Centrally-mediated (CNS) adverse effects were the most frequently occurring reactions during buspirone clinical trials and were among the most common events resulting in discontinuation of therapy (3.4%). Common causes of treatment discontinuation included dizziness, insomnia, nervousness, drowsiness, and lightheadedness. During clinical trials of buspirone in the treatment of anxiety, the following CNS effects occurred in at least 1% of patients receiving buspirone and with a frequency greater than in placebo patients: dizziness (12%), drowsiness (10%), nervousness (5%), lightheadedness (3%), excitability (2%), anger/hostility (2%), confusion (2%), numbness (2%), paresthesias (1%), incoordination (1%), tremor (1%), and headache (6%). During other premarketing evaluations, dream disturbances (abnormal dreams) were reported in at least 1% of patients. CNS effects reported in 0.1% to 1% of patients included depersonalization, dysphoria, noise intolerance, euphoria, akathisia, fearfulness, loss of interest, dissociative reaction, hallucinations, involuntary movements, slowed reaction time, suicidal ideation, and seizures. Rarely reported effects (less than 0.1%) included claustrophobia, cold intolerance, stupor, dysarthria, psychosis, and roaring sensation in the head. During postmarketing use, extrapyramidal symptoms (EPS) including pseudoparkinsonism (i.e., cogwheel rigidity, dyskinesia), dystonic reaction, akathisia, and tardive dyskinesia have been reported. Although causality has not been established, buspirone affects central dopamine receptors which may be a contributing factor in the development of extrapyramidal reactions. Other postmarketing events include dizziness/vertigo, ataxia, emotional lability, serotonin syndrome, transient difficulty with recall, restless legs syndrome (RLS), and restlessness. Because individual response and tolerability to CNS active drugs are unpredictable, patients should be advised to avoid driving or engaging in activities requiring mental alertness until they know how the drug affects their cognition. Unlike many other anxiolytics, buspirone does not appear to cause physical or psychological dependence.[28501]

During clinical trials of buspirone in the treatment of anxiety, musculoskeletal pain or aches (myalgia) occurred in 1% of patients receiving buspirone and more frequently than in patients receiving placebo. During other premarketing evaluations, musculoskeletal effects reported in 0.1% to 1% of patients included muscle cramps, muscle spasms, rigid/stiff muscles, and arthralgia. Myasthenia was reported rarely (less than 0.1%).[28501]

During clinical trials of buspirone in the treatment of anxiety, the following dermatologic effects occurred in at least 1% of patients receiving buspirone and more frequently than in patients receiving placebo: skin rash (1%) and hyperhidrosis or clamminess (1%). During other premarketing evaluations, adverse dermatologic effects reported in 0.1% to 1% of patients included edema, pruritus, flushing, easy bruising (hematoma), hair loss (alopecia), xerosis, facial edema, and blisters. Acne vulgaris and thinning of nails were reported rarely (less than 0.1%). During postmarketing use, allergic reactions (e.g., urticaria, angioedema) and ecchymosis have been reported. Because of the uncontrolled nature of these spontaneous postmarketing reports, a causal relationship to buspirone has not been determined.[28501]

During premarketing evaluation of buspirone, adverse hematologic effects including eosinophilia, leukopenia, bleeding disturbance (unspecified), and thrombocytopenia were reported in less than 0.1% of patients.[28501]

During clinical trials of buspirone in the treatment of anxiety, the following adverse gastrointestinal (GI) effects occurred in at least 1% of patients receiving buspirone and more frequently than in patients receiving placebo: nausea (8%) and diarrhea (2%). During other premarketing evaluations, adverse GI effects reported in 0.1% to 1% of patients included elevated hepatic enzymes, flatulence, anorexia, appetite stimulation, hypersalivation, irritable colon, weight gain, weight loss, and rectal GI bleeding. Burning of the tongue was reported rarely (less than 0.1%).[28501]

During premarketing evaluation of buspirone, the following adverse respiratory effects or infections were reported in at least 1% of patients: sore throat and nasal congestion. Adverse effects reported in 0.1% to 1% of patients included hyperventilation, dyspnea, chest congestion, and fever. Epistaxis and hiccups were reported rarely (less than 0.1%).[28501]

During premarketing evaluation of buspirone, chest pain (unspecified) was reported in at least 1% of patients. Adverse cardiovascular effects reported in 0.1% to 1% of patients included syncope, hypotension, and hypertension. Rarely reported cardiovascular or cerebrovascular effects (less than 0.1%) included stroke, congestive heart failure, myocardial infarction, cardiomyopathy, and bradycardia.[28501]

During clinical trials of buspirone in the treatment of anxiety, blurred vision occurred in 2% of patients receiving buspirone and more frequently than in patients receiving placebo. During other premarketing evaluations, adverse effects related to the special senses reported in 0.1% to 1% of patients included tinnitus, redness of the eyes, ocular pruritus, dysgeusia, parosmia, and conjunctivitis. Inner ear abnormality, ocular pain, photophobia, pressure on the eyes, and loss of voice were reported rarely (less than 0.1%). Visual impairment (including tunnel vision) has been reported during postmarketing use. Because of the uncontrolled nature of spontaneous postmarketing reports, a causal relationship to buspirone treatment has not been determined.[28501]

During premarketing evaluation of buspirone, adverse endocrine effects including galactorrhea and thyroid abnormality (unspecified) were reported in less than 0.1% of patients.[28501]

During premarketing evaluation of buspirone, the following adverse genitourinary effects or changes in sexual functioning were reported in 0.1% to 1% of patients: increased urinary frequency, urinary hesitancy, menstrual irregularity and spotting, dysuria, libido decrease, and libido increase. Rarely reported effects (less than 0.1%) included amenorrhea, pelvic inflammatory disease, enuresis, nocturia, ejaculation dysfunction (delayed ejaculation), and impotence (erectile dysfunction). Urinary retention has been reported during postmarketing use. Because of the uncontrolled nature of spontaneous postmarketing reports, a causal relationship to buspirone treatment has not been determined.[28501]

During clinical trials of buspirone in the treatment of anxiety, weakness occurred in 2% of patients receiving buspirone and more frequently than in patients receiving placebo. During other premarketing evaluations, malaise was reported in 0.1% to 1% of patients. Alcohol abuse was reported rarely (less than 0.1%).[28501]

The use of monoamine oxidase inhibitor therapy (MAOI therapy) intended to treat depression with buspirone or within 14 days of stopping treatment with buspirone is contraindicated because of an increased risk of serotonin syndrome and/or elevated blood pressure. The use of buspirone within 14 days of stopping an MAOI intended to treat depression is also contraindicated. Starting buspirone in a patient who is being treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome. Use other serotonergic medications with caution in patients taking buspirone due to a potential increase in serotonin syndrome risk. If serotonin syndrome occurs, discontinue serotonergic agents and institute appropriate treatment.[28501]

Buspirone has a slow onset of action; buspirone does not exhibit cross-tolerance with benzodiazepines and other common sedative/hypnotic drugs. Buspirone will not block the withdrawal syndrome often seen with cessation of therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, it is advisable to withdraw patients gradually from the benzodiazepine or other prior CNS depressant treatment. Patients who are being converted from a benzodiazepine to buspirone therapy may need to overlap buspirone initiation with the downward titration of the benzodiazepine or other treatment. Rebound or withdrawal symptoms may occur over varying time periods, depending in part on the type of drug, and its effective half-life of elimination.[28501]

Because buspirone can bind to central dopamine receptors, a question has been raised about its potential to cause acute and chronic changes in dopamine-mediated neurological function (e.g., dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia). Clinical experience in controlled trials has failed to identify any significant antipsychotic-like activity; however, a syndrome of restlessness, appearing shortly after initiation of treatment, has been reported in some small fraction of buspirone-treated patients. The syndrome may be explained in several ways. For example, buspirone may increase central noradrenergic activity; alternatively, the effect may be attributable to dopaminergic effects (i.e., represent akathisia).[28501]

Buspirone is metabolized by the liver and excreted by the kidneys. A pharmacokinetic study in patients with impaired renal function demonstrated increased plasma levels and a prolonged half-life of buspirone. Therefore, the administration of buspirone to patients with severe renal impairment or with renal failure is not recommended.[28501]

Buspirone is metabolized by the liver and excreted by the kidneys. A pharmacokinetic study in patients with impaired hepatic function demonstrated increased plasma levels and a lengthened half-life of buspirone. Therefore, the administration of buspirone to patients with severe hepatic disease is not recommended.[28501]

Studies indicate that buspirone is less sedating than other anxiolytics and that it does not produce significant functional impairment. However, its CNS effects in any individual patient may not be predictable. Therefore, patients should be cautioned about driving or operating machinery until they are reasonably certain that buspirone treatment does not affect them adversely. While formal studies of the interaction of the drug with alcohol indicate that buspirone does not increase alcohol-induced impairment in motor and mental performance, it is prudent to avoid ethanol ingestion while taking buspirone.[28501]

The safety and efficacy profiles of buspirone in geriatric patients are similar to those in younger adults; however, greater sensitivity of some older patients cannot be ruled out; a lower initial dosage is recommended in geriatric patients.[28501] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). When buspirone is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.[60742]

Clinical studies related to the use of buspirone in pregnancy and subsequent outcomes are limited. In a prospective analysis of data from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications, 68 women who gave birth to 72 infants reported use of buspirone during the first trimester of pregnancy. No major malformations were reported in any infants who were exposed to buspirone during the first trimester. Additional well-controlled studies with larger populations of pregnant patients are needed to further assess for potential risks related to buspirone exposure in pregnancy. No teratogenic effects have been observed in animal studies when using approximately 30 times the maximum recommended human dose (MRHD); however, animal reproduction studies are not always predictive of human response. The effects of buspirone during labor and delivery are unknown.[69030] [28501] [62732]

Buspirone and its metabolites are excreted in the milk of lactating rats. Limited information indicates that maternal doses of buspirone up to 45 mg/day produce low levels in human milk and adverse events have not been reported; however, there are no data on the long-term use of buspirone during lactation and the prescribing label recommends avoidance if clinically possible. Consider if an alternative would be appropriate. A pooled analysis found that maternal use of paroxetine usually produced undetectable or low drug concentrations in infant serum; this agent may be an option when initiating chronic therapy for generalized anxiety disorder (GAD) in a breast-feeding individual. For acute anxiety requiring a benzodiazepine, short-acting agents such as oxazepam or lorazepam may be considered; however, the breastfed infant should be monitored for sedation, feeding difficulties, or other signs of toxicity which would indicate the need to discontinue the benzodiazepine.[28501] [45642] [46229] [61269] [62732] [69031]

Buspirone is not approved by the FDA for any indication in infants, children, or adolescents. Buspirone has been used clinically in children and adolescents 6 years of age and older for the treatment of anxiety. However, efficacy in pediatric patients is uncertain; two placebo-controlled 6-week trials for generalized anxiety disorder (GAD) in pediatric patients 6 to 17 years of age reported no significant differences in efficacy between buspirone and placebo with regard to the symptoms of GAD following doses recommended for the treatment of GAD in adults. No unexpected safety findings were associated with buspirone in these trials. There are no long-term safety or efficacy data in pediatric patients.[28501] [62489] [62490]