Abstract
Synopsis
Buspirone is an anxiolytic agent from the azapirone class of compounds. It differs structurally and pharmacologically from the benzodiazepines. Although the exact anxiolytic mechanism of action of buspirone is unknown, its primary pharmacological action is its binding to serotonin 5-HT1A receptors in the brain. Unlike benzodiazepines, buspirone has no demonstrated sedative effect and has little effect on psychomotor performance or cognition. In addition, animal and human studies have found little evidence that buspirone has abuse potential or dependence liability.
Recent large comparative trials have confirmed that buspirone is superior to placebo and has similar efficacy to benzodiazepines in the treatment of patients with anxiety. In comparative trials, patients receiving buspirone had reductions in Hamilton Anxiety Rating Scale (HAM-A) total scores ranging from 37 to 60%. By comparison, those receiving benzodiazepines had HAM-A total score reductions of 29 to 69%. Buspirone usually produced significant reductions in HAM-A total scores within 1 to 2 weeks of treatment initiation. Some studies have noted a faster onset of action with benzodiazepines than with buspirone, but larger, more recent trials have not confirmed this.
Buspirone has also demonstrated efficacy in patients with anxiety and coexisting alcohol (ethanol) abuse/dependence or depression. Buspirone not only reduces symptoms of anxiety in these patients but produces improvements in the comorbid disorder. In most studies, alcohol-dependent patients were significantly more likely to remain on treatment than those receiving placebo. In patients with mixed anxiety-depression, treatment with buspirone produced significant reductions in both the HAM-A and Hamilton Depression Rating Scale total scores. Buspirone produced significant improvements in the cardinal symptoms of depression (depressed mood, guilt, work and interest, anergia and diurnal variation of mood) which indicates that it may have an antidepressant effect independent of its anxiolytic activity.
In summary, recent clinical trials have verified the efficacy of buspirone in the treatment of anxiety disorders and confirmed its role as a well established alternative to benzodiazepines. Buspirone is particularly useful in patients wishing to avoid adverse effects associated with the benzodiazepines, such as sedation and performance and cognitive impairment, or those in whom abuse and dependence potential are a concern.
Pharmacodynamic Properties
Although the exact anxiolytic mechanism of action of buspirone is unknown, the drug is believed to act primarily through effects on central serotonergic systems. Buspirone binds both presynaptically and postsynaptically to serotonin 5-HT1A receptors in the brain. At presynaptic receptors in the dorsal raphé, buspirone acts as a full agonist; postsynaptically, it acts as a partial agonist at 5-HT1A receptors in the hippocampus. Buspirone also has a moderate affinity for presynaptic dopamine D2 receptors. Unlike benzodiazepines, it has no effect on the γ-amino-butyric acid (GABA)—benzodiazepine complex.
Buspirone has a low potential for producing sedation or impairment of psychomotor performance and cognition. When compared with various benzodiazepines, buspirone produces significantly less daytime sedation and has less effect on tests designed to measure psychomotor performance, including driving ability. Benzodiazepines significantly impaired memory function, but buspirone had no effect.
The abuse and dependence potential of buspirone appears to be minimal. In animal drug discrimination and drug self-administration studies, buspirone had no acute subjective intoxicating or reinforcing properties. In addition, benzodiazepines were significantly more likely to be preferred to buspirone in study participants with a history of substance abuse. The dependence liability of buspirone is lower than that of benzodiazepines as measured by significantly fewer withdrawal symptoms after drug discontinuation. Furthermore, buspirone is not cross-tolerant with benzodiazepines, as evidenced by the inability of buspirone to prevent benzodiazepine withdrawal symptoms after long term treatment with these drugs.
Pharmacokinetic Properties
Buspirone is well absorbed after oral administration; however, substantial first-pass metabolism reduces oral bioavailability to approximately 4%. At therapeutic dosages there is a linear relationship between dose and area under the plasma concentration-time curve (AUC). Administration of buspirone with food substantially increases the AUC.
Buspirone undergoes extensive metabolism to at least 7 major and 5 minor metabolites. Less than 1% of an administered dose is excreted unchanged in the urine. The elimination half-life of buspirone ranges from 2 to 11 hours.
The elimination of buspirone is reduced in patients with cirrhosis; however, interpatient variation is considerable. Some studies have also reported decreases in buspirone clearance in patients with renal impairment. The pharmacokinetic properties of buspirone do not appear to be changed in the elderly.
Therapeutic Efficacy
Data from several recent large comparative studies have confirmed that buspirone is superior to placebo and has equivalent efficacy to benzodiazepines in the treatment of patients with anxiety. After treatment periods of 3 to 6 weeks, buspirone 10 to 60 mg/day produced reductions in Hamilton Anxiety Rating Scale (HAM-A) total scores ranging from 37 to 60%. This compared with reductions in HAM-A total scores of 29 to 69% for patients receiving benzodiazepines. Buspirone also produced significant reductions in HAM-A total scores in a few trials in patients aged ≥ 65 years. HAM-A scores in patients receiving buspirone declined progressively over the treatment period and were usually significantly different from baseline or placebo within 1 to 2 weeks of treatment. Results of a few studies have shown that benzodiazepines have a faster onset of effect than buspirone, although this was not confirmed in recent, larger studies. Buspirone is effective in alleviating both the psychic and the somatic symptoms of anxiety; however, psychic symptoms generally declined first. Studies evaluating the long term efficacy of buspirone have confirmed that the drug is effective after treatment periods lasting up to 1 year.
Patients with anxiety and co-existing alcohol (ethanol) use disorders receiving buspirone were significantly more likely to remain on treatment than those receiving placebo in 3 of 4 studies. In these studies, buspirone also produced significantly greater reductions in anxiety and alcohol consumption than placebo.
The addition of buspirone to treatment with selective serotonin reuptake inhibitors (SSRIs) in patients with major depression who had failed to respond, or had partially responded, to an adequate trial with an SSRI improved depressive symptoms. Preliminary studies suggest that buspirone may be useful in the treatment of agitation in patients with dementia.
In patients with mixed anxiety-depression, buspirone was significantly superior to placebo in reducing HAM-A total scores. It was also associated with significant reductions in Hamilton Depression Rating Scale (HAM-D) total scores. Significant reductions in the cardinal symptoms of depression (depressed mood, guilt, work and interest, anergia and diurnal variation of mood) in patients receiving buspirone indicated that the drug has intrinsic antidepressant properties.
Preliminary studies of the use of buspirone in other indications such as smoking cessation and of buspirone alone or combined with an SSRI in obsessive-compulsive disorder have been conducted. Results of these studies were inconclusive, and further research is needed to establish whether buspirone has a role in these conditions.
Tolerability
Buspirone is generally well tolerated. In pooled data from 17 clinical trials, the most commonly reported adverse events not seen at equivalent incidence in placebo recipients include dizziness, nausea, headache, nervousness, lightheadedness and dry mouth. However, the frequencies of drowsiness, insomnia and excitement were similar to those reported in patients receiving placebo. Neither age nor duration of treatment appears to affect the frequency of adverse events. There have been rare case reports of buspirone-induced psychological (psychosis, mania, panic attack) and neuromuscular (dystonia, dyskinesia) adverse events.
Data concerning the effects of buspirone overdose are limited; however, the drug appears to produce relatively mild symptoms. There are no reported deaths after overdose when buspirone was the sole ingestant.
Dosage and Administration
Buspirone should be initiated at a dosage of 15 mg/day, administered in 2 divided doses. The target therapeutic dosage is 30mg daily, which can be achieved by the second week of treatment. Maximum dosage is 45mg daily in the UK and 60 mg/day in the US. Dosage adjustments may be necessary in patients with severe hepatic or renal dysfunction, as there is some decreased elimination of buspirone in such patients (although interpatient variation is considerable). Dosage adjustments in the elderly do not appear to be necessary.
No pharmacokinetic or pharmacodynamic interactions have been found between buspirone and tricyclic antidepressants or benzodiazepines. Buspirone should not be coadministered with monoamine oxidase inhibitors because of reports of elevated blood pressure with combined use.
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References
Goa KL, Ward A. Buspirone: a preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. Drugs 1986 Aug; 32(2): 114–29
Eison MS. Azapirones: mechanism of action in anxiety and depression. Drug Ther 1990 Aug; 20 Suppl.: 3–8
Pecknold JC. Serotonin 5-HT1a agonists: a comparative review. CNS Drugs 1994 Sep; 2: 234–51
Robinson DS, Shrotriya RC, Alms DR, et al. Treatment of panic disorder: nonbenzodiazepine anxiolytics, including buspirone. Psychopharmacol Bull 1989 Jan; 25: 21–6
Tunnicliff G. Molecular basis of buspirone’s anxiolytic action. Pharmacol Toxicol 1991 Sep; 69: 149–56
Tanquary J. Trichotillomania and body dysmorphic disorder. J Clin Psychiatry 1994 Jan; 55: 35
Dement WC, Seidel WF, Cohen SA, et al. Effects of alprazolam, buspirone and diazepam on daytime sedation and performance. Drug Invest 1991; 3(3): 148–56
Alford C, Bhatti JZ, Curran S, et al. Pharmacodynamic effects of buspirone and clobazam. Br J Clin Pharmacol 1991 Jul; 32: 91–7
Boulenger JP, Squillace K, Simon P, et al. Buspirone and diazepam: comparison of subjective, psychomotor and biological effects. Neuropsychobiology 1989; 22(2): 83–9
De Roeck J, Cluydts R, Schotte C, et al. Explorative single-blind study on the sedative and hypnotic effects of buspirone in anxiety patients. Acta Psychiatr Scand 1989 Feb; 79: 129–35
Manfredi RL, Kales A, Vgontzas AN, et al. Buspirone: sedative or stimulant effect?. Am J Psychiatry 1991 Sep; 148: 1213–7
Greenblatt DJ, Harmatz JS, Gouthro TA, et al. Distinguishing a benzodiazepine agonist (triazolam) from a nonagonist anxiolytic (buspirone) by electroencephalography: kinetic-dynamic studies. Clin Pharmacol Ther 1994 Jul; 56: 100–11
Schaffler K, Klausnitzer W. Placebo-controlled study on acute and subchronic effects of buspirone vs bromazepam utilizing psychomotor and cognitive assessments in healthy volunteers. Pharmacopsychiatry 1989 Jan; 22: 26–33
Fafrowicz M, Unrug A, Marek T, et al. Effects of diazepam and buspirone on reaction time of saccadic eye movements. Neuropsychobiology 1995; 32(3): 156–60
Unrug-Neervoort A, van Luijtelaar G, Coenen A. Cognition and vigilance: differential effects of diazepam and buspirone on memory and psychomotor performance. Neuropsychobiology 1992; 26(3): 146–50
Bourin M, Auget JL, Colombel MC, et al. Effects of single oral doses of bromazepam, buspirone and clobazam on performance tasks and memory. Neuropsychobiology 1990 Aug; 22: 141–5
Mattila M, Seppälä T, Mattila MJ. Combined effects of buspirone and diazepam on objective and subjective tests of performance in healthy volunteers. Clin Pharmacol Ther 1986 Dec; 40: 620–6
Erwin CW, Linnoila M, Hartwell J, et al. Effects of buspirone and diazepam, alone and in combination with alcohol, on skilled performance and evoked potentials. J Clin Psychopharmacol 1986 Aug; 6: 199–209
Moskowitz H, Smiley A. Effects of chronically administered buspirone and diazepam on driving-related skills performance. J Clin Psychiatry 1982 Dec; 43(12): 45–55
van Laar MW, Volkerts ER, van Willigenburg AP. Therapeutic effects and effects on actual driving performance of chronically administered buspirone and diazepam in anxious outpatients. J Clin Psychopharmacol 1992 Apr; 12: 86–95
Lucki I, Rickels K, Giesecke MA, et al. Differential effects of the anxiolytic drugs, diazepam and buspirone, on memory function. Br J Clin Pharmacol 1987 Feb; 23: 207–11
Barbee JG, Black FW, Kehoe CE, et al. A comparison of the single-dose effects of alprazolam, buspirone, and placebo upon memory function. J Clin Psychopharmacol 1991 Dec; 11: 351–6
Hart RP, Colenda C, Hamer RM. Effects of buspirone and alprazolam on the cognitive performance of normal elderly subjects. Am J Psychiatry 1991 Jan; 148: 73–7
Lawlor BA, Hill JL, Radcliffe JL, et al. A single oral dose challenge of buspirone does not affect memory processes in older volunteers. Biol Psychiatry 1992 Jul 1; 32: 101–3
Lader M. Can buspirone induce rebound, dependence or abuse?. Br J Psychiatry 1991 Sep; 159 Suppl. 12: 45–51
Balster RL. Abuse potential of buspirone and related drugs. J Clin Psychopharmacol 1990 Jun; 10 Suppl.: 31–7
Balster RL, Woolverton WL. Intravenous buspirone self-administration in rhesus monkeys. J Clin Psychiatry 1982 Dec; 43(12): 34–7
Troisi II JR, Critchfield TS, Griffiths RR. Buspirone and lorazepam abuse liability in humans: behavioral effects, subjective effects and choice. Behav Pharmacol 1993 Jun; 4: 217–30
Sellers EM, Schneiderman JF, Romach MK, et al. Comparative drug effects and abuse liability of lorazepam, buspirone, and secobarbital in nondependent subjects. J Clin Psychopharmacol 1992 Apr; 12: 79–85
Evans SM, Griffiths RR, de Wit H. Preference for diazepam, but not buspirone, in moderate drinkers. Psychopharmacol-ogy 1996 Jan; 123(2): 154–63
Fontaine R, Beaudry P, Beauclair L, et al. Comparison of withdrawal of buspirone and diazepam: a placebo controlled study. Prog Neuropsychopharmacol Biol Psychiatry 1987; 11: 189–97
Murphy SM, Owen R, Tyrer P. Comparative assessment of efficacy and withdrawal symptoms after 6 and 12 weeks’ treatment with diazepam or buspirone. Br J Psychiatry 1989 Apr; 154: 529–34
Petracca A, Nisita C, McNair D, et al. Treatment of generalized anxiety disorder: preliminary clinical experience with buspirone. J Clin Psychiatry 1990 Sep; 51 Suppl.: 31–9
Rickels K, Schweizer E, Csanalosi I, et al. Long-term treatment of anxiety and risk of withdrawal. Prospective comparison of clorazepate and buspirone. Arch Gen Psychiatry 1988 May; 45: 444–50
Dimitriou EC, Parashos AJ, Giouzepas JS. Buspirone vs alprazolam: a double-blind comparative study of their efficacy, adverse effects and withdrawal symptoms. Drug Invest 1992; 4(4): 316–21
Ashton CH, Rawlins MD, Tyrer SP. A double-blind placebo-controlled study of buspirone in diazepam withdrawal in chronic benzodiazepine users. Br J Psychiatry 1990 Aug; 157: 232–8
Lader M, Olajide D. A comparison of buspirone and placebo in relieving benzodiazepine withdrawal symptoms. J Clin Psychopharmacol 1987 Feb; 7: 11–5
Delle Chiaie R, Pancheri P, Casacchia M, et al. Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam: a placebo-controlled, double-blind study. J Clin Psychopharmacol 1995 Feb; 15: 12–9
Craven J, Sutherland A. Buspirone for anxiety disorders in patients with severe lung disease [letter]. Lancet 1991 Jul 27; 338: 249
Rapoport DM, Greenberg HE, Goldring RM. Differing effects of the anxiolytic agents buspirone and diazepam on control of breathing. Clin Pharmacol Ther 1991 Apr; 49: 394–401
Argyropoulou P, Patakas D, Koukou A, et al. Buspirone effect on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease. Respiration 1993 Jul–Aug; 60: 216–20
Singh NP, Despars JA, Stansbury DW, et al. Effects of buspirone on anxiety levels and exercise tolerance in patients with chronic airflow obstruction and mild anxiety. Chest 1993 Mar; 103: 800–4
Datta AK, Muzzin S, Gene-Cos N, et al. Breathing during wakefulness and sleep in anxious patients with chronic obstructive airways disease: effect of buspirone anxiolysis [letter]. Thorax 1991 Oct; 46: 744P
Mendelson WB, Maczaj M, Holt J. Buspirone administration to sleep apnea patients [letter]. J Clin Psychopharmacol 1991 Feb; 11: 71–2
Meltzer HY, Lee HS, Nash JJF. Effect of buspirone on prolactin secretion is not mediated by 5-HT-1a receptor stimulation [letter]. Arch Gen Psychiatry 1992 Feb; 49: 163
Gregory CA, Anderson IM, Cowen PJ. Metergoline abolishes the prolactin response to buspirone. Psychopharmacology (Berl) 1990; 100: 283–4
Anderson IM, Cowen PJ. Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers. Psychopharmacology (Berl) 1992 Mar; 106: 428–32
Dinan TG, Barry S, Yatham LN, et al. The reproducibility of the prolactin response to buspirone: relationship to the menstrual cycle. Int Clin Psychopharmacol 1990 Apr; 5: 119–23
Tollefson GD, Godes M, Montague-Clouse J, et al. Buspirone: effects on prolactin and growth hormone as a function of drug level in generalized anxiety. J Clin Psychopharmacol 1989 Apr; 9: 132–6
Gianola D, Pagani G, Montini M, et al. Neuroendocrine effects of buspirone, a new anti-serotoninergic agent [abstract]. J Endocrinol Invest 1991; 14(6 Suppl. 4): 79
Mayol RF, Adamson DS, Gammans RE, et al. Pharmacokinetics and disposition of 14C-buspirone HCL after intravenous and oral dosing in man [abstract no. B36]. Clin Pharmacol Ther 1985; 37(2): 210
Gammans RE, Mayol RF, Mackenthun AV, et al. The relationship between buspirone bioavailability and dose in healthy subjects. Biopharm Drug Dispos 1985; 6: 139–45
Gammans RE, Mayol RF, Labudde JA. Metabolism and disposition of buspirone. Am J Med 1986 Mar 31; 80 Suppl. 3b: 41–51
Jajoo HK, Mayol RF, LaBudde JA, et al. Metabolism of the antianxiety drug buspirone in human subjects. Drug Metab Dispos 1989 Nov–Dec; 17: 634–40
Gammans RE, Kerns EH, Bullen WW. Capillary gas chromatographic-mass spectrometric determination of buspirone in plasma. J Chromatogr 1985 Dec 13; 345(2): 285–97
Mayol RF, Gammans RE, Mackenthun AV, et al. The effect of food on the bioavailability of buspirone HC1 [abstract]. Clin Res 1983; 31(2): 631a
Bullen WW, Bivens DL, Gammans RD, et al. The binding of buspirone to human plasma proteins [abstract]. Fed Proc 1985; 44: 1123
Dalhoff K, Poulsen HE, Garred P, et al. Buspirone pharmacokinetics in patients with cirrhosis. Br J Clin Pharmacol 1987 Oct; 24: 547–50
Barbhaiya RH, Shukla UA, Pfeffer M, et al. Disposition kinetics of buspirone in patients with renal or hepatic impairment after administration of single and multiple doses. Eur J Clin Pharmacol 1994; 46(1): 41–7
Caccia S, Vigano GL, Mingardi G, et al. Clinical pharmacokinetics of oral buspirone in patients with impaired renal function. Clin Pharmacokinet 1988 Mar; 14: 171–7
Gammans RE, Westrick ML, Shea JP, et al. Pharmacokinetics of buspirone in elderly subjects. J Clin Pharmacol 1989 Jan; 29: 72–8
Hamilton MA. The assessment of anxiety states by rating. Br J Med Psychol 1959; 32: 50–5
Sacchetti E, Zerbini O, Banfi F, et al. Overlap of buspirone with lorazepam, diazepam and bromazepam in patients with generalized anxiety disorder: findings from a controlled, multi-centre, double-blind study. Hum Psychopharmacol 1994 Nov–Dec; 9: 409–22
Goldberg HL, Finnerty R. Comparison of buspirone in two separate studies. J Clin Psychiatry 1982 Dec; 43(12): 87–91
Cohn JB, Rickels K. A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety. Curr Med Res Opin 1989; 11: 304–20
Feighner JP, Merideth CH, Hendrickson GA. A double-blind comparison of buspirone and diazepam in outpatients with generalized anxiety disorder. J Clin Psychiatry 1982 Dec; 43(12): 103–7
Pecknold JC, Matas M, Howarth BG, et al. Evaluation of buspirone as an antianxiety agent: buspirone and diazepam versus placebo. Can J Psychiatry 1989 Nov; 34: 766–71
Rickels K, Weisman K, Norstad N, et al. Buspirone and diazepam in anxiety: a controlled study. J Clin Psychiatry 1982 Dec; 43(12): 81–6
Wheatley D. Buspirone: multicenter efficacy study. J Clin Psychiatry 1982 Dec; 43(12): 92–4
Strand M, Hetta J, Rosen A, et al. A double-blind, controlled trial in primary care patients with generalized anxiety: a comparison between buspirone and oxazepam. J Clin Psychiatry 1990 Sep;51 Suppl.: 40–5
Steinberg JR. Anxiety in elderly patients: a comparison of azapirones and benzodiazepines. Drugs Aging 1994 Nov; 5: 335–45
Enkelmann R. Alprazolam versus buspirone in the treatment of outpatients with generalized anxiety disorder. Psychopharma-cology (Berl) 1991; 105(3): 428–32
Ansseau M, Papart P, Gérard M-A, et al. Controlled comparison of buspirone and oxazepam in generalized anxiety. Neuropsychobiology 1991 Jun; 24: 74–8
Joshi V, Worlikar P, Karbhari A. Effect of coffee on psychomotor effects of buspirone [abstract]. Can J Physiol Pharmacol 1994; 72 Suppl. 1: 450
Feighner JP, Cohn JB. Analysis of individual symptoms in generalized anxiety — a pooled, multistudy, double-blind evaluation of buspirone. Neuropsychobiology 1990 Feb; 21: 124–30
Buspirone: the product monograph. 2nd ed. Chester: Adis International Limited, 1996
Schweizer E, Rickels K, Lucki I. Resistance to the anti-anxiety effect of buspirone in patients with a history of benzodiazepine use [letter]. N Engl J Med 1986 Mar 13; 314: 719–20
Lader M. Long-term anxiolytic therapy: the issue of drug withdrawal. J Clin Psychiatry 1987 Dec; 48 Suppl.: 12–6
Feighner JP. Buspirone in the long-term treatment of generalized anxiety disorder. J Clin Psychiatry 1987 Dec; 48 Suppl: 3–6
Singh AN, Beer M. A dose range-finding study of buspirone in geriatric patients with symptoms of anxiety [letter]. J Clin Psychopharmacol 1988 Feb; 8: 67–8
Ritchie LD, Cox J. A multicentre study of buspirone in the treatment of anxiety disorders in the elderly. Br J Clin Res 1993; 4: 131–9
Böhm C, Robinson DS, Gammans RE, et al. Buspirone therapy in anxious elderly patients: a controlled clinical trial. J Clin Psychopharmacol 1990 Jun; 10 Suppl.: 47–51
Levine S, Napoliello MJ, Domantay AG. An open study of buspirone in octogenarians with anxiety. Hum Psychopharmacol 1989; 4: 51–3
Robinson D, Napoliello MJ, Schenk J. The safety and usefulness of buspirone as an anxiolytic drug in elderly versus young patients. Clin Ther 1988; 10(6): 740–6
Tollefson GD, Montague-Clouse J, Lancaster SP. Buspirone in comorbid alcohol dependency and generalized anxiety disorders. Drug Ther 1990 Aug; 20 Suppl.: 35–51
Kranzler HR, Burleson JA, Del BFK, et al. Buspirone treatment of anxious alcoholics: a placebo-controlled trial. Arch Gen Psychiatry 1994 Sep; 51: 720–31
Tollefson GD, Montague-Clouse J, Tollefson SL. Treatment of comorbid generalized anxiety in a recently detoxified alcoholic population with a selective serotonergic drug (buspirone). J Clin Psychopharmacol 1992 Feb; 12: 19–26
Malcolm R, Anton RF, Randall CL, et al. A placebo-controlled trial of buspirone in anxious inpatient alcoholics. Alcohol Clin Exp Res 1992 Dec; 16: 1007–13
Bruno F. Buspirone in the treatment of alcoholic patients. Psychopathology 1989; 22 Suppl 1: 49–59
Malec E, Malec T, Gagné MA, et al. Buspirone in the treatment of alcohol dependence: a placebo-controlled trial. Alcohol Clin Exp Res 1996; 20(2): 307–12
Gammans RE, Stringfellow JC, Hvizdos AJ, et al. Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies. Neuropsychobiology 1992; 25(4): 193–201
Fabre LF. Buspirone in the management of major depression: a placebo-controlled comparison. J Clin Psychiatry 1990 Sep; 51 Suppl.: 55–61
Rickels K, Amsterdam JD, Clary C, et al. Buspirone in major depression: a controlled study. J Clin Psychiatry 1991 Jan; 52: 34–8
Sramek JJ, Tansman M, Suri A, et al. Efficacy of buspirone in generalized anxiety disorder with coexisting mild depressive symptoms. J Clin Psychiatry 1996; 57: 287–91
Hamilton MA. Rating for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56–62
Schweizer E, Rickels K, Hassman H. A double-blind, placebo-controlled comparison of imipramine and buspirone in the treatment of major depression in the elderly in the community [abstract]. Psychopharmacol Bull 1994; 30(4): 639
Robinson DS, Rickels K, Feighner J, et al. Clinical effects of the 5-HT1a partial agonists in depression: a composite analysis of buspirone in the treatment of depression. J Clin Psychopharmacol 1990 Jun; 10 Suppl.: 67–76
Proulx J, Fontaine R, Dallai A. Buspirone in patients with atypical depression with panic attacks. Curr Ther Res 1991 Jul; 50: 127–32
Cottraux J, Note I-D, Cungi C, et al. A controlled study of cognitive behaviour therapy with buspirone or placebo in panic disorder with agoraphobia. Br J Psychiatry 1995 Nov; 167: 635–41
Sheehan DV, Raj AB, Harnett-Sheehan K, et al. The relative efficacy of high-dose buspirone and alprazolam in the treatment of panic disorder: a double-blind placebo-controlled study. Acta Psychiatr Scand 1993 Jul; 88: 1–11
Sheehan DV, Raj AB, Sheehan KH. Is buspirone effective for panic disorder?. J Clin Psychopharmacol 1990 Feb; 10: 3–11
Schweizer E, Rickels K. Buspirone in the treatment of panic disorder: a controlled pilot comparison with clorazepate [letter]. J Clin Psychopharmacol 1988 Aug; 8: 303
Hilleman DE, Mohiuddin SM, Del Cove MG. Effect of buspirone on withdrawal symptoms associated with smoking cessation. Arch Intern Med 1992 Feb; 152: 350–2
West R, Hajek P, McNeill A. Effect of buspirone on cigarette withdrawal symptoms and short-term abstinence rates in a smokers clinic. Psychopharmacology (Berl) 1991; 104(1): 91–6
Hilleman DE, Mohiuddin SM, Delcore MG. Comparison of fixed-dose transdermal nicotine, tapered-dose transdermal nicotine, and buspirone in smoking cessation. J Clin Pharmacol 1994 Mar; 34: 222–4
Cinciripini PM, Lapitsky L, Seay S, et al. A placebo-controlled evaluation of the effects of buspirone on smoking cessation: differences between high- and low-anxiety smokers. J Clin Psychopharmacol 1995 Jun; 15: 182–91
McNair DM, Lorr M. An analysis of mood in neurotics. J Abnorm Soc Psychology 1964; 69: 620–7
Robinson MD, Pettice YL, Smith WA, et al. Buspirone effect on tobacco withdrawal symptoms: a randomized placebo-controlled trial. J Am Board Fam Pract 1992 Jan–Feb; 5: 1–9
Pigott TA, L’Heureux F, Hill JL, et al. A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder. J Clin Psychopharmacol 1992 Feb; 12: 11–8
Jenike MA, Baer L, Buttolph L. Buspirone augmentation of fluoxetine in patients with obsessive compulsive disorder. J Clin Psychiatry 1991 Jan; 52: 13–4
Markovitz PJ, Stagno SJ, Calabrese JR. Buspirone augmentation of fluoxetine in obsessive-compulsive disorder. Am J Psychiatry 1990 Jun; 147: 798–800
McDougle CJ, Goodman WK, Leckman JF, et al. Limited therapeutic effect of addition of buspirone in fluvoxamine-refrac-tory obsessive-compulsive disorder. Am J Psychiatry 1993 Apr; 150: 647–9
Grady TA, Pigott TA, L’Heureux F, et al. Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder. Am J Psychiatry 1993 May; 150: 819–21
Pato MT, Pigott TA, Hill JL, et al. Controlled comparison of buspirone and clomipramine in obsessive-compulsive disorder. Am J Psychiatry 1991 Jan; 148: 127–9
Khanna S. Double blind cross over trial of fluoxetine and buspirone in obsessive compulsive disorder [abstract]. 9th World Congress of Psychiatry: 1993 Jun 6-12; Rio de Janeiro, Brazil: 277
Joffe RT, Levitt AJ, Sokolov STH. Augmentation strategies: focus on anxiolytics. J Clin Psychiatry 1996; 57 Suppl. 7: 25–31
Jacobsen FM. Possible augmentation of antidepressant response by buspirone. J Clin Psychiatry 1991 May; 52: 217–20
Bakish D. Fluoxetine potentiation by buspirone: three case histories. Can J Psychiatry 1991 Dec; 36: 749–50
Joffe RT, Schuller DR. An open study of buspirone augmentation of serotonin reuptake inhibitors in refractory depression. J Clin Psychiatry 1993 Jul; 54: 269–71
Dimitriou EC. Augmenting the effects of antidepressant medication by adding buspirone. 10th World Congress of Psychiatry: 1996 Aug 23-24; Madrid
Van Ameringen M, Mancini C, Wilson C. Buspirone augmentation of selective serotonin reuptake inhibitors (SSRIs) in social phobia. J Affect Disord 1996; 39: 115–21
Ratey J, Sovner R, Parks A, et al. Buspirone treatment of aggression and anxiety in mentally retarded patients: a multiple-baseline, placebo lead-in study. J Clin Psychiatry 1991 Apr; 52: 159–62
Sakauye KM, Camp CJ, Ford PA. Effects of buspirone on agitation associated with dementia. Am J Geriatr Psychiatry 1993; 1(1): 82–4
Herrmann N, Eryavec G. Buspirone in the management of agitation and aggression associated with dementia. Am J Geriatr Psychiatry 1993; 1(3): 249–53
Cantillon M, Brunswick R, Molina D, et al. Buspirone vs haloperidol. A double-blind trial for agitation in a nursing home population with Alzheimer’s disease. Am J Geriatr Psychiatry 1996; 4(3): 263–7
Stanislav SW, Fabre T, Crismon ML, et al. Buspirone’s efficacy in organic-induced aggression. J Clin Psychopharmacol 1994 Apr; 14: 126–30
Package Insert, Mead Johnson Pharmaceuticals, A Division Bristol-Myers Squibb, Princeton, New Jersey, USA. 1995 Jan
Newton RE, Marunycz JD, Alderdice MT, et al. Review of the side-effect profile of buspirone. Am J Med 1986 Mar 31; 80 Suppl. 3B: 17–21
Rakel RE. Long-term buspirone therapy for chronic anxiety: a multicenter international study to determine safety. South Med J 1990 Feb; 83: 194–8
Ghazal A, Abdel Meguid AK, Egyptian Multicentre Collaborative Study Group. An open, non-comparative multicentre study of the efficacy and tolerability of buspirone in generalised anxiety and anxiety-associated symptoms. Eur J Clin Res 1996; 8: 121–31
Othmer E, Othmer SC. Effect of buspirone on sexual dysfunction in patients with generalized anxiety disorder. J Clin Psychiatry 1987 May; 48: 201–3
Norden MJ. Buspirone treatment of sexual dysfunction associated with selective serotonin re-uptake inhibitors. Depression 1994; 2(2): 109–12
Friedman R. Possible induction of psychosis by buspirone [letter]. Am J Psychiatry 1991 Nov; 148: 1606
Trachman SB. Buspirone-induced psychosis in a human immunodeficiency virus-infected man. Psychosomatics 1992; 33(3): 332–5
Pantelis C, Barnes TRE. Acute exacerbation of psychosis with buspirone? J Psychopharmacol 1993; 7(3): 295–300
Soni P, Weintraub AL. Buspirone-associated mental status changes. J Am Acad Child Adolesc Psychiatry 1992 Nov; 31: 1098–9
Mclvor RJ, Sinanan K. Buspirone-induced mania. Br J Psychiatry 1991 Jan; 158: 136–7
McDaniel JS, Ninan PT, Magnuson JV. Possible induction of mania by buspirone [letter]. Am J Psychiatry 1990 Jan; 147: 125–6
Price WA, Bielefeld M. Buspirone-induced mania [letter]. J Clin Psychopharmacol 1989 Apr; 9: 150–1
Robillard M, Lieff S. Augmentation of antidepressant therapy by buspirone: three geriatric case histories. Can J Psychiatry 1995 Dec; 40: 639–40
Chignon JM, Lepine JP. Panic and hypertension associated with single dose of buspirone [letter]. Lancet 1989 Jul 1; II: 46–7
LeWitt PA, Walters A, Hening W. Persistent movement disorders induced by buspirone. Mov Disord 1993 Jul; 8: 331–4
Boylan K. Persistent dystonia associated with buspirone [letter]. Neurology 1990 Dec; 40: 1904
Metz A. Interaction between fluoxetine and buspirone. Can J Psychiatry 1990 Nov; 35: 722–3
Bonifati V, Fabrizio E, Cipriani R. Buspirone in levodopa-induced dyskinesias. Clin Neuropharmacol 1994 Feb; 17(1): 73–82
Bernardi F, Chillotti C, Loi V, et al. Buspirone in the management of dyskinesias induced by L-dopa [abstract]. Mov Disord 1994 Mar; 9: 254
Kleedorfer B, Lees AJ, Stern GM. Buspirone in the treatment of levodopa induced dyskinesias. J Neurol Neurosurg Psychiatry 1991 Apr; 54: 376–7
Moss LE, Neppe VM, Drevets WC. Buspirone in the treatment of tardive dyskinesia. J Clin Psychopharmacol 1993 Jun; 13: 204–9
Neppe VM. High-dose buspirone in case of tardive dyskinesia [letter]. Lancet 1989 Dec 16; II: 1458
D’Mello DA, McNeil JA, Harris W. Buspirone suppression of neuroleptic-induced akathisia: multiple case reports [letter]. J Clin Psychopharmacol 1989 Apr; 9: 151–2
Ko S-M. Pharmacotherapy of obsessive-compulsive disorder. Br J Clin Pract 1995 Jan–Feb; 49: 36–9
Goetz CM, Krenzelok EP, Lopez G, et al. Buspirone toxicity: a prospective study [abstract]. Ann Emerg Med 1990 Jun; 19: 630
Langlois RP, Paquette D. Sustained bradycardia during fluvoxamine and buspirone intoxication. Can J Psychiatry 1994 Mar; 39: 126–7
Pollicino AM, Spina E, Campo GM, et al. Pharmacokinetic interactions between tricyclic antidepressants and other psy-chotropic drugs in depressed patients. Pharmacol Res 1992 May–Jun; 25 Suppl. 2: 210–1
Napoliello MJ. A study of buspirone coprescribed with antidepressants in 184 anxious ambulatory patients. Curr Ther Res 1986; 40: 917–23
Baetz M, Malcolm D. Serotonin syndrome from fluvoxamine and buspirone [letter]. Can J Psychiatry 1995 Sep; 40: 428–9
Goldberg RJ, Huk M. Serotonin syndrome from trazodone and buspirone. Psychosomatics 1992; 33(2): 235–6
Lebert F, Pasquier F, Goudemand M. Euphoria with buspirone after fluoxetine treatment [letter]. Am J Psychiatry 1993 Jan; 150: 167
Grady TA, Pigott TA, L’Heureux F, et al. Seizure associated with fluoxetine and adjuvant buspirone therapy. J Clin Psychopharmacol 1992 Feb; 12: 70–1
Tanquary J, Masand P. Paradoxical reaction to buspirone augmentation of fluoxetine [letter]. J Clin Psychopharmacol 1990 Oct; 10: 377
Bodkin JA, Teicher MH. Fluoxetine may antagonize the anxiolytic action of buspirone [letter]. J Clin Psychopharmacol 1989 Apr; 9: 150
Boulenger J-P, Gram LF, Jolicoeur FB, et al. Repeated administration of buspirone: absence of pharmacodynamic or pharmacokinetic interaction with triazolam. Hum Psychopharmacol 1993 Mar–Apr; 8: 117–24
Buch AB, Van Harken DR, Seidehamel RJ, et al. A study of pharmacokinetic interaction between buspirone and alprazolam at steady state. J Clin Pharmacol 1993 Nov; 33: 1104–9
Jann MW, Huang HF, Chang TP, et al. Lack of pharmacokinetic interaction between buspirone and haloperidol in schizophrenic patients [abstract no. P-2-1]. Eur Neuropsychopharmacol 1996; 6 Suppl. 3: 37
D’Souza M, Nuyen N, Archer D, et al. Cyclosporine buspirone interaction [abstract]. Pharm Res 1990 Sep; 7 Suppl.: S–253
Gammans RE, Pfeffer M, Westrick ML, et al. Lack of interaction between cimetidine and buspirone. Pharmacotherapy 1987; 7: 72–9
Lader MH, Napoliello MJ. A study of buspirone co-presented with antihistamines in 68 anxious ambulatory patients [letter]. J Clin Psychopharmacol 1988 Apr; 8: 146–8
Levine S, Napoliello MJ. A study of buspirone coprescribed with histamine H2-receptor antagonists in anxious outpatients. Int Clin Psychopharmacol 1988 Jan; 3: 83–6
Kiev A, Domantay AG. A study of buspirone coprescribed with bronchodilators in 82 anxious ambulatory patients. J Asthma 1988; 25: 281–4
Kiev A, Domantay AG. A study of buspirone coprescribed with nonsteroidal anti-inflammatory drugs in 150 anxious ambulatory patients. Curr Ther Res 1989 Dec; 46: 1086–90
Degruy F. Management of mixed anxiety and depression. Am Fam Physician 1994 Mar; 49: 860–6
Rickeis K, Schweizer E. The treatment of generalized anxiety disorder in patients with depressive symptomatology. J Clin Psychiatry 1993 Jan; 54 Suppl.: 20–3
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Various sections of the manuscript reviewed by: R.L. Bolster, Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond, Virginia, USA; P.M. Cinciripini, Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; E.C. Dimitriou, Second Department of Psychiatry, Aristotelian University of Thessaloniki Medical School, Thessaloniki, Greece; S.M. Evans, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians of Columbia University, New York, New York, USA; J.C. Pecknold, Research Centre and Community Psychiatry Centre, Douglas Hospital, Verdun, Quebec, Canada; K. Rickets, Department of Psychiatry, University of Pennsylvania, University Science Center, Philadelphia, Pennsylvania, USA; EM. Sellers, Addiction Research Foundation, Toronto, Ontario, Canada; M.W. van Laar, Netherlands Institute for Drugs and Doping Research, University of Utrecht, Utrecht, The Netherlands.
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Fulton, B., Brogden, R.N. Buspirone. CNS Drugs 7, 68–88 (1997). https://doi.org/10.2165/00023210-199707010-00007
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DOI: https://doi.org/10.2165/00023210-199707010-00007