Buspirone placebo-controlled studies

The extent of Buspirone experience in children and adolescents is limited to open studies and case reports. There are no published double-blind placebo-controlled studies of Buspirone for pediatric anxiety disorders or any other psychiatric disorder. Results of a recently completed large (n = 350 ages 6-17 years), industry-sponsored, multisite study of Buspirone for children (15-30 mg/day) and adolescents (45-60 mg/ day) with GAD have not been published or presented at open academic conferences. Until such data are made available, the use of Buspirone for treatment of pediatric anxiety disorders remains speculative. 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

Buspirone This has been an agent in search of a use. As with pindolol, most initial reports were open label. The only double-blind, placebo-controlled study did not support the usefulness of buspirone augmentation however, the placebo response in patients with alleged treatment refractory depression was 47% ( 382). Generally, the dose of buspirone as an augmentation strategy has been 5 to 15 mg twice a day. 

The effects of hydroxyzine 50 mg/day, buspirone 20 mg/day, and placebo have been studied in 244 patients with generalized anxiety disorder in a double-bhnd placebo-controlled study (16). Hydroxyzine (n = 81) was considerably better than placebo (n = 81), and buspirone (n = 82) was intermediate. The main adverse effects were headache and migraine with buspirone (6.1 versus 4.9% with hydroxyzine and 1.2% with placebo). Somnolence occurred in 9.9% with hydroxyzine, 4.9% with buspirone, and none with placebo. Dizziness occurred in 6.1% with buspirone, none with hydroxyzine, and 2.5% with placebo. 

Schaffler K, Klauznitzer W. Placebo-controlled study on acute and subacute effects of buspirone versus bromazepam utilizing psychomotor and cognitive assessments in healthy volunteers. Pharmacopsychiatry 1989 22 26-33. 

In a placebo-controlled study, 8 healthy subjects were given buspirone 10 mg, before and after taking itraconazole 100 mg twice daily for 4 days. It was found that the buspirone maximum plasma levels and its AUC were increased 13-fold and 19-fold, respectively, by itraconazole. These increased buspirone levels caused a moderate impairment of psychomotor performance (digital symbol substitution, body sway, drowsiness, etc.) and an increase in adverse effects. ... 

Placebo-controlled studies In a placebo-controlled study of the use of buspirone (maximum 60 mg/day for 12 weeks) and motivational interviewing in 50 subjects with marijuana dependence, all the adverse events were mild to moderate in intensity [2 "]. Most of those who took buspirone (96%) had at least one adverse event compared with 78% of those who took placebo. Dizziness was more common with buspirone (RR = 3.52 95% Cl = im,ll).Drymouth = 2.35), flushing/sweating (RR = 2.93), and cold-like symptoms (RR = 2.35) were also more common with buspirone than placebo, but not significantly so. 

Delle Chiaie, R., Pancheri, P., Casacchia, M., Stratta, P., Kotzalidis, G.D. and Zibellini, M. (1995) Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam a placebo-controlled, doubleblind study. Journal of Clinical Psychopharmacology, 15,... 

As of the date of this chapter (circa March, 2002), labeling changes regarding pediatric use have resulted from only two programs—the study of buspirone in pediatric GAD and a pharmacokinetic study of fluvoxamine in pediatric OCD (fluvoxamine already had a controlled clinical trial in pediatric patients). Two placebo-controlled trials with buspirone in pediatric GAD did not reveal a treatment effect, and this negative outcome is reflected in Buspar labeling. A pharmacokinetic study of fluvoxamine dosed at 100 mg bid in pediatric... 

Richelson E, Nelson A Antagonism by neuroleptics of neurotransmitter receptors of normal brain in vitro. Eur J Pharmacol 103 197-204, 1984 Rickels K, Schweizer E The treatment of generalized anxiety disorder in patients with depressive symptomatology. J Clin Psychiatry 54 [suppl) 20-23, 1993 Rickels K, Weisman K, Norstad N, et al Buspirone and diazepam in anxiety a controlled study. J Chn Psychiatry 43(12 pt 2) 81-86, 1982 Rickels K, Feighner JP, Smith WT Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Arch Gen Psychiatry 42 134-141, 1985 Rickels K, Schweizer E, Weiss S, et al Maintenance drug treatment for panic disorder, 11 short- and long-term outcome after drug taper. Arch Gen Psychiatry 50 61-68, 1993... 

Numerous clinical trials have also attested to the anxiolytic efficacy of hydroxyzine. Controlled trials have confirmed its efficacy and safety at a fixed dose of 50 mg in GAD (64). In a double-blind, parallel-group, multicenter study in France and Great Britain, a total of 244 patients with GAD were allocated randomly to treatment with hydroxyzine (12.5 mg t.i.d.), buspirone 5 mg morning and midday and 10 mg in the evening, or placebo. The results showed both hydroxyzine and buspirone to be more efficacious than placebo, indicating that hydroxyzine can be a useful treatment for GAD (65). 

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