Buspirone has an affinity for brain D(2)-dopamine receptors, where
it acts as an antagonist and agonist, and for the 5-HT(1A) receptors,
where it acts as an agonist, but does not block the neuronal
reuptake of monoamines and, on chronic administration, it does
not lead to changes in receptor density in the models investigated.
However, the mechanism of action of buspirone remains to be fully
elucidated.
Buspirone is rapidly absorbed in man and undergoes extensive
first pass metabolism, as soon as 40 to 90 minutes after a single 20 mg dose. In a number of studies
performed in healthy volunteers, the mean half-life of buspirone
ranged from 2 to 3 hours up to approximately 11 hours with considerable
variation in individual values.
Buspirone is metabolized primarily by oxidation.
In man, the effect of buspirone
on drug metabolism or concomitant drug disposition has not been
studied. The pharmacokinetics of buspirone in patients with hepatic
or renal dysfunction, and in the elderly, has also not been clearly
established.
Indications
Short-term symptomatic relief of excessive anxiety in patients
with generalized anxiety disorder (psychoneurotic disorder).
Contraindications
In patients hypersensitive to buspirone HCl. Buspirone is contraindicated in patients with severe hepatic
or severe renal impairment.
Warnings
The occurrence of elevated blood pressure in patients receiving
both buspirone and a MAO inhibitor has been reported. Therefore,
it is recommended that buspirone should not be used concomitantly
with a MAO inhibitor.
Since buspirone can bind to central dopaminergic receptors, the
possibility of acute and chronic changes in dopamine mediated
neurological function (e.g. dystonia, pseudo-parkinsonism, akathisia
and tardive dyskinesia) should be considered (see Precautions).
Since the effects of buspirone have not been evaluated in patients
with a history of convulsive disorders and since it lacks anticonvulsant
activity in animals, buspirone is not recommended for patients
with seizure disorders.
Patients who have previously taken benzodiazepines may be less
likely to respond to buspirone than those who have not.
A drug-free interval is desirable
between withdrawal of the benzodiazepine and initiation of buspirone,
in order to increase the likelihood of distinguishing between
benzodiazepine withdrawal effects and unrelieved anxiety due to
possible failure of buspirone in this category of patients.
Benzodiazepine 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. These symptoms may appear
as any combination of irritability, anxiety, agitation, insomnia,
tremor, abdominal cramps, muscle cramps, vomiting, sweating, flu-like
symptoms without fever and, occasionally, seizures, and should
be treated symptomatically.
Pregnancy and Lactation:
The safety of buspirone during pregnancy and lactation has not
been established and, therefore, it should not be used in women
of childbearing potential or nursing mothers, unless, in the opinion
of the physician, the potential benefits to the patient outweigh
the possible hazards to the fetus. Buspirone and its metabolites
are excreted in milk in rats. The extent of excretion in human
milk has not yet been determined.
Precautions
Effects on Cognitive and Motor Performance
In controlled studies in healthy volunteers, single doses of buspirone
up to 20 mg had little effect on most tests of cognitive and psychomotor
function, although performance on a vigilance task was impaired
in a dose-related manner. The effect of higher single doses of
buspirone on psychomotor performance has not been investigated.
When 10 mg were given 3 times daily for 7 days to healthy
volunteers produced considerable subjective sedation but no significant
effect on psychomotor performance (no vigilance tasks were used
in this study). It also caused transient dizziness, especially
on standing and walking.
Occupational Hazards
Until further experience is obtained with buspirone, patients
should be warned not to operate an automobile or undertake activities
requiring mental alertness, judgment and physical coordination,
until they are reasonably certain that buspirone does not affect
them adversely.
Drug Abuse and Dependence
Although preliminary animal and human investigations suggest that
buspirone may be significantly devoid of potential for producing
physical or psychological dependence, only extensive clinical
experience with the drug will provide conclusive evidence.
Patients with Impaired Hepatic or Renal Function:
Since it is metabolized by the liver and excreted by the kidneys,
buspirone should be used with caution in patients with a history
of hepatic or renal impairment. It is contraindicated in patients
with severe hepatic or renal impairment.
Children
The safety and effectiveness of buspirone in individuals below
the age of 18 years have not been established.
Geriatrics
Buspirone has not been systematically evaluated in older patients.
Adverse Effects
The most common adverse reactions encountered with buspirone are
dizziness, headache, drowsiness and nausea.
Dosage
The recommended initial dose is 5 mg 2 to 3 times daily. This
may be titrated according to the needs of the patient and the
daily dose increased by 5 mg increments every 2 to 3 days up to
a maximum of 45 mg daily in divided doses. The usual therapeutic
dose is 20 to 30 mg daily in 2 or 3 divided doses.
Note:
If buspirone is administered to patients with compromised hepatic
or renal function, careful monitoring will be required together
with appropriate dosage adjustment.
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