psilocybin injections over 3.5 h had no effect on marble burying and the effect of bolus injection was not persistent. (3) Co-administration of buspirone with psilocybin blocked its effect on HTR. These data suggest that neither 5-HT2A nor 5-HT1A receptors are pivotally implicated in the effect of psilocybin on marble burying. Co-administration with buspirone may block the psychedelic effects of psilocybin without impeding its anti-obsessional effects.
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Alucinógenos , Trastorno Obsesivo Compulsivo , Animales , Masculino , Ratones , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/uso terapéutico , Buspirona/farmacología , Buspirona/uso terapéutico , Escitalopram , Alucinógenos/farmacología , Ratones Endogámicos ICR , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Psilocibina/farmacología , Serotonina , Receptor de Serotonina 5-HT1ARESUMEN
BACKGROUND: Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5-HT1 receptor agonist, may improve fundic accommodation. AIM: To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis. METHODS: This 4-week multi-centre clinical trial randomised patients with symptoms of gastroparesis and moderate-to-severe symptoms of fullness (Gastroparesis Cardinal Symptom Index [GCSI] early satiety/postprandial fullness subscore [ES/PPF]) to buspirone (10 mg orally) or placebo three times per day. The primary outcome was a change in the ES/PPF from baseline to 4 weeks. The primary analysis was per protocol intention-to-treat ANCOVA of between-group baseline vs. 4-week differences (DoD) in ES/PPF adjusted for baseline ES/PPF. Results are reported using both nominal and Bonferroni (BF) p values. RESULTS AND CONCLUSIONS: Ninety-six patients (47 buspirone, 49 placeboes; 92% female, 50% delayed gastric emptying, 39% diabetic) were enrolled. There was no between-groups difference in the 4-week ES/PPF primary outcome: -1.16 ± 1.25 (SD) on buspirone vs -1.03 ± 1.29 (SD) on placebo (mean DoD: -0.11 [95% CI: -0.68, 0.45]; p = 0.69). Buspirone performed better than placebo in patients with severe-to-very severe bloating at baseline compared to patients with none to moderate: (ES/PPF DoD = -0.65 vs. 1.58, pTX*GROUP = 0.003; pBF = 0.07). Among individual GCSI symptoms, only bloating appeared to improve with buspirone vs. placebo. CONCLUSIONS: Patients with moderate-to-severe early satiety/postprandial fullness and other symptoms of gastroparesis did not benefit from buspirone treatment to improve the ES/PPF primary outcome compared with placebo. There was a suggestion of the benefit of buspirone in patients with more severe bloating. TRIAL REGISTRATION: ClinicalTrials.gov NCT0358714285.
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Buspirona , Gastroparesia , Humanos , Femenino , Masculino , Buspirona/uso terapéutico , Gastroparesia/tratamiento farmacológico , Gastroparesia/diagnóstico , Método Doble Ciego , Vaciamiento GástricoRESUMEN
BACKGROUND: A patient, with a mental disorder caused by an intracranial infection, treated with olanzapine, fluvoxamine, and buspirone. The plasma exposure of olanzapine was too high at standard doses, with evidence indicating that it was caused by drug-drug interactions. METHODS: Using pharmacogenomics and therapeutic drug monitoring to guide drug dose adjustment for a patient in clinical practice. RESULTS: The patient underwent pharmacogenetic testing in addition to therapeutic drug monitoring as part of a pharmacist-led comprehensive evaluation of medication therapy management in a clinical setting, resulting in improved clinical efficacy that allowed discharge from a psychiatric hospital. CONCLUSIONS: This case study demonstrates that therapeutic drug monitoring combined with pharmacogenetic-guided dose adjustment can aid in the management of patients receiving complex pharmacological treatments.
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Buspirona , Fluvoxamina , Humanos , Olanzapina , Fluvoxamina/uso terapéutico , Buspirona/uso terapéutico , Farmacogenética , Monitoreo de Drogas/métodos , BenzodiazepinasAsunto(s)
Ansiolíticos , Trastorno Autístico , Humanos , Buspirona/uso terapéutico , Trastorno Autístico/complicaciones , Trastorno Autístico/tratamiento farmacológico , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/epidemiología , Ansiedad/complicaciones , Ansiedad/tratamiento farmacológico , Comorbilidad , Ansiolíticos/uso terapéutico , Método Doble CiegoRESUMEN
BACKGROUND: The gold standard for symptomatic relief of Parkinson's disease (PD) is L-DOPA. However, long-term treatment often leads to motor complications such as L-DOPA-induced dyskinesia (LID). While amantadine (Gocovri™) is the only approved therapy for dyskinesia in PD patients on the American market, it is associated with neurological side effects and limited efficacy. Thus, there remains a high unmet need for addressing LID in PD patients worldwide. OBJECTIVE: The objective of this study was to evaluate the efficacy, safety and performance compared to approved treatments of the serotonin receptor 1A (5-HT1A) and 5-HT1B/D agonists buspirone and zolmitriptan in the 6-hydroxydopamine unilaterally lesioned rat model for PD. METHODS: The hemiparkinsonian 6-OHDA-lesioned rats underwent chronic treatment with L-DOPA to induce dyskinesia and were subsequently used for efficacy testing of buspirone, zolmitriptan and comparison with amantadine, measured as abnormal involuntary movement (AIM) scores after L-DOPA challenge. Safety testing was performed in model and naïve animals using forelimb adjusting, rotarod and open field tests. RESULTS: 5-HT1A and 5-HT1B/D agonism effectively reduced AIM scores in a synergistic manner. The drug combination of buspirone and zolmitriptan was safe and did not lead to tolerance development following sub-chronic administration. Head-to-head comparison with amantadine showed superior performance of buspirone and zolmitriptan in the model. CONCLUSIONS: The strong anti-dyskinetic effect found with combined 5-HT1A and 5-HT1B/D agonism renders buspirone and zolmitriptan together a meaningful treatment for LID in PD.
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Discinesia Inducida por Medicamentos , Enfermedad de Parkinson , Amantadina/uso terapéutico , Animales , Antiparkinsonianos/efectos adversos , Buspirona/farmacología , Buspirona/uso terapéutico , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/etiología , Levodopa/farmacología , Oxazolidinonas , Oxidopamina/toxicidad , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/etiología , Ratas , Ratas Sprague-Dawley , Receptores de Serotonina , Serotonina , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Agonistas del Receptor de Serotonina 5-HT1/uso terapéutico , TriptaminasRESUMEN
OBJECTIVE: Reports on the pharmacologic treatment of anxiety, including generalized anxiety disorder (GAD), in individuals with Down syndrome (DS) are lacking. METHODS: We present the case histories of 1 adolescent and 2 young adults with DS and the treatment course of comorbid GAD with buspirone. RESULTS: Treatment with buspirone was safe and well-tolerated and resulted in sustained improvement in symptoms of anxiety for a minimum of 2 years in all 3 cases. CONCLUSION: Buspirone's generally benign adverse effect profile makes it well suited for treating anxiety in individuals with DS in light of their common medical comorbidities.
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Buspirona , Síndrome de Down , Adolescente , Ansiedad , Trastornos de Ansiedad/epidemiología , Buspirona/farmacología , Buspirona/uso terapéutico , Comorbilidad , Síndrome de Down/complicaciones , Síndrome de Down/tratamiento farmacológico , Humanos , Adulto JovenRESUMEN
RATIONALE: Irritable bowel syndrome (IBS) is a chronic and debilitating functional disorder of the gastrointestinal tract manifested by abdominal pain and bowel habit dysregulation. The pathophysiology is complex and management targets symptom resolution. Therapeutic interventions range from dietary modification, psychological interventions, exercise, to the use of antispasmodics, antibiotics, and antidepressants. Anecdotal reports have suggested that buspirone may be beneficial in the treatment of functional dyspepsia and IBS and its physiological effect of reducing gastric tone provides a rational for its benefit. PATIENT CONCERNS: A 28-year-old man with unremarkable past medical and psychiatric history presented with worsening abdominal pain, bloating, and bowel movement dysregulation of over 6-year duration. DIAGNOSES: Physical examination revealed mild distension and discomfort on deep palpation. Thorough blood investigations, stool analysis and culture, and imaging were unremarkable except for the detection of mucus with stool. The patient was diagnosed with irritable bowel syndrome with mixed habits. INTERVENTIONS: Dietary adjustment and a range of medications (mebeverine, simethicone, loperamide, rifaximin, sertraline and amitriptyline) yielded unsatisfactory response of were not tolerated. Buspirone was eventually introduced. OUTCOMES: Buspirone was associated with a significant and sustained improvement in IBS symptoms and quality of life. LESSONS: This case suggests that buspirone was effective in treating refractory IBS. Further research is needed to assess the role of buspirone in IBS management.
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Buspirona/uso terapéutico , Síndrome del Colon Irritable/tratamiento farmacológico , Agonistas de Receptores de Serotonina/uso terapéutico , Dolor Abdominal/tratamiento farmacológico , Dolor Abdominal/etiología , Adulto , Humanos , Masculino , Calidad de VidaRESUMEN
Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.
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Antidepresivos/uso terapéutico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Antidepresivos de Segunda Generación/uso terapéutico , Buspirona/uso terapéutico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Trastorno Depresivo Resistente al Tratamiento/psicología , Humanos , Ketamina/uso terapéutico , Litio/uso terapéuticoRESUMEN
OBJECTIVE: The aim of the study was to describe the efficacy of buspirone in controlling nonpharmacological awake and sleep bruxism. METHODS: Four cases of nonpharmacological awake and sleep bruxism, one of them with a 20-year-long history, in which buspirone succeeded to control bruxism, are described and discussed. RESULTS: Two of the 4 cases had sleep bruxism, and the other 2 cases had sleep and awake bruxism. Besides anxiety, no other predisposing condition was identified. Buspirone was effective in reducing bruxism symptoms in the 4 cases. Mean percentage of bruxism reduction after buspirone was ranked as 65% by subjects. CONCLUSIONS: In this small series of cases, buspirone proved effective in the control of nonpharmacological awake and sleep bruxism.
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Bruxismo , Bruxismo del Sueño , Ansiedad , Buspirona/uso terapéutico , Humanos , Sueño , Bruxismo del Sueño/tratamiento farmacológico , VigiliaRESUMEN
STUDY DESIGN: Retrospective analysis of treated inpatients compared to expected neurorecovery from a propensity score-matched national database cohort. OBJECTIVE: Evaluate the effectiveness of buspirone on clinical neurorecovery following traumatic SCI when started during acute inpatient rehabilitation. SETTING: University-based hospital in Boston, USA. METHODS: Chart review yielded thirty-one individuals with acute, traumatic SCI treated with buspirone during inpatient rehabilitation from 2011-2017. Propensity score matching to a cohort of individuals from the spinal cord injury model systems (SCIMS) national database was completed. Changes in upper extremity motor score (UEMS), lower extremity motor score (LEMS), American Spinal Injury Association Impairment Scale (AIS), neurological level of injury (NLI), and functional impairment measure (FIM) from admission to discharge and discharge to 1 year were computed and compared between matched pairs (buspirone and mean national SCIMs cohort). A local control cohort not treated with buspirone was similarly compared to a matched mean national SCIMs group to identify location-specific effects. RESULTS: From admission to discharge from inpatient rehabilitation, 95% confidence intervals of changes in UEMS (-2.43 to +2.78), LEMS (-1.02 to +6.02), AIS (-0.04 to +0.35), NLI (-0.42 to +1.08), and FIM (-4.42 to +6.40) were not significantly different between those individuals who received buspirone and their propensity-matched SCIMS cohort. Similarly, changes in these metrics were not significantly different at 1-year follow up. Buspirone group individuals with initial clinically complete SCI demonstrated a higher 1-year conversion rate to incomplete injury (6 out of 14; 42.9%) compared to the matched national SCIMS cohort (14 out of 70; 21.2%, p = 0.047) though this was not significantly different from non-buspirone local controls (p = 0.25). CONCLUSIONS: Retrospective analysis shows no statistically significant difference in gross markers of neurorecovery following acute traumatic SCI when buspirone is initiated indiscriminately during acute inpatient rehabilitation. In individuals with clinically complete SCI, findings suggest possible increased rates of 1-year conversion to incomplete injury.
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Buspirona , Traumatismos de la Médula Espinal , Buspirona/uso terapéutico , Estudios de Cohortes , Humanos , Puntaje de Propensión , Recuperación de la Función , Estudios Retrospectivos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/tratamiento farmacológicoRESUMEN
Serotonergic agents can improve the recovery of motor ability after a spinal cord injury. Herein, we compare the effects of buspirone, a 5-HT1A receptor partial agonist, to fluoxetine, a selective serotonin reuptake inhibitor, on forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. After injury, single pellet reaching performance and forelimb muscle activity decreased in all rats. From 1 to 6 weeks after injury, rats were tested on these tasks with and without buspirone (1-2 mg/kg) or fluoxetine (1-5 mg/kg). Reaching and grasping success rates of buspirone-treated rats improved rapidly within 2 weeks after injury and plateaued over the next 4 weeks of testing. Electromyography (EMG) from selected muscles in the dominant forelimb showed that buspirone-treated animals used new reaching strategies to achieve success after the injury. However, forelimb performance dramatically decreased within 2 weeks of buspirone withdrawal. In contrast, fluoxetine treatment resulted in a more progressive rate of improvement in forelimb performance over 8 weeks after injury. Neither buspirone nor fluoxetine significantly improved quadrupedal locomotion on the horizontal ladder test. The improved accuracy of reaching and grasping, patterns of muscle activity, and increased excitability of spinal motor-evoked potentials after buspirone administration reflect extensive reorganization of connectivity within and between supraspinal and spinal sensory-motor netxcopy works. Thus, both serotonergic drugs, buspirone and fluoxetine, neuromodulated these networks to physiological states that enabled markedly improved forelimb function after cervical spinal cord injury.
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Médula Cervical/lesiones , Miembro Anterior/efectos de los fármacos , Recuperación de la Función/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Agonistas de Receptores de Serotonina/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Buspirona/farmacología , Buspirona/uso terapéutico , Electromiografía/efectos de los fármacos , Electromiografía/métodos , Potenciales Evocados Motores/efectos de los fármacos , Potenciales Evocados Motores/fisiología , Femenino , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Miembro Anterior/inervación , Miembro Anterior/fisiología , Fuerza de la Mano/fisiología , Ratas , Ratas Long-Evans , Recuperación de la Función/fisiología , Agonistas de Receptores de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
INTRODUCTION: In Parkinson's disease (PD), anxiety is common, associated with lower health-related quality of life, and undertreated. The primary objective of this study was to determine the tolerability of buspirone for the treatment of anxiety in PD. METHODS: Individuals with PD and clinically significant anxiety were randomized 4:1 to flexible dosage buspirone or placebo for 12 weeks. Treatment was initiated at 7.5 mg twice daily and titrated based on response and tolerability to an optimal dosage (maximum 30 mg twice daily). The primary outcome was the proportion of participants who failed to complete the study on study drug. Secondary outcomes included adverse events, dosage reductions, motor function, dyskinesias, and anxiety. RESULTS: A total of 21 participants enrolled, 4 were randomized to placebo and 17 to buspirone (mean (SD) age 65.5 (9.8), 76.5% male, 88% on concomitant antidepressant or anxiolytic). In the buspirone group, 7 (41%) failed to complete the study on drug, 5 due to intolerability. The median buspirone dosage was 7.5 mg twice daily. No serious adverse events occurred. A total of 9 (53%) buspirone participants experienced adverse events consistent with worsened motor function. In the buspirone group, mean (SD) improvement from baseline to week 12 in Hamilton Anxiety Rating Scale was -3.9 (3.8) and Parkinson Anxiety Scale -7.1 (6.4). CONCLUSION: Tolerability concerns do not support moving immediately forward with a large-scale efficacy trial. However, concomitant anxiolytics may have affected tolerability and a signal of efficacy was seen suggesting that future studies of buspirone monotherapy be considered.
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Ansiolíticos/uso terapéutico , Ansiedad/tratamiento farmacológico , Buspirona/uso terapéutico , Enfermedad de Parkinson/psicología , Anciano , Antidepresivos/uso terapéutico , Ansiedad/psicología , Reducción Gradual de Medicamentos , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Brote de los SíntomasRESUMEN
We studied the effects of stress exposure during the adolescent period of development (SAPD) on the parameters of inflammatory painful response and the level of depression-like behavior in prenatally stressed adult male rats. In addition, we analyzed the effects of selective serotonin (5-HT) reuptake inhibitor fluoxetine and 5-HT1A receptor agonist buspirone injected chronically to pregnant mothers for correction of behavioral disturbances caused by prenatal stress in their adult male progeny. In the formalin test, SAPD decreased integrated at the supraspinal level pain-like response that was increased by prenatal stress; under these conditions, buspirone and fluoxetine were ineffective in contrast to their antinociceptive action on spinally integrated pain-like response increased by SAPD. In the forced swimming test, SAPD had no effect on the level of depression-like behavior in prenatally stressed males; no differences in plasma corticosterone level were found in these animals.
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Antidepresivos/uso terapéutico , Inflamación/tratamiento farmacológico , Dolor/tratamiento farmacológico , Agonistas del Receptor de Serotonina 5-HT1/uso terapéutico , Animales , Conducta Animal/efectos de los fármacos , Buspirona/uso terapéutico , Femenino , Fluoxetina/uso terapéutico , Masculino , Embarazo , Ratas , Receptor de Serotonina 5-HT1A/metabolismo , Estrés Psicológico/tratamiento farmacológico , NataciónRESUMEN
INTRODUCTION: Pharmacological interventions have not been successful in the treatment of childhood functional abdominal pain (FAP) hitherto. Buspirone is suggested to be efficacious in some of the abdominal pain-related functional gastrointestinal disorders based on evidences from the studies on adults. We aim to investigate the efficacy of buspirone on childhood FAP. METHODS: This randomized clinical trial was conducted on 117 patients with childhood FAP aged 6-18 years. We randomly assigned patients to receive buspirone or placebo for 4 weeks, with the adjusted dosage for age. Participants completed the questionnaires assessing pain, depression, anxiety, somatization, and sleep disturbances at baseline, at the end of the 4-week therapy (first follow-up), and at 8 weeks after medication discontinuation (second follow-up). The primary outcome was treatment response rate, defined as reduced pain score of ≥2 or reporting no pain at the follow-up assessments. RESULTS: Ninety-five patients completed the 4-week therapy (48 and 47 in buspirone and placebo groups, respectively). Both buspirone and placebo reduced pain after 4 weeks of treatment, and these effects were persistent 8 weeks after medication discontinuation (P < 0.001 for both groups at weeks 4 and 12). Treatment response rates for buspirone and placebo were 58.3% and 59.6% at week 4 (P = 0.902) and 68.1% and 71.1% at week 12 (P = 0.753), respectively. DISCUSSION: Buspirone effectively improves pain and associated psychological symptoms including depressive symptoms, anxiety, somatization, and sleep disturbances in childhood FAP but has no superiority over placebo. Further studies, with the higher doses of buspirone and longer follow-ups are recommended.
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Dolor Abdominal/tratamiento farmacológico , Buspirona/uso terapéutico , Agonistas de Receptores de Serotonina/uso terapéutico , Dolor Abdominal/psicología , Adolescente , Ansiedad/psicología , Niño , Depresión/psicología , Femenino , Humanos , Masculino , Dimensión del Dolor , Trastornos del Sueño-Vigilia/psicología , Trastornos Somatomorfos/psicología , Resultado del TratamientoRESUMEN
Co-morbid anxiety disorders, including generalized anxiety disorder (GAD), are highly prevalent among individuals with Williams syndrome (WS). However, reports of the pharmacologic treatment of only a limited number of previous anxiety disorders in WS have appeared in the literature. Here, we review the case histories of three adolescents/young adults with WS and the treatment course of co-morbid GAD with buspirone. Treatment with buspirone was well-tolerated and resulted in sustained response in all three cases. Common medical disorders in WS are highlighted with regards to safe and appropriate pharmacologic treatment of GAD. Buspirone's generally benign side effect profile is a major benefit of its use for treating GAD in individuals with WS.