- ACRONYMS AND DEFINITIONS
- APA - American Psychiatric Association
- AUC - Area under the curve
- CrCl - Creatinine clearance
- ECG - Electrocardiogram
- GAD - Generalized anxiety disorder
- DRUGS IN CLASS
- Buspirone is a member of a class of drugs called azapirones
- Azapirones are used to treat anxiety. They are not chemically or pharmacologically related to the benzodiazepines, barbiturates, or other sedative/anxiolytic drugs.
- Buspirone is the only azapirone available in the U.S.
- MECHANISM OF ACTION
- The mechanism by which buspirone treats anxiety is not completely understood
- Buspirone has a high affinity for serotonin (5-HT1A) receptors
- Buspirone has moderate affinity for brain D2-dopamine receptors
- Buspirone has no significant affinity for benzodiazepine receptors and does not affect GABA binding in vitro or in vivo
- FDA-APPROVED INDICATIONS
- Anxiety disorders - for the management of anxiety disorders or the short-term relief of the symptoms of anxiety
- Anxiety disorder
- Buspirone was FDA-approved in 1986
- One randomized controlled trial and a meta-analysis that looked at the effects of buspirone in treating anxiety are summarized below
- Design: Randomized controlled trial (N=162, length - 6 weeks)
- Exposure: Buspirone titrated from 15 to 45 mg/day vs Placebo
- Primary outcomes: Change in Hamilton Rating Scale for Anxiety (HAM-A) over the course of the study
- Buspirone-treated patients averaged a 12.4-point reduction from their baseline total HAM-A score of 24.9, while their counterparts on placebo averaged a 9.5-point reduction from their mean baseline total HAM-A score of 25.6. This 2.9-point difference in HAM-A reductions between treatment groups was significantly different (p <0.03)
- Overall, the incidence of adverse events was similar for both treatment groups, but buspirone-treated patients reported significantly more nausea, dizziness, somnolence, and sweating than placebo patients
- Findings: Buspirone is superior to placebo in improving anxiety and depressive symptoms in GAD patients who have coexisting depressive symptoms
- Design: Meta-analysis of randomized controlled trials comparing azapirones to placebo and/or other medications and/or psychological treatments (36 studies, N=5908)
- Primary outcome: Treatment of anxiety (treatment measures varied by study)
- Findings: Azapirones appeared to be useful in the treatment of GAD, particularly for those participants who had not been on a benzodiazepine. Azapirones may not be superior to benzodiazepines and do not appear as acceptable as benzodiazepines. Side effects appeared mild and non serious in the azapirone treated group. Longer term studies are needed to show that azapirones are effective in treating GAD, which is a chronic long-term illness.
- SIDE EFFECTS
- In general, buspirone is well tolerated
- The table below lists side effects reported in controlled trials
|Buspirone side effects in controlled trials|
|Anger / Hostility||2%||<1%|
- Known hypersensitivity to buspirone
- Buspirone should not be given with MAO inhibitors
- KIDNEY DISEASE
- Buspirone is excreted by the kidneys. After multiple-dose administration of buspirone to renally impaired (CrCl = 10 - 70 mL/min) patients, steady-state AUC of buspirone increased 4-fold compared with healthy (CrCl > 80 mL/min) subjects
- Manufacturer makes no specific dosing recommendations and only states that buspirone should not be used in patients with severe renal impairment
- LIVER DISEASE
- Buspirone is metabolized by the liver. After multiple-dose administration of buspirone to patients with hepatic impairment, steady-state AUC of buspirone increased 13-fold compared with healthy subjects.
- Manufacturer makes no specific dosing recommendations and only states that buspirone should not be used in patients with severe hepatic impairment
- COGNITIVE IMPAIRMENT
- Buspirone does not interact with the GABA system like benzodiazepines, and in studies, it has not been shown to cause significant functional impairment. However, because it is a psychoactive medication, the potential for sedation in some patients does exist.
- Patients should be advised to avoid operating an automobile or using complex machinery until they are reasonably certain that buspirone treatment does not affect their cognition
- EXTRAPYRAMIDAL SYMPTOMS (EPS)
- Buspirone binds to D2-dopamine receptors. Because of this, there is concern that it may precipitate extrapyramidal symptoms (e.g. akathisia, parkinsonism, dystonias).
- In studies, an EPS syndrome has not been observed with buspirone therapy, although restlessness has been reported in a small number of patients shortly after initiating therapy
- DRUG INTERACTIONS
- NOTE: The drug interactions presented here are NOT A COMPREHENSIVE LIST of all known interactions. Other interactions exist. The interactions below are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- HIGH ALERT INTERACTIONS
- MAO inhibitors - DO NOT COMBINE. Cases of elevated blood pressure have been reported with concomitant therapy.
- CYP3A4 inducers and inhibitors
- Buspirone is a CYP3A4 sensitive substrate. CYP3A4 inhibitors and inducers may affect buspirone levels.
- When taken with CYP3A4 strong or moderate inhibitors, the starting dose of buspirone should be 2.5 mg once or twice daily. Subsequent dose adjustments should be based on clinical effect.
- When taken with CYP3A4 inducers, the dose of buspirone may need to be increased
- Erythromycin may increase buspirone levels. If used together, the recommended dose of buspirone is 2.5 mg twice a day. Subsequent dose adjustments should be based on clinical effect.
- Grapefruit juice
- Grapefruit juice may increase buspirone levels. Patients taking buspirone should not drink large amounts of grapefruit juice.
- Itraconazole may increase buspirone levels. If used together, the recommended dose of buspirone is 2.5 mg once daily. Subsequent dose adjustments should be based on clinical effect.
- Nefazodone may increase buspirone levels. If used together, the recommended dose of buspirone is 2.5 mg once daily. Subsequent dose adjustments should be based on clinical effect.
- Rifampin may decrease buspirone levels by as much as 90%. If used together, the dose of buspirone may need to be increased.
- METABOLISM AND ELIMINATION
- CYP3A4 - sensitive substrate
- Serotonergic medications - buspirone has serotonergic activity. When taken with other serotonergic medications, the risk of serotonin syndrome may be increased.
- Diltiazem - diltiazem may increase buspirone levels. Monitor for side effects when combining.
- Verapamil - verapamil may increase buspirone levels. Monitor for side effects when combining.
- Cimetidine - cimetidine may increase buspirone levels. Monitor for side effects when combining.
- Diazepam - buspirone may increase diazepam levels. Monitor for side effects when combining.
- Haloperidol - buspirone may increase haloperidol levels. Monitor for side effects when combining.
- Dosage forms
- 5 mg
- 7.5 mg
- 10 mg
- 15 mg
- 30 mg ($)
- NOTE: 15 mg tablet is scored to provide 5, 7.5, 10, and 15 mg dose depending on where cut
- Anxiety disorders
- Starting: 7.5 mg twice a day
- Maintenance: 10 - 15 mg twice a day
- Max: 60 mg/day
- Increase dose by 5 mg/day at intervals of 2 - 3 days
- See drug interactions for dosing with CYP3A4 inhibitors and inducers
- Food increases the absorption of buspirone
- Buspirone should be taken in a consistent manner, either always with or always without food
- GENERIC AVAILABILITY
- Generic available:
- Buspirone has a generic
- LONG TERM SAFETY
- Buspirone has been prescribed in the U.S. since the 1980s to treat anxiety
- Buspirone has been shown to be safe for long-term use
- What is PMID?
- PI = Manufacturer's Package Insert
- # PMID
- 1 - Manufacturer's Package Insert