8 Important facts of buspirone

Buspirone is one of the azaspiro ketones, which is given in the form of buspirone hydrochloride. This drug is an anxiolytic indicated for the short-term treatment of anxiety. This drug is available under the brand name Buspar. Buspirone hydrochloride can be used for short-term management of anxiety, but when this drug is going to be taken, a few things should be considered because this drug can be given safely with a few of the other drugs, but along with a few of the centrally acting drugs,this drug is contraindicated. Care should be taken when this drug is taken along with a few of the fruits. When a few of the anxiolytics, like benzodiazepines, are replaced with buspirone, a few precautions should be maintained in order to avoid a few of the central side effects.

Here in this article, let’s explore the eight important facts that should be considered while taking buspirone hydrochloride.

What are the uses of buspirone?

Buspirone is an anxiolytic, so this drug can be given when a few of the symptoms are observed in the patient, such as repeated tension, increased anxiety, insomnia, lack of sleep, and intense fear with palpitations and sweating. If any of these symptoms are observed for more than one month, it may indicate generalized anxiety disorder, commonly known as GAD. In such conditions, buspirone can be given to control anxiety as well as other associated symptoms. But for the treatment of anxiety, we can have a category of drugs called anxiolytics; benzodiazepines are the one category of drugs that are widely used as anxiolytics. We have drugs like lorazepam, clonazepam, and alprazolam. All these drugs are indicated for the treatment of anxiety, and they are classified as anxiolytics as well as sedatives.

On the other hand, we have another drug, buspirone, which has a few advantages over benzodiazepines. Buspar shows somewhat less sedation compared with benzodiazepines, and this drug also has less motor as well as cognitive impairment. So these are the two advantages of buspirone over benzodiazepines. That's why, in order to control the anxiety, sometimes buspirone can be preferred over benzodiazepines, particularly in the elderly, where motor and cognitive impairment is troublesome with the use of benzodiazepines.

In such conditions, buspirone can be given, and it is available as a tablet at different strengths, starting at 5 mg, 7.5 mg, 10 mg, 15 mg, and 30 mg. Initially, it is started at a low dose, and the dose can also be reduced based on the patient's conditions, but so many factors can influence the therapy with buspirone. In this article, we will explore these factors.

1. Switching from the benzodiazepine

Already, we have discussed that benzodiazepines are well prescribed as anxiolytics, but when they produce few of the troublesome side effects such as motor and cognitive impairment and significant sedation, then these benzodiazepines can be replaced with buspirone. But buspirone is not an immediate replacement for benzodiazepines because it belongs to a different chemical category and is a non-benzodiazepine, so it will not act like benzodiazepine, but it can still reduce anxiety by different mechanisms.

Interestingly, buspirone shows beneficial effects after one to three weeks of treatment, so it will not produce any acute response as observed with benzodiazepines. As a result, if these benzodiazepines are abruptly discontinued, they may experience a number of withdrawal symptoms. However, buspirone cannot reduce these withdrawal effects because it is a non-benzodiazepine. Even buspirone takes at least one to three weeks to show its beneficial effects, so sudden replacement of benzodiazepines with buspirone may lead to a few of the withdrawal effects in the patients, which just resemble the symptoms of anxiety disorder.

It may cause insomnia, particularly during the daytime, increased anxiety, unexpected abdominal pain, muscle pain, and even flu-like symptoms like shivering and shakiness. If it is left untreated, it may also lead to seizures. That's why benzodiazepines should not be suddenly stopped; instead, the dose should be slowly reduced over a few weeks. At the same time, buspirone therapy should be started so that it can slowly replace the pharmacological effects of benzodiazepines.

2. restlessness

Buspirone acts through different mechanisms. It acts as a partial agonist on 5HT-1A receptors, so it's a 5HT-1A receptor agonist. But apart from this action, buspirone can also inhibit the D2 receptors, the dopamine receptors, which are responsible for controlling motor activities. When these receptors are blocked, it may produce some central side effects. That's why buspirone may produce some restlessness in the patients. This condition is also called akathesia, where restlessness is observed because of any extrapyramidal side effects that may be produced with buspirone due to its antagonistic activity on D2 receptors. This side effect is not observed with benzodiazepines.

3.Effect on memory

Benzodiazepines mainly produce central side effects, resulting in the loss of memory. They produce anterograde amnesia, the loss of memory of current events, which is more troublesome in the elderly. They can also produce muscle paralysis, resulting in decreased grip strength so that the patient cannot hold the objects in a perfect way. Even buspirone shows somewhat less central side effects like amnesia and muscle paralysis, but still, care should be taken while driving vehicles or operating machinery because a high dose of buspirone may also produce cognitive and motor impairment, which may affect daytime activities. So when this drug is used, particularly at high doses, caution should be taken, particularly in the elderly.

4. Effects of alcohol

Generally, alcohol acts as a CNS depressant, so when the alcohol is consumed, it can act on the CNS and produce some sedation in the patient. Even though buspirone is not producing sedation directly, when it is combined with alcohol, it can increase the sedative effect, which may be significant. That's why care should be taken when buspirone is co-administered with alcohol because the sedative effect may be increased in the presence of alcohol.

5. Effects of grapefruit juice

Buspirone is metabolized to 1-pyrimidinyl piperazine by one of the metabolic enzymes, the CYP3A4 enzyme. This is the metabolic enzyme present in the liver that is responsible for the metabolism of buspirone. This metabolite, 1-pyrimidinyl piperazine, is the active metabolite, which also has some anxiolytic activity but somewhat less action compared with buspirone. Grapefruits can act as CYP3A4 inhibitors, so when this grapefruit juice is taken in large amounts, it can inhibit CYP3A4 activity, thereby inhibiting the metabolism of buspirone. This results in the increased toxic effects of this drug, which may produce increased central side effects and restlessness in the patients.

6. Effects of food

Generally, buspirone has better absorption, and it is given at an initial dose of 7.5 mg twice daily, so the initial daily dose is 15 mg per day. When this drug is given along with food, it increases absorption. However, this drug can be given either with food or without food.

7. MAO Inhibitors

Buspirone shows interactions with non-selective MAO inhibitors like phenelzine, tranylcypromine, and isocarboxazid. All of these drugs act as antidepressants. There are a few other drugs, like selegiline, a MAO-B selective inhibitor used for the treatment of Parkinson's disease, and linezolid, one of the antibiotics, and a dye like methylene blue, all of which have MAO inhibitory activity.

When these compounds are combined with buspirone, they can produce one of the syndromes, serotonin syndrome, resulting in severe hypertension in the patients. This is a fatal condition that should be immediately treated. That's why buspirone should not be given along with MAO inhibitors. And at least a two-week gap should be maintained with the use of buspirone and MAO inhibitors in order to eliminate this severe hypertension in the patients.

8. Effects of other medications

Few of the drugs can affect the metabolism of buspirone, either by inducing or inhibiting the enzymatic activity. Drugs like ketoconazole and ritonavir are strong CYP3A4 inhibitors, thereby inhibiting the metabolism of buspirone. When this metabolism is inhibited, it increases the levels of buspirone, resulting in increased toxic effects. These drugs, when combined with buspirone, can increase central effects like sedation. Therefore, the dose of buspirone should be reduced in the presence of strong CYP3A4 inhibitors.

Similarly, a few of the drugs, like phenobarbital, phenytoin, and carbamazepine, all act like CYP3A4 inducers. They induce metabolic enzyme activity, thereby increasing the metabolism of buspirone, resulting in the decreased efficacy of this drug. So when these drugs are combined with buspirone, they can increase anxiety due to the decreased pharmacological response of this drug. That's why, in the presence of CYP3A4 enzyme inducers, the dose of buspirone should be increased in order to produce significant anxiolytic activity.

Conclusion

Buspirone is one of the anxiolytics used for the short-term management of anxiety, particularly in the treatment of generalized anxiety disorder. But before taking this buspirone, a few precautions should be considered. When this drug is used in patients who are switching from benzodiazepine therapy, the dose of benzodiazepine should not be stopped suddenly as it increases the withdrawal symptoms, which are not affected by buspirone because buspirone is a non-benzodiazepine.

In addition, buspirone shows pharmacological activity after one to three weeks of treatment, so it is not suitable for acute treatment. That's why the benzodiazepine dose should not be suddenly stopped; it should be tappered over a few weeks where buspirone therapy has already been initiated. And this drug should be carefully given along with alcohol and grapefruit juice, as they increase the central side effects, along with CYP3A4 inducers and inhibitors. This drug shows some drug interaction where the dosage adjustment should be done in order to reduce toxic effects as well as increase the efficacy of this drug.