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Vistaril (Hydroxyzine) vs. Xanax (Alprazolam)

Hydroxyzine, also referred to under its brand names “Vistaril” (hydroxyzine pamoate) and “Atarax” (hydroxyzine hydrochloride), is a first-generation diphenylmethylpiperazine antihistamine.  Alprazolam, most commonly referred to under its brand name “Xanax,” is a benzodiazepine, or more specifically, a triazolobenzodiazepine anxiolytic.

In the United States, Vistaril is medically approved as an adjunctive treatment for: psychoneurosis-related anxiety and tension; anxiety in organic disease states; and perioperative sedation.  Vistaril is also approved as a standalone treatment for pruritus due to histamine or allergic conditions (e.g. urticaria, atopic dermatitis, contact dermatitis).  Xanax is medically approved in the U.S. for the treatment of generalized anxiety disorder and panic disorder.

The Belgian pharmaceutical company UCB (Union Chimique Belge) is credited for the synthesis of hydroxyzine in 1956 – whereas Upjohn Laboratories (acquired by Pfizer Inc.) is credited for the synthesis of alprazolam in 1960s.  Atarax (hydroxyzine hydrochloride) and Vistaril (hydroxyzine pamoate) were introduced to the U.S. pharmaceutical market in 1956 and 1968, respectively, whereas Xanax was introduced in 1981.

Vistaril (Hydroxyzine) vs. Xanax (Alprazolam)

Highlighted below are general attributes of the medications Vistaril (hydroxyzine) and Xanax (alprazolam) in the format of a chart.  The chart should help determine basic similarities and differences between Vistaril and Xanax.

 VistarilXanax
IngredientHydroxyzine pamoateAlprazolam
Drug classificationDiphenylmethylpiperazineTriazolobenzodiazepine
Approved medical usesAnxiety and tension associated with psychoneurosis (adjunct).

Anxiety associated with organic disease states (adjunct).

Pruritus due to histamine and/or allergic conditions (e.g. urticaria, atopic dermatitis, contact dermatitis).

Perioperative sedation (adjunct).
Generalized anxiety disorder.

Panic disorder.
Off-label usesAcute pain. Insomnia. Opioid withdrawal. Nausea & vomiting.Chemotherapy-induced nausea and vomiting. Insomnia. Agitation. Premenstrual dysphoric disorder.
Bioavailability~93% (oral)~90% (oral)
FormatsCapsule. Tablet. Oral solution. Vial (Intramuscular injection).Tablet. Extended-release (XR or ER) pill. Oral disintegrating tablet. Oral solution.
DosagesCapsule (Vistaril): 25 mg, 50 mg, 100 mg (Vistaril)

Tablet (Atarax): 10 mg, 25 mg, 50 mg

Oral solution (Atarax): 10 mg/5ml

Vial (Atarax): 25 mg/ml, 50 mg/ml
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
ManufacturerPfizer Inc. (Roerig Pharmaceuticals, Union Chimique Belge)Pfizer Inc. (Upjohn Laboratories)
Legal statusRx (Prescription)-only (U.S.)Schedule IV (U.S.)
Mechanism of actionH1 receptor inverse agonist.

5-HT2A receptor antagonist (weak).

D2 receptor antagonist (weak).

Alpha-1 adrenergic receptor antagonist (weak).
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-Life20 to 37 hours (adults).

~7.1 hours (children).
9 to 16 hours (~12 hours)
Common side effectsDrowsiness or somnolence. Fatigue. Dry mouth. Headache. Dizziness. Blurred vision. Upset stomach.Drowsiness. Lightheadedness. Dry mouth. Depression. Headache. Constipation. Diarrhea.
Date approved1956 (Atarax). 1968 (Vistaril).1981
Duration of effect4 to 6 hoursStandard: ~5 hours

Extended-release: ~11 hours
MetabolismHepatic: ADH (Alcohol Dehydrogenase).Hepatic: CYP3A4.
Onset of action15 to 30 minutes20 to 40 minutes

Note: The above chart may be subject to inaccuracies and/or change in the event of new scientific findings.  If you have any specific questions about how Vistaril compares to Xanax that weren’t addressed in this chart, consult a medical doctor or pharmacist.

Vistaril (Hydroxyzine) vs. Xanax (Alprazolam): What are some notable differences?

Although hydroxyzine and Xanax can each be utilized for the management of anxiety, the medications differ in many ways.  Notable differences between hydroxyzine and Xanax (alprazolam) in the United States include: drug classification; approved medical uses; formatting; mechanism of action; legal scheduling; and elimination half-life.

With regard to drug classification, Vistaril and Xanax differ significantly.  Vistaril (hydroxyzine) is classified as a diphenylmethylpiperazine (i.e. benzhydrylpiperazine) antihistamine due to its core chemical structure containing a piperazine ring with a diphenylmethyl (benzhydryl) group bound to one of the nitrogens – whereas Xanax (alprazolam) is classified as a triazolobenzodiazepine anxiolytic due to its core chemical structure containing a benzene ring fused to a diazepine ring with an attached triazole ring.

The official FDA (Food & Drug Administration) medical indications for Vistaril and Xanax also differ.  Vistaril is approved by the FDA as an adjuvant treatment for: psychoneurosis-related anxiety and tension; anxiety during organic disease; and perioperative sedation – and as a standalone treatment for: pruritus associated with allergic conditions (e.g. urticaria, atopic dermatitis, contact dermatitis).

Xanax is approved by the FDA as a treatment for generalized anxiety disorder and panic disorder.  Although Vistaril and Xanax are both utilized to alleviate symptoms of anxiety, Vistaril is medically indicated as an adjunct to treat anxiety among persons with neurosis and/or organic disease (Xanax is not) – whereas Xanax is medically indicated as a standalone or adjunct to treat generalized anxiety disorder and panic disorder (Vistaril is not).

Additionally, unlike Xanax, Vistaril is medically indicated for the induction of perioperative sedation and for the management of pruritus associated with chronic allergic conditions and/or elevated histamine.  In addition to disparities in the respective formal medical indications of Vistaril and Xanax, there may be slight differences in the off-label medical uses of each agent.

As an off-label intervention, Vistaril is commonly used to manage acute pain and symptoms of opioid withdrawal – whereas Xanax is commonly used to manage agitation and premenstrual dysphoric disorder.  The available formats of hydroxyzine (Vistaril and Atarax) also differ slightly from the available formats of alprazolam (Xanax).

Hydroxyzine is available in several formats, including: immediate-release capsules and tablets, oral solution, and vials (intramuscular injection) – whereas alprazolam is available in formats such as: immediate-release tablets, extended-release tablets, orally-disintegrating tablets, and oral solution.  Hydroxyzine is available in the format of injectable vials intended for intramuscular administration (alprazolam is not) – and alprazolam is available as an extended-release tablet and orally-disintegrating tablet (hydroxyzine is not).

In addition to the aforementioned formatting differences, Vistaril and Xanax differ in mechanism of action.  Vistaril functions primarily as a H1 receptor inverse agonist wherein it binds to H1 receptors and exerts the opposite effect of histamine to generate an antihistamine response.

Xanax functions primarily as a positive allosteric modulator of GABAA receptors wherein it allosterically binds to GABAA receptors to generate a GABAergic response.  Differences in the respective mechanisms of action for Vistaril and Xanax probably account for some dissimilarities in: off-label uses, legal scheduling (standard prescription vs. Schedule IV controlled substance), and common side effects.

Common side effects of Vistaril that are less common for Xanax include: dizziness, blurred vision, and upset stomach.  Common side effects of Xanax that are less common for Vistaril include: lightheadedness, depression, constipation, and diarrhea.

Lastly, although the routes of metabolism for Vistaril and Xanax are similar, the respective average elimination half-life ranges differ at: 20 to 37 hours (Vistaril) and 9 to 16 hours (Xanax).  The longer average elimination half-life for Vistaril versus Xanax means that Vistaril will remain in the body for a longer duration following cessation – but this might reduce the severity of discontinuation symptoms (relative to Xanax).

Addiction & Abuse Potential

The addiction and abuse potential for Vistaril (hydroxyzine) is significantly less than that of Xanax (alprazolam).  Although Vistaril can alleviate anxiety and induce sedation by inversely agonizing H1 histamine receptors throughout the brain, it hasn’t been shown to significantly activate reward pathways in the brain to induce psychological reinforcement.

For this reason, Vistaril isn’t suggested to carry clinically relevant addiction or abuse potential – hence its legal scheduling as a standard prescription medication.  Comparatively, Xanax alleviates anxiety and induces sedation via allosteric modulation of GABAA receptors throughout the brain.

As a downstream effect of this GABAA receptor modulation, inhibitory interneurons begin firing less frequently within the ventral tegmental area (VTA) which subsequently decreases the firing of dopamine-containing neurons.  The decline in firing of dopamine-containing neurons causes dopamine to accumulate in extracellular spaces.

The accumulation of dopamine leads to increased dopaminergic signaling and stimulation of reward pathways in the brain, causing some Xanax users to experience euphoriant effects.  The aggregation of euphoriant, anxiolytic, and myorelaxant effects following a rapid onset of action can be psychologically-reinforcing and lead to abuse and/or addiction in select users.

For this reason, Xanax is suggested to exhibit clinically relevant addiction and abuse potential – hence its legal scheduling as a “Schedule IV” controlled-substance.  While there are reports of antihistamine abuse, addiction, and/or dependence – these are significantly less common than reports of benzodiazepine abuse, addiction, and/or dependence.

Of all benzodiazepines in pharmaceutical circulation, Xanax is reportedly the most abused/misused in the United States.  Moreover, some experts suggest that benzodiazepines like Xanax are among the most addictive drugs in mainstream medical use.

Persons who intentionally abuse or misuse Xanax, such as by using it in ways and/or at dosages that are not consistent with medical instruction – are suggested to be at highest risk for developing benzodiazepine dependence.  That said, when Xanax is administered in accordance with medical instruction (e.g. mode of administration, dosing, etc.), risk for dependence is low.

Overall, because Vistaril does not activate reward pathways within the brain to induce psychological reinforcement, it is not regarded as a substance of abuse.  Xanax is psychologically-reinforcing and significantly more likely to be abused and/or lead to addiction than Vistaril.

Approved medical uses

There are distinct differences in the official (FDA approved) medical uses for Vistaril (hydroxyzine) and Xanax (alprazolam).  Vistaril is formally approved as a standalone treatment for chronic allergic conditions such as: urticaria, atopic dermatitis, and contact dermatitis – and as an adjunct (i.e. add-on therapy) for psychoneurosis-related anxiety and tension, anxiety in organic disease states, and the induction of perioperative sedation.

Xanax is formally approved as a standalone treatment for generalized anxiety disorder (GAD) and panic disorder.  Comparing the official medical uses for Vistaril and Xanax, it is apparent that Vistaril is medically indicated to treat chronic allergic conditions – whereas this is not an accepted medical indication of Xanax.

Moreover, while Vistaril and Xanax are each prescribed as anxiolytics, there are differences in: (1) the specific types of anxiety for which each agent is medically indicated, and (2) the specific ways in which each agent is used (e.g. monotherapy vs. adjunct therapy).  Vistaril is medically approved for the treatment of psychoneurosis-related anxiety and tension – and anxiety in organic disease states (Xanax is not).

For reference, “psychoneurosis” is defined as a mild mental illness [not caused by organic disease] characterized by symptoms of stress such as anxiety, depression, hypochondria, obsessive behavior – and anxiety in “organic disease” is anxiousness that occurs as a result of physical or physiological change to tissues or organs within the body.

Unlike Vistaril, Xanax is approved for the treatment of generalized anxiety disorder (or severe anxiety that interferes with daily functioning) and panic disorder (a condition in which debilitating anxiety and panic emerge without a specific cause).  Additionally, although Xanax is medically approved to treat anxiety disorders as a monotherapy, Vistaril is solely approved to treat anxious conditions as an adjunct.

With regard to common off-label (i.e. non-official) medical uses for Vistaril and Xanax, both medications are used to treat insomnia and emetic reactions (nausea and vomiting).  That said, Vistaril is hypothesized to be utilized off-label more frequently than Xanax to treat acute pain and opioid withdrawal symptoms – whereas Xanax is hypothesized to be utilized off-label more frequently than Vistaril to treat agitation and premenstrual dysphoric disorder.

Nevertheless, because the off-label usage rates of Vistaril and Xanax for specific medical conditions remain unknown, it’s unclear as to whether Vistaril is legitimately used more frequently than Xanax for acute pain and opioid cessation – and/or whether Xanax is legitimately used more frequently than Vistaril for agitation and premenstrual dysphoric disorder.  The suggested differences in off-label usage of Vistaril and Xanax are speculative.

Though there are differences in the official respective medical indications of Vistaril and Xanax, it’s reasonable to suggest that medication might be capable of treating anxious conditions for which only the other agent is medically approved.  Preliminary evidence suggests that Vistaril (hydroxyzine) is more effective than a placebo for the treatment of generalized anxiety disorder – and case reports have highlighted its efficacy in managing panic disorder.

Furthermore, because Xanax (alprazolam) is an extremely potent anxiolytic with myorelaxant properties, it would likely be effective in the management of psychoneurosis-related anxiety and muscle tension – and anxiety in organic disease states.  Chronic allergic conditions are likely the only conditions for which Vistaril would be significantly more effective than Xanax – due to its antihistamine effect.

Cost: How do the prices compare?

At most pharmacies, generic formats of Atarax (hydroxyzine hydrochloride), Vistaril (hydroxyzine pamoate), and Xanax (alprazolam) sell for a low price.  That said, the average price range for generic Xanax (alprazolam) may be slightly cheaper than the average price ranges for generic Atarax (hydroxyzine hydrochloride) and Vistaril (hydroxyzine pamoate).

Atarax & Vistaril cost (hydroxyzine)

  • Vistaril (generic): $10 to $44 (60 capsules)
  • Vistaril (brand): $155 to $201 (60 capsules)
  • Atarax tablets (generic): $6 to $31 (60 tablets)
  • Atarax oral solution (generic): $6 to $10 (60 ml – 10 mg/5 ml)
  • Atarax vials (generic): $26 to $141 (10 vials of 1 ml – 50 mg/ml)
  • Atarax (brand): N/A (Discontinued in 2009)

Xanax cost (alprazolam)

  • 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)

A total of 60 standard generic Atarax (hydroxyzine hydrochloride) tablets retail within the range of $6 to $31 (on average); 60 standard generic Vistaril (hydroxyzine pamoate) capsules retail within the range of $10 to $44 (on average); and 60 standard generic Xanax (alprazolam) tablets retail within the range of $7 to $21 (on average) – at most pharmacies.

This translates to standard generic Atarax (hydroxyzine hydrochloride) selling for $0.10 to $0.52 per tablet; standard generic Vistaril (hydroxyzine pamoate) selling for $0.17 to $0.74 per capsule; and standard generic Xanax (alprazolam) selling for $0.05 to $0.35 per tablet.  Though all standard generic formats are low cost, standard generic Xanax (alprazolam) is the lowest-priced.

While it is most common for consumers to purchase generic formats of hydroxyzine and alprazolam due to their lower pricing than “brand name” formats, select individuals may prefer “brand name” formats due to perceived superiority in domains of efficacy and/or tolerability.  If comparing the brand name versions of Vistaril and Xanax, it appears as though Vistaril is less expensive.

A total of 60 brand name Vistaril capsules retail within the range of $155 to $201 (on average) – and 60 brand name Xanax tablets retail within the range of $245 to $800 (on average).  For consumers who insist on using brand name formats, Vistaril will be lower-priced than Xanax.

Although brand name Atarax was discontinued in 2009, generic Atarax (hydroxyzine hydrochloride) is available in oral solution format just like generic Xanax (alprazolam).  The cost of hydroxyzine hydrochloride oral solution ranges from $6 to $10 for 1 bottle of 60 ml with doses of 10 mg/5ml – whereas the cost of alprazolam oral solution ranges from $47 to $103 for 1 bottle of 30 ml with doses of 1 mg/ml.

If comparing the oral solution prices of hydroxyzine hydrochloride and alprazolam, it seems as though hydroxyzine hydrochloride is cheaper per dose if dosages are 10 mg (hydroxyzine hydrochloride) and 1 mg (alprazolam), respectively.  However, 10 mg is the lowest dosing increment of hydroxyzine hydrochloride – and 1 mg alprazolam is the third-highest dosing increment of alprazolam.

Assuming the lowest dosing increment of alprazolam (0.25 mg) is also used (rather than the third-highest), the cost per dose for alprazolam oral solution shouldn’t differ much from the cost of hydroxyzine hydrochloride oral solution.  In fact, alprazolam oral solution would be slightly less expensive at around $0.39 to $0.86 per dose (on average) – relative to hydroxyzine hydrochloride oral solution at around $0.50 to $0.84 per dose (on average).

Unlike generic Xanax (alprazolam), generic Atarax (hydroxyzine hydrochloride) is also manufactured in the format of injectable vials intended for intramuscular administration.  Each hydroxyzine hydrochloride vial contains 1 ml of 50 mg/ml solution – and a pack of 10 vials retails for $26 to $141 (on average).

Unlike generic Atarax and Vistaril, generic Xanax (alprazolam) is available in formats of an orally-disintegrating tablet (ODT) and extended-release tablet (ER or XR).  The orally-disintegrating tablets retail for $29 to $183 (30 tablets) and the extended-release tablets retail for $16 to $67 (30 tablets).

To summarize: Standard generic formats of Atarax (hydroxyzine hydrochloride), Vistaril (hydroxyzine pamoate), and Xanax (alprazolam) are inexpensive at most pharmacies – but alprazolam is the cheapest.  Alprazolam oral solution may be slightly cheaper (per dose) than hydroxyzine hydrochloride oral solution.

Brand name versions of Vistaril and Xanax are relatively expensive, but brand name Vistaril is significantly less expensive than brand name Xanax.  Additional formats of hydroxyzine (injectable vials) and alprazolam (orally-disintegrating tablet, extended-release tablet) are moderately priced.

Note: The prices of Atarax, Vistaril, and Xanax may be subject to future fluctuation such that the estimated prices listed above are rendered incorrect.  Furthermore, understand that the pricing of each medication may vary significantly among retailing pharmacies.  The prices of Atarax, Vistaril, and Xanax are also dose-dependent such that higher-doses tend to cost more than lower doses.

Dosage & Formats

Vistaril and Xanax are each manufactured in immediate-release formats.  The immediate-release format of Vistaril is suggested to take effect within 15 to 30 minutes of administration and alleviate symptoms for 4 to 6 hours – whereas the immediate-release format of Xanax is hypothesized to take effect within 20 to 40 minutes and alleviate symptoms for 4 to 6 hours. (Read: “How long does it take for Xanax to kick in?”)

Available dosages for standard generic Vistaril capsules (hydroxyzine pamoate) include: 25 mg, 50 mg, and 100 mg; brand name Vistaril is solely available at dosages of 25 mg and 50 mg.  Available dosages for standard generic Atarax tablets (hydroxyzine hydrochloride) include: 10 mg, 25 mg, and 50 mg.  Available dosages for standard generic and brand name Xanax tablets (alprazolam) include: 0.25 mg, 0.5 mg, 1 mg, and 2 mg.

If specifically comparing the formatting and dosage increments of standard immediate-release hydroxyzine (Vistaril or Atarax) and alprazolam (Xanax) there are subtle differences.  Hydroxyzine is available in both capsule (hydroxyzine pamoate) and tablet (hydroxyzine hydrochloride) formats – whereas alprazolam (Xanax) is only available in tablet format.

That said, having the option to use a capsule or tablet of hydroxyzine shouldn’t be regarded as an advantage for users relative to only being able to use a tablet of alprazolam.  In fact, standard alprazolam (Xanax) may be slightly advantageous over standard hydroxyzine (Vistaril or Atarax) in that it offers 1 additional dosing increment to users.

Standard alprazolam (Xanax) is available in 4 dosing increments – whereas standard hydroxyzine (Vistaril or Atarax) is only available in 3 dosing increments (regardless of whether capsule or tablet).  Because an additional dosing increment might make it easier for titration (or adjustment) of dosing, this could be a reason as to why select patients and/or medical doctors would prefer to use Xanax over Vistaril as an anxiolytic.

In addition to their availabilities in immediate-release formats, hydroxyzine hydrochloride (Atarax) and alprazolam (Xanax) are each available in the form of an oral solution.  The oral solution of hydroxyzine hydrochloride (Atarax) is sold at a dosage of 10 mg/5ml – and can be purchased in bottles of 60 ml, 120 ml, 150 ml, 240 ml, or customized amounts.

The oral solution of alprazolam (Xanax) is available at a dosage of 1 mg/ml with 30 ml of solution per bottle.  There are a greater number of bottle sizing options for hydroxyzine hydrochloride (Atarax) oral solution than alprazolam (Xanax) oral solution, however, the relative dosage of alprazolam “per milligram” of oral solution is stronger than the relative dose of hydroxyzine; (1 mg of alprazolam is a moderate-to-high dose, whereas 10 mg of hydroxyzine hydrochloride is a low dose).

Hydroxyzine (Vistaril or Atarax) differs from alprazolam (Xanax) in the availability of various alternative formats.  Unlike alprazolam (Xanax), hydroxyzine hydrochloride (Atarax) is available in vial format with doses of 50 mg/ml solution intended for intramuscular injection.

Unlike hydroxyzine (Vistaril or Atarax), alprazolam (Xanax) is available in the formats of orally-disintegrating tablet (ODT) and extended-release (ER or XR) tablet.  Orally-disintegrating tablets (ODT) of alprazolam are available at dosages of 0.25 mg, 0.5 mg, 1 mg, and 2 mg – and extended-release tablets (ER or XR) of alprazolam are available at dosages of 0.5 mg, 1 mg, 2 mg, and 3 mg.

Though hydroxyzine is available in vials for intramuscular injection (and alprazolam isn’t), this format isn’t substantially more advantageous than existing alprazolam formats because: (1) it may be difficult to administer; (2) it may cause injection site reactions that do not occur with oral formats; and (3) it doesn’t provide a longer duration of action than oral formats.  The immediate-release alprazolam is available in an additional dosing increment than immediate-release hydroxyzine.

Furthermore, orally-disintegrating alprazolam may be more convenient for some patients to administer (based on the fact that it dissolves in the mouth without swallowing) – and extended-release alprazolam provides a significantly longer duration of action (10 to 12 hours) than other formats (4 to 6 hours).  Overall, it’s reasonable to suggest that alprazolam (Xanax) is favorable over hydroxyzine (Atarax or Vistaril) in its dosing and formatting.

Efficacy: Which medication is more effective?

It is important to underscore the fact that Vistaril (hydroxyzine pamoate) and Xanax (alprazolam) are not medically approved to treat the same conditions.  As was already mentioned, Vistaril is medically-approved for the treatment of pruritus associated with chronic allergic conditions; anxiety associated with psychoneurosis or organic disease (as an adjunct); and the induction of sedation (as an adjunct) – and Xanax is medically-approved for the treatment of generalized anxiety disorder and panic disorder.

Considering the respective mechanisms of action for each medication, it’s logical to speculate that Vistaril is significantly more effective than Xanax for the treatment of pruritus associated with chronic allergic conditions (e.g. urticaria, atopic dermatitis, contact dermatitis).  As an antihistamine, Vistaril is capable of attenuating the histaminergic response in allergy to counteract the itchiness of pruritus; Xanax does not generate a clinically relevant antihistamine effect and has not been shown to treat allergy-related pruritus.

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Although Vistaril is likely more efficacious than Xanax in the treatment of pruritus, it’s unclear as to whether there are significant differences in the respective efficacies of each medication in the management of anxious conditions.  Because Xanax is an extremely potent anxiolytic, it’s likely that Xanax is as effective as Vistaril for the treatment of anxiety and tension associated with psychoneurosis or organic disease.

In fact, a small-scale study (30 outpatients) by Kerry and McDermott (1983) reported that alprazolam (Xanax) at a dosage of 0.5 mg to 1 mg (three times per day) was more effective than a placebo for the treatment of “neurotic anxiety” – over a 4-week period.  The effectiveness of Xanax in treating neurotic anxiety was evidenced by significant improvements on the Hamilton Anxiety Rating Scale, Physician Global Impressions scale, and Patient Global Impressions scale.

Moreover, while Vistaril is not specifically approved as a treatment for generalized anxiety disorder and panic disorder, preliminary evidence suggests that it may be effective.  For example, a randomized, double-blind, placebo-controlled study by Ferreri et al. (1994) reported that hydroxyzine (50 mg per day) was significantly more effective than a placebo in treating generalized anxiety disorder.

The aforementioned study included 133 patients who had been formally diagnosed with generalized anxiety disorder.  Another randomized, double-blind, placebo-controlled study by Lader and Scotto (1998) compared the efficacies of hydroxyzine (12.5 mg morning, 12.5 mg afternoon, 25 mg evening), buspirone (5 mg morning, 5 mg afternoon, 10 mg evening), and a placebo (1 capsule morning, afternoon, evening) – for the treatment of generalized anxiety disorder in a sample of 244 patients.

Results of the trial indicated that hydroxyzine was significantly more effective than a placebo for the treatment of generalized anxiety disorder – as evidenced by score improvements on the Hamilton Anxiety Scale, Clinical Global Impressions scale, and self-rating scales over a 4-week period.  One of the largest and longest-term trials evaluating the effectiveness of hydroxyzine in the treatment of generalized anxiety disorder was conducted by Llorca et al. (2002).

The trial by Llorca et al. implemented a randomized, placebo-controlled, double-blind design with a 2-week single-blind placebo “run in” phase, 12-week double-blind randomized treatment phase, and a 4-week single-blind “run out” phase.  The trial compared the therapeutic effectiveness of hydroxyzine (50 mg/day), bromazepam (6 mg/day), and a placebo – among 334 outpatients who had been diagnosed with generalized anxiety disorder.

Results of this trial suggested that both bromazepam and hydroxyzine were significantly more effective than a placebo for the treatment of generalized anxiety disorder.  It was also noted that there were no significant differences between hydroxyzine and bromazepam in magnitude of anxiolytic efficacy.

Although a report by Guaiana et al. (2010) in the Cochrane Library noted that hydroxyzine appears more effective than a placebo as a treatment for generalized anxiety disorder, it also suggested that this evidence may be unreliable due to: bias; a limited number of studies; and/or small sample sizes within most studies.  Because existing evidence supporting the efficacy of hydroxyzine for generalized anxiety disorder may be unreliable, Guaiana et al. state that it cannot be recommended as a first-line intervention for generalized anxiety disorder.

Nevertheless, if existing evidence accurately reflects the therapeutic efficacy of hydroxyzine for generalized anxiety disorder – it’s reasonable to assume that hydroxyzine as effective as alprazolam.  Because the effectiveness of hydroxyzine for generalized anxiety disorder appears equal to that of buspirone, and the effectiveness of buspirone for generalized anxiety disorder appears equal to that of alprazolam (read: “Buspar vs. Xanax“) – it’s reasonable to suspect that Vistaril (hydroxyzine) is of similar efficacy to Xanax (alprazolam) for generalized anxiety disorder.

A case report by Iskandar et al. (2011) documented that hydroxyzine (25 mg) three times per day successfully treated panic disorder in a 25-year-old patient.  Prior to initiation of hydroxyzine treatment, the patient had been experiencing symptoms such as: chest pain, derealization, tachycardia, palpitations, hyperventilation, shortness of breath, sweating, nausea, and vomiting.

Although hydroxyzine hasn’t been formally evaluated in large-scale, long-term trials as a panic disorder treatment, the aforementioned case report supports its efficacy as an anti-panic agent.  Though more research is needed to fully elucidate the anti-panic efficacy of hydroxyzine, it’s possible that hydroxyzine might be as effective as Xanax (alprazolam) in the treatment of panic disorder.

In summary, as of current, Vistaril may be a favorable intervention (relative to Xanax) for the treatment of anxiety associated with psychoneurosis or organic disease states – due to the fact that its use for these conditions is substantiated by strong evidence.  Additionally, Xanax may be a favorable intervention (relative to Vistaril) for the treatment of generalized anxiety disorder or panic disorder – due to the fact that its use for these conditions is substantiated by strong evidence.

That said, it remains unclear as to whether Vistaril or Xanax is significantly more effective than the other for the treatment of anxious conditions.  No studies have directly compared the effectiveness of hydroxyzine to that of alprazolam for the treatment of a specific anxious condition.  For this reason, neither Vistaril nor Xanax should be considered more effective than the other as treatments for anxious conditions.

Mechanism of action

Despite the fact that Vistaril and Xanax are each capable of treating anxiety, their respective mechanisms of action (i.e. pharmacodynamics) markedly differ.  Vistaril (hydroxyzine) functions primarily as an H1 receptor inverse agonist whereby it binds to H1 receptors, shifts H1 receptors toward an inactive state, and inhibits the action of histamine (the endogenous ligand of H1) to facilitate an antihistamine response.

  • Vistaril (Hydroxyzine): H1 receptor inverse agonist
  • Xanax (Alprazolam): GABA(A) receptor modulator (GABA)

The antihistamine response derived from hydroxyzine-mediated H1 receptor inverse agonism is what makes Vistaril effective in treating allergy-induced pruritus.  In addition to alleviating pruritus, the H1 inverse agonism of hydroxyzine can facilitate an anxiolytic response – such that Vistaril alleviates anxiety associated with psychoneurosis and organic disease.

Furthermore, it is hypothesized that H1 inverse agonism suppresses activity in subcortical brain regions; yields downstream increases in serotonin and norepinephrine within various brain regions; and reduces sympathetic nervous system activity.  Concurrent modulation of histamine receptors, subcortical activity, monoamines (serotonin and norepinephrine), and sympathetic nervous system function – may account for the anxiolytic effect of hydroxyzine.

Additional (albeit weaker) neurochemical actions of hydroxyzine include: 5-HT2A receptor antagonism, D2 receptor antagonism, and alpha-1 adrenergic receptor antagonism.  The antagonism of 5-HT2A receptors is associated with decreased arousal, increased sedation, and enhanced slow-wave sleep (SWS) – all of which might alleviate anxiety.  Moreover, antagonism of alpha-1 adrenergic receptors and D2 receptors might counteract excessive excitatory neurotransmission to promote relaxation and/or bolster a preexisting anxiolytic effect.

Distinct from the primary neurochemical action of Vistaril (hydroxyzine), Xanax (alprazolam) functions predominantly as a GABAA receptor positive allosteric modulator.  More specifically, alprazolam binds to GABAA receptors wherein it potentiates the binding efficiency of GABA (gamma-aminobutyric acid), an endogenous inhibitory neurotransmitter, upon GABAA receptors.

Potentiation of GABA binding to GABAA receptors (as facilitated by alprazolam) enables negatively-charged chloride ions to accumulate and penetrate neurons to induce a state of neuronal hyperpolarization.  Following the induction of neuronal hyperpolarization: (1) the internal contents of neurons exhibit greater negative charge than the external contents; (2) neurons become less responsive to excitatory stimulation; and (3) activity within the central nervous system (CNS) decreases.

The GABAergic modulation and subsequent induction of CNS depression by alprazolam generate its anxiolytic effect.  Hypothesized secondary neurochemical actions that may also contribute to the therapeutic efficacy of alprazolam [to a lesser extent that its primary mode of action] include: modulating voltage-gated ion channels (e.g. calcium and/or sodium); increasing striatal dopamine receptors (D1 & D2); increasing norepinephrine; and increasing serotonin.

In summary: Vistaril (hydroxyzine) is capable of treating pruritus (associated with chronic allergic conditions) and anxiety (associated with psychoneurosis and organic disease) – predominantly through its antihistamine plus anxiolytic action as an H1 receptor inverse agonist.  Xanax (alprazolam) is capable of treating anxiety and panic predominantly through its anxiolytic action as a GABAA receptor positive allosteric modulator.

Note: Although this article primarily focuses on comparing Vistaril (hydroxyzine pamoate) to Xanax (alprazolam), information regarding Atarax (hydroxyzine hydrochloride) is included.  Understand that while Vistaril and Atarax are both salt forms of “hydroxyzine” with identical medical indications – it is thought that Vistaril (hydroxyzine pamoate) is superior over Atarax (hydroxyzine hydrochloride) for anxiety disorders due to the lipophilicity of “pamoate” – enabling it to cross the blood-brain-barrier (BBB) more efficiently than “hydrochloride.”

Metabolism & Half-Life

Pharmacokinetic research suggests that the metabolism of both Vistaril (hydroxyzine) and Xanax (alprazolam) occurs hepatically, or within the liver.  Although hydroxyzine is metabolized in the liver, it is unclear as to whether any specific CYP450 (cytochrome P450) isoenzymes are implicated in its metabolism.

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Nevertheless, it is known that hydroxyzine undergoes oxidation via the alcohol dehydrogenase (ADH) enzyme to form its chief metabolite “cetirizine” (45%) and additional [less significant] metabolites, including: an N-dealkylated metabolite and an O-dealkylated metabolite.  The cetirizine metabolite of hydroxyzine is bioactive, non-dialyzable (not subject to dialysis), and undergoes metabolism via CYP3A4 and CYP3A5 hepatic enzymes.

The metabolism of alprazolam is well-elucidated and is understood to primarily involve CYP3A4 enzymes.  More specifically, hepatic CYP3A4 enzymes are chiefly responsible for facilitating the biotransformation of alprazolam to form bioactive and water-soluble metabolites:  alpha-OHALP (alpha-hydroxy alprazolam) and 4-OHALP (4-hydroxy alprazolam).

In addition to disparities in aspects of metabolism and biotransformation, hydroxyzine and alprazolam exhibit respective differences in elimination half-life.  The elimination half-life of hydroxyzine in falls within the range of 20 to 37 hours (on average), whereas the elimination half-life of alprazolam falls within the range of 9 to 16 hours (on average) – in healthy adults.

Based on respective elimination half-lives for hydroxyzine and alprazolam, we can estimate that it takes approximately 4.58 to 8.5 days to eliminate hydroxyzine from systemic circulation following cessation – and between 2.06 to 3.7 days to eliminate alprazolam from systemic circulation following cessation.  That said, a minor metabolite of hydroxyzine exhibits a 59-hour elimination half-life whereby it may require over 13.5 days for systemic elimination.

Popularity

Medications containing hydroxyzine (Atarax and Vistaril) entered the United States pharmaceutical market long before alprazolam (Xanax).  Atarax (hydroxyzine hydrochloride) became available in 1956; Vistaril (hydroxyzine pamoate) became available in 1968; and Xanax (alprazolam) became available in 1981 – within the United States.

Because hydroxyzine was available ~25 years before alprazolam, it’s reasonable to suspect that hydroxyzine may have been the more popular medication for a period of time after alprazolam entered the pharmaceutical scene in 1981.  When Xanax (alprazolam) first hit the market, hydroxyzine was: (1) already available as a generic, lower-cost treatment; (2) a familiar medication (among doctors and patients); and (3) had likely been subject to more research that substantiated its safety, efficacy, and tolerability.

For the aforementioned reasons of (1) generic availability; (2) widespread familiarity; and (3) evidence supporting its safety, efficacy, and tolerability – it may have been utilized more frequently in the 1980s than alprazolam.  That said, because the exact prescribing rates for medications in the 1980s and 1990s within the U.S. remain unknown – it’s unclear as to whether hydroxyzine was definitively more popular than alprazolam during these periods.

In any regard, the ClinCalc DrugStats database reports that over 27 million alprazolam (generic Xanax) prescriptions were filled during 2015 – making it the most-prescribed benzodiazepine and 23rd most-prescribed pharmaceutical medication in the U.S.  In comparison, the same database reports that nearly 8.3 million hydroxyzine prescriptions were filled during 2015 – making it the 95th most-prescribed pharmaceutical medication in the U.S.

Based upon prescription numbers from 2015, it’s apparent that alprazolam (generic Xanax) is significantly more popular than hydroxyzine (generic Atarax or Vistaril) – and is prescribed around 3.25-times more frequently.  The greater popularity of alprazolam relative to hydroxyzine might be attributable to its: specific medical indications; variety of available formats; side effect profile; anxiolytic potency; and/or recreational appeal.

Side Effects

Several of the most common hydroxyzine (Atarax and Vistaril) side effects include: drowsiness or somnolence (10%+), fatigue (1% to 10%), dry mouth (1% to 10%), headache (1% to 10%), dizziness (1%), blurred vision, and upset stomach.  Several of the most common alprazolam (Xanax) side effects [according to FDA Access Data] include: drowsiness, lightheadedness, dry mouth, depression, headache, constipation, and diarrhea.

Because both hydroxyzine and alprazolam bolster inhibitory neurotransmission and inhibit excitatory neurotransmission to generate anxiolytic effects, many common side effects associated with these agents are similar.  Drowsiness is regarded as the most-frequently occurring side effect for both hydroxyzine and alprazolam.  Other frequently-occurring side effects for both hydroxyzine and alprazolam include:  dry mouth, headache, dizziness/lightheadedness, and gastrointestinal abnormalities.

It is unclear as to whether there are significant differences in the incidences and/or magnitudes of side effects between hydroxyzine and alprazolam users.  Assuming there are substantial differences in the frequencies and/or severities of hydroxyzine and alprazolam side effects, these differences may be attributable to diverging: (1) pharmacodynamics; (2) potencies; and (3) pharmacokinetics (e.g. metabolism pathways).

Both hydroxyzine and alprazolam can also cause adverse reactions such as: incoordination, psychomotor impairment, cognitive dysfunction, confusion, depression, decreased libido, disorientation, derealization, and weakness.  Moreover, epidemiological research suggests that long-term use of benzodiazepines and antihistamines may increase risk of dementia.

Some might argue that specific hydroxyzine side effects are less frequent and/or severe than alprazolam side effects based on the fact that alprazolam induces markedly greater CNS depression.  That said, because (1) no studies have directly compared the side effects of these agents and (2) both agents reduce excitatory neurotransmission – it is unclear as to whether side effects, adverse reactions, and long-term effects of each agent significantly differ.

When utilized in accordance with medical instruction, both hydroxyzine (Atarax or Vistaril) and alprazolam (Xanax) are considered safe and well-tolerated.  Although the agents differ in pharmacodynamics and pharmacokinetics, there’s significant overlap in their most common side effects, and no convincing data to suggest that one medication would be better tolerated than the other.

Withdrawal

Cessation of Vistaril (hydroxyzine pamoate) or Xanax (alprazolam) following moderate-term and/or long-term treatment may yield noticeable and/or unpleasant withdrawal symptoms.  Withdrawal symptoms associated with hydroxyzine discontinuation are generally considered either nonexistent OR modest, short-lived, and clinically insignificant – whereas withdrawal symptoms associated with alprazolam discontinuation are generally considered severe, long-lasting, clinically significant, and potentially life-threatening.

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A randomized, double-blind, placebo-controlled trial by Ferreri et al. (1994) reported no significant rebound anxiety or withdrawal symptoms following abrupt discontinuation of hydroxyzine (50 mg/day) after a 4-week treatment period.  Additionally, a 3-month randomized controlled trial by Llorca et al. (2002) reported no significant discontinuation symptoms among hydroxyzine (50 mg/day) users in a 4-week single-blind “run out” phase.

Though there’s no strong data to substantiate the existence of clinically-relevant hydroxyzine withdrawal symptoms, many studies in which hydroxyzine was evaluated: (1) were extremely short-term; (2) were extremely small-scale; and/or (3) failed to investigate withdrawal symptoms.  This considered, it’s possible that a subset of hydroxyzine users will experience withdrawal symptoms following treatment cessation.

Nevertheless, a paper by Cherry (1949) supports the idea that antihistamine withdrawal can occur in select individuals.  Antihistamine withdrawal symptoms typically emerge after the medication and its bioactive metabolites have been eliminated from systemic circulation – and persist for an average of 7 to 10 days from the date of onset.

Available case reports suggest that common antihistamine withdrawal symptoms include: nausea, vomiting, and diarrhea.  The severity and duration of withdrawal is thought to be influenced by variables such as: frequency of administration, dosing, and total duration of use – such that frequent, high-dose, and/or long-term use is associated with harsher and longer-lasting withdrawal.

Withdrawal symptoms associated with both hydroxyzine and alprazolam are hypothesized to stem from (1) neurophysiologic adaptations in response to frequent and/or long-term medication use that linger after medication cessation – and (2) the neurochemical transition from a medication-adapted state to homeostasis (pre-medication neurochemistry).  When hydroxyzine or alprazolam is administered consistently and/or frequently for a long-term, the user’s neurochemistry adapts to its presence.

For example, adaptations to chronic hydroxyzine administration might include upregulation of H1 receptors and super-sensitivity of H1 receptors to histamine.  Additionally, hypothesized adaptations to benzodiazepines like alprazolam include: altered mRNA transcription for GABA receptor subunits; GABA receptor subunit degradation; lower production of GABAA receptor-associated helper proteins; shifts in GABAA receptor endocytosis; alterations in glutamatergic transmission; and changes in levels of neurotrophic factors.

As a result of the aforementioned prospective adaptations to hydroxyzine and alprazolam, long-term and/or frequent users will require continued medication administration to maintain neurochemical balance.  If either hydroxyzine or alprazolam treatment ends, neurochemical disequilibrium ensues – leading to unpleasant withdrawal symptoms.

Only when the neurochemistry of a former user has completed the transition from “medication-adapted” to “homeostasis” (pre-medication activity) will the withdrawal symptoms cease.  It is thought that withdrawal is shorter-lived among hydroxyzine (and antihistamine) users than alprazolam (and benzodiazepine) users.

In fact, a subset alprazolam users may be at risk of experiencing post-acute withdrawal syndrome (PAWS) in which withdrawal symptoms persist for months after the date of cessation.  Moreover, the GABAergic adaptations to alprazolam coupled with its short elimination half-life (9 to 16 hours) can cause life-threatening or deleterious adverse reactions in withdrawal such as: seizures, tremor, severe anxiety, palpitations, sweating, racing thoughts, panic attacks, high blood pressure, and heightened muscle tension.

Compared to alprazolam, hydroxyzine: (1) probably induces histaminergic (rather than GABAergic) adaptations and (2) exhibits a longer elimination half-life (20 to 37 hours) – each of which should make for shorter-lived, less prevalent, and/or lower-severity withdrawal symptoms (relative to alprazolam).  In closing, there’s minimal evidence to suggest that hydroxyzine (Atarax or Vistaril) withdrawal exists – whereas there’s ample evidence to substantiate the existence of alprazolam (Xanax) withdrawal.

If comparing hydroxyzine (Atarax or Vistaril) and alprazolam (Xanax) in the specific domain of withdrawal – hydroxyzine should be considered superior over alprazolam because its withdrawal: (1) is less likely to occur; (2) is not life-threatening; (3) yields fewer symptoms; and (4) is shorter-lived.  Alprazolam withdrawal can be life-threatening, dangerous, long-lasting – and requires guidance from a medical doctor.

Similarities (Recap): Vistaril (hydroxyzine) vs. Xanax (alprazolam)

Included below is a synopsis of general similarities associated with hydroxyzine (Atarax or Vistaril) and alprazolam (Xanax).  Various similarities between hydroxyzine and alprazolam include: cost; duration of action (standard formats); medical uses; effectiveness for respective medical indications; generic availability; and side effects.

  • Cost: The cost of standard generic hydroxyzine formats (pamoate and hydrochloride) does not substantially differ from the cost of standard generic alprazolam. Hydroxyzine pamoate ranges from $0.17 to $0.74 per capsule; hydroxyzine hydrochloride ranges from $0.10 to $0.52 per tablet; and alprazolam ranges from $0.05 to $0.35 per tablet.  Moreover, oral solution formats of hydroxyzine and alprazolam are analogously-priced when controlling for magnitude of dose.
  • Duration of action: The estimated duration of effect for standard hydroxyzine and alprazolam formats is 4 to 6 hours. Additionally, hydroxyzine and alprazolam exhibit similar onsets of action at 15 to 30 minutes (hydroxyzine) and 20 to 40 minutes (alprazolam).  In other words, both medications should “kick in” relatively quickly and alleviate symptoms for roughly the same duration.
  • Effectiveness: Although their official medical uses differ, hydroxyzine (Atarax or Vistaril) and alprazolam (Xanax) are both regarded as safe and effective medical interventions.  Hydroxyzine is considered clinically effective as a treatment for: (1) pruritus associated with chronic allergic conditions and (2) anxiety and/or tension associated with psychoneurosis or organic disease.  Alprazolam is considered clinically effective as a treatment for (1) generalized anxiety disorder and (2) panic disorder.  No studies have directly compared the efficacies of hydroxyzine and alprazolam for any specific condition.
  • Generic availability: Atarax (hydroxyzine hydrochloride) and Vistaril (hydroxyzine pamoate) were released for pharmaceutical sale in 1956 and 1968, respectively – and Xanax (alprazolam) was released for pharmaceutical sale in 1981 – throughout the U.S. Because the patents for these medications have long-expired, Atarax, Vistaril, and Xanax are available as low cost generics under the names: “hydroxyzine HCL,” “hydroxyzine PAM,” and “alprazolam.”
  • Medical uses: Despite differences in the official medical uses of hydroxyzine and alprazolam, there’s some degree of overlap in how each agent is used in medical settings. Both medications can be administered as anxiolytics – and each medication has shown therapeutic utility in treating anxious conditions for which only the other agent is officially approved.  For example, studies suggest hydroxyzine is effective for generalized anxiety disorder – and that alprazolam is effective in treating psychoneurosis-related anxiety.  Moreover, hydroxyzine and alprazolam are both used “off-label” to treat insomnia and emetic symptoms (e.g. nausea and vomiting).
  • Side effects: Though hydroxyzine and alprazolam exhibit substantially different mechanisms of action, the most common side effects for these medications are similar. The most prevalent side for both hydroxyzine and alprazolam is drowsiness – occurring in over 10% of users.  Other common side effects for both medications include: dizziness or lightheadedness, dry mouth, fatigue, headache, and gastrointestinal reactions.

Note: If you know of additional similarities between Vistaril (hydroxyzine) and Xanax (alprazolam), be sure to document them in the comments.

Differences (Recap): Vistaril (hydroxyzine) vs. Xanax (alprazolam)

Included below is a synopsis of general differences between hydroxyzine (Atarax or Vistaril) and alprazolam (Xanax).  Various differences between hydroxyzine and alprazolam include: abuse potential; approved medical uses; drug classification; availability of specific formats; elimination half-life; legal status; mechanism of action; popularity; metabolism; and withdrawal.

  • Abuse potential: Although there are case reports of antihistamine abuse and data from animal studies suggesting that H1 inverse agonists (like hydroxyzine) might lead to psychological reinforcement, antihistamines like hydroxyzine are seldom abused.  In comparison, benzodiazepines like alprazolam rapidly induce relaxation (via GABA modulation) and stimulate reward centers (via downstream increases in dopamine signaling) such that there’s a higher potential for abuse and/or addiction.  As of current, alprazolam is the most-abused benzodiazepine on the market and among the most-abused pharmaceutical medications in circulation.
  • Approved medical uses: There are notable disparities in the official FDA-approved medical uses for hydroxyzine and alprazolam.  Unlike alprazolam, hydroxyzine is specifically approved as a treatment for (1) pruritus associated with allergic conditions – plus as an adjunct treatment for (2) psychoneurosis-related anxiety and tension, and (3) anxiety associated with states of organic disease.  Unlike hydroxyzine, alprazolam is specifically approved as a treatment for generalized anxiety disorder and panic disorder.
  • Drug classification: Due to substantial differences in chemical structure and mechanism of action – hydroxyzine (Vistaril) and alprazolam (Xanax) differ in drug classification. Hydroxyzine is technically classified as a diphenylmethylpiperazine (i.e. benzhydrylpiperazine) antihistamine – based upon the fact that its core chemical structure contains a piperazine ring with a diphenylmethyl (benzhydryl) group bound to one of the nitrogens.  Alprazolam is technically classified as a triazolobenzodiazepine anxiolytic – based upon the fact that its core chemical structure contains a benzene ring fused to a diazepine ring with an attached triazole ring.
  • Formatting: Although hydroxyzine and alprazolam are both available in immediate-release and oral solution formats, additional formats for these medications differ. Hydroxyzine is available in the format of injectable vials for intramuscular administration (and alprazolam is not).  Unlike hydroxyzine, alprazolam is available as an orally-disintegrating tablet which dissolves in the mouth without swallowing and an extended-release tablet which provides a longer duration of action.
  • Half-life: The elimination half-life of Vistaril (hydroxyzine) ranges from 20 to 37 hours in healthy adults (on average) – whereas the elimination half-life of Xanax (alprazolam) ranges from 9 to 16 hours in healthy adults (on average). Furthermore, a minor hydroxyzine metabolite exhibits a half-life of around 59 hours (longer than the parent compound) – whereas alprazolam metabolites exhibit half-lives lesser than the parent compound.  As a result, hydroxyzine and its metabolites linger in systemic circulation for a longer duration following cessation – than alprazolam and its metabolites.
  • Legal status: In the United States, Vistaril (hydroxyzine) is considered a prescription-only (Rx-only) substance – whereas Xanax (alprazolam) is considered a “Schedule IV” controlled-substance. The “Schedule IV” scheduling likely makes it more difficult to receive a prescription and/or refills for alprazolam – relative to standard prescriptions like hydroxyzine.  (Refills for controlled-substances like alprazolam require frequent checkups and handwritten authorization – whereas refills for standard prescriptions like hydroxyzine can be issued electronically without regular checkups).
  • Mechanism of action: The predominant mechanism of action for Vistaril (hydroxyzine pamoate) involves H1 receptor inverse agonism – and the predominant mechanism of action for Xanax (alprazolam) involves positive allosteric modulation of GABAA receptors. In other words, Vistaril mostly modulates the neurotransmission of histamine and Xanax mostly modulates the neurotransmission of GABA.
  • Ingredients: The active ingredient within Vistaril is the chemical “hydroxyzine pamoate” – whereas the active ingredient within Xanax is the chemical “alprazolam.” Hydroxyzine pamoate is a diphenylmethylpiperazine – and alprazolam is a triazolobenzodiazepine.
  • Inventors: Hydroxyzine was synthesized by chemists at Union Chimique Belge (UCB) in the 1950s – whereas alprazolam was synthesized by chemists at Upjohn Laboratories in the 1960s. Roerig pharmaceuticals first attained the rights to market hydroxyzine in the U.S. – and Upjohn Laboratories marketed alprazolam in the U.S.  Because Pfizer owns Roerig and Upjohn, both Vistaril and Xanax were under Pfizer Inc. ownership.
  • Metabolism: The specific process by which hydroxyzine is metabolized differs from that of alprazolam. Though both substances are metabolized hepatically (i.e. within the liver), hydroxyzine undergoes oxidation via the ADH (alcohol dehydrogenase) enzyme to form the major metabolite “cetirizine” (45%) and minor N-dealkylated and O-dealkylated metabolites.  Alprazolam undergoes oxidation via the CYP3A4 enzyme to form alpha-OHALP (alpha-hydroxy alprazolam) and 4-OHALP (4-hydroxy alprazolam) metabolites.
  • Popularity: There are marked differences in the respective popularities of Vistaril (hydroxyzine) and Xanax (alprazolam) in the United States. As of 2015, over 27 million prescriptions were filled for alprazolam – whereas 8.3 million prescriptions were filled for hydroxyzine.  Based on annual prescription numbers, generic Xanax (alprazolam) appears significantly more popular than generic Vistaril (hydroxyzine).
  • Withdrawal: Although long-term and/or frequent use of antihistamines like hydroxyzine may yield withdrawal symptoms following discontinuation, these symptoms are reportedly of minor severity and short-lived (7 to 10 days). Furthermore, there are no strong data in medical literature to substantiate the existence of hydroxyzine withdrawal.  In comparison, there are strong data substantiating the existence of alprazolam withdrawal.  Alprazolam withdrawal may yield severe and/or long-lasting symptoms – some of which can be life-threatening.

Note: If you know of additional differences between Vistaril (hydroxyzine) and Xanax (alprazolam), be sure to document them in the comments.

Which medication is “better”? Vistaril (hydroxyzine) vs. Xanax (alprazolam)

If comparing the general medical usefulness of Vistaril (hydroxyzine pamoate) and Xanax (alprazolam), it’s unclear as to whether one medication can be considered “better” than the other.  Each medication understood to be safe, effective, and well-tolerated for different medical conditions: hydroxyzine for pruritus AND psychoneurosis-related anxiety and tension AND anxiety associated with organic disease – and alprazolam for generalized anxiety disorder AND panic disorder.

Assuming we’re comparing Vistaril and Xanax in the treatment of medical conditions for which only the other agent has received medical approval – it’s unclear as to whether the agents would differ in efficacy (other than in the treatment of pruritus).  Logically, one would expect Vistaril to outperform Xanax as a treatment for pruritus [associated with chronic allergic conditions] – based on the fact that Vistaril is an antihistamine and Xanax is not.

As treatments for anxious conditions, preliminary evidence suggests that hydroxyzine (Vistaril) is effective for the treatment of generalized anxiety disorder and panic disorder (conditions for which alprazolam is approved) – and that alprazolam (Xanax) is effective for the treatment of psychoneurosis-related anxiety (a condition for which hydroxyzine is approved).  Because no studies have directly compared hydroxyzine to alprazolam for the treatment of any anxious condition – we cannot know whether these agents differ in anxiolytic efficacy.

However, multiple studies have compared the effectiveness of hydroxyzine to that of buspirone and bromazepam, respectively, in the treatment of generalized anxiety disorder.  These studies suggested that hydroxyzine was as efficacious as buspirone (an agent that’s medically approved to treat generalized anxiety disorder) and bromazepam (an agent with the same primary neurochemical action and classification as alprazolam).

Although the anxiolytic efficacy of hydroxyzine might differ from the anxiolytic efficacy of alprazolam, there are no data to substantiate hypothesized differences.  For this reason, we cannot definitively conclude that one medication exhibits superior anxiolytic efficacy for any specific anxious condition – relative to the other.

Nevertheless, hydroxyzine may be a “better medication choice” than alprazolam among patients with: pruritus associated with chronic allergic conditions; anxiety and tension associated with psychoneurosis; and anxiety associated with organic disease states – because its use for these conditions is supported by quality evidence.  Similarly, alprazolam may be a “better medication choice” than hydroxyzine among patients with: generalized anxiety disorder and panic disorder – because its use for these conditions is supported by quality evidence.

In addition to there being zero documented differences in anxiolytic efficacy, hydroxyzine and alprazolam are similar in: onset of action (15 to 30 minutes – hydroxyzine vs. 20 to 40 minutes – alprazolam); standard duration of action (4 to 6 hours); long-term effects (e.g. cognitive impairment, increased risk of dementia, etc.); and side effects (e.g. drowsiness, headache, dry mouth, etc.).  That said, some might consider hydroxyzine or alprazolam as superior over the other in different aspects.

Hydroxyzine might be regarded as superior over alprazolam in aspects of: abuse potential; formatting; half-life; legal status; and withdrawal symptoms.  This is because hydroxyzine: (1) has a lower abuse potential than alprazolam; (2) provides formatting options (hydrochloride vs. pamoate, intramuscular) that alprazolam doesn’t; (3) has a longer elimination half-life and predictably easier withdrawal than alprazolam; and (4) is available as a standard prescription (unlike alprazolam) – which makes for easier prescription refills.

Alprazolam might be regarded as superior over hydroxyzine in aspects of: cost; formatting; and medical indications.  This is because alprazolam: (1) sells for a slightly lower average price than hydroxyzine; (2) provides formatting options that hydroxyzine doesn’t (e.g. orally-disintegrating tablet and extended-release tablet); and (3) is approved to treat generalized anxiety disorder and panic disorder as a standalone – whereas hydroxyzine is only approved as an adjunct in the treatment of anxious conditions.

Hypothetically assuming that hydroxyzine and alprazolam were equally safe, effective, and tolerable in treating a specific medical condition – then hydroxyzine should probably be regarded as the better intervention (over alprazolam) on the basis of its: (1) lower abuse potential and (2) nonexistent OR low-severity, short-lived withdrawal.  Moreover, the legal status of hydroxyzine as a standard-prescription enables patients to attain refills with less hassle – relative to alprazolam.

Alprazolam may have some [albeit less significant] advantages over hydroxyzine in aspects of (1) cost; (2) availability as an orally-disintegrating tablet (providing a convenient mode of administration) and extended-release tablet (providing a longer duration of action); and (3) medical indications (generalized anxiety disorder and panic disorder).  That said, neither medication appears substantially favorable over the other in: long-term effects; tolerability; therapeutic efficacy; and onset of action.

Select patients and/or medical doctors may prefer using one medication (hydroxyzine or alprazolam) over the other based on variables such as: cost, legal status, mechanism of action, metabolism, and/or formatting.  Nevertheless, the specific medical condition being treated and/or physiologic signature of the patient (genetics, epigenetics, neurochemical footprint, etc.) – will probably determine whether one medication ends up being more tolerable and/or effective relative to the other.

Note: In the event that you’re attempting to determine whether hydroxyzine or alprazolam is better for the management of your anxiety, consider using a journal to document how you feel each day while using these medications.  Maintaining a journal makes it easier to evaluate and compare efficacy and tolerability (i.e. side effects) of each agent over an extended period.

Which medication do you prefer: Vistaril (hydroxyzine) or Xanax (alprazolam)?

Assuming you’ve tried both hydroxyzine (Vistaril or Atarax) and alprazolam (Xanax) for the treatment of anxiety (or another medical condition), leave a comment comparing your experiences with each medication.  In your comment, document any similarities and/or differences that you noticed between hydroxyzine and alprazolam.

After having used hydroxyzine and alprazolam, have you developed a preference for using one medication over the other?  Or do you consider the medications to be equally efficacious medical treatments?  If you prefer using hydroxyzine over alprazolam (or vice-versa), mention reasons for your preference such as: faster onset of action; greater effectiveness; longer-lasting symptom relief; lower cost; fewer and/or less debilitating side effects; and/or an easier withdrawal process.

If you’re a person who found one medication (hydroxyzine or alprazolam) to be more effective than the other for your anxiety (or medical condition), might the differences in efficacies be attributable to disparities in: relative dosage (i.e. potency); concurrent substance use (along with each agent); frequency of administration; length of use; and/or routes of metabolism?

To help others fully understand your experiences with hydroxyzine and alprazolam, consider noting things like: (1) dosages that were administered; (2) frequencies and durations of use; (3) specific formats administered; (4) concurrent substance usage (medications, supplements, etc.); and (5) the specific medical condition for which these agents were prescribed.

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