Buspirone: Uses, Side Effects, Dosage, Warning, and Contraindications

Overview

Buspirone is prescribed for the management of anxiety disorders of generalized or moderate degree. The drug is ineffective in treating panic disorders, severe anxiety, or obsessive-compulsive disorder. However, in patients with generalized anxiety disorders, symptoms of depression can be treated with Buspirone. The drug was approved by the Food and Drug Administration (FDA) in 1986 for treating anxiety disorders, such as symptoms of anxiety (tension, fear, irritability, pounding heartbeat, or dizziness) and generalized anxiety disorders (GAD).

Indications

• FDA-Approved Indication: The drug is indicated for the treatment of anxiety disorders or for relieving the short-term symptoms of anxiety. In addition, the drug can also be used in managing generalized anxiety disorder (GAD).

• Off-Label Clinical Use: It can also be used for the treatment of unipolar depression. In addition, Buspirone, in combination with melatonin, can promote neurogenesis and treat major depressive disorders (MDD); however, these uses of Buspirone are not approved by the FDA.

For Patients

What Is Anxiety?

Anxiety is an excessive, intense, and persistent fear and worry about every life situation. Anxiety symptoms include sweating, rapid or fast breathing, nervousness, restlessness, feelings of weakness or tiredness, and trembling.

Why Is Buspirone Prescribed?

Buspirone is used to treat anxiety disorder or to relieve the short-term symptoms of anxiety. The drug belongs to the class of medication called anxiolytics, and it works by changing specific amounts of natural substances in the brain.

What Precautions Should One Follow Before Taking This Medication?

• A person should inform the doctor or pharmacist about any allergic reaction to this drug, any of the medication's ingredients, or any other medicine. They should ask the pharmacist about the list of elements in the drug.

• Inform the doctor about all the prescription and non-prescription drugs, herbal products, vitamins, and nutritional supplements a person is taking or is planning to take. The doctor may need to change the medication dosage or monitor a person for side effects. Therefore, one must mention all the drugs that they are taking as these drugs can interact with Buspirone and cause adverse reactions.

• The person should also inform the doctor if they take a monoamine oxidase inhibitor (MAOI). These two drugs, when taken together, can elevate blood pressure; therefore they should, Buspirone should be concomitantly used with MAOIs.

• A person should also inform the doctor about any past or present medical history, such as liver or kidney disease or history of drug or alcohol abuse.

• Also, inform the doctor if one is pregnant, or planning to get pregnant, or gets pregnant while they are on Buspirone.

• This drug can make a person dizzy; therefore, one must avoid driving a car or operating heavy machinery while taking this drug.

• If a person is undergoing any surgery, including dental procedures, they must inform the doctor that they are taking Buspirone.

• Do not consume alcohol while taking Buspirone, as alcohol can add to the drowsiness caused by Buspirone.

What Are the Side Effects of Buspirone?

Common Side Effects

• Dizziness.

• Nausea.

• Excitement.

• Fatigue.

• Lightheadedness.

• Weakness.

• Sweating.

• Headache.

• Confusion.

• Nervousness.

• The feeling of hostility or anger.

• Difficulty falling asleep.

• Numbness.

• Increased sweating.

Serious Side Effects

• Itching.

• Hives.

• Rash.

• Blurred vision.

• Irregular or fast heartbeat.

• Uncontrollable body shivering.

• Fever, sweating, agitation, confusion, flushing, dizziness, shivering, rapid heartbeat, muscle twitching or stiffness, hallucinations, seizures, nausea, diarrhea or vomiting, and loss of coordination.

Drug Dosage and Administration

Adult Drug Dosage

• Initial Dose: 5 mg (milligrams) thrice or 7.5 mg twice daily.

• Maintenance Dose: In divided doses, the drug dosage can be increased in increments of 5 mg every two to three days up to 20 to 60 mg per day.

• Maximum Dose: Up to 60 mg per day.

Pediatric Drug Dosage

The pediatric drug dosage has not been well-established; however, the drug is occasionally used off-label for pediatric anxiety disorder. In a pilot study of children from six to 14 years, the daily drug dosage of 5 mg was started and increased by 5 mg every week, maintaining an average maximum dosage of 20 mg. In another study on children six to 17 years, the total daily dosage was suggested to be 60 mg.

Missed Dose

A person should take the missed drug dosage as soon as they remember it. If it is already time for the next scheduled dose, one must skip the missed dose and continue with the next one. One should not take the double dosage to make up for the forgotten dose of the drug.

Overdose

In drug overdose cases, contact the nearest poison control helpline; however, if a person faints or collapses, has troubled breathing, or has seizures, emergency medical services should be called. The signs and symptoms of Buspirone overdose are as follows:

• Vomiting.

• Nausea.

• Dizziness.

• Miosis (excessive constriction of the pupil of the eye).

• Drowsiness.

• Gastric distress.

Treatment for Drug Overdose:

• Supportive and symptomatic measures should be taken in case of drug overdose, followed by gastric lavage.

• Blood pressure, pulse, and respiration should be monitored, as done in all drug overdose cases.

• Antidotes for Buspirone overdose are not known, and also dialyzability (capable of diffusing through a dialyzing membrane) is not yet established.

Drug Storage and Disposal

The drug must be stored in the air-tight container it came in and away from the children’s reach. It should be stored at room temperature, away from excess heat, moisture, and light. Expired or unneeded medicines should be discarded in special ways to ensure that children, pets, and others cannot accidentally consume them. However, the drug should not be flushed into the toilets rather, it should be disposed of through a medicine take-back program. This can be done by contacting the nearest pharmacy or local recycling or garbage disposal department. In addition, the treatment can also be disposed of by following the FDA’s safe disposal of medication.

For Doctors:

Clinical Pharmacology

Mechanism of Action:

Buspirone has a strong affinity for serotonin 5HT 1a receptors and a weak affinity for 5HT2 receptors, where it acts as a partial agonist and an ineffective antagonist on dopamine D2 autoreceptors, respectively. The drug does not have any effect on GABA receptors of Benzodiazepines. However, the exact mechanism of action of Buspirone has yet to be discovered clearly.

Pharmacodynamics:

Buspirone takes about two to four weeks to alleviate the symptoms of generalized anxiety disorders. However, the delayed onset of action of Buspirone suggests that the therapeutic effectiveness of this condition may have induced adaptation of 5HT 1a receptors, or it has involved more than its molecular mechanism of action at 5HT 1a receptors.

Pharmacokinetics:

Absorption

Buspirone goes extensively under first-pass metabolism and is rapidly absorbed following oral administration. Also, within 40 to 90 minutes, peak plasma levels are attained.

Distribution

Buspirone has approximately 86 percent plasma protein binding.

Metabolism

Buspirone is metabolized following administration, which is metabolized by oxidation, which CYP3A4 mediates. This leads to hydroxylated derivatives and an active metabolite (pharmacologically), 1-pyrimidinyl piperazine (1-PP).

Excretion

The elimination half-life of Buspirone (unchanged) is approximately two to three hours. About 29 to 63 percent of the drug is eliminated as a metabolite in the urine, and about 18 to 38 percent of the drug is excreted in feces.

Ingredients:

• Active Ingredients: Buspirone.

• Inactive Ingredients: Lactose monohydrate, colloidal silicon dioxide, microcrystalline cellulose, Magnesium stearate, and Sodium starch glycolate.

Dose Form and Strength:

• 5 mg (milligrams) tablet - Bottles of 100 tablets.

• 10 mg tablets - Bottles of 100 tablets.

• 15 mg tablets - Bottles of 60 and 180 tablets.

• 30 mg tablets - Bottles of 60 tablets.

Contraindications

• The drug is contraindicated in a person who is hypersensitive to Buspirone.

• The drug should also be avoided within 14 days before and after Buspirone therapy in patients receiving MAO inhibitors. This is recommended due to the risk of developing elevated blood pressure and serotonin syndrome.

• In addition, the drug should also be avoided in patients receiving methylene blue or Linezolid, a reversible MAO inhibitor that can cause serotonin syndrome.

Drug Interactions

Psychotropic Agents

• MAO Inhibitors: Buspirone is not recommended for use along with MAO inhibitors.

• Diazepam: Coadministration of Buspirone and Diazepam shows no significant difference in the drug's pharmacokinetic properties (Cmax, AUC, and Cmin). However, minor adverse effects were observed, such as headache, dizziness, and nausea.

• Amitriptyline: Coadministration of Buspirone and Amitriptyline show no significant difference in the pharmacokinetic properties [Cmax (highest drug concentration), AUC(area under the curve), and Cmin (minimum drug plasma concentration)]of the drug

• Trazodone: Three to six-fold elevation in SGPT (ALT) was observed in a single case study, suggesting the concomitant use of Buspirone and Trazodone.

• Haloperidol: Serum Haloperidol concentration increases with concomitant use of Buspirone with Haloperidol. However, the clinical significance of this finding still needs to be discovered.

• Flurazepam or Triazolam: Coadministration of Buspirone with Flurazepam or Triazolam does not intensify or prolong the effect of Benzodiazepines.

Inhibitors and Inducers of Cytochrome P450 3A4 (CYP3A4)

• Verapamil and Diltiazem: Concomitant administration of Buspirone with Verapamil or Diltiazem not only increases the plasma concentration of Buspirone (Diltiazem increases AUC and Cmax 5.5-fold and 4-fold, and Verapamil increased AUC and Cmax of buspirone 3.4-fold, respectively) but also causes adverse effects attributable to Buspirone.

• Erythromycin: Buspirone and Erythromycin also cause an increase in Buspirone plasma concentration (five-fold increase in Cmax and six-fold increase in AUC), along with side effects. Therefore, dose adjustment is needed for Buspirone.

• Itraconazole: Coadministration of Buspirone with Itraconazole not only increases the plasma concentration of Buspirone (13-fold increase in Cmax and 19-fold increase in AUC) but also causes side effects. Therefore, Buspirone should be prescribed in low dosage in such cases, or the dose can be adjusted after clinical assessment.

• Grapefruit Juice: The plasma concentration of Buspirone (4.3-fold increase in Cmax; 9.2-fold increase in AUC) increases when administered along with grapefruit juice. Therefore, patients should be advised to limit the consumption of grapefruit juice along with Buspirone.

• Nefazodone: Coadministration of Nefazodone and Buspirone increases the plasma concentration of Buspirone (increases up to 20-fold in Cmax and up to 50-fold in AUC) and decreases the plasma concentration of Buspirone metabolite 1-PP. Therefore, a low dosage of Buspirone is recommended if given along with Nefazodone.

• Rifampin: Coadministration of Buspirone and Rifampin decreases the pharmacodynamic effects and plasma concentration of Buspirone (83.7 percent decrease in Cmax; 89.6 percent decrease in AUC). Therefore, dose adjustment is needed for Buspirone to maintain the anxiolytic effect.

Other Drugs:

• Cimetidine: Administration of Buspirone with this drug increases Tmax and Cmax increases Cmax (40 percent) and Tmax (2-fold), but the area under the curve (AUC) remains has minimal effect.

Use in Specific Population

• Pregnancy Category B: Reproduction studies on rabbits and rats show no fetal damage or fertility impairment at a dose of Buspirone 30 times more than that of the maximum recommended human dose. However, well-controlled studies are not yet established, and animal studies are not always accurate for human response. Therefore, the drug should be cautiously prescribed to a pregnant woman only if the medication is needed. Additionally, no effects of Buspirone were noted in rat reproductive studies. Also, no adverse effects were observed on labor and delivery in humans.

• Nursing Mothers: The excretion of Buspirone in human milk is also not known; however, the drug is excreted in milk in studies on rats. Therefore, the drug should be avoided by nursing mothers.

• Pediatric Use: There is no long-term data available for the safety and efficacy of Buspirone in the pediatric population. However, in two placebo-controlled trials on pediatric patients with generalized anxiety disorders, no significant difference was observed in Buspirone and placebo following the doses recommended for the treatment of anxiety disorders in adults.

• Geriatric Use: The safety and efficacy of Buspirone in adults are similar to that of the pediatric population. The age of a person does not affect the pharmacokinetics of Buspirone; therefore, the sensitivity of the drug to older people cannot be ruled out quickly.

Use in Patients With Hepatic and Renal Impairment

The drug is metabolized and excreted in the liver and kidney. Therefore, the half-life and plasma concentration of the drug increases in patients with impaired renal and hepatic function. Thus, the drug is not recommended in such cases.