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Buspar (Buspirone) vs. Xanax (Alprazolam)

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Buspar and Xanax are two anxiolytic medications most frequently administered for the management of anxiety.  Buspar (buspirone) is medically approved by the U.S. FDA for the treatment of anxiety disorders (short-term and long-term) and acute anxiety – and Xanax (alprazolam) is medically approved by the U.S. FDA for the treatment of anxiety disorders and panic disorder.

Chemists at Mead Johnson (a company acquired by Bristol-Myers Squibb) are credited for the synthesis of buspirone in 1968 (whereafter it was patented in 1975) – and chemists at Upjohn Laboratories (a company acquired by Pfizer) are known to have synthesized alprazolam.  Buspar initially became available in 1986 within the United States as a pharmaceutical drug – approximately 5 years after Xanax which hit the market in 1981.

Buspar (Buspirone) vs. Xanax (Alprazolam)

Documented below are general attributes of Buspar and Xanax in the format of a comparative chart.  The chart highlights clear similarities and differences between Buspar and Xanax.  In the event that you have further questions regarding specific similarities and/or differences between these anxiolytic medications, it is recommended to consult a pharmacist and/or medical doctor.

BusparXanax
IngredientBuspironeAlprazolam
Drug classificationAzapironeTriazolobenzodiazepine
Approved medical usesGeneralized anxiety disorder. Acute anxiety.Generalized anxiety disorder. Panic disorder.
Off-label usesMajor depressive disorder. Sexual dysfunction. Cerebellar ataxia. ADHD.Chemotherapy-induced nausea and vomiting. Insomnia. Agitation. Premenstrual dysphoric disorder.
Bioavailability~3.9% (oral)~90% (oral)
FormatsTablet.Tablet. Extended-release (XR or ER) pill. Oral disintegrating tablet. Oral solution.
Dosages5 mg, 7.5 mg, 10 mg, 15 mg, 30 mg Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Oral disintegrating tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Extended-release (XR) pills: 0.5 mg, 1 mg, 2 mg, 3 mg

Oral solution: 30 ml 1 mg/ml
ManufacturerBristol-Myers Squibb (Mead Johnson)Pfizer Inc. (Upjohn)
Legal statusPrescription (Rx)-only (U.S.)Schedule IV (U.S.)
Mechanism of actionPresynaptic 5-HT1A full agonist.

Postsynaptic 5-HT1A partial agonist.

Oxytocin releaser.

5-HT2B agonist.

Modulates serotonin.

Increases dopamine.

Increases norepinephrine.

Enhances activity in the locus coeruleus.

May reduce oxidative stress and inflammation.

HPA-axis modulator.		GABAA receptor positive allosteric modulator (PAM).

Suppresses activity within the HPA (hypothalamic-pituitary-adrenal) axis.

Increases extracellular D1 and D2 dopamine concentrations in the striatum.
Generic version (?)Yes.Yes.
Half-Life2 to 11 hours (~2.8 hours)9 to 16 hours (~12 hours)
Common side effectsDizziness. Nausea. Headache. Nervousness. Lightheadedness. Excitement.Drowsiness. Lightheadedness. Dry mouth. Depression. Headache. Constipation. Diarrhea.
Date approved19861981
Duration of effect6 to 8 hoursStandard: ~5 hours

Extended-release: ~11 hours
MetabolismHepatic: CYP3A4.Hepatic: CYP3A4.
Onset of action30 to 60 minutes20 to 40 minutes

Buspar vs. Xanax: What are some notable differences?

General differences between Buspar and Xanax include: drug classification; off-label medical uses; available formats; mechanism of action; elimination half-life, and duration of effect.  Buspar is classified as an azapirone anxiolytic based on its core chemical structure containing azaspirodecanedione and pyrimidinylpiperazine connected via a butyl chain.

Xanax is considered a triazolobenzodiazepine based on its core chemical structure containing a benzene ring fused to a diazepine ring with an additional triazole ring (relative to standard non-triazolo benzodiazepines).  Medically, Buspar and Xanax are each frequently utilized to treat anxiety disorders.

Technically, Buspar has received FDA approval to treat anxiety disorders and acute anxiety – whereas Xanax has received FDA approval to treat anxiety disorders and panic disorder.  Though the respective approved medical uses of Buspar and Xanax are nearly identical, there are significant differences in the off-label uses for each medication.

As an off-label intervention, Buspar is sometimes administered to treat major depressive disorder, sexual dysfunction (e.g. hypoactive sexual desire disorder), cerebellar ataxia, and attention-deficit/hyperactivity disorder (ADHD).  Comparatively, Xanax is sometimes administered off-label to treat chemotherapy-related nausea and vomiting, insomnia, agitation, and premenstrual dysphoric disorder.

Although Buspar and Xanax are manufactured in tablet format, only Xanax is available in several alternative formats including: oral solution, orally-disintegrating tablet (ODT), and extended-release (ER or XR) tablet.  Additionally, while Buspar and Xanax each take effect relatively quickly following administration, Xanax kicks in slightly quicker than Buspar (20 to 40 minutes vs. 30 to 60 minutes).

Furthermore, the average onset of therapeutic action (i.e. anxiety relief) among Buspar users is 2 to 4 weeks – whereas the average onset of therapeutic action among Xanax users is 1 to 14 days.  In other words, persons administering Xanax for anxiety will probably experience a faster reduction in anxious symptoms than individuals using Buspar.

The primary mechanism of action also differs significantly between Buspar and Xanax.  Buspar functions chiefly as a 5-HT1A receptor modulator – whereas Xanax functions chiefly as a GABAA receptor positive allosteric modulator (PAM).  Disparities in respective mechanisms of action likely account for differences in off-label uses, side effects, and scheduling (standard prescription vs. Schedule IV controlled substance).

The bioavailability of orally-administered Buspar is extremely low (~3.9%) with an elimination half-life range of 2 to 11 hours (~2.8 hours) – whereas the bioavailability of orally-administered Xanax is relatively high (~90%) with an elimination half-life range of 9 to 16 hours (~12 hours).  Routes of metabolism are similar between Buspar and Xanax and involve microsomal oxidation within the liver facilitated by the CYP3A4 enzyme.

Finally, there are some similarities and differences in specific side effects associated with Buspar and Xanax.  The most common side effects associated with Buspar include: dizziness, nausea, headache, nervousness, lightheadedness, and excitement – and the most common side effects associated with Xanax include: drowsiness, lightheadedness, dry mouth, depression, and headache.

Addiction & Abuse Potential

Although Buspar modulates a variety of neurotransmitters and receptors within the brain, it isn’t known to carry significant addiction and abuse potential – hence its availability as a standard prescription medication.  On the other hand, Xanax carries modest addiction and abuse potential whereby it may induce modest psychological and/or physical dependence in a subset of users – hence its regulation as “Schedule IV” controlled substance in the United States.

In fact, Xanax is documented as being the single most frequently abused/misused benzodiazepine on the market (likely in part due to its popularity).  Worth mentioning is that some research indicates that Xanax and related benzodiazepines are among the most addictive drugs in modern-day pharmaceutical circulation.

Individuals who deliberately misuse Xanax or administer it in ways that are inconsistent with medical instruction are thought to be at greatest risk of developing psychological and/or physical dependence.  The risk of developing psychological and/or physical dependence on Xanax is attributable to its mechanism of action involving GABA receptor modulation.

When administered, Xanax alters subunit activation of GABAA receptors to decrease firing of inhibitory interneurons located throughout the ventral tegmental area (VTA).  Decreased firing of inhibitory interneurons in the ventral tegmental area (VTA) causes a simultaneous reduction in firing of dopamine-secreting neurons – causing extracellular increases in dopamine.

Heightened concentrations of extracellular dopamine can generate a euphoriant (i.e. pleasurable) feeling in select users.  This euphoriant feeling combined with the relaxing (psychological and physical) anxiolytic effect of Xanax, and with its rapid onset of action, can lead to addiction and/or dependence in susceptible individuals.

Because Buspar does not induce a rapid euphoriant or reinforcing effect via activation of reward pathways, it is not considered a medication of abuse.  Although the abuse and addiction potential of Xanax is low if administered as medically instructed, it has reinforcing properties and significant potential for abuse and addiction when misused.

Approved medical uses

Buspar is approved by the FDA for medical use in the United States as a treatment for anxiety disorders and acute anxiety.  Xanax is approved by the FDA for medical use in the United States as a treatment for anxiety disorders and for the specific management of panic disorder.

Though Buspar and Xanax are both approved for the treatment of anxiety disorders, only Buspar has received official FDA approval as a treatment for acute anxiety (Xanax has not).  That said, unlike Buspar, only Xanax has received official FDA approval as a treatment for panic disorder.

Despite some minor discrepancies in the FDA approved indications for Buspar and Xanax, some medical professionals may consider these medications as being equally practical interventions for various types of anxiety (e.g. generalized anxiety, acute anxiety, etc.).  Still, worth noting is the fact that Buspar is deemed ineffective for panic disorder, a condition for which Xanax is effective.

Moreover, Buspar and Xanax are commonly utilized “off-label” to manage symptoms of medical conditions for which their FDA approval (as treatments) is lacking.  Buspar is occasionally administered “off-label” to treat: major depressive disorder (as an adjunct); sexual dysfunction; cerebellar ataxia; and attention-deficit/hyperactivity disorder (ADHD) – and Xanax is occasionally administered “off-label” to treat: chemotherapy-related nausea and vomiting; insomnia; agitation; and premenstrual dysphoric disorder.

Cost: Which is more expensive?

The cost of generic Buspar (buspirone) and Xanax (alprazolam) tablets should be similar at a majority of retailing pharmacies.  At the lowest dose (5 mg), a total of 60 generic Buspar tablets sell within the price range of $4 to $19 (on average) – whereas a total of 60 standard generic Xanax tablets at the lowest dose (0.25 mg) sell within the price range of $8 and $21 (on average).

Buspar cost

  • 5 mg Buspar tablets (generic): $4 to $19 (60 tablets)
  • 5 mg Buspar tablets (generic): $33 to $69 (60 tablets)
  • 10 mg Buspar tablets (generic): $4 to $21 (60 tablets)
  • 15 mg Buspar tablets (generic): $10 to $34 (60 tablets)
  • 30 mg Buspar tablets (generic): $16 to $106 (60 tablets)

Xanax cost

  • Xanax tablets (generic): $7 to $21 (60 tablets)
  • Xanax standard (brand): $245 to $800 (60 tablets)
  • Xanax ODT (orally disintegrating tablet): $29 to $183 (30 tablets)
  • Xanax XR or ER (extended release): $16 to $67 (30 tablets)
  • Xanax (oral solution): $47 to $103 (1 bottle – 30 ml of 1 mg/ml)

At the highest dosage (30 mg), a total of 60 generic Buspar tablets sell within the price range of $16 to $106 (on average).  At the highest dosage (20 mg), a total of 60 standard generic Xanax tablets sell within the price range of $10 to $21 (on average).

Reflecting upon the pricing of generic Buspar and Xanax tablets, it seems as though cost is relatively similar at most pharmacies – especially at lower doses.  That said, select pharmacies appear to sell the highest dosage of generic Buspar (30 mg) tablets at a significantly higher cost (e.g. $106) relative to the highest dosage of standard generic Xanax (2 mg) tablets (e.g. $21).

Unlike Xanax, Buspar is no longer sold in “brand name” format.  Xanax can still be attained in standard “brand name” format within the price range of $245 to $800 for 60 tablets.  Additionally, generic Xanax is sold in the format of: orally-disintegrating tablet (ODT) for $29 to $183 (30 tablets); extended-release tablet (XR or ER) for $16 to $67 (30 tablets); and oral solution for $47 to $103.

To recap: Generic Buspar (buspirone) and Xanax (alprazolam) tablets are similarly-priced at most pharmacies.  Brand name Buspar is no longer manufactured, but brand name Xanax can be attained at a high cost.  Alternative formats of generic Xanax (e.g. orally-disintegrating tablet, extended-release, oral solution) can be attained at a low-to-moderate cost.

Note: Understand that the cost of Buspar and Xanax may be subject to future change whereby average costs documented in this article are rendered inaccurate.  Furthermore, know that the cost of medications is commonly dose-dependent such that high doses tend to be more expensive than low doses.  Lastly, the cost of Buspar and Xanax likely varies among retailing pharmacies.

Dosage & Formats

Buspar and Xanax are each available in the format of immediate-release tablets (standard).  Buspar tablets are manufactured in dosage increments of: 5 mg, 7.5 mg, 10 mg, 15 mg, and 30 mg – and standard Xanax tablets are manufactured in dosage increments of: 0.25 mg, 0.5 mg, 1 mg, and 2 mg.

If solely comparing standard immediate-release formats of Buspar and Xanax, some individuals may prefer using Buspar as an anxiolytic based on (1) total number of available dosing increments (5 for Buspar vs. 4 for Xanax) and/or (2) longer duration of action (~6-8 hours for Buspar vs. ~4-6 hours for Xanax).  That said, the differences are relatively modest in terms of dosing increments and duration of action.

In addition to its availability as a standard immediate-release tablet, Xanax is available in several alternative formats such as: orally-disintegrating tablet (ODT); extended-release tablet (XR or ER); and oral solution.  Orally-disintegrating tablet (ODT) Xanax is manufactured in dosage increments of: 0.25 mg, 0.5 mg, 1 mg, and 2 mg; extended-release Xanax is manufactured in dosage increments of: 0.5 mg, 1 mg, 2 mg, and 3 mg; and oral solution Xanax is sold as 1 bottle (30 ml) of 1 mg/ml.

Because Xanax is available in a variety of formats and Buspar is solely available in a single format (standard immediate-release tablet), it’s reasonable to suspect that certain medical professionals and/or patients will prefer using Xanax instead of Buspar as an anxiolytic.  The orally-disintegrating tablet (ODT) format of Xanax may be more convenient to administer than standard Buspar because it dissolves within the mouth – there’s no need for swallowing (with a beverage).

Moreover, the extended-release (XR or ER) Xanax format exerts a longer duration of action (~10-12 hours) than Buspar (~6-8 hours) – meaning patients won’t need to administer extended-release Xanax as frequently as they would Buspar for the management of anxious symptoms. Considering the available dosages and formats of Buspar and Xanax (respectively), it seems as though dosing options are similar – but Xanax is advantageous in its variety of available formats.

Efficacy: Which medication is more effective?

After examining data from studies in which the therapeutic efficacy Buspar (buspirone) is directly compared to that of Xanax (alprazolam) as a treatment for generalized anxiety disorder (a condition for which each medication is medically-indicated), it appears as though there’s no substantial evidence to support the idea that one medication exhibits greater efficacy – relative to the other.

While there are data to suggest that Xanax is more effective than Buspar for treating panic disorder – this should be expected (as panic disorder is a condition for which Buspar is not medically-indicated).  For example, a study by Sheehan et al. (1993) compared the efficacy of high-dose buspirone (Buspar) to that of alprazolam (Xanax) in the treatment of panic disorder.

The study implemented a parallel-group, placebo-controlled, double-blind, flexible-dose design over an 8-week span in which 101 patients with panic disorder were assigned at random to receive either: buspirone (34 patients), alprazolam (34 patients), or a placebo (33 patients).

It was noted that 92 of 101 patients (~91%) completed at least 3 weeks of the trial (27 receiving buspirone; 34 receiving alprazolam; 31 receiving placebo) – and 85 patients (~84%) completed the entire 8-week trial (23 receiving buspirone; 33 receiving alprazolam; 29 receiving placebo).  The average doses administered among groups were as follows: ~26.5 mg/day buspirone and ~5.2 mg/day alprazolam.

Results indicated that recipients of alprazolam exhibited significant reductions in the occurrence of panic attacks and symptoms of panic disorder beginning within 1 week of administration and persisting throughout the entire 8-week trial.  However, neither buspirone recipients nor buspirone recipients exhibited significant reductions in the frequency or symptoms of panic disorder throughout the entire 8-week trial.

Though this study was relatively small-scale and conducted over a moderate term (8 weeks), it was well-designed and supports the idea that alprazolam is highly effective as a treatment for panic disorder – whereas buspirone is ineffective.  Still, it’s worth underscoring the fact that alprazolam is FDA approved as an intervention for panic disorder, yet Buspar is not.

Another different double-blind trial by Dimitriou, Parashos, and Giouzepas (1992) compared the respective efficacies of buspirone and alprazolam in the treatment of generalized anxiety disorder.  A total of 60 outpatients with generalized anxiety disorder were assigned to receive a placebo for 1 week, then randomized to receive either buspirone (15 mg/day) or alprazolam (1.5 mg/day) for 4 weeks.

After the 4-week treatment phase, the patients received a placebo for an additional 2 weeks.  It was noted that 13 patients in the buspirone group received dosage increases (to 25 mg/day) and 12 patients in the alprazolam group received dosage increases (to 2.5 mg/day).

Results of the trial suggested that both buspirone and alprazolam were equally efficacious in reducing symptoms of generalized anxiety disorder.  Despite the equal efficacy of medications in managing generalized anxiety disorder – authors noted that buspirone caused significantly fewer side effects and discontinuation symptoms.

Additionally, a study by Enkelmann (1991) sought to compare the effectiveness of buspirone with that of alprazolam in the treatment of generalized anxiety disorder.  A total of 94 outpatients with generalized anxiety disorder participated in this 6-week, double-blind, randomized, placebo-controlled trial.

Documentation of average daily doses throughout the trial revealed: ~18.7 mg/day buspirone and ~1.9 mg/day alprazolam.  A variety of measures (Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Physician’s Global Improvement Scale, et al.) reported that buspirone and alprazolam significantly reduced symptoms of anxiety relative to the placebo – over a 6-week span.

It was also stated that neither medication (buspirone vs. alprazolam) was more efficacious than the other in overall efficacy (i.e. significance of anxiety reduction).  That said, alprazolam delivered a significantly quicker onset of therapeutic effect (within the first week) – relative to buspirone which delivered a gradual onset of therapeutic effect (as evidenced by consistent symptomatic improvement throughout the trial among recipients).

One of the earliest studies comparing buspirone to alprazolam was conducted by Cohn and Wilcox (1986).  The researchers implemented a randomized, double-blinded design in which 60 patients with generalized anxiety disorder were assigned to receive either buspirone, alprazolam, or lorazepam – over a 4-week span.

It was noted that all 3 medications (buspirone, alprazolam, lorazepam) significantly reduced symptoms of anxiety – as evidenced by changes in scores on anxiety rating scales and physician evaluation – from pre-trial baseline.  None of the aforementioned medications were superior in efficacy relative to the others – supporting the idea that Buspar and Xanax are equally effective in treating generalized anxiety disorder.

If directly comparing the therapeutic efficacy of Buspar to Xanax for generalized anxiety disorder (a condition for which both medications have received FDA approval to treat) – data indicate that neither medication is more effective than the other.  That being said, evidence suggests that Xanax delivers a faster onset of therapeutic effect relative to Buspar (within ~1 week vs. 2 to 4 weeks, respectively).

Because Xanax kicks in faster than Buspar – some patients and/or medical professionals may consider a quicker onset of action as being an advantage in the domain of “efficacy.”  Still, once each medication has been given adequate time to take effect, there are no significant differences in therapeutic effectiveness between Buspar and Xanax among patients with generalized anxiety disorder.

When considering overall effectiveness as an anxiolytic, it’s reasonable to suggest that Xanax is probably a superior option to Buspar.  Not only does Xanax appear to deliver a significantly quicker onset of therapeutic effect than Buspar in the treatment of generalized anxiety disorder, but Xanax is highly effective for the treatment of panic disorder, a specific anxious condition for which Buspar is notoriously ineffective.

Mechanism of action

Although Buspar and Xanax are considered equally efficacious anxiolytics in the treatment of generalized anxiety disorder, their respective mechanisms of action (i.e. pharmacodynamics) differ significantly.  Buspar functions chiefly as a 5-HT1A receptor modulator whereby it acts as a full agonist at 5-HT1A presynaptic receptors (autoreceptors) and as a partial agonist at 5-HT1A postsynaptic receptors (heteroreceptors).

  • Buspar: 5-HT1A receptor modulator (Serotonin)
  • Xanax: GABA(A) receptor modulator (GABA)

The full agonism of Buspar upon 5-HT1A presynaptic autoreceptors inhibits the synthesis of serotonin and the firing rate of serotonin-secreting neurons and the partial agonism of Buspar upon 5-HT1A postsynaptic heteroreceptors is suggested to normalize preexisting irregularities in the neurotransmission of serotonin.  The serotonergic actions of Buspar via 5-HT1A receptors are suggested to generate its clinically significant anxiolytic effect.

Compared to Buspar, Xanax functions chiefly as a positive allosteric modulator (PAM) of GABA receptors, specifically, GABAA receptor subunits.  Modulation of GABAA receptor subunits [as is facilitated by Xanax] enhances the binding efficiency of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) to GABAA receptors.

Enhancement of GABA binding efficiency to GABAA receptors causes chloride ions (carrying negative charge) to accumulate within neurons and induce a state of hyperpolarization whereby the neuron’s internal content exhibits greater negative charge relative to its external content.  After the induction of hyperpolarization, neuronal activity becomes less responsive to excitatory stimulation and CNS activation decreases – yielding a clinically significant anxiolytic effect.

In addition to clear distinctions in respective primary mechanisms of action, Buspar and Xanax differ in hypothesized secondary neurochemical actions.  Hypothesized secondary neurochemical actions for Buspar include: DA2 receptor modulation; 5-HT2B agonism; oxytocin modulation; serotonin modulation; dopamine increaser; norepinephrine increaser; oxidative stress reducer; and inflammation reducer.

Hypothesized secondary neurochemical actions for Xanax include: voltage-gated ion channel modulation (calcium and/or sodium channels); dopamine receptor (D1 & D2) increaser (in the striatum); norepinephrine increaser; and serotonin increaser.  In summary, Buspar treats anxiety mostly through 5-HT1A receptors and the serotonin system – whereas Xanax treats anxiety mostly through GABAA receptors and the GABA system.

Metabolism & Half-Life

While there may be significant differences in respective mechanisms of action associated with Buspar and Xanax – their routes of metabolism are similar.  Each medication is metabolized primarily in the liver via the enzyme CYP3A4 (cytochrome P450 3A4).

Research suggests that Buspar undergoes: N-dealkylation to form 1-pyrimidinylpiperazine (1-PP); N-oxidation to form buspirone-N-oxide (Bu N-oxide); and hydroxylation to form 3′-hydroxybuspirone (3′-OH-Bu), 5-hydroxybuspirone (5-OH-Bu), and 6′-hydroxybuspirone (6′-OH-Bu).  To a significantly lesser extent than CYP3A4, enzymes such as CYP2D6 and CYP3A5 may contribute to Buspar metabolism.

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Hepatic metabolism of Xanax involves its biotransformation (via CYP3A4) to form water-soluble metabolites such as: alpha-OHALP (alpha-hydroxy alprazolam) and 4-OHALP (4-hydroxy alprazolam); the former being more bioactive than the latter.  Despite similarities between Buspar and Xanax in route of metabolism, the elimination half-life of each substance differs significantly.

On average, the elimination half-life of Buspar ranges from 2 to 11 hours (~2.8 hours) whereas the elimination half-life of Xanax ranges from 9 to 16 hours (~12 hours).  This means that Buspar is eliminated from systemic circulation in around ~15.4 hours following discontinuation and Xanax is eliminated from systemic circulation in around ~2.75 days following discontinuation.

Popularity

Buspar entered the pharmaceutical market in 1986 approximately 5 years after Xanax which entered the pharmaceutical market in 1981.  Because Xanax was available years before Buspar, and because there were likely more data substantiating the safety and efficacy of Xanax as an anxiolytic – it’s logical to surmise that Xanax was of greater popularity than Buspar throughout the 1980s and 1990s.

That said, there are no publicly-available data of pharmaceutical prescription rates in the 1980s and 1990s – making it difficult to know whether Xanax was definitively prescribed more frequently than Buspar (or vice-versa) in years when both medications were attainable.  Still, it is known that Xanax became available as a generic (alprazolam) before Buspar became available as a generic (buspirone).

According to data compiled by the ClinCalc DrugStats database, ~6.94 million prescriptions were filled for generic Buspar (buspirone hydrochloride) in 2015 – making it the 104th most-prescribed pharmaceutical medication in the United States.  Comparatively, the ClinCalc DrugStats database reported that over 27 million prescriptions were filled for generic Xanax (alprazolam) in 2015 – making it the top-prescribed anxiolytic and 23rd most-prescribed pharmaceutical medication in the United States.

Considering available data, it appears as though Xanax is a substantially more popular medication than Buspar.  The greater popularity of Xanax (relative to Buspar) may be related to: its faster onset of therapeutic action, its ability to treat all types of anxiety (including panic disorder), its availability in a variety of formats, the potency of its anxiolytic effect, and/or its appeal as a recreational drug.

Side Effects

The most common Buspar side effects (according to FDA Access Data) include: dizziness, nausea, headache, nervousness, lightheadedness, and excitement.  The most common Xanax side effects (according to FDA Access Data) include: drowsiness, lightheadedness, dry mouth, depression, headache, constipation, and diarrhea.

Comparing similarities in common side effects associated with Buspar and Xanax (based on FDA Access Data reports), it seems as though both medications frequently cause: headache and lightheadedness.  However, FDA Access Data suggests that Buspar may be more likely to cause dizziness, nervousness, and excitement as side effects (relative to Xanax) – and that Xanax may be more likely to cause drowsiness, dry mouth, depression, constipation, and diarrhea (relative to Buspar).

Based on the fact that Buspar and Xanax exhibit completely different primary mechanisms of action (5-HT1A receptor modulation vs. GABAA receptor modulation, respectively), differences in the rates of specific side effects should be expected.  In addition to FDA Access Data for each medication, differences in side effects and tolerability were reported in a subset of comparison studies.

For example, a 7-week double-blind study by Dimitriou, Parashos, and Giouzepas (1992) involving 60 patients with generalized anxiety disorder documented significantly fewer adverse effects among buspirone recipients – compared to alprazolam recipients.  In this study, the most common side effects among buspirone users were: nausea, dizziness and headache – whereas the most common side effects among alprazolam users were: poor concentration, drowsiness, fatigue, tremor, insomnia, and dry mouth.

A double-blind study by Barbee et al. (1991) compared the single-dose effect of buspirone, alprazolam, and a placebo – on memory function in 125 healthy, young adults.  While none of the interventions impaired visuomotor reaction time, alprazolam (1 mg) significantly impaired performance in various domains of memory function (as determined by a memory battery).

Another double-blind study by Hart, Colenda, and Hamer (1991) compared the cognitive side effects of buspirone (5 mg, t.i.d.) and alprazolam (5 mg, t.i.d.) in 60 elderly adults over a 2-week period.  Results indicated that while buspirone did not affect reaction time, vigilance, psychomotor speed, or memory function – alprazolam modestly impaired vigilance, psychomotor speed, and memory on the first day of treatment.

However, according to researchers, the cognitive impairment attributable to alprazolam ceased after the first day of treatment – suggesting that cognitive side effects associated with alprazolam are transient and/or extremely short-lived.

A 4-week double-blind study conducted by Cohn and Wilcox (1986) compared side effects of buspirone, alprazolam, and lorazepam in 60 patients with generalized anxiety disorder.  Patients receiving buspirone experienced significantly lower rates of drowsiness, lethargy, and/or fatigue than alprazolam recipients (16% vs. 60%) and lorazepam recipients (16% vs. 65%).

Although buspirone and alprazolam are equally efficacious in the treatment of generalized anxiety disorder, considering that buspirone may cause fewer unwanted side effects, some believe that it’s a superior intervention to alprazolam among patients with generalized anxiety.

Despite some evidence suggesting that buspirone may cause fewer unwanted side effects than alprazolam, other research suggests that the medications are equally tolerable.  For example, a 6-week double-blind, randomized, placebo-controlled trial by Enkelmann (1991) involving 94 patients with generalized anxiety disorder – noted that there were no clinically relevant differences in tolerability (side effects, vital signs, laboratory test results) among buspirone and alprazolam recipients.

Though no clinically-relevant differences in tolerability were found between buspirone and alprazolam in the trial by Enkelmann (1991), there were differences between medications in the specific types of common side effects that occurred.  Buspirone recipients were more likely to experience gastrointestinal side effects (e.g. appetite changes, abdominal complaints, etc.) whereas Xanax recipients were more likely to experience central nervous system side effects (e.g. drowsiness, sedation, etc.).

Considering side effect data associated with Buspar and Xanax, it appears as though both medications are equally well-tolerated for the treatment of anxiety disorders.  However, because Buspar is less likely than Xanax to cause side effects of drowsiness, sedation, and cognitive impairment (some of which may interfere with occupational productivity, coordination, motivation, etc.) – some patients and/or professionals may regard Buspar as advantageous over Xanax in the domain of tolerability.

Withdrawal severity

Discontinuation of Buspar or Xanax after frequent long-term administration may cause noticeable withdrawal symptoms.  Although the withdrawal symptoms resulting from Buspar cessation are often regarded as being insignificant or [perhaps incorrectly] suggested to be nonexistent by medical professionals, data from comparison studies indicate that Buspar withdrawal is generally less debilitating than Xanax withdrawal.

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A 7-week randomized controlled trial by Dimitriou, Parashos, and Giouzepas (1992) involving 60 outpatients with generalized anxiety disorder compared the severities and rates of discontinuation symptoms among buspirone recipients, alprazolam recipients, and placebo recipients – in a 2-week withdrawal phase. The most common symptoms of buspirone discontinuation were: nervousness and insomnia.

The most common symptoms of alprazolam discontinuation were: nervousness, insomnia, aches, pains, and sweating.  Authors of this study concluded that buspirone is superior to alprazolam in tolerability during withdrawal – based on the fact that buspirone causes fewer debilitating discontinuation symptoms.

It is understood that Xanax discontinuation can be dangerous among regular high-dose users such that seizures and death could result – this is not the case during Buspar discontinuation.  Moreover, even if Xanax is discontinued in accordance with medical instruction, former users prone to post-acute withdrawal syndrome (PAWS) whereby adverse withdrawal reactions might persist for months (or years) beyond the final date of discontinuation – this is less likely to occur among former Buspar users.

The neurochemical signature of Buspar withdrawal differs substantially from the neurochemical signature of Xanax withdrawal.  Among those who discontinue Buspar, abnormalities in 5-HT1A receptor activity and the neurotransmission of serotonin are likely culpable for withdrawal reactions – whereas among persons who discontinue Xanax, abnormalities in GABA receptor activity and the neurotransmission of GABA are likely culpable for withdrawal reactions.

Until the neurochemistry of a former Buspar or Xanax user is able to fully transition from a medication-adapted state to pre-medication homeostasis, withdrawal symptoms will persist.  It generally takes weeks and/or months for neurochemical receptor sites and neurotransmitter concentrations to normalize – and for discontinuation symptoms to cease.

Anyone attempting to discontinue Buspar or Xanax should work closely with a psychiatrist or medical doctor experienced with neuropsychiatric medication cessation.  Both Buspar and Xanax have extremely short elimination half-life ranges (2-11 hours vs. 9-16 hours, respectively) – meaning that both drugs exit the body quickly after cessation such that the former user’s neurochemistry isn’t given time to gradually readjust to functioning without the medication.

For this reason, a medical doctor may recommend transitioning to a similarly-acting agent with a longer half-life to help mitigate discontinuation symptoms of Buspar or Xanax.  For example, transitioning from Xanax to Valium is frequently recommended to minimize the severity of Xanax withdrawal.

Because Valium has an extremely long half-life, a patient can stabilize on Valium, conduct a gradual taper, and eventually stop using Valium without experiencing life-threatening symptoms that might’ve occurred following Xanax cessation.  In sum, there’s a paucity of evidence to support the idea that Buspar withdrawal exists and an abundance of evidence to support the idea that Xanax withdrawal exists.

If comparing Buspar and Xanax in the domain of withdrawal, most patients and medical professionals would regard Buspar as advantageous over Xanax.  Xanax discontinuation can be life-threatening, protracted, and debilitating – the same cannot be said for Buspar discontinuation.

Similarities (Recap): Buspar vs. Xanax

Outlined below are basic similarities associated with Buspar (buspirone) and Xanax (alprazolam).  There appear to be very few similarities between Buspar and Xanax aside from: average cost; effectiveness; medical uses; and route of metabolism.

  • Cost: In most cases, the price of generic Buspar (buspirone) tablets is similar to the price of generic Xanax (alprazolam) tablets.  At most pharmacies, 60 Buspar tablets can be attained within the price range of $4 to $33 (regardless of the dose) and 60 Xanax tablets can be attained within the price range of $7 to $21 (regardless of the dose).
  • Efficacy: If comparing the respective efficacies of Buspar and Xanax for the treatment of generalized anxiety disorder (the only medical condition for which each medication has received FDA approval), there are zero significant differences. Each medication has proven efficacious in large-scale, double-blind, randomized controlled trials as a treatment for generalized anxiety disorder – relative to a placebo.  Moreover, all comparison trials (Buspar vs. Xanax) are unanimous in reporting equal efficacy among patients with generalized anxiety disorder.
  • Generic availability: Buspar and Xanax became available for medical use (throughout the U.S.) in 1986 and 1981, respectively.  Because the patent for each medication has long expired, Buspar and Xanax are available in generic formats.  Generic Buspar is sold under the chemical name “buspirone” and generic Xanax is sold under the chemical name “alprazolam.”
  • Medical uses: Both Buspar and Xanax are medically indicated (i.e. have received FDA approval) as treatments for generalized anxiety disorder (GAD). Furthermore, Buspar and Xanax are commonly utilized to treat acute anxiety and as antidepressant adjuncts among patients with major depressive disorder plus comorbid anxiety.
  • Route of metabolism: The primary route by which Buspar and Xanax are metabolized is similar. The hepatic enzyme CYP3A4 (cytochrome P450 3A4) is chiefly responsible for facilitating the biotransformation of Buspar and Xanax into various metabolites.

Note:  If you know of additional noteworthy similarities between Buspar and Xanax, feel free to report them in the comments section.

Differences (Recap): Buspar vs. Xanax

Outlined below are basic differences between Buspar (buspirone) and Xanax (alprazolam).  It appears as though Buspar and Xanax differ in many aspects, including: abuse potential; classification; duration of effect; formatting; elimination half-life; legal status; mechanism of action; popularity; side effects; and withdrawal.

  • Abuse potential: Evidence suggests that Xanax is presently: one of the most frequently-abused pharmaceutical medications on the market and the most-abused benzodiazepine. The abuse and addiction potential of Xanax is attributable to its ability to rapidly induce relaxation (via GABA modulation) with concurrent rewarding effects (via dopamine secretion).  Because Buspar lacks the psychologically reinforcing and rewarding properties of Xanax – it is not considered a drug of abuse.
  • Brand name availability: The brand name version of Buspar was discontinued in 2015, whereas the brand name of Xanax is still available. While most consumers probably prefer generic formats for their lower cost – a subset of individuals may remain convinced that brand name medications are superior to generics.  Unfortunately, persons who prefer using brand name Buspar over generic buspirone no longer have the option.
  • Drug classification: Buspar is classified as an “azapirone” as a result of its chemical structure containing azaspirodecanedione with pyrimidinylpiperazine linked via a butyl chain. Xanax is classified as a “triazolobenzodiazepine” as a result of its chemical structure containing a benzene ring fused to a diazepine ring (with an additional triazole ring versus standard benzodiazepines).
  • Duration of action: The duration of effect for Buspar is estimated to range from 6 to 8 hours. The duration of effect for standard Xanax is estimated to range from 4 to 6 hours, however, the duration of effect for the extended-release Xanax is estimated to range from 10 to 12 hours.
  • Format variety: Buspar and Xanax are each manufactured as conventional immediate-release tablets. However, the immediate-release tablet is the only format in which Buspar has ever been available.  Furthermore, unlike Buspar, Xanax is available in additional formats such as: orally-disintegrating tablet (ODT), extended-release tablet (ER or XR), and oral solution.
  • Half-life: The elimination half-life of Buspar (2 to 11 hours) is generally significantly faster than the elimination half-life of Xanax (9 to 16 hours).  On average, the elimination half-life of Buspar is ~2.8 hours and the elimination half-life of Xanax is ~12 hours.
  • Legal status: From a legal perspective, Buspar is considered a prescription-only (Rx-only) substance – whereas Xanax is considered a “Schedule IV” controlled substance in the U.S. Refills for Buspar can be attained electronically without frequent medical checkups, but refills for Xanax cannot be attained without the consultation and signature of a medical doctor.
  • Mechanism of action: The chief mechanism of action for Buspar involves modulation of 5-HT1A receptors – and the chief mechanism of action for Xanax involves modulation of GABAA receptors. Buspar primarily alters activity of serotonin receptors and serotonergic transmission –and Xanax primarily alters activity of GABA receptors and GABAergic transmission.
  • Ingredients: The active ingredient in the medication Buspar is the chemical “buspirone.” The active ingredient in the medication Xanax is the chemical “alprazolam.”
  • Manufacturers: Buspar was originally developed by the company Mead Johnson and manufactured by Bristol-Myers Squibb. Xanax was originally developed by the company Upjohn and manufactured by Pfizer Inc.
  • Medical approvals: Xanax is medically approved for the treatment of panic disorder – but Buspar is not. In fact, evidence suggests that Buspar is ineffective for the management of panic disorder.  Buspar is medically approved for the treatment of acute anxiety – but Xanax is not.  That said, evidence substantiates the idea that Xanax is as effective as Buspar for the treatment of acute anxiety.
  • Popularity: There are stark differences in the number of prescriptions being filled each year for Buspar and Xanax, respectively. In the year 2015, an estimated 6.94 million prescriptions were filled for generic Buspar (buspirone) and an estimated 27 million prescriptions were filled for generic Xanax (alprazolam).  Clearly Xanax is utilized significantly more often in medical settings than Buspar.
  • Side effects: It is thought that Buspar users may experience fewer debilitating side effects than Xanax users. Common Buspar side effects such as dizziness, nausea, nervousness, and excitement – are not common Xanax side effects.  Common Xanax side effects such as drowsiness, dry mouth, depression, constipation, and diarrhea – are not common Buspar side effects.  Side effects associated with Buspar are more likely to be gastrointestinal-related and side effects of Xanax are more likely to be CNS-related.
  • Withdrawal: Cessation of Buspar treatment isn’t associated with severe discontinuation symptoms in the medical literature. In fact, some evidence suggests that Buspar withdrawal symptoms are nonexistent.  Comparatively, cessation of Xanax treatment can induce severe, protracted, and potentially life-threatening withdrawal symptoms.

Note: If you’re aware of additional noteworthy differences between Buspar and Xanax – report these differences in the comments.

Which medication is “better” for anxiety disorders? (Buspar vs. Xanax)

If comparing the general anxiolytic usefulness of Buspar and Xanax for all anxiety disorders, an argument could be made that Xanax is the superior intervention.  Xanax is capable of: treating anxious conditions for which Buspar is ineffective (e.g. panic disorder); delivering a faster onset of therapeutic effect than Buspar; and treating acute anxiety (a condition for which only Buspar is FDA approved) as well as Buspar.

However, if comparing the usefulness of Buspar and Xanax for generalized anxiety disorder (the sole medical condition for which both medications have received FDA approval) – neither medication is inherently advantageous over the other in terms of efficacy.  All data from large-scale, double-blind, randomized controlled trials consistently indicate that Buspar and Xanax are more effective than placebos in reducing symptoms of generalized anxiety disorder.

Furthermore, all studies that’ve directly compared the efficacy of Buspar and Xanax among patients with generalized anxiety disorder – report zero differences in therapeutic efficacy between the medications.  However, there is some evidence to suggest that Xanax recipients exhibit quicker symptom reduction (within ~1 week) relative to Buspar recipients (within ~2 to 4 weeks).

Although evidence suggests that the maximal efficacy of Buspar and Xanax in the treatment of generalized anxiety disorder is equal, some patients and/or medical professionals might consider Xanax as a favorable intervention over Buspar as a result of its quicker onset of therapeutic action.  Still, one could argue that the “better” or “superior” pharmaceutical option (Buspar vs. Xanax) for generalized anxiety disorder shouldn’t be decided by onset of action.

An argument in favor of using Xanax over Buspar for generalized anxiety disorder could be strengthened by the fact that Xanax is available in a greater number of dosing increments than Buspar which could make for easier dosage adjustments.  Moreover, while Buspar is solely available as an immediate-release tablet format, Xanax is available in a variety of formats such as: immediate-release tablet; orally-disintegrating tablet; extended-release tablet; and oral solution.

The availability of numerous formats may be advantageous for select patients who prefer one particular format over another due to ease of administration and/or duration of action.  For example, a patient might find that the oral solution of Xanax is easier to administer than the standard tablet – which may increase his/her compliance.

Additionally, a patient may prefer to administer just 1 daily dose of extended-release Xanax to reduce anxiety over a ~12-hour period – compared to administering 2-3 immediate-release Xanax tablets OR multiple Buspar tablets.  Furthermore, if a patient requires long-lasting anxiety relief one day and brief anxiety relief on another – he/she can transition between using extended-release and standard Xanax formats; this is not possible with Buspar.

Although Xanax may be favorable over Buspar in its onset of action, number of dosing increments, and available formats – Buspar may be preferred over Xanax by patients and/or medical professionals for numerous reasons.  Buspar appears favorable over Xanax in domains of: abuse potential; tolerability (i.e. side effects); implications of side effects (e.g. lower productivity); withdrawal symptoms; prospective long-term health effects.

Buspar does not appear to harbor any abuse potential – whereas Xanax carries modest abuse potential such that its users are at risk for developing psychological and/or physical dependence.  Additionally, Buspar is less likely than Xanax to cause severe or intolerable side effects – and is substantially less likely than Xanax to cause side effects that impair cognitive function and/or motor performance.

Xanax users may struggle to perform cognitively-demanding tasks in occupational settings and/or safely execute motor tasks requiring optimal coordination (e.g. operating heavy machinery) – as a result of its side effects.  The potential implications of cognitive and/or motor impairment among Xanax users could be serious.

Additionally, while Buspar is unlikely to cause severe withdrawal symptoms in most users, Xanax is associated with severe, protracted, and occasionally life-threatening withdrawal symptoms.  What’s more, the long-term administration of benzodiazepines is linked to dementia; implying that using Xanax over an extended duration may increase dementia risk. No such links between long-term Buspar administration and dementia have been established.

To recap: Buspar may be regarded as advantageous over Xanax as a treatment for generalized anxiety disorder on the basis of: tolerability (i.e. side effects); withdrawal severity; prospective deleterious long-term effects; and/or abuse potential.  Conversely, Xanax may be regarded as advantageous over Buspar as a treatment for generalized anxiety disorder on the basis of: onset of therapeutic action; dosage increments; and/or formatting (convenience of administration, multiple durations of action, etc.).

Lastly, because Xanax is capable of treating panic disorder and Buspar is not – Xanax could be considered a more universally effective anxiolytic.  Nevertheless, the specific type of anxiety that needs treating; the physiologic signature (genetic/epigenetic, neurochemical, etc.) of a patient’s anxiety; and/or patient or doctor preferences (formatting, dosing, side effects, etc.) – will determine whether one medication might be preferred over the other.

A majority of persons will necessitate medically-supervised “trial and error” before they’re able to determine whether Buspar, Xanax, or another medication is the ideal anxiolytic for a particular anxious condition.  For a subset of persons, Xanax and Buspar might be equally efficacious anxiolytics.

Note #1: If you’re attempting to elucidate whether Buspar is better than Xanax (or vice-versa) in managing your anxiety – consider tracking how you feel in a journal while undergoing treatment.  A journal will make it easier to document and reflect upon (1) efficacy and (2) side effects – of all interventions over an extended duration.

Note #2: Generally speaking, Xanax may be better suited for persons with severe anxiety who require immediate symptomatic relief – whereas Buspar may be better suited for persons with milder anxiety who don’t require immediate relief.  It should also be emphasized that Buspar is arguably one of the safest psychiatric medications on the market and certainly one of the best anxiety medications (in terms of safety, tolerability, long-term effects, and withdrawal).

Which medication do you prefer: Buspar or Xanax?

If you’ve personally used both Buspar (buspirone) and Xanax (alprazolam) – feel free to leave a comment about your experience with each medication.  In your comment, discuss some similarities and/or differences that you noticed with each of the medications – and mention whether you prefer to use one medication over the other for the management of anxiety (or another medical condition).

To help others best understand your experience taking Buspar and Xanax, provide extra details like: (1) the dosages of each medication that you used; (2) respective durations of treatment; (3) the specific format that you used (of Xanax); (4) whether you used additional substances (medications, supplements, etc.) with either treatment; and (5) the specific medical condition for which Buspar and Xanax were prescribed.

In the event that you prefer one medication over the other, note some specific reasons as to why you’ve developed this preference.  Hypothetical reasons that someone might prefer one medication over the other (Buspar vs. Xanax) might include: quicker onset of therapeutic action; more pronounced anxiety reduction; longer duration of effect; lower price; fewer side effects; fewer serious long-term effects; and/or less severe discontinuation symptoms.

Assuming you believe that Buspar or Xanax is superior to the other in reducing your anxiety – have you considered that the respective dosages that you administered (i.e. potency) could’ve accounted for the greater efficacy of one versus the other?

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