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One of my favorite medicines that I never bothered to prescribe is BuSpar. Buspirone, the generic, is an oddball. It might not do much. It's got data and clinical trials that it does something. It never seems to catch on in clinical practice. It's the kind of thing you offer as an option. According to the FDA:
BuSpar is indicated for the management of anxiety disorders or the short-term relief of the symptoms of anxiety.
For reasons that are not clear to me, the FDA goes on to opine on the stress of ordinary life in the very following sentence…
Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
When it comes to buspirone as “another option” for anxiety, it’s rarely the belle you take to the ball. Every time psychiatrists do, they are disappointed. Your patients are disappointed. And you learn that it won't do anything useful, so you don't bother anymore. I still am not sure if it’s because benzos, like Xanax or Klonopin, generate positive feedback for psychiatrists from their patients due to their rapid onset… or what? This article is my attempt to figure this out for myself.
My favorite academic article title, perhaps of all time, was presented to your author by Google Scholar on the advent of preparing this article. It is…wait for it…
“You can get a couple of ramen noodle packs for a BusparⓇ“: A qualitative examination of southern jails' medication access, policy, and procedures.
This article, despite the amazing title, isn't really about Buspar specifically, but I will point out that a copay is charged in jails to prisoners for their medicines, which is not my favorite fact.
Buspar is, theoretically, a medicine for anxiety. While writing this series of articles, I have developed a combination of “oh, that’s cute-feeling” as an emotional response when reading the introduction to an article about medicines like this one. Here is one such typical nonsense-y introduction:
Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely1 complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors.2
azaspiro…that sounds like medication! I’m a psychiatrist. I am also an award-winning educator among the top 10 MCAT instructors in America— 2 years running—specializing in teaching organic chemistry. I HAVE NO IDEA HOW TO BREAKDOWN THAT WORD.
And if I’m lost, I am guessing I am not alone… moving on. It’s FDA approval letter gets a bit more into the weeds:
BuSpar® (buspirone hydrochloride tablets, USP) is an anti-anxiety agent that is not chemically or pharmacologically related to benzodiazepines, barbiturates, or other sedative/anxiolytic drugs.
Buspirone hydrochloride is a white crystalline, water-soluble compound with a molecular weight of 422.0. Chemically, buspirone hydrochloride is 8-[4-[4-(2-pyrimidinyl)-1piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dionemonohydrochloride.
Buspirone was initially developed as an antipsychotic compound because it also has a binding affinity for Dopamine D2 receptors, which is a quality in keeping with all historical antipsychotic drugs.
Large-scale trials have confirmed that buspirone, in samples of patients who met inclusion criteria for anxiety studies, is non-inferior to benzodiazepines:
In comparative trials, patients receiving buspirone had reductions in Hamilton Anxiety Rating Scale (HAM-A) total scores ranging from 37 to 60%. By comparison, those receiving benzodiazepines had HAM-A total score reductions of 29 to 69%. Buspirone usually significantly reduces HAM-A total scores within 1 to 2 weeks of treatment initiation.3
This isn’t that different from the FDA labeling, which is very specifically for GAD:
The efficacy of BuSpar has been demonstrated in controlled clinical trials of outpatients whose diagnosis roughly corresponds to Generalized Anxiety Disorder (GAD). Many of the patients enrolled in these studies also had coexisting depressive symptoms, and BuSpar relieved anxiety in the presence of these coexisting depressive symptoms.
The data from meta-analysis back up this efficacy— buspar is better(!) than placebo:
Overall, patients treated with buspirone demonstrated significant (p < or = 0.001) improvement over baseline in total HAM-A scores compared to patients who received a placebo. Buspirone also produced significant (p < or = 0.001) global improvement compared to placebo as assessed by the attending physician.4
Large-scale reviews demonstrate that buspirone is less sedating and side-effect ridden and just as—but not more—effective than SSRIs, Benzos (BZD), and SNRIs:
A systematic review…report showed that buspirone resulted in less drowsiness, fatigue, nervousness, depression, insomnia, and sleep problems than BZD. BZD, however, resulted in less nausea and dizziness than buspirone.
However, patients stop taking buspirone (a.k.a. drop out) more often than benzos because Duh.5
When I finally drilled down into the comparative effect sizes data, I found some support for the contention I walked into this article with—that buspirone doesn’t do much. Readers of this daily publication, which is too much to keep up with for anyone, will recall that Effect Size is a measure of “how much of a big deal a drug is” beyond simply documenting its “difference by some amount.” The Effect Size Breakdown:
Pregabalin: 0.506
Antihistamines: 0.45
SNRI (like Effexor): 0.42
Benzodiazapines: 0.38,
Buspirone: 0.17
And “homeopathic complementary medicines”: -0.317
Using the Muir-Skee Lo EQE, if buspirone were as medicine for height, it would add 0.45 inches. It works; it’s just not that big of a deal.
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What is the difference between complex and extremely complex?
Jann, M. W. (1988). Buspirone: an update on a unique anxiolytic agent. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 8(2), 100-116.
Fulton, Bret, and Rex N. Brogden. "Buspirone: an updated review of its clinical pharmacology and therapeutic applications." Cns Drugs 7 (1997): 68-88.
Gammans RE, Stringfellow JC, Hvizdos AJ, Seidehamel RJ, Cohn JB, Wilcox CS, Fabre LF, Pecknold JC, Smith WT, Rickels K. Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies. Neuropsychobiology. 1992;25(4):193-201. doi: 10.1159/000118837. PMID: 1454160.
A Cochrane review showed that dropout rates were significantly in favour of BZD over buspirone (RR: 1.24, 95% CI 1.01, 1.52, p=0.04).5 No significant differences were found between the number that dropped out on buspirone versus venlafaxine XR 75 mg or 150 mg.5 Patients on buspirone reported less fatigue, depression, sleepiness, sleep problems and dry mouth compared with BZD recipients. BZD users reported less nausea and dizziness compared with buspirone users.
I’m sure my guest author
will be thrilled to see pregabalin at the top of the list….Hidalgo RB, Tupler LA, Davidson JR. An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol. 2007 Nov;21(8):864-72. doi: 10.1177/0269881107076996. PMID: 17984162.
I am indeed as ecstatic as is possible to be for a number associated with a medication. On the other hand, I had a rare and severe reaction to number 5 on the leaderboard. So, you win some , you lose some...
Do we have a lavender essential oil vs Buspirone RCT? We need one.