Anti-anxiety effect guaranteeing safety of buspirone

Anxiety disorder is one of the most common mental health disorders in the elderly. According to the National Health Insurance Corporation data, the number of patients with anxiety disorders increased 1.3 times in 2013 compared to 2008, from 398,000 to 522,000. In particular, in the analysis by age, the prevalence rate per 100,000 people was 1,490 in their 50s, 2,147 in their 60s, and 3051 in their 70s, showing an increasing trend with age. Unlike normal anxiety, general anxiety disorder can be divided into the manifestation of cognitive, behavioral, and physiological symptoms such as phobias, palpitations, and hyperventilation. However, in the case of elderly patients, the symptoms of anxiety disorder are not clear, and the risk of anxiety disorders is higher in the elderly population because it can be caused by various causes, such as the morbidity of various chronic diseases such as cardiovascular disease, and socioeconomic environment.

Anxiety Disorder Treatment Strategies
The diagnosis of anxiety disorder was summarized after DSM-IV, and it was also reflected in the Korean-style generalized anxiety disorder drug treatment algorithm announced in 2009. In the algorithm, benzodiazepine anti-anxiety drugs, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), antidepressants such as mirtazapine, anticonvulsants such as pregabalin, and antihistamines such as hydroxyzine are used for the treatment of generalized anxiety disorder. SSRIs, SNRIs, and buspirone were recommended as first-line treatment while atypical antipsychotics such as antipsychotics and quetiapine are being used.

Among them, as of 2009, the US Food and Drug Administration (FDA) approved paroxetine and escitalopram for SSRI, venlafaxine XR for SNRI, alprazolam, lorazepam, diazepam, and azipyrone buspirone for anxiety disorders. recommended as a drug.

Harm of benzodiazepines
While various drugs are being proposed as therapeutic drugs, benzodiazepines, a representative anti-anxiety drug, are caught in a number of adverse events. While dependence and withdrawal symptoms, increased risk of falls and fractures, interaction with alcohol, abnormal exercise capacity, high sedation effect, and death have already been reported as adverse events, various side effects have been reported in the elderly aged 65 years or older.

Recently, the effect on cognitive function and increased risk of dementia has also been discussed. In a 2014 study that analyzed 7184 patients with Alzheimer’s disease over the age of 65 in Canada, the risk of developing Alzheimer’s disease was up to 51% in the group taking benzodiazepines. The longer the duration of use, the higher the risk. This study drew attention in that it presented consistent results with the study published in 2012. In a 2012 study, among elderly patients aged 65 years and older, the risk of dementia was 50% higher in the group taking benzodiazepines for a long time.

Conversely, a study published in May of this year analyzed elderly patients enrolled in the Alzheimer’s Disease Neuroimaging Initiatives, and as a result, there was no risk of dementia or cognitive impairment, such as cognitive decline or increased beta-amyloid protein, in the group taking benzodiazepines. However, some are still raising awareness, saying that although this study shows that benzodiazepines do not have a “direct link” to cognitive function, “indirect effects” cannot be ruled out.

Buspirone secured safety
In this situation, interest is being drawn on buspirone, a non-benzodiazepine class. Buspirone acts entirely on the 5-HT1A receptor at the front of the synapse and partially acts on the 5-HT1A receptor at the back of the synapse to normalize the activity of serotonin. Buspirone, an azipyrone drug, is considered a drug that can compensate for the safety problems presented by benzodiazepines based on various evidences.

In a study comparing diazepam, a benzodiazepine drug (British Journal of Psychiatry 1989; 154:529-534), at 14 weeks of comparison, anxiety symptoms were controlled without withdrawal symptoms, and a study evaluating the effect on driving ability ( Journal of Clinical Psychopharmacology 1992;12:86-95) also showed anti-anxiety effects compared to diazepam without lowering driving ability. In addition, the sedative effect is not greater than that of benzodiazepines and placebo, so it is well tolerated (Am J Med 1986;80:17-21).

Consistent management effect
Buspirone is approved for the treatment of general and persistent anxiety disorders and for short-term relief of anxiety symptoms such as motor tension, autonomic nervous system hypersensitivity, and alertness. As a strategy of administering 20 to 30 mg three times a day, 5 mg, 10 mg, and 15 mg doses are on the market. The guidelines recommend a starting dose of 15 mg per day, and if necessary, it can be increased by 5 mg per day at intervals of 2-3 days. However, the daily dose cannot exceed 60 mg.

In an open-label, multinational, multicenter clinical trial involving 852 patients with generalized anxiety disorder, the effect of buspirone 15-75 mg/day was evaluated. As a result, the HAM-A scale score compared to the baseline was 10.6 points at 1 to 3 months, 4 A decrease of 14.9 points at ~6 months and 16.4 points at 6 months or longer showed a significant improvement in anxiety disorders. The responses of patients and doctors about whether symptoms improved or not consistently increased over time.

In a double-blind, multicenter, placebo-controlled study conducted for 4 weeks, the mean HAM-A score was also significantly decreased as a result of comparing the buspirone 10-60 mg/day group (234 patients) and the placebo group (225 patients). Anger and tension were also relieved.

On the other hand, in a small but double-blind study of 94 patients compared to benzodiazepine alprazolam and placebo for 6 weeks, both drugs relieved anxiety disorder scales to a similar extent at 6 weeks compared to placebo.