Klonopin and Xanax are widely-utilized benzodiazepine medications for the management of panic disorder with or without agoraphobia. The medications differ in that Klonopin is approved by the FDA for the treatment of seizure disorders such as: Lennox-Gastaut syndrome, akinetic seizures, and myoclonic seizures (Xanax is not) – and Xanax is approved by the FDA for the treatment of generalized anxiety disorder (Klonopin is not).
Chemist Leo Sternbach is credited as being first to synthesize Klonopin while working for the pharmaceutical company Hoffmann-La Roche – whereas Xanax was synthesized by chemists at Upjohn Laboratories (now Pfizer Inc.). Klonopin entered the United States pharmaceutical market in 1975 – whereas Xanax entered the United States pharmaceutical market in 1981.
Klonopin vs. Xanax (Comparison Chart)
Highlighted below are general attributes associated with Klonopin and Xanax compiled in chart format. This chart should showcase some basic similarities and/or differences between Klonopin (Clonazepam) and Xanax (Alprazolam). In the event that you have specific questions regarding similarities or differences between these medications – consult a medical doctor and/or pharmacist.
| Klonopin | Xanax | |
|---|---|---|
| Ingredient | Clonazepam | Alprazolam |
| Drug classification | Benzodiazepine | Triazolobenzodiazepine |
| Approved medical uses | Seizure disorders (Lennox-Gastaut syndrome, akinetic seizures, and myoclonic seizures). Panic disorder. | Generalized anxiety disorder. Panic disorder. |
| Off-label uses | Social phobia. Acute mania. Restless leg syndrome (RLS). Bruxism. Rapid eye movement behavior disorder. Akathisia. Spasticity (associated with ALS). Alcohol withdrawal syndrome. Aggression (associated with psychosis). Hyperekplexia. Parasomnia. | Chemotherapy-induced nausea and vomiting. Insomnia. Agitation. Premenstrual dysphoric disorder. |
| Average duration of use | ~3 months | ~8 months |
| Bioavailability | ~90% (oral) | ~90% (oral) |
| Formats | Tablet. Oral disintegrating tablet. | Tablet. Extended-release (XR or ER) pill. Oral disintegrating tablet. Oral solution. |
| Dosages | Tablet: 0.5 mg, 1 mg, 2 mg Oral disintegrating tablet: 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, 2 mg | Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg Oral disintegrating tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg Extended-release (XR) pills: 0.5 mg, 1 mg, 2 mg, 3 mg Oral solution: 30 ml 1 mg/ml |
| Manufacturer | Hoffmann-La Roche | 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 calcium channels (VGCCs) and high-frequency repetitive neuronal firing. Decreases the utilization of serotonin (5-HT) by neurons. | 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 | 18.7 to 60 hours (~40 hours) | 9 to 16 hours (~12 hours) |
| Common side effects | Somnolence. Fatigue. Depression. Dizziness. Abnormal coordination. Ataxia. | Drowsiness. Lightheadedness. Dry mouth. Depression. Headache. Constipation. Diarrhea. |
| Date approved | 1975 | 1981 |
| Duration of effect | 8 to 12 hours | Standard: ~5 hours Extended-release: ~11 hours |
| Metabolism | Hepatic: CYP3A4. | Hepatic: CYP3A4. |
| Onset of action | 20 to 60 minutes | 20 to 40 minutes |
Klonopin vs. Xanax: What are some basic differences?
Basic differences between Klonopin and Xanax include: medical indications; off-label uses; available formats; elimination half-life; duration of effect; and severity of withdrawal. Furthermore, while each of these medications are commonly referred to as benzodiazepines, Xanax is technically a “triazolobenzodiazepine” and Klonopin isn’t.
The triazolobenzodiazepine classification for Xanax is based upon the fact that Xanax is comprised of an additional fused triazole ring that aren’t present within the chemical structure of standard benzodiazepines like Klonopin. In addition to differences in chemical structure, each medication is prescribed for different medical purposes.
Both Klonopin and Xanax are approved by the United States FDA to treat panic disorder, however, of the two medications – only Klonopin is approved by the FDA to treat seizure disorders. That said, Xanax is FDA approved to treat generalized anxiety disorder – whereas Klonopin lacks approval for this condition.
Despite the fact that both medications are available in the format of standard tablet and oral disintegrating tablet – only Xanax is manufactured in formats such as: extended-release (XR) pills and an oral (liquid) solution. In other words, Xanax users have a greater number of formats to choose from while Klonopin users are restricted to standard and oral-disintegrating tablets.
Although Klonopin and Xanax can take effect rapidly, most sources suggest that Xanax kicks in at a slightly faster rate (usually within 40 minutes) than Klonopin (which can take up to 60 minutes). The duration of effect is also understood to be longer for standard Klonopin tablets relative to standard Xanax tablets.
On average, standard Klonopin tablets are estimated to exert a psychoactive effect for 8 to 12 hours, whereas standard Xanax and extended-release tablets are estimated to exert an effect for ~5 hours and ~11 hours, respectively. While the routes of metabolism for Klonopin and Xanax are similar such that each medication is “broken down” in the liver by the CYP3A4 enzyme (primarily), their elimination half-lives are markedly different.
Klonopin exhibits an average elimination half-life of ~40 hours, whereas Xanax exhibits an average elimination half-life of ~12 hours. This suggests that Klonopin stays in your system for a substantially longer term following cessation than Xanax stays in your system.
Due to exerting similar mechanisms of action, side effects are relatively comparable between Klonopin and Xanax. That said, the severity and/or difficulty of withdrawal following Klonopin may be slightly lesser than that of Xanax, largely because Klonopin exhibits a longer elimination half-life.
Addiction & abuse potential
Klonopin and Xanax are understood to exhibit relatively equivalent addiction and abuse potential. As “Schedule IV” controlled-substances, Klonopin and Xanax can induce modest psychological and/or physical dependence in a subset of users, especially in patients who deliberately misuse these medications, administering them in ways that are inconsistent with medical instruction.
Of all mainstream pharmaceutical medications and illicit drugs, benzodiazepines are regarded by experts as being among the most addictive drugs in the world. The addiction potential stems from the fact that Klonopin and Xanax are efficiently absorbed and penetrate the brain quickly after administration to bolster the neurotransmission of GABA (gamma-aminobutyric acid) via positive allosteric modulation – which suppresses CNS activation.
As a downstream effect of modulating GABAergic neurotransmission (via GABAA receptor subunits), Klonopin and Xanax decrease the firing rates of inhibitory interneurons within a brain region known as the ventral tegmental area (VTA). As a consequence of this effect, dopamine-secreting neurons fire less and extracellular levels of dopamine increase, leading some users to experience a euphoriant effect (i.e. pleasurable intoxication).
Because benzodiazepines like Klonopin and Xanax are absorbed quickly and facilitate an anxiolytic effect and myorelaxant effect (via GABAergic modulation) coupled with a euphoriant effect (via dopamine increases), a subset of users may become addicted to these substances. One could make the argument that Xanax is slightly more addictive than Klonopin due to its shorter half-life, however, each medication could trigger a benzodiazepine overuse disorder in certain persons.
Approved medical uses
Klonopin is approved by the United States FDA as a standalone or adjunct treatment for various seizure disorders (Lennox-Gastaut syndrome (petit mal variant), akinetic seizures, myoclonic seizures) and panic disorder with or without agoraphobia. Xanax is approved by the United States FDA for the treatment of generalized anxiety disorder and panic disorder.
In brief, both Klonopin and Xanax are medically-indicated for the treatment of panic disorder. However, Klonopin is considered effective for the treatment of various seizure disorders (whereas Xanax isn’t) and Xanax is considered effective for the treatment of generalized anxiety disorder (whereas Klonopin isn’t).
Each of these medications are regularly prescribed “off-label” to treat medical conditions for which they haven’t received FDA approval. Klonopin is occasionally prescribed off-label to treat: social anxiety disorder, acute mania, restless leg syndrome (RLS), bruxism, rapid eye movement disorder, akathisia, spasticity (associated with ALS), alcohol withdrawal syndrome, aggression (associated with psychosis), hyperekplexia, and parasomnia.
Xanax is occasionally prescribed off-label to treat: chemotherapy-induced nausea and vomiting, insomnia, agitation, premenstrual dysphoric disorder, and social anxiety disorder. Although Klonopin appears to have more off-label utility than Xanax – many consider the medications to be equally effective and somewhat interchangeable as off-label treatments.
- Source: Klonopin (FDA Access Data)
- Source: Xanax (FDA Access Data)
Cost: Which is more expensive?
The cost of Klonopin and Xanax in generic formats (clonazepam and alprazolam, respectively) is relatively similar. A 60-tablet supply of generic Klonopin (clonazepam) retails within the range of $7.78 to $31 (on average), whereas a 60-tablet supply of generic Xanax retails within the range of $7.75 to $21 (on average).
Klonopin cost
- Klonopin tablets (generic): $7.78 to $31 (60 tablets)
- Klonopin standard (brand): $160 to $267 (60 tablets)
- Klonopin ODT (orally disintegrating tablets): $21 to $106 (30 tablets)
Xanax cost
- Xanax tablets (generic): $7.75 to $21 (60 tablets)
- Xanax standard (brand): $245 to $730 (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 of 30 ml – 1 mg/ml)
Despite the fact that it is rare for consumers to deliberately purchase “brand name” Klonopin and Xanax (as generics are readily available and much cheaper), the brand name versions of each medication still retail. A 60-tablet supply of brand name Klonopin retails for $160 to $267 (on average), whereas a 60-tablet supply of brand name Xanax retails for $245 to $730 (on average) – making Xanax the more expensive medication.
A total of 30 orally-disintegrating tablets (ODT) of generic Klonopin (clonazepam) retail for $21 to $106 (on average), whereas the same quantity of orally-disintegrating tablets (ODT) of generic Xanax (alprazolam) retail for $29 to $183 – indicating that the orally-disintegrating format (ODT) of Klonopin is slightly less expensive.
It is worth noting that Xanax is available in the formats of: (1) an oral solution (30 ml of 1 mg/ml) which sells for $47 to $103 (on average) and (2) a generic extended-release tablet (XR or ER) that sells for $16 to $67 (on average) for 30 tablets. (Klonopin is not manufactured as an oral solution or in the form of an extended-release tablet).
In summary, generic Xanax (alprazolam) tablets tend to be slightly cheaper than generic Klonopin (clonazepam) tablets, however, most people probably won’t consider the pricing of generic versions to be of any major significance. Both brand name Klonopin tablets and generic orally-disintegrating Klonopin (clonazepam) tablets are cheaper than brand name Xanax tablets and generic orally-disintegrating Xanax (alprazolam) tablets.
Note: The pricing for both Klonopin and Xanax is dose-dependent such that lower doses are generally less expensive than larger doses – regardless of the format. Additionally, the pricing of Klonopin and Xanax may vary depending on the retailing pharmacy.
Dosage & Formats
In terms of formatting, both Klonopin and Xanax are manufactured as: (1) immediate-release tablets (standard) and (2) orally-disintegrating tablets (ODT) that dissolve on the tongue (and don’t require swallowing). Immediate-release Klonopin tablets are available in dosages of 0.5 mg, 1 mg, and 2 mg – and immediate-release Xanax tablets are available in dosages of 0.25 mg, 0.5 mg, 1 mg, and 2 mg.
Orally-disintegrating Klonopin tablets are available in dosages of 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, and 2 mg, whereas orally-disintegrating Xanax tablets are available in dosages of 0.25 mg, 0.5 mg, 1 mg, and 2 mg. Some may perceive standard Xanax tablets as being advantageous over standard Klonopin tablets and/or orally-disintegrating Klonopin tablets as being advantageous over orally-disintegrating Xanax tablets – due to additional dosing increments relative to the other medication.
Unlike Klonopin, Xanax is manufactured in the format of an oral solution that provides 30 ml of 1 mg/ml. Oral solution formats are frequently utilized by patients attempting to gradually taper off of Xanax because it’s generally easier and more precise to measure liquid doses than split tablets.
Furthermore, Xanax is manufactured in the format of an extended-release tablet (XR or ER) at dosages of 0.5 mg, 1 mg, 2 mg, and 3 mg – whereas extended-release Klonopin is not available. Many patients and medical professionals and patients like the convenience of the extended-release (XR or ER) format of Xanax based on its ability to exert an anxiolytic effect for ~11 hours.
In the event that medical professionals and/or patients prefer medications that are available in a variety of different formats, Xanax (available in 4 formats) is superior to Klonopin (available in 2 formats). That said, the orally-disintegrating format of Klonopin may be preferred by some over the orally-disintegrating format of Xanax based on its additional dosing increment.
Efficacy: Which medication is more effective?
Reflecting upon available medical literature, there’s no convincing evidence to suggest that Klonopin is significantly more effective than Xanax (or vice-versa) for the management of panic disorder – a condition for which each medication is FDA approved to treat. Both Klonopin and Xanax have undergone randomized controlled trials and extensive testing wherein each consistently appeared safe, tolerable, and effective in the management of panic disorder.
Several studies have attempted to compare the efficacy and tolerability of Klonopin (clonazepam) and Xanax (alprazolam) in a “head-to-head” manner. For example, a 6-week double-blind, placebo-controlled study by Tesar et al. (1991) compared the anti-panic effect of Klonopin and Xanax among 72 patients with panic disorder.
In the study by Tesar et al. (1991), it was discovered that Klonopin and Xanax significantly reduced the frequency of panic attacks, phobia ratings, and the extent of disability – relative to a placebo control. However, no significant differences were discovered in measures of anti-panic efficacy or tolerability – indicating that neither medication is more effective than the other in the treatment of panic disorder.
An earlier study by Herman et al. (1987) involved transitioning 48 patients with panic disorder receiving Xanax and inter-dose anxiety (i.e. anxious symptoms between doses) – to Klonopin. Researchers reported that 82% of patients who transitioned to Klonopin rated Klonopin as “better” in that it required less frequent administration and abolished inter-dose anxiety.
According to researchers, both medications were effective for panic disorder at comparable doses. Nevertheless, considering the results of this small-scale study, one might hypothesize that Klonopin: exhibits a slightly longer duration of effect (than Xanax) and/or is more likely to prevent inter-dose anxiety.
An analysis of data by Tesar et al. (1987) from a randomized, double-blind, placebo-controlled trial reported that Klonopin and Xanax were significantly more effective than a placebo in reducing: number of panic attacks, percentage of time experiencing anticipatory anxiety, extent of phobic avoidance, and fear – among patients with panic disorder. However, Klonopin and Xanax did not significantly differ (from one another) in terms of efficacy.
A study by Wang et al. (2016) involving 180 patients with anxiety disorder taking antidepressants and benzodiazepines reported that Klonopin was as effective as other benzodiazepines (Xanax and Ativan) in reducing anxiety and was better tolerated (as evidenced by fewer adverse effects); 26.7% vs. 48.4% and 49.3%. Though this was a relatively small-scale study, it suggests that Klonopin may be better tolerated than Xanax.
Because both Klonopin and Xanax are FDA-approved for the treatment of panic disorder and there are no strong data to suggest that one medication is more effective or tolerable relative to the other – medical professionals generally regard Klonopin and Xanax as being equally effective and useful interventions in treating panic disorder.
That said, because the FDA-approved uses (i.e. indications) of each medication differ, it’s fair to suspect that Klonopin would be superior over Xanax for the treatment of seizure disorders (e.g. Lennox-Gastaut syndrome, akinetic seizures, myoclonic seizures) – and that Xanax might be superior to Klonopin for the treatment of generalized anxiety disorders.
Furthermore, considering popular off-label uses of Klonopin, one might suspect that Klonopin would be more effective than Xanax for the treatment of social phobia, acute mania, RLS, bruxism, rapid eye movement behavior disorder, akathisia, spasticity (associated with ALS), alcohol withdrawal, aggression (associated with psychosis), hyperekplexia, and/or parasomnia.
Comparatively, considering popular off-label uses of Xanax, one might suspect that Xanax would be more effective than Klonopin for the treatment of chemotherapy-induced nausea and vomiting, insomnia, agitation, and premenstrual dysphoric disorder.
Overall, because Klonopin hasn’t been directly compared to Xanax in large-scale randomized controlled trials for the treatment of any specific medical condition – no conclusions should be made to suggest that one medication is of superior efficacy or tolerability relative to the other.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/1993639
- Source: https://www.ncbi.nlm.nih.gov/pubmed/3597803
- Source: https://www.ncbi.nlm.nih.gov/pubmed/3312179
- Source: https://www.ncbi.nlm.nih.gov/pubmed/27121429
Mechanism of action
Pharmacodynamic evaluations of Klonopin and Xanax indicate that the medications exhibit similar mechanisms of action. Both Klonopin and Xanax act primarily as GABAA receptor positive allosteric modulators (PAM) whereby they enhance the ability of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, to bind to the GABAA receptor.
GABAA receptors are positioned throughout the central nervous system (CNS) and are comprised of 5 protein subunits (2-alpha, 2-beta, 1-gamma). In a state of sobriety (devoid of benzodiazepines), GABA binds modestly to the GABAA receptor’s alpha subunit – enabling negatively-charged chloride ions to penetrate the neuron.
Following the administration of Klonopin or Xanax, each medication allosterically binds to the GABAA receptor’s gamma subunit. Allosteric binding to the gamma subunit of the GABAA receptor substantially enhances the binding of endogenous GABA to the GABAA receptor’s alpha subunit.
Due to the enhancement of GABA binding to the GABAA receptor (alpha subunit), negatively-charged chloride ions are able to penetrate the neuron and generate a state of hyperpolarization. (Hyperpolarization means that the inside of the neuron is more negatively charged than the outside of the neuron).
As a result of neuronal hyperpolarization, neuronal activity slows and/or becomes inhibited. In other words, neurons are less responsive or non-responsive to stimulation from excitatory postsynaptic potentials which yields decreased or suppressed activity throughout the central nervous system (CNS).
This mechanism of action is understood to significantly attenuate symptoms of panic disorder, various anxiety disorders, and seizure disorders. Nevertheless, while the principal mechanisms of action associated with Klonopin and Xanax are nearly identical, it is thought that there are subtle differences in terms of secondary actions and magnitude of action within specific brain regions.
For example, Xanax has been shown to increase serotonin release in the hippocampal region, whereas Klonopin has been shown to decrease serotonin utilization by neurons throughout the brain. Research indicates that Xanax can increase dopamine (D1 and D2) in the striatum, yet it remains unknown as to whether Klonopin acts similarly. Moreover, animal model data indicate that Klonopin and Xanax exert different effects within the immune system; the former appears to be less deleterious than the latter.
Metabolism & Half-Life
The route of metabolism associated with Klonopin and Xanax is similar in that each medication is metabolized within liver predominantly via the CYP3A4 (cytochrome P450 3A4) enzyme. Despite the fact that both Klonopin and Xanax are “fat soluble” and metabolized via the same enzyme, the elimination half-life of each medication significantly differs.
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The elimination half-life of Klonopin falls within the range of 18.7 to 60 hours (~40 hours), whereas the elimination half-life of Xanax falls within the range of 6.3 to 26.9 hours (~12 hours). Considering elimination half-life times, it appears as though Xanax is eliminated from the body at a significantly faster rate than Klonopin.
When Klonopin undergoes hepatic metabolism (via CYP3A4), it forms the metabolite “7-aminoclonazepam” which exhibits a shorter half-life than the parent compound. When Xanax undergoes hepatic metabolism (via CYP3A4), it forms the metabolites: alpha-hydroxyalprazolam (alpha-OHALP) and 4-hydroxyalprazolam (4-OHALP); the former being more bioactive than the latter.
Popularity
Klonopin initially hit the market in 1975, whereas Xanax wasn’t introduced until 1981. Because Klonopin was around for approximately 6 years before Xanax, one might hypothesize that Klonopin may have been initially more popular than Xanax.
As of 2018, both generic Klonopin (clonazepam) and generic Xanax (alprazolam) remain popular medications. According to ClinCalc DrugStats database, over 21.8 million prescriptions were filled within the past year (2017-2018) for generic Klonopin (clonazepam) and over 27 million prescriptions were filled within the past year (2017-2018) for generic Xanax (alprazolam).
Klonopin is the 38th most-prescribed pharmaceutical medication and Xanax is the 23rd most-prescribed pharmaceutical medication – in the United States (as of 2018). Although both medications are popular, over 5 million more prescriptions are given for Xanax each year than Klonopin – making Xanax the more popular medication.
Differences in popularity could be due to the fact that Xanax is available in a greater number of formats and/or is approved to treat anxiety disorders (e.g. generalized anxiety disorder) that Klonopin is not. Moreover, in popular culture such as music, the news, social media, etc. – Xanax is discussed more frequently.
Side effects
The most common side effects associated with Klonopin (based on FDA database data) include: somnolence, fatigue, depression, dizziness, abnormal coordination, and ataxia. The most common side effects associated with Xanax (based on FDA database data) include: drowsiness, lightheadedness, dry mouth, depression, headache, constipation, and diarrhea.
Considering available side effect data, it appears as though both medications induce roughly the same number of side effects. Furthermore, reflecting upon side effect data, one might conclude that Klonopin is less likely to cause lightheadedness, dry mouth, headache, constipation, and diarrhea – than Xanax.
Similarly, side effect data suggest that Xanax is less likely to cause somnolence, dizziness, abnormal coordination, and ataxia – than Klonopin. One small-scale study by Wang et al. (2016) reported that adjunct Klonopin was better tolerated than adjunct Xanax among 180 patients receiving newer antidepressants to treat anxiety disorders.
Specifically, 26.7% of patients receiving adjunct Klonopin experienced adverse effects, whereas 48.4% of patients receiving adjunct Xanax experienced adverse effects. Nonetheless, the aforementioned study by Wang et al. (2016) was extremely small scale and cannot be referenced as definitive proof that Klonopin exhibits favorable tolerability over Xanax.
Due to subtle differences in mechanisms of action – side effects and tolerability of Klonopin and Xanax will likely be contingent upon the specific user. Moreover, because the mechanisms of action associated with each medication are similar – the differences in number of side effects, magnitude of side effects, and/or specific side effects may not be as significant as one might hypothesize (based on FDA database data).
- Source: Klonopin (FDA Access Data)
- Source: Xanax (FDA Access Data)
- Source: https://www.ncbi.nlm.nih.gov/pubmed/27121429
Withdrawal
Discontinuation of Klonopin and Xanax can induce severe withdrawal symptoms and post-acute withdrawal syndrome (PAWS) in a subset of long-term or chronic users. Severe withdrawal symptoms are thought to manifest as a result of the former user’s neurophysiology recalibrating or transitioning back to neurophysiologic homeostasis from a benzodiazepine-adapted state.
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Specifically, anyone who administers Klonopin or Xanax regularly for an extended duration will incur medication-induced neurophysiologic adaptations – most notable of which is GABAA receptor subunit downregulation (i.e. fewer GABAA receptor subunits than pre-treatment) due to excessive activation. After adaptations are incurred, Klonopin or Xanax becomes required to maintain neurotransmitter balance.
In the event that treatment with Klonopin or Xanax ends, the former user’s neurotransmission becomes temporarily imbalanced because it remains in a benzodiazepine-adapted state. Essentially, continued GABAA receptor modulation from Klonopin or Xanax is expected by the body and required to maintain neurotransmitter balance.
Because GABAA receptor subunits will have downregulated as a neurophysiologic adaptation to chronic Klonopin or Xanax administration, neurochemical dysregulation emerges when Klonopin or Xanax treatment is over. Although neurophysiology will gradually transition itself back to homeostasis from a benzodiazepine-adapted state, this transition requires time (e.g. days, weeks, months, etc.).
While transitioning to homeostasis, GABAA receptors will remain underactive and former users may exhibit excessive signaling of excitatory neurotransmitters. This excess excitatory neurotransmission can provoke severe discontinuation symptoms such as: rebound anxiety, panic attacks, hypertension, muscle tension, heart palpitations, rapid heart rate, and seizures.
Because withdrawal symptoms from Klonopin and Xanax can be severe, it is usually necessary for patients attempting to discontinue either of these medications to work closely with a medical doctor – preferably a psychiatrist. Nevertheless, some experts believe that Klonopin may be easier for patients to discontinue [relative to Xanax] due to its longer elimination half-life.
The elimination half-life of Klonopin ranges from 18.7 to 60 hours (~40 hours), whereas the elimination half-life of Xanax ranges from 6.3 to 26.9 hours (~12 hours). A longer elimination half-life is generally advantageous in benzodiazepine withdrawal because the body is given more time to gradually recalibrate its functioning towards homeostasis before the medication is completely eliminated from systemic circulation – making for a smoother neurophysiologic transition.
As a matter of fact, many medical doctors will recommend that patients switch from Xanax to Klonopin for withdrawal based on the idea that a longer half-life reduces the severity of discontinuation symptoms. While it may be slightly easier to discontinue Klonopin relative to Xanax – evidence indicates that it’s still challenging to withdraw from Klonopin.
In summary, users of Klonopin and Xanax may develop severe withdrawal symptoms upon cessation of treatment. Klonopin withdrawal may be slightly easier to manage than Xanax withdrawal due to its longer half-life, however, it’s generally recommended that medical professionals transition patients from these medications to Valium (as diazepam exhibits a substantially longer half-life than both).
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/
- Source: https://www.ncbi.nlm.nih.gov/pubmed/2889723
Similarities (Summary): Klonopin vs. Xanax
Included below is a summary of some similarities between Klonopin and Xanax.
- Abuse potential: Klonopin and Xanax have a modest potential for abuse and misuse. Both medications rapidly induce anxiolytic and myorelaxant effects following administration (via actions upon GABAA receptors) and euphoriant effects (via promoting downstream secretion of dopamine). The rapid onset of action accompanied by desirable neurophysiologic effects can lead to addiction and increase likelihood of abuse. Each of these medications are pursued as “recreational” or “party” drugs to attain a relaxing high (i.e. intoxication).
- Cost: The generic standard tablet and ODT (orally-disintegrating tablet) versions of Klonopin and Xanax are relatively similar in price. A total of 60 standard generic Klonopin (clonazepam) tablets retail for $7.78 to $31 and a total of 60 standard generic Xanax (alprazolam) tablets retail for $7.75 to $21. A total of 30 generic Klonopin orally-disintegrating tablets retail for $21 to $106 – and a total of 30 generic Xanax orally-disintegrating tablets retail for $29 to $183. At low doses of generics, pricing is nearly identical for both standard tablets and orally-disintegrating tablets. At higher doses, standard generic Klonopin tablets may be slightly more expensive at certain pharmacies than standard generic Xanax tablets – yet the opposite may be true for the generic orally-disintegrating tablets (i.e. Xanax ODT is costlier than Klonopin ODT).
- Drug classification: Klonopin and Xanax are classified as “benzodiazepines” based on the fact that their core chemical composition includes a benzene ring fused to a diazepine ring. As benzodiazepines, Klonopin and Xanax exert an effect by interacting with GABA receptors and the neurotransmission of GABA.
- Effectiveness: Both Klonopin and Xanax have undergone extensive testing (in large-scale double-blind, randomized, controlled trials) and proven to be effective for the management of panic disorder. Each medication is capable of significantly reducing the frequency and severity of panic attacks (relative to a placebo) – and neither medication is considered to be of superior efficacy (relative to the other) among patients with panic disorder.
- Generic availability: The patents for brand name formats of Klonopin and Xanax have long expired and each medication is available as a generic. Generic Klonopin retails under the chemical name “clonazepam” in standard tablet and orally-disintegrating tablet formats. Generic Xanax retails under the chemical name “alprazolam” in standard tablet, orally-disintegrating tablet, extended-release tablet, and oral solution formats.
- Legal status: In the United States, Klonopin and Xanax are considered “Schedule IV” substances. This scheduling suggests that these medications: (1) have low abuse potential compared to Schedule III substances; (2) have accepted medical uses; (3) could induce limited physical and/or psychological dependence if abused.
- Mechanism of action: The primary mechanism of action associated with Klonopin and Xanax is similar. Each medication primarily functions as a positive allosteric modulator (PAM) of the GABAA receptor. This action bolsters the efficiency of GABA binding to GABAA receptor subunits, allows negatively-charged chloride ions to penetrate neurons for induction of neuronal hyperpolarization whereby CNS activation decreases.
- Metabolism: Klonopin and Xanax exhibit identical routes of metabolism. After ingestion, each medication is metabolized in the liver by the enzyme CYP3A4.
- Medical uses: Klonopin and Xanax are approved by the United States FDA for the treatment of panic disorder. Additionally, each of these medications are commonly prescribed for the treatment of various anxiety disorders (in addition to panic disorder).
- Side effects: The side effects associated with Klonopin and Xanax are relatively similar – which should be expected considering each medication acts primarily as a positive allosteric modulator of the GABAA receptor. The most common side effect of each medication is drowsiness or sleepiness. Furthermore, each medication can cause mental confusion, cognitive impairment, depression, weakness, and motor dysfunction (e.g. abnormal coordination).
- Withdrawal: Discontinuation of Klonopin or Xanax can be difficult for long-term or chronic users. When a user’s neurophysiology fully adapts to the regular presence of Klonopin or Xanax – cessation of treatment can yield a compensatory physiologic reaction whereby taxing (and occasionally life-threatening) symptoms can emerge.
Differences (Summary): Klonopin vs. Xanax
Included below is a summary of notable differences between Klonopin and Xanax.
- Cost: While the price of generic Klonopin and generic Xanax (standard tablets and orally-disintegrating tablets) doesn’t differ much – the cost of brand name Klonopin differs substantially from the cost of brand name Xanax. A total of 60 brand name Klonopin tablets retail from $160 to $267 and a total of 60 brand name Xanax tablets retail from $245 to $730 – making brand name Klonopin the more affordable option.
- Duration of effect: The duration of effect for standard Klonopin and Xanax tablets differs significantly. Standard Klonopin tablets deliver a therapeutic effect that lasts 8 to 12 hours, whereas standard Xanax tablets deliver a therapeutic effect that lasts for 4 to 6 hours (~5 hours). That said, Xanax is manufactured in an extended-release tablet that remains active for 10 to 12 hours.
- Formats: Klonopin and Xanax are each manufactured in the format of immediate-release standard tablets and orally-disintegrating tablets. However, unlike Klonopin, Xanax is available in two additional formats including: extended-release and oral solution.
- Half-life: The elimination half-life of Klonopin is longer than the elimination half-life of Xanax. Research indicates that the elimination half-life of Klonopin ranges from 18.7 to 60 hours and that the elimination half-life of Xanax ranges from 9 to 16 hours.
- Ingredients: The active ingredient in Klonopin is the chemical “clonazepam” – which is classified as a chloro-nitro benzodiazepine based on the fact that it’s a chlorinated derivative of nitrazepam. The active ingredient in Xanax is the chemical “alprazolam” – which is classified as a triazolobenzodiazepine based on the fact that it has a triazole ring fused to its diazepine ring.
- Manufacturers: Klonopin was developed and sold by the pharmaceutical company Hoffman-La Roche – and Xanax was developed and sold by the pharmaceutical company Upjohn (now merged with Pfizer Inc.).
- Medical uses: Although Klonopin and Xanax are medically-approved for the treatment of panic disorder, only Xanax is approved for the treatment of generalized anxiety disorders. However, unlike Xanax, Klonopin is medically-approved for the treatment of Lennox-Gastaut syndrome, akinetic seizures, and myoclonic seizures.
- Popularity: Prescribing data indicate that over 27 million prescriptions were filled for generic Xanax (alprazolam) and ~21.8 million prescriptions were filled for Klonopin (clonazepam) within the past year (2018). As of current, Xanax is the most-prescribed benzodiazepine and appears to be significantly more popular than Klonopin.
- Withdrawal severity: As was mentioned, Klonopin and Xanax can be difficult to discontinue for long-term and/or chronic users due to the emergence of harsh withdrawal symptoms following cessation. That said, because Klonopin has a significantly longer half-life than Xanax, some have argued that Klonopin should be easier to discontinue (relative to Xanax).
Which medication is “better” for panic disorder? (Klonopin vs. Xanax)
As of current, there’s no evidence to suggest that Klonopin is superior to Xanax (or vice-versa) for the treatment of panic disorder (the only medical condition for which both of these medications are FDA approved). Large-scale randomized controlled trials indicate that Klonopin and Xanax are safe, tolerable, and more effective than a placebo control in treating panic disorder.
However, there’s no strong evidence supporting the idea that one medication: (1) alleviates symptoms to a greater extent; (2) exhibits higher response rates (in the general population); (3) is more tolerable (i.e. causes fewer side effects) – relative to the other. For this reason, most medical doctors and psychiatrists consider Klonopin and Xanax to be equally useful options in the management of panic disorder.
A study by Herman et al. (1987) involved transitioning 48 patients with panic disorder from Xanax to Klonopin and noted that 82% of patients who completed the transition rated Klonopin as being subjectively “better” than Xanax. Reasons for rating Klonopin as “better” than Xanax among patients included: administration frequency (Klonopin is longer acting and didn’t need to be administered as often) and inter-dose anxiety (patients experienced no inter-dose anxiety that they had been experiencing while using Xanax).
Still, this study is limited by: its size, duration, lack of adequate controlling (patients should’ve also been transitioned from Klonopin to Xanax). Moreover, Xanax is now available in an extended-release (XR or ER) format that exerts an effect for 8 to 12 hours – which would negate the alleged superiority of Klonopin over Xanax in terms of administration frequency and inter-dose anxiety – as were highlighted by Herman et al. (1987).
That said, if we compare standard immediate-release formats, it’s reasonable to surmise that some persons might consider standard Klonopin tablets as being superior over standard Xanax tablets due to their longer duration of action, longer half-life, and less severe discontinuation symptoms (attributable to a longer half-life). Furthermore, although generic extended-release Xanax tablets exert roughly the same duration of effect as generic Klonopin tablets – the generic Klonopin tablets are less expensive (which could be considered an advantage for patients).
Some research by Wang et al. (2016) indicates that Klonopin may produce fewer side effects (26.7%) than Xanax (48.4%) when administered as an adjunct with newer antidepressants among patients with anxiety disorders. That said, the aforementioned study by Wang et al. (2016) was relatively small-scale and differences in rates of side effects among patients could’ve been due to random chance.
Research by Tesar et al. (1987) based on data from a randomized, double-blind, placebo-controlled trial that compared Klonopin and Xanax in the treatment of panic disorder reported no significant differences in measures of effectiveness, safety, or tolerability between the two medications. Each medication was more effective than a placebo for decreasing: number of panic attacks, anticipatory anxiety, phobic avoidance, and fear – in patients with panic disorder.
Because both medications are metabolized similarly via CYP3A4 enzymes in the liver, peak plasma concentrations should be similar for each medication – regardless of a patient’s gene expression. In other words, a patient who is a poor metabolizer of Klonopin will also be a poor metabolizer of Xanax – due to an overlap in the route of metabolism.
That said, there may be individual differences in genetics, epigenetic expression, preexisting neurophysiology, preexisting medical conditions, concurrent substance use, etc. – that might account for one medication being more effective and/or tolerable relative to the other for the treatment of panic disorder. This might explain why some patients claim that Klonopin works better than Xanax (or vice-versa) for the management or prophylaxis of panic.
Overall, both Klonopin and Xanax are safe, tolerable, and efficacious interventions for the treatment of panic disorder when utilized in a medically-acceptable manner. It may take some trial and error before you’re able to find the most effective and/or tolerable benzodiazepine (or anxiolytic medication) for the treatment of panic disorder.
When attempting to choose between Klonopin and Xanax, it is highly recommended to consult an experienced medical doctor (e.g. psychiatrist) and weigh the “pros” and “cons” of each option. During treatment, it may help to keep a journal documenting: (1) how well you perceive each medication is working and (2) the side effects that you’re experiencing over an extended duration.
Which medication do you prefer: Klonopin or Xanax?
If you’ve personally used Klonopin (clonazepam) and Xanax (alprazolam), leave a comment regarding whether you prefer one medication over the other. If you prefer one medication over the other, share specific reasons as to why you have this preference.
Reasons for preferring one medication over the other could include: effectiveness (e.g. greater symptom reduction); tolerability (e.g. fewer adverse effects); lower cost; easier discontinuation process. Assuming that you perceive one of these medications as being more effective than the other – have you considered that the relative dosages might be different (thus accounting for differences in perceived efficacy or potency)?
In your experience, did you notice any major differences in side effects or discontinuation symptoms between Klonopin and Xanax? To ensure that others get an accurate understanding of your experience with Klonopin and Xanax, mention things like: how long you used each medication; the dosages and formats that you used; the medical condition being treated with each medication (e.g. panic disorder); and whether you used substances (medications, supplements, etc.) along with Klonopin and/or Xanax.