We are continuing our conversation on the medications classified as "anxiolytics" in the treatment of anxiety disorders and other conditions. Today we will discuss buspirone.
Today's content level: Intermediate
INTRODUCTION AND MECHANISM OF ACTION
•Buspirone = Buspar
•Buspirone is considered a non-benzodiazepine anxiolytic that is commonly used in anxiety disorders and for other indications such as augmentation of antidepressants.
•Buspirone is not considered as effective as other agents, and so it is often used as a second-line agent in combination with another medication such as an SSRI or SNRI.
The major mechanisms of action of buspirone include:
Partial agonist at serotonin (5HT-1A) receptors (postsynaptic receptors in the hippocampus and cortex).
Full agonist at serotonin (5HT-1A) receptors (presynaptic inhibitor auto-receptors)
Weak antagonist at presynaptic dopamine (D1-D4) receptors, however this relationship is complex and at a lower dose range can actually lead to increased dopamine levels in the central nervous system.
Partial agonist at alpha-1 receptors.
No activity on GABA receptors.
It takes weeks to see full benefit (some studies show 3-6 weeks). Much slower onset compared to benzodiazepines.
Half-life is 2-11 hours, so it requires dosing 2-3 times a day for full effect.
Metabolized by cytochrome P450 3A4.
FDA approved indications:
Anxiety Disorders: Received FDA approval based on studies for the treatment of anxiety disorders whose diagnosis "roughly corresponds to" generalized anxiety disorder in DSM-3. Used as second-line agent for GAD, since studies and clinical experience show it is likely inferior to benzodiazepines, SSRIs/SNRIs, pregabalin, and possibly even antihistamines although this is debated. 1 Commonly used to augment SSRI/SNRI for anxiety disorders or for maintenance treatment. Can be useful to treat anxiety in patients with alcohol use disorder as it has low potential for abuse/addiction and it does not potentiate the CNS depression of alcohol. Some evidence that it may reduce aggression and hostility in anxiety better than benzodiazepines but is significantly less effective in managing somatic symptoms of anxiety.
Other off-label indications:
Depression and mixed anxiety/depression: Buspirone can be used for augmentation of antidepressants (ex: SSRI or SNRI) in treatment resistant depression, and was included in the STAR*D trials for this purpose. Has been used as monotherapy for MDD and mixed anxiety/depression, but evidence is limited and monotherapy is not recommended.
Sexual dysfunction: Commonly used to treat sexual dysfunction caused by antidepressants (SSRIs, SNRIs, TCAs, etc.) or caused by the depression/anxiety itself. In particular, it has been found to help with decreased libido and anorgasmia. Effective in one study for citalopram or paroxetine induced sexual dysfunction but ineffective in another study with fluoxetine. 2 Proposed mechanism is through inhibition of 5HT2 and dopamine (D2) agonism.
Bruxism: Bruxism = teeth grinding. Some medications, including antidepressants and antipsychotics, can lead to drug-induced bruxism. There is evidence that buspirone can be an effective treatment. 3
Experimental: Limited or mixed results available for use in ADHD, hostility/aggression, and use in autism spectrum disorder for restricted/repetitive behaviors and irritability.
Common side effects include:
Nausea -> more likely if timing of dosing is inconsistent or in relation to food.
Sedation -> not common but also not unusual. Risk increases at higher doses but is usually mild/moderate.
Restlessness/Akasthisia -> (dopamine blockade)
Unlike most antidepressants (SSRIs, SNRIs, TCAs, MAOIs, etc) there are little to no sexual dysfunction, weight gain, or discontinuation syndrome.
Serious side effects include:
Serotonin syndrome: Rare but has been seen, especially in high doses or drug reaction.
Abuse/Dependence: Does not cause tolerance, dependence, or withdrawal. It also does not potentiate the sedative effects of alcohol, barbiturates, and benzodiazepines (does not act on GABA receptors).
Overdose: Symptoms include sedation, dizziness, nausea, vomiting, and constricted pupils. No evidence for significant lethality in overdose. No deaths have been reported in monotherapy overdose.
Great work today. In our next post we will discuss gabapentin and pregabalin.
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