Ativan and Xanax are two of the most popular benzodiazepine medications commonly administered for the treatment of anxiety. Ativan is indicated (FDA approved) for the treatment of anxiety disorders, acute anxiety, and/or anxiety associated with depressive symptoms – and Xanax is indicated (FDA approved) for the treatment of anxiety disorders and panic disorder.
D.J. Richards, president of research at Wyeth Pharmaceuticals, is credited for the development of Ativan (also formerly sold under the name “Temesta”) – and chemists at Upjohn Laboratories (eventually acquired by Pfizer Inc.) are understood to have synthesized Xanax. In the United States, Ativan was first available as a prescription in 1977 and Xanax became available in 1981.
Ativan vs. Xanax (Comparison)
Included below is a breakdown of general attributes of Ativan compared with those of Xanax in the format of a chart. The chart showcases basic similarities and differences between Ativan (Lorazepam) and Xanax (Alprazolam). If you happen to have questions about particular similarities and/or differences between these agents – it is recommended to consult a medical doctor or pharmacist.
|Approved medical uses||Anxiety disorders. Acute anxiety. Anxiety associated with depressive symptoms.||Generalized anxiety disorder. Panic disorder.|
|Off-label uses||Seizures (Convulsive status epilepticus, Resistant absence seizures). Alcohol withdrawal syndrome. Sedation induction. Agitation. Catatonia. Chemotherapy-induced nausea and vomiting. Restless leg syndrome. Insomnia.||Chemotherapy-induced nausea and vomiting. Insomnia. Agitation. Premenstrual dysphoric disorder.|
|Bioavailability||~90% (oral)||~90% (oral)|
|Formats||Tablet. Oral solution.||Tablet. Extended-release (XR or ER) pill. Oral disintegrating tablet. Oral solution.|
|Dosages||Tablet: 0.5 mg, 1 mg, 2 mg|
Oral solution: 30 mg of 2 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
|Manufacturer||Wyeth Pharmaceuticals||Pfizer Inc. (Upjohn)|
|Legal status||Schedule IV (U.S.)||Schedule IV (U.S.)|
|Mechanism of action||GABAA receptor positive allosteric modulator (PAM).|
Increases GABAergic activity throughout the cerebral cortex and enhances synaptic GABA responses.
Inhibits voltage-gated sodium channels (VGSCs) and high-frequency repetitive neuronal firing.
Decreases D2 & D3 receptor binding in medial temporal, and dorsolateral prefrontal cortex.
|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-Life||10 to 20 hours (~12 hours)||9 to 16 hours (~12 hours)|
|Common side effects||Sedation. Dizziness. Weakness. Unsteadiness.||Drowsiness. Lightheadedness. Dry mouth. Depression. Headache. Constipation. Diarrhea.|
|Duration of effect||4 to 8 hours||Standard: ~5 hours|
Extended-release: ~11 hours
|Metabolism||Hepatic: UGT2B15. (Glucuronidation)||Hepatic: CYP3A4. (Microsomal oxidation)|
|Onset of action||5 to 30 minutes||20 to 40 minutes|
Ativan vs. Xanax: What are some notable differences?
Notable differences between Ativan and Xanax include: approved medical uses; off-label uses; available formats; and onset of effect. Historically, Ativan is regarded as a “classical” benzodiazepine (as a result of its inception in the 1970s), whereas Xanax is classified as a newer “triazolo” benzodiazepine (as a result of its chemical structure containing an additional triazole ring).
In medical settings, both Ativan and Xanax are administered for anxiety disorders, however, Ativan is approved by the U.S. FDA to treat acute episodes of anxiety and anxiety associated with depressive symptoms – whereas Xanax is not. On the other hand, Xanax is approved by the U.S. FDA as a specific treatment for panic disorder – whereas Ativan is not.
Though there’s some overlap in off-label uses for Ativan and Xanax, Ativan is more frequently utilized off-label to treat seizure disorders (e.g. convulsive status epilepticus and resistant absence seizures) and catatonia, as well as induce sedation. Xanax might be more frequently utilized off-label for the treatment of premenstrual dysphoric disorder.
Moreover, while Ativan and Xanax are manufactured in standard tablet and oral solution formats, only Xanax is available in additional formats such as: orally-disintegrating tablet and extended-release tablet. This means that Xanax users have two additional formats of the medication to utilize that remain unavailable to Ativan users.
Some users claim that Ativan takes effect (i.e. “kicks in”) at a faster rate than Xanax kicks in – 5 to 30 minutes versus 20 to 40 minutes, respectively. However, whether Ativan legitimately exhibits a universally significant faster onset of action relative to Xanax remains scientifically unsubstantiated.
Routes of metabolism also differ between Ativan and Xanax. Following oral ingestion, Ativan is metabolized primarily within the liver via a process known as glucuronidation. The glucuronidation of Ativan is thought to be facilitated primarily by the enzyme UGT2B15.
Although Xanax is also metabolized primarily within the liver, its metabolism is facilitated by the enzyme CYP3A4. Lastly, the most common effects associated with Ativan include: sedation, dizziness, weakness, and unsteadiness – whereas the top side effects associated with Xanax include: drowsiness, lightheadedness, dry mouth, and depression.
Addiction & abuse potential
Although Xanax is the most abused and misused benzodiazepine, this is largely due to its popularity. Comparatively, Ativan and Xanax do not differ in addiction and abuse potential.
Ativan and Xanax are each classified as “Schedule IV” substances – indicating that both medications can induce modest psychological and/or physical dependence in select users. Patients who intentionally misuse or administer these medications in ways that are inconsistent with medical recommendations are thought to be at highest risk for developing dependence.
Despite the “Schedule IV” status of Ativan and Xanax, it is important to underscore the fact that benzodiazepines as a drug class are considered by researchers as being among the most addictive drugs in mainstream use. The addiction and abuse potential of Ativan and Xanax is related to their mechanism of action involving modulation of GABA receptors.
Specifically, Ativan and Xanax modulate subunits of the GABAA receptor to reduce inhibitory interneuron firing rates within the ventral tegmental area (VTA) of the brain. In response to reduced inhibitory interneuron firing in the ventral tegmental area, neurons responsible for secreting dopamine are less likely to fire – yielding increased dopamine levels in the extracellular space.
The increase in extracellular dopamine can cause some users to report a euphoriant effect or state of pleasurable intoxication. This “feel good” intoxication coupled with the rapid onset of action, anxiolytic effect, and myorelaxant effect of Ativan and Xanax can lead to an addiction or dependence in a subset of the populace.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/3061941
- Source: https://www.ncbi.nlm.nih.gov/pubmed/2051498
- Source: https://www.ncbi.nlm.nih.gov/pubmed/3234245
- Source: https://www.ncbi.nlm.nih.gov/pubmed/7625464
Approved medical uses
Ativan is approved by the U.S. FDA for the treatment of anxiety disorders, acute anxiety, and anxiety associated with depressive symptoms. Xanax is approved by the U.S. FDA for the treatment of anxiety disorders, and specifically, for the treatment of panic disorder.
Despite the fact that Ativan and Xanax are both indicated as treatments for anxiety disorders, only Xanax is indicated as a specific treatment for panic disorder (Ativan is not). However, unlike Xanax, only Ativan is indicated as a specific treatment for acute anxiety and anxiety associated with depressive symptoms.
While official medical uses of Ativan and Xanax (based on U.S. FDA approvals) slightly differ, each of these medications are used somewhat interchangeably to treat various types of anxiety. It isn’t uncommon for Ativan to be prescribed for managing panic disorder – and it isn’t uncommon for Xanax to be prescribed for managing acute anxiety or anxiety associated with depressive symptoms.
Additionally, both Ativan and Xanax are frequently prescribed “off-label” to address symptoms of medical conditions for which FDA approval hasn’t been attained. Ativan is sometimes used as an off-label intervention for seizures (convulsive status epilepticus and resistant absence seizures), alcohol withdrawal syndrome, to enhance sedation (prior to anesthesia), agitation, catatonia, chemotherapy-induced nausea and vomiting, restless leg syndrome, and insomnia.
Xanax is sometimes used as an off-label intervention for chemotherapy-induced nausea and vomiting, insomnia, agitation, and premenstrual dysphoric disorder. Even though Ativan might have more off-label appeal than Xanax – most experts consider the medications to be relatively comparable and somewhat exchangeable as off-label interventions.
Cost: Which is more expensive?
The price of generic Ativan (lorazepam) and Xanax (alprazolam) tablets is nearly identical; most consumers wouldn’t consider the pricing to really differ between the generics. To acquire 60 tablets of generic Ativan (lorazepam) – it costs between $8 and $23 (on average), whereas to acquire 60 tablets of generic Xanax (alprazolam) – it costs between $7 and $21 (on average).
- Ativan tablets (generic): $8.03 to $23 (60 tablets)
- Ativan standard (brand): $1392.93 to $3200 (60 tablets)
- Ativan dropper (oral solution): $21.06 to $27 (1 bottle – 30 ml of 2 mg/ml)
- 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)
Though it’s extremely uncommon for modern-day consumers to pursue “brand name” formats of Ativan or Xanax due to the fact that generics contain the same chemical, are widely available, and substantially cheaper – some patients may be convinced that brand name options are somehow superior. To purchase 60 standard brand name Ativan tablets – it’ll cost between $1393 and $3200 (on average).
To purchase 60 standard brand name Xanax tablets – it’ll cost between $245 and $800 (on average). Upon comparison of brand name Ativan and Xanax, it appears as though the brand name Xanax is considerably (4 to 5-fold) less expensive.
The generic oral solution of Ativan (sometimes referred to as “dropper” format) costs between $21 and $27 (on average) for a bottle with 30 ml of 2 mg/ml – and the generic oral solution of Xanax costs between $47 and $103 for a bottle with 30 ml of 1 mg/ml. Comparing the cost of generic Ativan and Xanax oral solution – it seems as though Ativan oral solution is notably (2 to 4-fold) less expensive.
It is necessary to highlight the fact that Xanax is manufactured in the format of a generic orally-disintegrating tablet (ODT) and generic extended-release tablet (XR or ER) – whereas Ativan is not. The cost of generic Xanax ODT ranges from $29 to $183 (on average) and the cost of generic Xanax XR or ER ranges from $16 to $67 (on average).
To summarize: generic Ativan (lorazepam) and Xanax (alprazolam) tablets are of relatively equal price; brand name Ativan tablets are substantially more expensive than brand name Xanax tablets; and generic Ativan (lorazepam) oral solution is less expensive than generic Xanax (alprazolam) oral solution.
Note: It is important to keep in mind that pricing for Ativan and Xanax could be subject to future change. Additionally, the cost of each medication is generally dose-dependent; larger doses tend to be costlier than smaller doses (regardless of whether brand name or generic). Pricing may also vary depending on the vendor or pharmacy.
Dosage & Formats
Ativan and Xanax are each manufactured in the format of: (1) immediate-release tablets (standard) and (2) oral solution (i.e. dropper). Immediate-release Ativan tablets are sold in dosages of: 0.5 mg, 1 mg, and 2 mg – whereas immediate-release Xanax tablets are sold in dosages of: 0.25 mg, 0.5 mg, 1 mg, and 2 mg.
For some individuals, standard Xanax might be perceived as advantageous over standard Ativan due to its additional and smaller dosage increment of 0.25 mg. The smaller dosage increment of 0.25 mg might make it easier to titrate on or tapering off the medication – particularly if splitting or cutting pills is necessary.
Furthermore, some individuals might find that using low doses of 0.25 mg (or 0.125 mg) of Xanax effectively addresses symptoms of their medical condition. Though Ativan can be split and reduced to 0.25 mg, it’s probably more difficult to split Ativan to reach doses of 0.125 mg or 0.0625 mg – versus Xanax, largely due to the availability of a lower Xanax dose (0.25 mg).
A bottle of Ativan oral solution (i.e. dropper) contains a total of 30 ml with 2 mg/ml doses, whereas a bottle of Xanax oral solution contains a total of 30 ml with 1 mg/ml doses. One might argue that a bottle of Ativan oral solution (30 ml) is be a better value than a bottle of Xanax oral solution (30 ml) based upon the fact Ativan contains 2 mg/ml versus the 1 mg/ml in Xanax.
However, studies indicate that 0.5 to 1 mg of Xanax doses is equivalent to 10 mg diazepam – whereas 1 to 2 mg of Ativan is equivalent to 10 mg diazepam. This supports the idea that Xanax might be more potent than Ativan. If Xanax is more potent than Ativan, then Ativan oral solution might not be significantly more cost-effective than Xanax oral solution – as some might have initially suspected based on milligram listings.
Unlike Ativan, Xanax is available in generic formats of orally-disintegrating tablet (ODT) and extended-release tablet (ER or XR). Orally-disintegrating Xanax tablets are sold at doses of: 0.25 mg, 0.5 mg, 1 mg, and 2 mg – and extended-release Xanax tablets are sold at doses of: 0.5 mg, 1 mg, 2 mg, and 3 mg.
Reflecting upon the available dosages and formats of Ativan and Xanax, Xanax users have more options in both dosing and formats. Medical professionals and/or patients may prefer to have a greater number of dosing options and formats for the sake of general convenience, dosage titration, discontinuation, and/or modifying the duration of benzodiazepine action.
In domains of dosing and formatting, Xanax should be regarded as a superior option to Ativan. Xanax is available: (1) in additional dosing increments in standard formats (convenient for dosage adjustments), (2) as an orally-disintegrating tablet (an alternative and convenient mode of administration), and (3) in the form of an extended-release tablet (which delivers an anxiolytic effect for ~11 hours).
Effectiveness: Which medication is more effective?
Upon evaluation of medical literature, there’s no conclusive data indicating that Ativan is more effective than Xanax (or vice-versa) for the treatment of anxiety disorders. Both Ativan and Xanax have undergone extensive testing in the form of large-scale randomized controlled trials with results of these trials supporting their safety, tolerability, and effectiveness in managing anxiety – relative to a placebo control.
Nevertheless, there are various studies that have directly compared the head-to-head efficacy and side effects of Ativan and Xanax. For example, a French study by Botte et al. (1981) involving 74 outpatients with anxiety compared the clinical efficacy and safety of Ativan and Xanax in a double-blind, randomized manner.
In the aforementioned study by Botte et al. (1981), 37 patients received Ativan (3 mg to 12 mg per day) and 37 patients received Xanax (0.75 mg to 3 mg per day) – each at flexible doses. The results of this small-scale study revealed that Ativan and Xanax medications were equally effective at weeks 2 and 4 of treatment based upon patient and physician scales.
It was noted by researchers that Ativan appeared more effective in the first week of treatment than Xanax, however, this may have been attributable to differences in dosing (~4.14 mg Ativan vs. ~0.99 mg Xanax). Another 16-week study by Cohn and Wilcox (1984) compared the anxiolytic effectiveness and safety of Ativan and Xanax in 200 patients diagnosed with moderate-to-severe anxiety.
The study was double-blinded, placebo-controlled, and implemented flexible dosing (2 mg to 9 mg per day for Ativan and 1 mg to 4.5 mg per day for Xanax). Results indicated that both Ativan and Xanax were substantially more effective than the placebo in reducing symptoms of anxiety – based on changes in scores on the Hamilton Anxiety Rating Scale.
It was noted by researchers that there was a trend towards greater efficacy with Xanax (relative to Ativan) in the later weeks of the study, but the difference in efficacy failed to reach statistical significance. Measures such as Target Symptoms, Physician and Patient Global Impressions, and the Self Rating Symptom Scale further supported the idea that Ativan and Xanax were equally efficacious (relative to a placebo) in treating anxiety.
A double-blind study by Italian researchers Bernardi et al. (1984) directly compared the efficacy of Ativan and Xanax for the treatment of “anxiety neurosis” among 58 patients. The 58 patients were divided into two groups (Ativan vs. Xanax) and matched for age, sex, marital status, and symptoms.
In this study, a total of 30 patients received Ativan (3 mg to 12 mg per day) and 28 patients received Xanax (0.75 mg to 3 mg per day) – for a total of 4 weeks. Results of the study indicated that both groups exhibited equally significant decreases in symptoms of anxiety – as evidenced by marked changes in scores on the Hamilton Anxiety Rating Scale and Clinical Global Impression scale at week 1, week 2, and week 4 – relative to baseline.
Throughout the trial there were no significant differences in levels of anxiety between the two groups at any checkpoint (e.g. week 1, week 2, week 4) – supporting the idea that Ativan and Xanax do not significantly differ in onset of therapeutic effect or overall anxiolytic efficacy.
Another study by Schweizer et al. (1990) compared the efficacy of Ativan and Xanax as interventions for panic disorder. A total of 67 patients diagnosed with panic disorder received a placebo for 1 week before a 6-week randomized double-blind phase in which they were randomly assigned to receive either Ativan (~7 mg per day) or Xanax (~3 mg per day).
Results of this study revealed that both Ativan and Xanax exhibited clinically significant and comparable efficacy in the treatment of panic disorder throughout the entire 6-week trial period. Researchers concluded that Ativan appears to be as effective as Xanax as an acute intervention for panic disorder.
A randomized, double-blind, controlled trial conducted by Laakman et al. (1995) aimed to elucidate the antidepressant efficacy and onset of action associated with Ativan, Xanax, and Amitriptyline – relative to a placebo in 342 patients diagnosed with depression of mild-to-moderate severity. The trial involved: a 6-week treatment phase followed by a taper period; a 2-week control phase with placebo; and a 2-week control phase without placebo.
Results indicated that all medications (Ativan, Xanax, Amitriptyline) were of equal efficacy and markedly more effective than a placebo for the treatment of depression over a 6-week period – as was evidenced by changes in scores on various rating scales (e.g. Clinical Global Impressions, Hamilton Rating Scales for Depression and Anxiety) and self-ratings (e.g. Patient’s Global Impressions, Self-rating Depression Scale and Visual Analogue Scale) relative to baseline.
In summary, findings from numerous head-to-head comparison-type studies are consistent in suggesting that Ativan and Xanax are of equal efficacy, safety, and tolerability as treatments for anxiety, panic disorder, and depression. Everything considered, there’s no reason to suspect that Ativan is more effective than Xanax or that Xanax more effective than Ativan as an anxiolytic.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/6125089
- Source: https://www.ncbi.nlm.nih.gov/pubmed/6144090
- Source: https://www.ncbi.nlm.nih.gov/pubmed/6571441
- Source: https://www.ncbi.nlm.nih.gov/pubmed/2187213
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Mechanism of action
The mechanisms of action (i.e. pharmacodynamics) associated with Ativan and Xanax are nearly identical. Ativan and Xanax function predominantly as positive allosteric modulators (PAMs) of GABAA receptor subunits whereby they increase the binding efficiency of GABA (gamma-aminobutyric acid), a major inhibitory neurotransmitter, to GABAA receptor sites.
GABAA receptors consist of 5 protein subunits (2-alpha, 2-beta, 1-gamma) and are ubiquitous throughout the central nervous system (CNS). Without the influence of benzodiazepines (such as in a sober state), the binding of GABA to GABAA receptor subunits is modest – but nothing significant.
When Ativan or Xanax is administered, the active respective chemicals lorazepam and alprazolam allosterically bind to the gamma subunits of GABAA receptors. In response to this allosteric binding, endogenous GABA binds with greater efficiency to alpha subunits of GABAA receptors.
Increased binding efficiency of GABA to alpha subunits of GABAA receptors allows negatively-charged chloride ions to enter neurons to induce neuronal hyperpolarization. Neuronal hyperpolarization occurs when the internal contents of a neuron is of greater negative charge than the external contents of a neuron.
After neuronal hyperpolarization has occurred, neuronal activity becomes inhibited or slowed such that neurons are less responsive (sometimes unresponsive) to stimulation from excitatory postsynaptic potentials. The inhibition of neuronal activity leads to a significant suppression of central nervous system (CNS) activation.
As a result of this action, users of Ativan or Xanax experience significant psychological and physical relaxation which counteracts preexisting symptoms of anxiety. Some researchers believe that, in addition to GABAergic actions, Ativan and Xanax modulate voltage-gated ion channels, including: voltage-sensitive calcium channels and voltage-gated sodium channels.
However, despite similarities in the primary mechanisms of action associated with Ativan and Xanax – the medications might differ in additional (e.g. secondary) neurophysiologic actions. For example, a study by van den Berg et al. (1996) reported that Xanax suppresses adrenomedullary activity but Ativan does not.
A study by Giardino et al. (1998) suggests that Xanax may increase D1 and D2 dopamine receptor density in the striatum. Additionally, according to Al-Tubuly et al. (2008), Xanax appears to generate an antidepressant effect by inducing norepinephrine release to stimulate β2 receptors and increases serotonin release in the hippocampus.
Research by Vilkman et al. (2009) reports that Ativan decreases D2 and D3 receptor binding potential in the medial temporal and dorsolateral prefrontal cortex to induce sedation. Although it remains unclear as to whether there’s any overlap between Ativan and Xanax in the aforementioned non-primary actions, it’s reasonable to expect subtle differences.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/8944402
- Source: https://www.ncbi.nlm.nih.gov/pubmed/19846281
- Source: https://www.ncbi.nlm.nih.gov/pubmed/9600648
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074285/
Metabolism & Half-Life
Although both Ativan (lorazepam) and Xanax (alprazolam) are metabolized primarily within the liver, their exact routes of metabolism differ significantly. Ativan is metabolized differently than most other benzodiazepines (except temazepam and oxazepam) in that it undergoes glucuronidation within the liver – likely facilitated by UGT2B15 enzymes.
Glucuronidation indicates that glucuronic acid is added to a substrate from UDP-glucuronic acid via a UDP glucuronosyltransferase. In other words, lorazepam (i.e. Ativan) is conjugated in the liver with glucuronic acid to form the water-soluble metabolite lorazepam-glucuronide.
Unlike Ativan, Xanax is metabolized via microsomal oxidation facilitated by CYP3A4 enzymes (cytochrome P450 3A4) in the liver. Xanax forms multiple active water-soluble metabolites such as: alpha-OHALP (alpha-hydroxy alprazolam) and 4-OHALP (4-hydroxy alprazolam); the former more bioactive than the latter.
The elimination half-life of Ativan generally falls within the range of 10 to 20 hours (~12 hours on average) and its biologically-inactive metabolite lorazepam-glucuronide exhibits an average elimination half-life of ~18 hours. The elimination half-life of Xanax and its biologically-active metabolites generally fall within the range of 9 to 16 hours (~12 hours on average).
Ativan became available as a prescription medication in 1977, whereas Xanax became available as a prescription medication in 1981. Considering that Ativan was released roughly 4 years prior to Xanax, it’s reasonable to speculate that Ativan may have been initially more popular than Xanax in the 1980s and/or 1990s.
However, because prescribing data from the 1980s and 1990s is unavailable, it remains unclear as to whether one medication was utilized at a significantly greater frequency than the other. Prescribing data included in the ClinCalc DrugStats database (2015) indicate that upwards of 15.6 million prescriptions were filled for generic Ativan (lorazepam) and that upwards of 27 million prescriptions were filled for Xanax (alprazolam) – making Xanax the more popular option.
In other words, approximately 11.4 million more prescriptions are filled for generic Xanax each year than generic Ativan. Comparatively, generic Ativan was the 55th most-prescribed medication and generic Xanax was the 23rd most-prescribed medication – in the United States (as of 2015).
Although there aren’t any major differences in safety, tolerability, or efficacy between Ativan and Xanax – Xanax is prescribed significantly more frequently. Perhaps the more frequent use (popularity) of Xanax is due to its availability in a greater number of formats and dosing increments (relative to Ativan) and/or its specific FDA approval for the management of panic disorder.
The most common Ativan side effects (according to FDA database reports) include: sedation, dizziness, weakness, and unsteadiness. The most common Xanax side effects (according to FDA database reports) include: drowsiness, lightheadedness, dry mouth, depression, headache, constipation, and diarrhea.
If basing side effect similarities and differences between Ativan and Xanax on FDA database reports, one might conclude that both medications cause similar rates of sedation or drowsiness. However, one might also conclude that Ativan is more likely to cause dizziness, weakness, and unsteadiness (relative to Xanax) – and that Xanax is more likely to cause lightheadedness, dry mouth, depression, headache, constipation, and diarrhea (relative to Ativan).
Because Ativan and Xanax exhibit nearly identical primary mechanisms of action (as GABAA receptor modulators), differences in side effects between the two medications is unlikely to be significant. Perhaps some differences in side effects are attributable to unique secondary mechanisms of action and/or differing routes of hepatic metabolism.
Most trials in which the tolerability of Ativan was compared with Xanax failed to report significant differences. For example, a randomized trial by Botte et al. (1981) reported no significant differences in rates of side effects among 74 patients with anxiety (37 received Ativan and 37 received Xanax); 57 side effects were reported in Ativan users and 61 side effects were reported in Xanax recipients.
A different 16-week trial by Cohn and Wilcox (1984) involving 200 patients with anxiety reported sedation and drowsiness as being the most common side effects of Ativan and Xanax (relative to a placebo). That said, there were no significant differences in side effect frequency between Ativan recipients and Xanax recipients; the medications appeared equally tolerable.
Another study by Schweizer et al. (1990) reported that while “sedation” is the most common side effect of both Ativan and Xanax, these medications are equally well-tolerated for the treatment of panic disorder. Still, worth noting is the fact that multiple studies have reported slight differences Ativan and Xanax side effects or side effect onset.
For example, a small-scale study (58 participants) by Bernardi et al. (1984) documented fewer side effects in recipients of Xanax (particularly less “confusion”) compared to recipients of Ativan. Another study by Block and Berchou (1984) noted that both Ativan and Xanax: impair memory and psychomotor performance, as well as increase sedation – each to a relatively equal extent.
However, according to these researchers, Xanax reportedly induces earlier memory and psychomotor impairment, as well as earlier recovery of these functions – in comparison to Ativan. Although it’s possible that the onset of certain side effects like memory and/or psychomotor impairment may be delayed in Ativan users relative to Xanax users – most data suggest that Ativan and Xanax induce similar side effects and rates of adverse reactions.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/6125089
- Source: https://www.ncbi.nlm.nih.gov/pubmed/6144090
- Source: https://www.ncbi.nlm.nih.gov/pubmed/2187213
- Source: https://www.ncbi.nlm.nih.gov/pubmed/6571441
- Source: https://www.ncbi.nlm.nih.gov/pubmed/6144110
Cessation of Ativan or Xanax after regular moderate-term or long-term use (or abuse) can yield debilitating withdrawal symptoms, and in select cases, post-acute withdrawal syndrome (PAWS). Debilitating discontinuation symptoms are understood to surface in the aftermath of benzodiazepine discontinuation due to neurophysiology undergoing transition from a benzodiazepine-adapted state to pre-benzodiazepine homeostasis.
Assuming Ativan or Xanax is administered daily for several months, the user’s neurophysiology will adapt to its presence and neurophysiologic effects – particularly within the GABA system. Ongoing exposure to Ativan or Xanax causes GABAA receptor subunits to “downregulate” or decrease in density relative to pre-treatment homeostasis – mostly due to excessive activation.
Once an individual becomes neurophysiologically-adapted to Ativan or Xanax treatment, the medication becomes mandatory to sustain neurotransmitter balance – particularly in the GABA system. If Ativan or Xanax treatment is discontinued, the former user’s neurotransmission can become grossly imbalanced or chaotic – because: (1) it’s still in a benzodiazepine-adapted state and (2) it’s no longer receiving the benzodiazepine necessary for neurotransmitter regulation.
Though the former user’s neurophysiology will slowly adjust itself back to pre-benzodiazepine homeostasis, the transition phase is not instantaneous – weeks or months may be required to attain homeostasis. Because neurotransmission is abnormal or chaotic in this transition phase (as evidenced by GABAA receptor subunit underactivation and excessive excitatory signaling), former Ativan or Xanax users experience discontinuation symptoms.
Examples of discontinuation symptoms include: rebound anxiety, racing thoughts, panic attacks, insomnia, hypertension, muscle tension, heart palpitations, rapid heart rate, seizures, and frequent urination. Knowing that withdrawal symptoms due to Ativan or Xanax discontinuation can be debilitating, it’s highly recommended that persons quitting either agent receive guidance from a psychiatrist or experienced medical doctor.
Comparatively, some might consider Ativan slightly easier to discontinue than Xanax due to the fact that it may have a slightly longer half-life range (on average); 10 to 20 hours for Ativan versus 9 to 16 hours for Xanax. A longer average elimination half-life should be advantageous in benzodiazepine cessation because the user’s neurophysiology ends up with more time to gradually adjust its functioning towards non-benzodiazepine homeostasis before the medication completely exits systemic circulation – allowing for an easier, less substantial transition from a benzodiazepine-adapted state to homeostasis.
Nevertheless, the half-life of standard Ativan tablets may not be significantly longer than the half-life of standard Xanax tablets – such that the Ativan withdrawal process may not be universally less difficult (i.e. easier) relative to Xanax withdrawal. Although some individuals may report that Ativan withdrawal is easier to manage than Xanax withdrawal as a result of its slightly longer elimination half-life, others may report that Xanax is easier to discontinue due to additional dosing increments and formats.
The bottom line is that Ativan and Xanax will be very similar in terms of both discontinuation symptoms and withdrawal difficulty for most users. Both medications will induce harsh withdrawal symptoms in long-term users – especially among individuals who quit abruptly (i.e. cold turkey) from high doses.
Professionals who are educated in managing Ativan or Xanax withdrawal may recommend transitioning patients Valium (diazepam) due to the fact that it has a markedly longer half-life than Ativan and Xanax. Once a patient has stabilized on Valium, the Valium can be gradually tapered with less severe and/or dangerous discontinuation symptoms – relative to Ativan or Xanax.
Similarities (Recap): Ativan vs. Xanax
Summarized below are similarities between Ativan (lorazepam) and Xanax (alprazolam).
- Abuse potential: Although Xanax is the most abused benzodiazepine on the market (mostly due to its popularity), the abuse potential is similar for Ativan and Xanax. Medical literature suggests that Ativan and Xanax exhibit low potential for abuse – when used in accordance with medical instruction. However, the abuse potential of Ativan and Xanax stems from a unique combination of rapid-onset anxiolytic and myorelaxant effects (due to GABA receptor modulation) and simultaneous euphoriant effects (due to dopamine release) – yielding a pleasurable state of intoxication.
- Cost: The cost of generic Ativan tablets and generic Xanax tablets is extremely similar. A supply of 60 generic Ativan tablets costs $8 to $23 (on average), whereas a supply of 60 generic Xanax tablets costs $7 to $21 (on average) – at most pharmacies.
- Drug classification: Ativan and Xanax are each broadly classified as “benzodiazepines” because their chemical composition consists of a benzene ring fused to a diazepine ring. As benzodiazepines, Ativan and Xanax function predominantly via allosterically modulating GABA receptors and GABA signaling.
- Duration of effect: The duration of effect for standard Ativan and Xanax tablets is similar. Each medication is thought to exert a psychoactive effect that lasts between 4 and 8 hours – following administration.
- Efficacy: Data from numerous large-scale, double-blind, randomized, controlled trials indicate that treatment with Ativan or Xanax significantly reduces symptoms of anxiety disorders. For this reason, each medication has received approval by the U.S. FDA for use as an anxiolytic in medically-appropriate circumstances. Moreover, comparison studies indicate that neither medication is of superior efficacy (relative to the other) among persons with anxiety.
- Generic availability: Because Ativan and Xanax were released in 1977 and 1981, respectively, the patents for brand name versions have long expired and each medication is available in generic formats. Generic Ativan is sold under the chemical name “lorazepam” and generic Xanax is sold under the chemical name “alprazolam.”
- Half-life: On average, the elimination half-life of Ativan ranges from 10 to 20 hours, whereas the elimination half-life of Xanax is 9 to 16 hours. However, some reports have documented an average half-life of ~12 hours for both Ativan and Xanax. Even if the half-life of Ativan is slightly longer than that of Xanax – most probably wouldn’t consider the difference to be significant.
- Legal status: Both Ativan and Xanax are legally considered “Schedule IV” substances in the United States. The “Schedule IV” status indicates that these substances: (1) exhibit lower abuse potential relative to Schedule III substances; (2) are approved for medical use; (3) may cause dependence (physical and/or psychological) when abused.
- Mechanism of action: The general primary mechanism of action associated with Ativan and Xanax is identical and involves positive allosteric modulation (PAM) of GABAA receptor subunits. Positive allosteric modulation of GABAA receptor subunits by Ativan and Xanax induces an influx of negatively-charged chloride ions into neurons whereby neuronal hyperpolarization occurs and CNS activation is suppressed.
- Medical uses: Ativan and Xanax are medically-approved as general treatments for anxiety disorders in the United States. Although Ativan is specifically approved to treat “acute anxiety” and “anxiety associated with depressive symptoms,” and Xanax is specifically approved to treat “panic disorder” – each medication is utilized primarily to reduce anxiety.
- Side effects: Because the primary mechanism of action associated with Ativan and Xanax is identical (positive allosteric modulator of GABAA receptors), the side effects are extremely similar. Both medications can cause cognitive deficits (e.g. memory problems), confusion, coordination deficits, depression, drowsiness, fatigue, motor impairment, and weakness.
- Withdrawal: Discontinuation of Ativan or Xanax can be challenging for long-term or chronic users – especially among persons who developed a tolerance to high doses. Once a user’s neurochemistry becomes adapted to the regular administration of Ativan or Xanax – discontinuation can induce a compensatory neurochemical reaction that may involve debilitating and potentially life-threatening reactions.
Differences (Recap): Ativan vs. Xanax
Summarized below are discernable differences between Ativan and Xanax.
- Cost: Despite there being no significant cost differences between generic Ativan tablets and generic Xanax tablets – there is a cost difference between the generic oral solution (i.e. dropper) formats and brand name tablets. A bottle (30 ml dosed at 2 mg/ml) of generic Ativan oral solution costs $21 to $27 (on average) and a bottle (30 ml dosed at 1 mg/ml) of generic Xanax oral solution costs $47 to $103 (on average). However, brand name Ativan is significantly more expensive than brand name Xanax ($1392 to $3200 vs. $245 to $800, respectively, for 60 tablets).
- Formats: Ativan and Xanax are both available in standard immediate-release tablet and oral solution formats. However, Xanax differs from Ativan in that it is also available in generic orally-disintegrating tablet (ODT) and generic long-acting or extended-release (ER or XR) formats.
- Half-life: Though the elimination half-life of Ativan is similar to the elimination half-life of Xanax, there are slight differences. Some reports note that the elimination half-life range for Ativan is 10 to 20 hours and that the elimination half-life range for Xanax is 9 to 16 hours. Other reports indicate that the full elimination half-life range for Xanax may span from 6.3 to 29 hours. There seem to be slight differences in typical elimination half-life ranges for each medication – and most speculate that the half-life of standard Ativan is slightly longer than the half-life of standard Xanax.
- Ingredients: The active ingredient in Ativan is the chemical “lorazepam” whereas the active ingredient in Xanax is the chemical “alprazolam.” Lorazepam is considered a classical benzodiazepine, whereas alprazolam is considered a newer “triazolo” benzodiazepine as a result of its structure containing an extra triazole ring attached to its diazepine ring.
- Manufacturers: Ativan was developed by Wyeth Pharmaceuticals and released in 1977, whereas Xanax was developed by Upjohn (acquired by Pfizer Inc.) and released in 1981.
- Metabolism: Although Ativan and Xanax both metabolized hepatically (within the liver), respective routes of metabolism for each medication differ. Ativan is metabolized through a process known as glucuronidation via the UGT2B15 enzyme. Xanax is metabolized through a process known as microsomal oxidation via the CYP3A4 enzyme.
- Medical approvals: While Ativan and Xanax are used for similar purposes and are generally considered interchangeable anxiolytic medications – the U.S. FDA approvals for each medication slightly differ. Ativan has received FDA approval to treat “acute anxiety” and “anxiety associated with depressive symptoms” – yet Xanax has not. Xanax has received FDA approval to treat panic disorder – yet Ativan has not.
- Popularity: Xanax remains the most popular and most-prescribed benzodiazepine on the market. Prescribing data from 2015 reveal that generic Xanax was prescribed over 27 million times over a 1-year span, whereas generic Ativan was prescribed over 15.6 million times during the same period. (Xanax is the ~23rd most-prescribed medication and Ativan is the ~55th most-prescribed medication).
Which medication is “better” for anxiety disorders? (Ativan vs. Xanax)
All data from large-scale randomized controlled trials are consistent in suggesting that Ativan and Xanax are safe, tolerable, and more effective than a placebo for the treatment of anxiety disorders – hence their FDA approval. Furthermore, studies that directly compare the safety, efficacy, and tolerability of Ativan and Xanax (in head-to-head manner) – report that neither medication exhibits superior efficacy relative to the other.
In other words, there’s no conclusive evidence suggesting that Ativan is superior in domains of safety, efficacy, tolerability to Xanax (or vice-versa) for the treatment of anxiety disorders. For this reason, most medical professionals consider Ativan and Xanax as being equally useful benzodiazepine anxiolytics for the management of anxiety.
Comparison studies documenting equivalent therapeutic efficacy for Ativan and Xanax include: Botte et al. (1981) – 74 outpatients with anxiety (4 weeks, double-blind, RCT); Cohn and Wilcox (1984) – 200 patients with moderate-to-severe anxiety (16 weeks, double-blind, RCT); Bernardi et al. (1984) – 58 patients with “anxiety neurosis” (4 weeks, randomized); Schweizer et al. (1990) – 67 patients with panic disorder (6 weeks, double-blind, RCT); Laakman et al. (1995) – 342 patients with mild-to-moderate depression (10 weeks, randomized, controlled).
No comparison studies suggest Ativan as being superior to Xanax – or Xanax as being superior to Ativan – for the treatment of anxiety disorders. The study by Botte et al. (1981) reported greater efficacy for Ativan in the first week of treatment (suggesting a faster onset of therapeutic action), however, the study was very small and differences in potency of dosing likely existed (~4.14 mg Ativan vs. ~0.99 mg Xanax).
The 16-week study by Cohn and Wilcox (1984) documented a trend towards greater efficacy with Xanax in the final weeks of treatment (relative to Ativan), however, differences weren’t of statistical significance. Although a subset of persons might assume that Ativan is superior to Xanax for “acute anxiety” and “anxiety associated with depressive symptoms” OR that Xanax is superior to Ativan for “panic disorder” (based on respective FDA approvals) – this assumption is scientifically unsubstantiated.
In fact, the study by Schweizer et al. (1990) reported that Ativan was as effective as Xanax for panic disorder (over a 6-week span) and that Xanax was as effective as Ativan (over a 10-week span) for mild-to-moderate depression. As treatments for anxiety disorders or anxious symptoms, there’s no reason to suggest that Ativan and Xanax differ in efficacy.
Additionally, in terms of tolerability, nearly all of the aforementioned comparison studies reported no significant differences in side effect frequency or severity among Ativan and Xanax users. Only one comparison study by Bernardi et al. (1984) documented fewer side effects in users of Xanax (specifically lower rates of “confusion”) compared to users of Ativan.
Considering the fact that Ativan is metabolized via hepatic glucuronidation – it may be more effective than Xanax among persons with abnormalities in expression of CYP3A4 (the enzyme that facilitates Xanax metabolism). Furthermore, because Ativan undergoes glucuronidation and Xanax undergoes microsomal oxidation (via CYP3A4), Ativan users may be at lower risk of experiencing deleterious pharmacokinetic interactions.
Nonetheless, knowing that Ativan and Xanax may differ in secondary neurochemical actions (i.e. actions beyond GABA receptor modulation), it’s possible that certain patients will report one medication as being subjectively more effective or tolerable than the other in treating anxiety. A unique combination of a user’s: genetics/epigenetics, preexisting neurochemistry, medical status, and concurrent substance use – will likely account for select patients preferring Ativan over Xanax (or the opposite).
On the basis of dosing and formatting, some medical professionals may regard Xanax as favorable over Ativan. Standard Xanax tablets are manufactured in more doses than standard Ativan tablets (which could make for easier titration) and Xanax is available in 2 formats that Ativan is not, including: extended-release and orally-disintegrating tablet (which may be preferred by patients).
To recap, Ativan and Xanax are considered clinically equal in measures of safety, tolerability, and effectiveness for the treatment of anxiety disorders. Most individuals will require some medically-supervised trial and error before they’re able to determine whether Ativan or Xanax is a better option for the management of anxiety.
In the event that you’re trying to choose between Ativan and Xanax for the treatment of anxiety, it is recommended to seek the help of an experienced medical doctor (particularly a psychiatrist) and discuss the “advantages” and “disadvantages” of each medication. While undergoing treatment, you may want to consider using a journal to track: (1) the subjective efficacy of each medication over time and (2) how well you’re tolerating each medication.
Which medication do you prefer: Ativan or Xanax?
In the event that you have personal experience using Ativan (lorazepam) and Xanax (alprazolam), share a comment discussing similarities and differences – and note whether you prefer one medication over the other for the treatment of anxiety (or another condition). Assuming you favor one medication over the other, highlight specific reasons for your favoritism.
Examples of reasons that you might prefer Ativan over Xanax (or the opposite) include: faster onset of action; longer duration of effect; greater anxiety reduction; superior tolerability; lower cost; and/or a lower-difficulty withdrawal process. If you consider one medication as being clearly superior to the other in efficacy – have you considered that relative dosages (i.e. potency) might account for the superiority?
Additionally, have you considered that your unique expression of the gene CYP3A4 (involved in Xanax metabolism) might explain why you find Xanax more effective OR less effective than Ativan? If you discontinued each medication separately, did you experience a more difficult withdrawal with one medication relative to the other?
To help readers understand your experiences using Ativan and Xanax, provide details such as: (1) your dosage; (2) how long you used each medication; (3) the dosage and/or format you used; (4) whether you administered other substances (medications, supplements, etc.) along with these benzodiazepines; (5) and the medical condition for which these medications were prescribed.