The P-I-E-N-O Parkinsn's List Drug Database
buspirone / BusparTM
LOW RISK
Description: Buspirone is an orally administered anxiolytic that is structurally and pharmacologically distinct from all other anxiolytics including benzodiazepines and barbiturates. Buspirone also differs from other anxiolytics in that it does not possess anticonvulsant or muscle-relaxant properties, does not impair psychomotor function, and does not cause sedation or physical dependence. Thus, an advantage of buspirone over benzodiazepine anxiolytics is that buspirone does not impair state of arousal or attentiveness. Buspirone is not used for immediate relief because its onset of anxiolytic effects can be as long as 2 weeks. It has recently been discovered that buspirone has immunosuppressive activity and it is currently undergoing phase II trials for the treatment of atopic dermatitis. The clinical use of buspirone is for the treatment of generalized anxiety disorder. Buspirone was approved by the FDA in September 1986.
Mechanism of action: The mechanism of action of buspirone is not clearly understood since anxiety may be mediated by more than one neuropathway. In general, buspirone suppresses serotonergic activity while enhancing noradrenergic and dopaminergic cell firing. Buspirone does not inhibit monoamine oxidase. Buspirone does not have any significant activity at benzodiazepine receptors, nor does it affect GABA receptors, however buspirone has some inhibitory actions on GABAergic pathways. In vitro, buspirone exhibits highest affinity for serotonin (5-HT) type 1A receptors, moderate affinity for dopamine type 2 (DAA) receptors, and weak affinity for serotonin type 2 (5-HTA) receptors. Type 1A serotonin receptors are found in high quantities in the dorsal raphe and the hippocampus. Buspirone binding to type 1A serotonin receptors occurs on presynaptic neurons in the dorsal raphe and on postsynaptic neurons in the hippocampus. Animal studies reveal that buspirone inhibits the firing rate of 5-HT-containing neurons in the dorsal raphe. The dominant action of buspirone is partial agonism or mixed agonism/antagonism at 5-HT type 1A receptors.
Buspirone also binds at dopamine type 2 (DAA) receptors, displaying properties of both a dopamine agonist and an antagonist. Buspirone blocks presynaptic dopamine receptors, however, effects on postsynaptic receptors are conflicting. Affinity for dopamine receptors differentiates buspirone from gepirone, a related investigational agent which does not interact with dopamine receptors.
Buspirone increases firing in the locus ceruleus, an area of brain where norepinephrine cell bodies are found in high concentration. Benzodiazepines, in contrast, decrease firing in the locus ceruleus. This may explain why benzodiazepines cause drowsiness while buspirone does not.
The net result of buspirone actions at serotonin and dopamine receptors and related secondary messengers is inhibition of the synthesis and release of serotonin, however, since anxiety is thought to be mediated via multiple CNS pathways, the effects on serotonin do not totally explain the anxiolytic action of buspirone. Clinically, buspirone relieves the symptoms associated with generalized anxiety disorder such as motor tension (restlessness, twitching, and muscle tension); autonomic hyperactivity (sweating, palpitations, and tachycardia); and vigilance and scanning.
The immunosuppressive action of buspirone appears to be distinct from its anxiolytic action. Buspirone has no muscle relaxant activity, anticonvulsant activity, and does not lead to dependence after chronic administration.
Pharmacokinetics: After oral administration, buspirone is rapidly and almost completely absorbed, but only about 4% of a dose reaches systemic circulation because of extensive first- pass metabolism in the liver. The onset of anxiolytic effect can take 3-6 weeks. Distribution of buspirone in the human body has not been fully elucidated. Buspirone and its metabolites are found in breast milk. Metabolism of buspirone occurs mainly in the liver where the drug is oxidized and its metabolites are further oxidized and/or conjugated. Buspirone has a major active metabolite, 1-PP, whose anxiolytic effect in humans has not been established. Elimination of the drug and its metabolites is mostly renal and, to a smaller degree, fecal via biliary secretion. The elimination half-life of buspirone is 2-4 hours in healthy adults and is longer in patients with liver or renal impairment.
CONTRAINDICATIONS/PRECAUTIONS: Buspirone is absolutely contraindicated in patients with a known hypersensitivity to the drug because it can produce an allergic reaction, including anaphylaxis, in these patients.
Caution should be used when administering buspirone to patients with renal impairment because the drug and its metabolites are eliminated mainly through the kidneys; decreased renal function could result in decreased excretion and possible accumulation of the drug and its metabolites.
Caution should be used when administering buspirone to patients with hepatic disease because the drug is metabolized by the liver, and decreased hepatic function could result in decreased clearance of the drug.
DRUG INTERACTIONS: Simultaneous use of buspirone with monoamine oxidase inhibitors (MAOIs) can increase blood pressure, so it is recommended that this combination be avoided. When switching drug therapy, it is recommended that there be a 14-day delay after discontinuing the MAOI before initiating buspirone treatment.
Buspirone can displace digoxin from plasma proteins, but the clinical significance of this effect has yet to be determined.
The combination of buspirone and ethanol or other CNS depressants can increase sedation.
Concomitant use of buspirone and haloperidol results in increased serum concentrations of haloperidol, possibly due to competition in the oxidative dealkylation pathway of metabolism. The clinical significance of this interaction has yet to be determined.
The combination of buspirone with fluoxetine has produced mixed results. Pharmacologically, these two drugs exert opposing actions: buspirone decreases the synthesis and release of serotonin via its effects on serotonin receptors while fluoxetine potentiates serotonin secondary to blocking serotonin reuptake. The addition of fluoxetine to a regimen consisting of buspirone and trazodone was reported to result in an increase in anxiety symptoms in one patient being treated for generalized anxiety disorder and panic. In patients with obsessive- compulsive disorder, however, this combination has been reported to improve efficacy. Until more data is available, careful monitoring should be undertaken when this combination is used.
ADVERSE REACTIONS: The most common adverse reactions occurring during therapy with buspirone are CNS effects such as dizziness (occurring in about 12% of patients), drowsiness (10%), headache (6%), and nausea/vomiting (6-8%). Some patients exhibited a syndrome of restlessness with nervousness (5%) and excitement (2%).
Less common adverse events occurring more frequently in buspirone treated patients than in placebo receiving patients include anger/hostility, confusion, blurred vision, myalgia, numbness, paresthesias, incoordination, tremor, weakness and diaphoresis.
In premarketing assessment adverse events were recorded by over 3500 patients. A causal relationship has not been established. The most frequently reported adverse events, occurring in more than 1% of patients were nonspecific chest pain, nightmares, tinnitus, sore throat, and nasal congestion.
PATIENT INFORMATION:
What do buspirone tablets do?
Buspirone (BusparTM ) helps to relieve certain states of anxiety. It is chemically different from other medicines that treat anxiety and has very little effect on mental alertness. Buspirone does not produce dependency problems. Buspirone is not for relieving the stress and anxiety of everyday life. Generic buspirone tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take buspirone?
They need to know if you have any of these conditions:
How should I take this medicine?
Take buspirone tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed.
Special precautions for use in children:
Buspirone is not for children under 18 years old.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with buspirone?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking buspirone?
Serious side effects with buspirone are rare, but serious allergic reactions and other effects have occurred; symptoms include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with buspirone include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take buspirone?
Visit your doctor for regular checks on your progress. It may be one or two weeks before your anxiety goes away. Do not stop taking buspirone except on your doctor's advice.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how buspirone affects you. Alcohol can increase possible drowsiness and dizziness and may make you more anxious. Avoid alcoholic drinks.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
Parkinsn's Archive Treasures Page
John Cottingham is the webmaster of this site.
