Side effects of Buspirone
From the nervous system and sensory organs:
dizziness (12%), drowsiness (10%), headache (6%), nervousness (5%), fatigue (4%), sleep disturbance (3%), decreased ability to concentrate (2%); extrapyramidal disorders (very rare); ≤2% - blurred vision, confusion or depression, weakness, numbness; ≤1% - neurological symptoms (muscle weakness, tingling, pain or weakness in the arms or legs, uncontrolled movements of the torso).
From the cardiovascular system and blood (hematopoiesis, hemostasis):
≤1% - tachycardia/palpitations.
From the gastrointestinal tract:
nausea (8%), dry mouth (3%), diarrhea (2%); ≤1% - vomiting, constipation; decreased appetite.
Other:
≤1% - myalgia, spasms, muscle cramps or stiffness, rash, sweating.
Material and methods
The purpose of the study was implemented within the framework of an observational (statistical) program conducted in the department of treatment of borderline states and psychotherapy of the St. Petersburg Research Psychoneurological Institute named after. V.M. Bekhterev. The study was open-label.
The study included 36 outpatients who sought help in the specified department.
Inclusion criteria
patients had a verified diagnosis of panic disorder (F 41.0) in accordance with ICD-10, age from 18 to 65 years, signed informed consent, the possibility of treatment on an outpatient basis.
Exclusion criteria
were acute and chronic somatic diseases in the stage of decompensation, pregnancy and lactation; metabolic disorders or cancer, epilepsy, organic diseases of the central nervous system, drug and alcohol addiction, psychotic conditions and severe personality disorders.
The patients included in the study constituted a nosologically and syndromatically homogeneous group. According to ICD-10 criteria, a diagnosis of panic disorder was made on admission to all 30 patients.
The period of active therapy was 6 weeks. For patients who were taking other psychotropic drugs at the start of the study, an additional one-week wash-out period was prescribed.
All patients of the 1st (main) group (30 people) were prescribed combination therapy: spitomin (buspirone) as a monopharmacotherapy at a dose of 30 mg/day (10 mg 3 times a day) for 6 weeks, as well as a course of individual short-term directive cognitive behavioral psychotherapy - 12-15 sessions, with a frequency of 2-3 sessions per week.
The method of psychotherapy used is based on the idea that patients with panic disorder have a specific cognitive style:
they are unable to realistically perceive their sensations and interpret them catastrophically, tend to consider any inexplicable symptom or sensation as a sign of the onset of a life-threatening condition, while they have irrational beliefs that their vital systems - cardiovascular, respiratory, central nervous - will collapse. In connection with this, cognitive restructuring was chosen as the main technique, and interventions were carried out to correct misconceptions and interpretations of bodily sensations. Due to the fact that dyspnea often occurs against the background of stress, which is assessed as threatening health and provokes or intensifies fear caused by external alarming stimuli, the patients were given training in breathing control followed by cognitive reattribution of the meaning of symptoms. Exercises were performed to attract/distract attention.
A number of scales were also used to assess anxiety and panic symptoms: the Hamilton Anxiety Scale (HAM-A); Clinical Global Impression (CGI); Montgomery-Asberg (MADRS), which allows you to assess the presence of concomitant depressive symptoms, the Spielberger-Hanin anxiety scale, which makes it possible to assess the level of situational and personal anxiety. The patients' condition was assessed at the beginning and end of treatment: before the prescription of spitomin (buspirone), and then on the 7th, 14th, 28th and 42nd days of therapy. The clinical and psychological method was represented by participant observation, which was constant during the treatment of patients throughout the observational program.
During the study, patients in the main group were compared with a group of patients with panic disorder who underwent outpatient treatment only using individual cognitive-behavioral psychotherapy - group 2 (30 people). The selection of subjects in both groups was carried out using the continuous sampling method. The majority of those examined from both groups sought help after visiting somatic specialists, assessing their condition as a manifestation of a cardiac, endocrinological or neurological disease, considering the alarming symptoms secondary, associated with concerns about their health and the lack of adequate care and an accurate diagnosis.
Groups 1 and 2 were homogeneous in all indicators, which made it possible to exclude the negative influence of heterogeneity factors on the reliability of the results obtained. Thus, in the 1st group there were 14 (46.7%) men and 16 (53.3%) women, in the 2nd group there were 12 (40%) men and 18 (60%) women. There were no significant differences in this parameter between the study groups. The study included patients from 18 to 58 years old. The average age in group 1 was 34.8±1.4 years, in group 2 - 35.9±1.5 years (Table 1). There were no significant differences in the average age of patients; The most common diagnosis of panic disorder was observed between the ages of 30 and 39 years.
Table 1. Distribution of patients by age
Characteristics of the social status of patients are presented in Table. 2.
Table 2. Characteristics of the social status of patients
From the table 2 also shows that in terms of social indicators, the selected groups of patients with panic disorder did not differ significantly from each other: Pearson’s χ2 test for the distribution of patients by gender was 2 ( p
<0.157), by age - 20 (
p
<0.22), by education - 6 (
p
<0.199), by marital status - 3 (
p
<0.223), by social status - 12 (
p
<0.213).
For mathematical and statistical processing, a research protocol was drawn up, which included passport, social, anamnestic, clinical and experimental psychological indicators. Further analysis of the data included in it was carried out using the statistical software package Statistica 6, SPSS for Windows - version 12.
Precautions for the substance Buspirone
Use with caution simultaneously with neuroleptics, antidepressants, cardiac glycosides, antihypertensive and antidiabetic drugs, and oral contraceptives. For renal and liver failure of mild to moderate severity, liver cirrhosis, it is prescribed in smaller doses and under the strict supervision of a physician. During the treatment period, alcohol consumption should be avoided. At the beginning of treatment, use with caution while working for drivers of vehicles and people whose profession is associated with increased concentration of attention.
Introduction
Currently, panic disorder is a widespread, chronic disease that manifests itself at a young, socially active age. Its prevalence, according to epidemiological studies [1], is 3-6% in the general population. The relevance of this problem is also determined by the fact that people diagnosed with panic disorder often do not come to the attention of psychiatrists at all and prefer to be treated by doctors of other specialties. In these cases, less than 50% of patients receive treatment, while less than 30% receive adequate therapy, which contributes to the transition of panic disorder into a chronic form.
Currently, more and more researchers [2–5] are inclined to use combination therapy using pharmacotherapy and psychotherapy for the treatment of panic disorder. Psychopharmacotherapy provides relief of attacks and an increase in the interictal period, and cognitive-behavioral psychotherapy leads to a change in patients’ assessment of their condition, helping them master effective methods of overcoming anxiety and its vegetosomatic manifestations and promoting successful social adaptation and improvement of interpersonal functioning [6].
Considering the need to provide psychotherapeutic assistance to an increasing number of patients with panic disorder in modern socio-economic conditions without increasing material costs while maintaining the effectiveness of therapeutic interventions, the need for the use of short-term methods of psychotherapy becomes obvious [7].
The main drugs for the treatment of panic disorder have traditionally been benzodiazepine anxiolytics and antidepressants of the selective serotonin reuptake inhibitor (SSRI) group and clomipramine. Having good anti-panic activity and effectively reducing anxiety levels, they have a number of disadvantages that limit the possibilities of their use. The main disadvantage of antidepressants is their delayed action, which contributes to the consolidation of anticipatory anxiety, a negative effect on sexual function and body weight, and benzodiazepines can also cause addiction to them and the development of dependence. Under these conditions, the appearance in the doctor’s arsenal of the non-benzodiazepine anxiolytic buspirone (spitomin), new to domestic specialists, opens up additional opportunities for the treatment of panic disorder.
Spitomin (buspirone) is an anxiolytic (anti-anxiety) non-benzodiazepine drug that also has an antidepressant effect. This drug came into practice in the 80s of the last century, and to date a sufficient evidence base has been accumulated for its effectiveness in both paroxysmal panic and generalized anxiety [8-10]. The advantages of its use are the speed of onset of effect, the absence of dependence and addiction, the possibility of combined use with other psychotropic drugs, the absence of negative effects on sexual functioning and body weight [11]. The mechanism of action of buspirone is associated with its effect on the serotonergic and dopaminergic systems. Buspirone does not have a negative effect on psychomotor functions, drug dependence or withdrawal symptoms.
Indications for the use of buspirone are generalized anxiety disorder, panic disorder, autonomic dysfunction syndrome, alcohol withdrawal syndrome, auxiliary therapy of depressive disorders.
The purpose of this study is to study the effectiveness of spitomin (buspirone) in the complex treatment of panic disorder.
Why the storm is raging across Europe, and what anomalies to expect from the weather in Moscow in the first days of winter
The snow will continue to fall, covering the top with a crust of ice and making the road surface even more slippery.
Photo: Mikhail FROLOV
On November 30, Moscow experienced both the last heavy autumn rain and the first winter snow storm. Two records were broken at once: for temperature and atmospheric pressure.
In all 140 years of meteorological observations, November 30 has never been as warm as in 2021. What is especially surprising is that the maximum was recorded at 7 am, +7.5 degrees. The previous record, +5.8 degrees, had stood since 1974.
Atmospheric pressure dropped to 712.5 mm Hg on Tuesday. Art. Until now, the “pressure bottom” for November 30 was considered to be 718.2 degrees, reached in 1988.
After 16 o'clock the temperature dropped below zero degrees, and by 17 o'clock the temperature dropped to -2. And although the snowstorm and windstorm subsided by evening in most areas of the capital, they were replaced by a new misfortune: black ice. Forecasters from the Phobos center warn:
— The snow will continue to fall, covering the top with a crust of ice and making the road surface even more slippery. In such a situation, the braking distance will increase significantly. Traffic will be difficult and traffic jams may last for hours. Be attentive and careful, both when driving and when walking.
“1–3 cm of snow fell during the day, another 2–4 cm will be added overnight,” says Tatyana Pozdnyakova, chief specialist of the Moscow Meteorological Bureau.
What weather can Muscovites expect in the first days of calendar winter? Should we prepare for new anomalies? The forecast of the Hydrometeorological Center of Russia is as follows:
On the night of Wednesday, December 1, it will freeze to -5...-7 degrees, in places there will be heavy snow and blizzards again, the roads will be very slippery. The wind will whistle with gusts of up to 22 m/sec, this speed is considered a storm according to meteorological classification. During the day -1...-3 degrees, light snow.
On Thursday, December 2, the night will be frosty, up to -11 degrees, in the daytime 0...-2, cloudy and snow again.
On Friday, December 3, it will become warmer: at night 0...-5, during the day +2 degrees, cloudy, with sleet.
Saturday, December 4th, will also be mostly snowy. In the morning up to -7, in the afternoon about 0 degrees.
On Sunday, December 5, a new cold snap will begin: night temperatures will drop to -11, daytime temperatures -3...-8 degrees. But the snowfalls will stop!
“Next week the weather will be truly winter,” says Tatyana Pozdyakova. — During the day at the beginning of the week -2...-4 degrees, then another couple of degrees lower. Night frost down to -8, and sometimes down to -11 degrees. The snow won't melt anymore. By the weekend, the snow cover will reach 5-7 cm, and a short thaw will not cope with it. Most likely, a stable snow cover has formed that will last until spring.
— Is it true that next week it will be -30 at night? People who are used to watching weather forecasts on their smartphones see just such frightening numbers.
- No, our models do not have such cold. It will be coldest at the end of next week, December 10–12, but we are talking about night frost down to -12…-15 degrees.
— In the last days of autumn, a storm hit not only Moscow, but also the UK - there were showers and snowfalls, winds up to 45 m/sec (twice as strong as ours today!), and Turkey - in Istanbul, due to the fault of the strongest meter, people died several people... Is the bad weather from the far west to the very east of Europe somehow connected?
— A completely different cyclone, Arwen, brought bad weather to the UK. But the Istanbul storm is really connected with the Moscow one. The cyclone formed over northern Italy, passed through the Balkans and Turkey, and brought bad weather, including to Crimea. Before reaching Moscow, it connected with the Atlantic cyclone and added strength. By the way, it was thanks to the southern origin of the cyclone that a temperature record was set in Moscow - we were in the warm sector of the atmospheric vortex.
MORE ON THE TOPIC
The “Genoese” raged in Moscow: the cyclone first brought heat and rain, and then began preparations for winter
The weather forecaster believes that the snow that fell in Moscow will not melt until spring (details)
Buspirone (pitomin) is a non-benzodiazepine anxiolytic that is a derivative of azapirone. Azapyrones are a class of drugs with high affinity for serotonin 5-HT1A receptors located on the body and in the endings of serotonergic neurons, as well as in the dendrites of postsynaptic neurons with which the serotonergic endings contact. The anti-anxiety effect of buspirone is not associated with an effect on GABA-benzodiazepine receptors. However, in terms of anxiolytic activity, buspirone is comparable to benzodiazepines such as diazepam, lorazepam or alprazolam, but unlike them, it does not cause drug dependence, cognitive and psychomotor impairment, or pronounced sedative and muscle relaxant effects [1].
Mechanism of action of buspirone
The mechanism of the anxiolytic action of buspirone, which determines its characteristics, is explained mainly by its effect on serotonin receptors. Buspirone has a high affinity for presynaptic serotonin (5-HT1A) receptors, of which it is an agonist, as well as for postsynaptic serotonin receptors, for which it can be considered a partial agonist [1].
Partial agonists are ligands that bind to receptors, but are able to cause only partial activation. If a partial agonist interacts with free receptors, it causes incomplete (50%) activation of the cell. If a partial agonist acts on a tissue whose receptors are already activated by a full agonist, then due to the displacement of the latter from communication with the receptor, the cell response decreases and, therefore, it has a blocking effect.
Thus, due to its receptor action, buspirone reduces the synthesis and release of serotonin, reduces the activity of serotonergic neurons of the raphe nuclei (“serotonin stabilizer”). Buspirone is also able to interact with postsynaptic 5-HT2 receptors, but has low affinity for them. Being a partial agonist, due to its postsynaptic action it can theoretically reduce serotonergic activity and cause an anxiolytic effect, and due to its action on somatodendritic serotonin presynaptic autoreceptors, it can theoretically enhance serotonergic activity and cause an antidepressant effect.
To a lesser extent, the drug selectively blocks pre- and postsynaptic D2-dopamine receptors. Moreover, it was originally developed as an antipsychotic drug, but it was later discovered that it has low affinity for dopamine receptors, and its presynaptic action predominates over the postsynaptic one, which prevents the neuroleptic effect.
Experimental studies have indicated a decrease in serotonin turnover with low doses of buspirone, reflecting stimulation of presynaptic autoreceptors. However, repeated administration of buspirone reduced the response of somatodendritic 5-HT1A receptors, since the decrease in 5-HT metabolism was less pronounced.
Buspirone may act as a partial agonist at postsynaptic serotonin 5-HT1A receptors in the hippocampus and prefrontal cortex, as well as at presynaptic autoreceptors on the cell bodies of serotonergic neurons. Since the effect of azapirones develops over several days, it does not appear to be due to their direct effect on the receptors. Animal studies suggest that the anxiolytic effect of these drugs is related to their action on presynaptic receptors, and the antidepressant effect is related to their action on postsynaptic receptors.
A decrease in serotonin turnover also occurs in the striatum, which may be accompanied by an inhibitory effect on dopaminergic transmission. This effect is reflected in the fact that coadministration of buspirone may attenuate apomorphine sensitization. Thus, buspirone at a relatively low dose may counteract the side effects of apomorphine. However, administration of buspirone at a higher dose caused sensitization of motor behavior [2].
This effect may be explained by blockade of presynaptic dopamine autoreceptors. The experimental administration of a relatively high dose of buspirone caused a sharp increase in the synthesis and metabolism of dopamine in the striatum.
The experiment showed that the administration of buspirone in brain dialysate reduces the level of serotonin by 50%, but increases the level of dopamine by 100% and norepinephrine by 140%, which indicates a complex effect of buspirone on monoaminergic neuromediation [3].
However, in addition to the effect on autoreceptors, buspirone also has another point of application, since the administration of haloperidol, which blocks D1- and D2-postsynaptic mesolimbic and striatal receptors, did not block the dopaminomimetic effect of buspirone. It has been shown that the antagonistic effect of the drug on D2 receptors is 15 times weaker than the effect on 5-HT1A receptors. Buspirone blocks postsynaptic dopamine receptors relatively weakly, even at high doses. It binds with higher affinity to D3 and D4 receptors than to D2 receptors. The effect on presynaptic dopamine receptors is stronger than blockade of postsynaptic receptors. Only in extremely large doses are postsynaptic striatal D1 and D2 receptors blocked quite actively. However, weak postsynaptic dopaminergic antagonism weakens the presynaptic dopaminomimetic effect of the drug, avoiding stereotypy [2, 3].
Use of buspirone for generalized anxiety and other affective disorders
The greatest experience with the use of buspirone has been accumulated in generalized anxiety disorder (GAD). Clinical research over the past 30 years has been accompanied by constant improvement of the nosological structure of anxiety disorders. At the beginning of the 20th century, understanding of anxiety disorders was rather vague, but over time their place among other mental disorders was more clearly defined, partly under the influence of pharmacological research.
Symptoms of GAD are chronic and often observed in patients visiting general practitioners. Typically, such patients present vague somatic complaints of fatigue, muscle pain or tension, and sleep disturbances.
Buspirone is the first nonbenzodiazepine anxiolytic to be approved by the FDA for the treatment of GAD based on studies showing it to be as effective as benzodiazepines.
According to DSM-V criteria [4], GAD is characterized by:
A. Excessive anxiety and worry (anxious expectations), occurring most days for at least 6 months and manifesting itself in a variety of events or actions (for example, when performing professional duties or while studying at school).
B. Difficulty controlling anxiety.
B. The presence of at least 3 of the following symptoms most days for 6 months: motor restlessness or a feeling of restlessness; fast fatiguability; difficulty concentrating and distractibility; irritability; muscle tension; sleep disturbance.
D. Clinically significant distress or impairment in social, occupational and other activities caused by anxiety, restlessness or physical (psychomotor) symptoms.
D. These disorders that cannot be explained by the physiological effect of a psychoactive substance or a somatic disease.
E. These disorders that cannot be explained by another mental illness.
Buspirone has also been successfully used for the prophylactic treatment of migraine and alcoholism in individuals with comorbid anxiety disorders, as well as for the treatment of anxious depression, anxiety, and agitation in patients with traumatic brain injury [5, 6].
The direct antidepressant effect of buspirone, independent of its anxiolytic effect, has also been demonstrated. It may be due to the fact that the sensitivity of 5-HT1A autoreceptors is increased in depression, while the properties of postsynaptic 5-HT1A and 5-HT2A receptors do not change in untreated patients with depression.
Data on the effectiveness of buspirone in obsessive-compulsive disorder are contradictory, but some studies show a positive effect of the drug, especially when combined with other psychopharmacological drugs, primarily antidepressants. An open-label study showed that adding buspirone (at a dose of 30-90 mg/day) to selective serotonin reuptake inhibitors (SSRIs) increased the effectiveness of treatment of body dysmorphic disorder in almost half of patients, mainly in those who had partial response to serotonergic antidepressants [ 7, 8].
Buspirone can be considered as an alternative to antidepressants in the treatment of social phobia. The effect of buspirone on social phobia was demonstrated in a placebo-controlled study. When added to SSRIs, buspirone can correct some of their side effects. For example, it has been shown that at a dose of 15-60 mg/day it can reduce sexual dysfunction and bruxism [8].
Anti-aggressive effect of buspirone
Special mention should be made of the anti-aggressive effect of buspirone in cases of agitation and aggressive actions in patients with dementia, attention deficit hyperactivity disorder, and traumatic brain injury [8]. At the same time, the effect of buspirone at a dose of 15-60 mg/day was noted in relation to both verbal (60%) and physical (90%) aggression [9-12].
Effect of buspirone on cognitive function
Data on the effect of buspirone on cognitive functions are contradictory; some studies showed a moderate positive effect on regulatory functions, while others showed no obvious effect [13]. In any case, unlike benzodiazepines and sedatives, buspirone does not have a negative effect on cognitive function, which distinguishes it from other drugs used to correct anxiety disorders [14].
Use of buspirone for the treatment of dependence syndrome
Due to its dopaminergic action, buspirone can be used to treat addiction syndrome. This quality was originally discovered in relation to cocaine addiction. It has been experimentally shown that intramuscular administration of buspirone blocks D2 and D3 receptors, while when administered orally, buspirone more selectively blocks D3 receptors, occupying more than 80% of the receptors. Thus, higher doses may be required to treat addiction—2 to 3 times higher than to treat anxiety (up to a maximum of 60 mg). Previous studies indicate that these doses are safe and well tolerated [15]. Correction of withdrawal anxiety under the influence of buspirone can also contribute to the treatment of alcohol and tobacco addiction [16–18].
Use of buspirone for extrapyramidal disorders
Experimental and clinical studies suggest that buspirone may be effective in treating tardive dyskinesia. Tardive dyskinesia is characterized by involuntary movements involving the muscles of the head, limbs, or trunk. It usually occurs during long-term therapy with antipsychotics, often manifesting itself or intensifying after their withdrawal. Tardive dyskinesia is usually resistant to various treatments. Although the evidence base for buspirone for tardive dyskinesia is weak, it may be an alternative to other drugs (particularly dopaminergic drugs) with dangerous side effects. The mechanism of action of buspirone in tardive dyskinesia is unclear [19, 20].
Buspirone may also be effective in patients with Parkinson's disease suffering from dyskinesias during long-term levodopa therapy. The mechanism of action of the drug is not clear enough in this case either, but the therapeutic effect depends on the dose. In recent years, it has been shown using pathomorphological and imaging methods that the serotonergic system is involved in the pathological process in Parkinson's disease, in particular in the pathogenesis of a number of non-motor symptoms, as well as drug-induced dyskinesias. Because of this, drugs acting on the serotonergic system can be effective against dyskinesias and non-motor symptoms such as depression, chronic fatigue, and psychotic disorders [21].
It has already been mentioned that 5-HT1A receptor agonists regulate the striatal concentration of dopamine formed from exogenous levodopa, due to which buspirone can attenuate drug-induced dyskinesias (“peak dose”) in Parkinson’s disease.
A clinical study [22] showed that sequential use of the drug for 3 days (at a dose of 15-30 mg/day), but not a single dose of the drug at a dose of 10 and 20 mg, led to a 20% decrease in dyskinesias (without an increase in parkinsonism symptoms ). In another study, 3 weeks of buspirone 20 mg/day reduced the severity of drug-induced dyskinesias by 71% without any negative effect on parkinsonian symptoms. Thus, buspirone can be considered as a potentially effective strategy in the correction of drug-induced dyskinesias.
These clinical data were confirmed experimentally - at a dose of 2 mg/kg, buspirone weakened violent movements by 45% in mice with an experimental model of dopaminergic dyskinesia. Administration of buspirone to rats at a dose of 0.25-2.5 mg/kg 30 minutes before levodopa reduced dyskinesias and improved locomotor activity. In an experiment, buspirone reduced catalepsy in rats induced by 6-OHDA and haloperidol.
The effectiveness of buspirone has also been shown for dyskinesias that occur after transplantation of fetal midbrain tissue. It is assumed that transplantation dyskinesias are associated with serotonergic neuromediation [23]. Correction of dyskinesias is more effective with the administration of a high dose of 5-HT1A agonist, which more completely blocks the release of the transmitter. Dopaminergic reinnervation after transplantation causes persistent dyskinesias due to the uncontrolled release of dopamine caused by serotonin. The release of dopamine occurs with less intensity than with “peak dose” dyskinesia. Accordingly, the effect in this situation is more pronounced with systemic administration of lower doses of 5-HT1A agonists [22, 23].
Buspirone may be effective in hereditary spinocerebellar ataxias, which is explained by the pronounced serotonergic innervation of the cerebellum [24]. It is believed that this effect may also be associated with an effect on noradrenergic pathways. This assumption has been supported by several studies showing that buspirone reduces mild to moderate cerebellar ataxia by 37%. The positive effect of buspirone on the severity of ataxia was confirmed in a small placebo-controlled study [25, 26].
Practical aspects of the use of buspirone (spitomin)
The main indications for the use of buspirone (spitomin) registered in the Russian Federation are generalized anxiety disorder (GAD), panic disorder, autonomic dysfunction syndrome, alcohol withdrawal syndrome (as an auxiliary therapy), depressive disorders (as an auxiliary therapy, but not prescribed for monotherapy of depression ). The literature describes the use of buspirone for various anxiety conditions, tobacco withdrawal, depression, as well as autism, obsessive-compulsive and premenstrual syndromes (in which the drug acts as an adjuvant). The mechanism of action allows its use for the treatment of resistant depression (in combination with an antidepressant) [27].
The therapeutic (anxiolytic) effect develops gradually, manifests itself after 7-14 days and reaches a maximum after 4 weeks.
The goal of treatment for mood disorders may be to achieve complete remission or, at a minimum, a reduction in symptoms, and, if possible, to prevent possible relapses. For chronic anxiety disorders, long-term maintenance therapy with buspirone may be required for long-term symptom control.
An important advantage of buspirone is that, unlike such classical anxiolytics as benzodiazepines, it does not have a negative effect on psychomotor functions, does not cause tolerance, drug dependence and withdrawal symptoms, and does not potentiate the effect of alcohol. However, alcohol consumption should be avoided during treatment with buspirone [28].
The absence of a therapeutic effect within 6-8 weeks requires an increase in the dose, but in some cases indicates resistance to the drug. If there is no effect, the drug is usually replaced with another drug (benzodiazepine or antidepressant). If the effect is partial, an antidepressant, sedative or hypnotic (for insomnia) can be added to enhance its effect. Buspirone is especially often used in combination with an SSRI or a selective serotonin norepinephrine reuptake inhibitor (SNRI) [29].
Use in persons under 18 years of age is contraindicated, according to the instructions for buspirone in force in the Russian Federation. No efficacy studies have been conducted in children and adolescents aged 6 to 18 years for anxiety disorders. Pregnancy and breastfeeding are also contraindications, although there is no direct evidence of danger.
Buspirone is usually well tolerated. Side effects, if observed, usually occur early in the course of treatment and then disappear despite continued use of the drug. In some cases, a dose reduction is necessary. As a side effect, the drug can cause dizziness, headache, weakness, sleep disturbance, decreased attention, extrapyramidal disorders (very rare), confusion, nausea, dry mouth, diarrhea, vomiting, constipation, weight loss, weight gain, myalgia, muscle spasms, rash, sweating, paresthesia. In case of overdose, vomiting, dizziness, miosis, and depression of consciousness are possible. The drug is combined with caution with antipsychotics, cardiac glycosides, antihypertensive and antidiabetic drugs, and oral contraceptives. Interaction with MAO inhibitors can lead to serotonin syndrome or hypertensive crisis with more limited symptoms; therefore, the simultaneous use of buspirone and MAO inhibitors is contraindicated in the instructions for medical use.
In the Russian Federation, the drug is presented in the form of divisible tablets of 10 mg. The initial dose is 5 mg/day, if necessary, it is increased by 5 mg every 5 days. The average daily dose is 15 mg. The maximum single dose is 30 mg, the maximum daily dose is 60 mg. The daily dose is usually divided into 2-3 doses. The advantages of the drug include safety, absence of dependence and withdrawal syndrome, sexual dysfunction and weight gain. Moreover, buspirone is able to attenuate sexual dysfunction caused by generalized anxiety and serotonergic antidepressants [28, 30].
The peculiarities of the drug include the gradual onset of the full clinical effect (within 4 weeks), while benzodiazepines act more quickly.
Buspirone is metabolized primarily by the microsomal enzyme CYP450 3A4. T½ is approximately 2-3 hours. Particular caution should be observed when combined with CYP450 3A4 inhibitors (for example, diltiazem, verapamil, itraconazole, erythromycin), which can reduce the clearance of buspirone and increase its level in the blood. You should also avoid drinking large amounts of grapefruit and grapefruit juice at the same time. The dose of buspirone should also be reduced when using HIV protease inhibitors or ketoconazole. Inducers of CYP450 3A4 (eg carbamazepine and rifampicin), on the contrary, may increase the clearance of buspirone. Buspirone increases blood levels of nordiazepam, the active metabolite of diazepam, which can cause dizziness, headache, and nausea.
For renal and liver failure of mild to moderate severity, liver cirrhosis, heart failure, and in the elderly, the drug is prescribed in lower doses. When discontinuing the drug, a gradual dose reduction is usually not necessary. In case of severe renal and liver failure, uncontrolled epilepsy, glaucoma, myasthenia gravis, the drug is contraindicated.
Thus, buspirone, with its unique neurotransmitter effects, significantly expands treatment options for a wide range of mental and neurological disorders - from anxiety disorders to dyskinesia in Parkinson's disease and ataxia. The relative safety of the drug makes its use in clinical practice very promising.
