Restoril (Temazepam) and Xanax (Alprazolam) are medications of the benzodiazepine classification that originally received U.S. FDA approval in 1981 as treatments for distinct medical interventions. Temazepam was approved as a short-term treatment for insomnia (intended to be used for 7 to 10 days) – whereas Alprazolam was approved as a treatment for generalized anxiety disorder and panic disorder.
The pharmaceutical company Sandoz (currently owned by Novartis) is credited for the synthesis of temazepam and was first to patent the drug in 1965 – and the pharmaceutical company Upjohn (acquired by Pfizer Inc.) is credited for the synthesis of alprazolam. Both temazepam and alprazolam exhibit a combination of anxiolytic, myorelaxant, and anticonvulsant properties.
Restoril (Temazepam) vs. Xanax (Alprazolam): Comparison
Included below is a general comparison of temazepam and alprazolam in chart format. The chart highlights basic commonalities and differences between temazepam and alprazolam. If you have additional questions about characteristics of temazepam and/or alprazolam, it is recommended to consult an experienced pharmacist or medical doctor.
|Approved medical uses||Insomnia.||Generalized anxiety disorder. Panic disorder.|
|Off-label uses||Sleep disorders. Military “No-Go Pill”. Acute anxiety. Anticonvulsant. Perioperative sedation.||Chemotherapy-induced nausea and vomiting. Insomnia. Agitation. Premenstrual dysphoric disorder.|
|Bioavailability||~96% (oral)||~90% (oral)|
|Formats||Capsule.||Tablet. Extended-release (XR or ER) pill. Oral disintegrating tablet. Oral solution.|
|Dosages||7.5 mg, 15 mg, 22.5 mg, 30 mg||Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg|
Oral disintegrating tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Extended-release (XR) pills: 0.5 mg, 1 mg, 2 mg, 3 mg
Oral solution: 30 ml 1 mg/ml
|Manufacturer||Novartis (Sandoz)||Pfizer Inc. (Upjohn)|
|Legal status||Schedule IV (U.S.)||Schedule IV (U.S.)|
|Mechanism of action||GABAA receptor positive allosteric modulator (PAM).|
Decreases cortisol levels.
May induce vasopressin release.
Reduces ACTH (adrenocorticotropic hormone) secretion.
|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||3.5 to 18.4 hours (~8.8 hours)||9 to 16 hours (~12 hours)|
|Common side effects||Drowsiness. Headache. Fatigue. Nervousness. Lethargy. Dizziness.||Drowsiness. Lightheadedness. Dry mouth. Depression. Headache. Constipation. Diarrhea.|
|Duration of effect||6 to 10 hours||Standard: ~5 hours|
Extended-release: ~11 hours
|Metabolism||Hepatic: Conjugation. Demethylation.||Hepatic: CYP3A4.|
|Onset of action||20 to 90 minutes||20 to 40 minutes|
|Dosage equivalence||20 mg||0.5 mg|
Temazepam vs. Xanax (Alprazolam): What are some basic differences?
Significant differences between the medications temazepam (Restoril) and alprazolam (Xanax) include: approved medical indications in the United States; available formats; metabolism; and potency (per milligram). There are also slight differences between temazepam and alprazolam in aspects such as: chemical structure; duration of effect; and elimination half-life.
In the U.S., temazepam is officially approved by the FDA for the treatment of insomnia (alprazolam is not) – and alprazolam is officially approved by the FDA for the treatment of generalized anxiety disorder and panic disorder (temazepam is not). Furthermore, while there may be some overlap in the off-label medical uses of temazepam and alprazolam (e.g. reducing acute anxiety), there might also be significant differences with regard to physician preferences.
It is thought that temazepam might be preferred over alprazolam as: an off-label treatment for sleep disorders; a perioperative sedative; a military “no-go pill”; and an anticonvulsant. That said, it is thought that alprazolam may be prescribed more frequently than temazepam as an off-label treatment for chemotherapy-induced nausea and vomiting; agitation; and premenstrual dysphoric disorder.
In addition to differences in primary and off-label medical uses, temazepam and alprazolam differ significantly in available formats. Temazepam is solely manufactured in the format of standard immediate-release capsules, whereas alprazolam is manufactured in four distinct formats, including: immediate-release tablet; orally-disintegrating tablet (ODT); extended-release tablet (ER or XR); and oral solution.
There are also differences in the respective chemical structures of temazepam and alprazolam. Temazepam is considered a 3-hydroxy metabolite and analogue of diazepam and is a benzodiazepine (contains a benzene ring fused to a diazepine ring) – whereas alprazolam is considered a triazolobenzodiazepine (contains a benzene ring fused to a diazepine ring plus a triazole ring).
The oral bioavailability of temazepam (~96%) slightly exceeds that of alprazolam (~90%) and the potency of temazepam (per milligram) is significantly (~40-fold) less than that of alprazolam (per milligram). Benzodiazepine equivalency research suggests that 20 mg temazepam is roughly equivalent in potency to 0.5 mg alprazolam.
The duration of effect for standard temazepam is thought to range from 6 to 10 hours, whereas the duration of effect for standard alprazolam is thought to range from 4 to 6 hours. Though standard alprazolam may be shorter-acting than standard temazepam, extended-release alprazolam is thought to exert an effect for 10 to 12 hours – exceeding that of standard temazepam.
Moreover, although temazepam and alprazolam are metabolized primarily within the liver, temazepam is minimally metabolized and undergoes conjugation just prior to elimination – whereas alprazolam is metabolized via CYP3A4 enzyme-mediated microsomal oxidation. The elimination half-life of temazepam ranges from 3.5 to 18.4 hours (~8.8 hours) and the elimination half-life of alprazolam ranges from 9 to 16 hours (~12 hours).
Addiction & Abuse Potential
Despite the fact that alprazolam (Xanax) is the most abused benzodiazepine in the United States, its addiction and abuse potential does not significantly differ from that of temazepam. In fact, research by Griffiths et al. (1985) comparing the abuse liabilities of benzodiazepines reported that subjects exhibited a strong preference for administering temazepam [and triazolam] over other benzodiazepines (one of which was alprazolam).
Based on the aforementioned findings in the study by Griffiths et al. (1985), it’s reasonable to surmise that temazepam might have greater abuse potential than Xanax (alprazolam). However, because temazepam and alprazolam exhibit similar pharmacodynamics and onsets of action, there’s no strong reason to assume that one medication would be substantially more addictive than the other.
It is important to underscore the fact that benzodiazepines as a classification are among the most addictive drugs in pharmaceutical production. The addiction potential of temazepam, alprazolam, and other benzodiazepines stems from a combination of: (1) rapid onset of action; (2) psychological reinforcement (via activation of reward pathways); (3) concurrent anxiety reduction plus muscle relaxation; and/or (4) tolerance onset (attributable to compensatory neurophysiologic reactions).
Both temazepam and Xanax (alprazolam) “take effect” quickly after ingestion (20-90 minutes vs. 20-40 minutes) whereby the medications allosterically modulate GABAA receptors which, as a downstream effect, reduces the firing of inhibitory interneurons throughout the ventral tegmental area (VTA). (Read more: How long does it take for Xanax to “kick in”?) The reduction of inhibitory interneuron firing in the ventral tegmental area limits or inhibits dopamine secretion via dopaminergic neurons and leads to increased dopamine signaling in extracellular spaces.
The increased extracellular dopamine concentration induces reward pathway activation whereby temazepam or alprazolam users may experience a euphoriant effect characterized by elevated mood and/or psychological pleasure. The resulting euphoriant effect in conjunction with an anxiolytic and/or myorelaxant effects could trigger addiction and/or abuse in users.
In the U.S., temazepam and alprazolam are classified as “Schedule IV” substances indicating a modest risk of psychological and/or physical dependence among users. Still, most experts believe that the potential for addiction and dependence among temazepam and alprazolam users is limited (i.e. minimal or nonexistent) when administered in accordance with qualified medical instruction.
In the event that temazepam or alprazolam is intentionally misused, such as by altering modality of administration (e.g. snorting) or increasing the dosage, one’s risk of dependence may increase significantly. In summary, temazepam and alprazolam likely do not differ much in liability of abuse, addiction, and dependence.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/2858078
- Source: https://www.ncbi.nlm.nih.gov/pubmed/6113025
- Source: https://www.ncbi.nlm.nih.gov/pubmed/2051498
- Source: https://www.ncbi.nlm.nih.gov/pubmed/28777203
Approved Medical Uses
The medical conditions for which temazepam and alprazolam have received official FDA (Food & Drug Administration) approval differ in the United States. Temazepam is medically indicated for the treatment of insomnia over a short-term (7 to 10 days) and Xanax (alprazolam) is medically indicated for the treatment of generalized anxiety disorder and panic disorder.
Temazepam is used principally as a hypnotic to induce and maintain sleep – whereas alprazolam is used principally as an anxiolytic to alleviate and/or prevent symptoms of anxiety and panic. Despite differences in approved medical uses for temazepam and alprazolam, it’s reasonable to surmise (based on similar mechanisms of action) that each substance might prove useful in managing conditions for which the other is approved.
In other words, temazepam might be capable of treating symptoms of generalized anxiety disorder and/or panic disorder – and alprazolam might be capable of treating insomnia. As off-label treatments, temazepam and alprazolam are generally regarded as being interchangeable sedative-hypnotic benzodiazepines due to their analogous principal mechanisms of action.
Though both temazepam and alprazolam are administered “off-label” for the treatment of acute anxiety, temazepam may be utilized off-label more frequently than alprazolam as: a hypnotic for sleep disorders; an anticonvulsant for seizures; a perioperative sedative; and a “no-go pill” in the military. Alprazolam may be utilized off-label more frequently than temazepam as a treatment for: chemotherapy-related nausea and vomiting; agitation; and premenstrual dysphoric disorder.
Cost: What are the prices?
The cost of standard generic temazepam is significantly greater than the cost of standard generic alprazolam. At most pharmacies, a total of 30 generic temazepam capsules can be attained within the price range of $8.50 to $198 (on average) – this equals roughly $0.28 to $6.60 per capsule.
- Temazepam (generic): $8.50 to $198 (30 capsules)
- Restoril (brand): $885 to $1062 (30 capsules)
- Alprazolam tablets (generic): $7 to $21 (60 tablets)
- Xanax standard (brand): $245 to $800 (60 tablets)
- Alprazolam ODT (orally disintegrating tablet): $29 to $183 (30 tablets)
- Alprazolam XR or ER (extended release): $16 to $67 (30 tablets)
- Alprazolam (oral solution): $47 to $103 (1 bottle – 30 ml of 1 mg/ml)
Perhaps due to consumer demand and/or fluctuations in production, temazepam capsules are cheaper at 15 mg and 30 mg dosage increments than at 7.5 mg and 22.5 mg dosage increments. For 30 capsules, the 15 mg and 30 mg dosages of generic temazepam cost $8.50 to $15.22 and $9 to $16, respectively, whereas the 7.5 mg and 22.5 mg dosages cost $74 to $198 and $98.50 to $267, respectively.
In comparison, 60 generic alprazolam tablets can be attained within the price range of $7 to $21 (on average) – this equals roughly $0.11 to $0.35 per tablet. Although generic temazepam at dosage increments of 15 mg and 30 mg is relatively inexpensive, it’s still around 2-fold more expensive than generic alprazolam.
The price of generic temazepam at dosage increments of 7.5 mg and 22.5 mg is substantially more expensive than generic alprazolam (irrespective of dosage). Moreover, while most consumers will prefer using generic temazepam and alprazolam over brand name formats due to their lower cost, a subset of consumers might seek out brand name formats Restoril and Xanax for various reasons.
A total of 30 brand name Restoril capsules can be attained within the price range of $885 to $1062 – or for $29.50 to $35.40 per capsule. A total of 60 brand name Xanax tablets can be attained within the price range of $245 to $800 – or for $4.08 to $13.33 per tablet. Brand name Restoril is significantly more expensive (2-to-7-fold) than brand name Xanax.
Additional formats of alprazolam differ in cost, such as: orally-disintegrating tablet (ODT) for $29 to $183 (30 tablets); extended-release tablets (ER or XR) for $16 to $67 (30 tablets); and oral solution for $47 to $103 (30 ml bottle of 1 mg/ml). In summary, generic temazepam and brand name Restoril are respectively more expensive than generic alprazolam and brand name Xanax.
Note: The prices of temazepam and alprazolam may be subject to future change. The cost of generic temazepam is significantly lower at 15 mg and 30 mg dosage increments than at 7.5 mg and 22.5 mg dosage increments. The cost of generic alprazolam is dose-dependent in that higher doses are slightly more expensive than lower doses. Prices of temazepam and alprazolam are also contingent upon the pharmacy from which they are purchased.
Dosage & Formats
Restoril (temazepam) and Xanax (alprazolam) are each sold in immediate-release formats, however, standard temazepam is manufactured as capsules and standard alprazolam is manufactured as tablets. The immediate-release temazepam capsules “kick in” within 20 to 90 minutes of administration and facilitate an effect that lasts 6 to 10 hours (on average).
The immediate-release alprazolam tablets “kick in” within 20 to 40 minutes of administration and facilitate an effect that lasts 4 to 6 hours (on average). Temazepam capsules are available in 4 dosage increments of: 7.5 mg, 15 mg, 22.5 mg, and 30 mg – whereas standard alprazolam tablets are available in 4 dosage increments of: 0.25 mg, 0.5 mg, 1 mg, and 2 mg.
If only comparing the standard immediate-release formats of temazepam and alprazolam, one might consider temazepam as being advantageous over alprazolam in that it facilitates a longer average duration of action. However, one might consider immediate-release alprazolam as advantageous over temazepam because: (1) its 4 dosages are respectively 1.3-fold, 1.3-fold, 1.7-fold, and 2.66-fold more potent and (2) it may take effect quicker in select users.
Additionally, unlike temazepam, alprazolam is sold in formats of: orally-disintegrating tablet (ODT) –which dissolves in the mouth without swallowing; extended-release tablet (ER or XR) – which provides a longer duration of action (10 to 12 hours); and oral solution – which may be easier for some patients to titrate and/or administer. Available dosages for the aforementioned alprazolam formats include: 0.25 mg, 0.5 mg, 1 mg, 2 mg (orally-disintegrating tablet); 0.5 mg, 1 mg, 2 mg, 3 mg (extended-release tablet); and 30 ml of 1 mg/ml (oral solution).
The orally-disintegrating tablet (ODT) and oral solution formats might be more convenient for some patients to administer relative to standard tablets and the extended-release tablets elicit a longer duration of effect than standard tablets. A subset of Xanax (alprazolam) users might also like the option to alternate between administering standard immediate-release and extended-release formats.
For example, extended-release tablets might be administered on days necessitating long-lasting anxiety reduction – and immediate-release tablets might be administered on days requiring brief anxiety reduction. Because Xanax (alprazolam) is manufactured in a greater number of formats (immediate-release, orally-disintegrating, extended-release, oral solution) than temazepam (immediate-release) – most would objectively consider Xanax as superior over temazepam in formatting.
Efficacy: Which medication is more effective?
Temazepam and Xanax (alprazolam) are approved by the U.S. FDA as treatments for different medical conditions: temazepam for insomnia (over a short-term) – and alprazolam for generalized anxiety disorder and panic disorder. Because temazepam and alprazolam differ in their approved medical uses, most researchers haven’t directly compared their respective efficacies in the treatment of any specific medical condition.
Temazepam has proven efficacious in well-designed (double-blind, randomized, placebo-controlled) trials for the treatment of insomnia – and alprazolam has proven efficacious in well-designed trials for the treatment of generalized anxiety disorder and panic disorder. Knowing that temazepam has proven effective as a treatment for insomnia – and alprazolam hasn’t, most would consider temazepam to be the superior intervention among patients with insomnia.
Oppositely, knowing that alprazolam has proven effective as a treatment for generalized anxiety disorder and panic disorder – and temazepam hasn’t, most would consider alprazolam to be the superior intervention among patients with anxiety disorders. However, because alprazolam and temazepam exert similar neurochemical effects (within the GABA system), it’s unclear as to whether the respective efficacies of each medication would significantly differ for any specific medical condition.
It’s possible that: temazepam is equally as effective as alprazolam for the treatment of anxiety disorders and/or that alprazolam is just as effective as temazepam for the treatment of insomnia. Though the standard format of alprazolam would likely be less effective than temazepam for insomnia due to its limited duration of action (4 to 6 hours), extended-release alprazolam may be as effective due to its long duration of action (10 to 12 hours).
Unless future well-designed studies compare the effectiveness of temazepam to that of alprazolam for specific medical conditions (e.g. insomnia, generalized anxiety disorder, panic disorder, etc.) – neither medication should be considered therapeutically superior over the other. In clinical settings, evidence substantiates usage of temazepam to treat insomnia – and the usage of alprazolam to treat anxiety disorders.
Mechanism of action
The principal mechanisms of action (i.e. pharmacodynamics) for temazepam and Xanax (alprazolam) are nearly identical in that each medication acts as a GABAA receptor positive allosteric modulator. Specifically, temazepam and alprazolam bind to GABAA receptor subunits at allosteric sites (i.e. non-orthosteric binding sites) – or sites at which the endogenous ligand (GABA) doesn’t stimulate.
In response to the allosteric binding of temazepam and alprazolam at GABAA receptor subunits, the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) binds more frequently to GABAA receptors. The increased frequency of GABA binding to GABAA receptors causes negatively-charged chloride ions to penetrate neurons and induce neuronal hyperpolarization in which internal negative charge surpasses external negative charge.
Induction of neuronal hyperpolarization makes neurons less responsive to stimulation from excitatory postsynaptic potentials, and as a consequence, central nervous system activity becomes depressed. Depressed central nervous system activity, attributable to the GABAergic modulation facilitated by temazepam and alprazolam, typically yields a combination of: anxiolytic, sedative, hypnotic, and/or myorelaxant effects.
It is the principal GABAergic actions of temazepam and alprazolam that generate therapeutic effects for medical conditions like: insomnia; generalized anxiety disorder; and panic disorder. Although the principal mechanism of action does not differ between temazepam and alprazolam, the agents may differ in secondary (or additional) neurochemical actions.
Proposed secondary neurochemical actions for temazepam include: dose-dependently inhibiting stress-induced ACTH (adrenocorticotropic hormone) release; enhancing vasopressin release (in certain brain regions); reducing cortisol concentrations; and modulating the HPA (hypothalamic-pituitary-adrenal) axis.
Proposed secondary neurochemical actions for alprazolam include: upregulating striatal dopamine receptors (D1 and D2); enhancing norepinephrine release (to activate β2 receptors); increasing hippocampal serotonin; inhibiting adrenomedullary activity; and suppressing activation of the HPA (hypothalamic-pituitary-adrenal) axis.
Because many of the proposed secondary neurochemical actions (associated with temazepam and alprazolam) are based upon data from animal research, it’s unclear as to whether these actions legitimately occur in humans. Furthermore, the respective magnitudes of secondary neurochemical actions (associated with temazepam and alprazolam) remain unknown.
It’s also unclear as to whether there could be overlap in various secondary neurochemical actions (or reactions) associated with temazepam and alprazolam treatment. Perhaps temazepam: upregulates striatal dopamine receptors (D1 and D2); enhances norepinephrine release (to activate β2 receptors); increases serotonin in the hippocampus; and/or inhibits adrenomedullary activity – analogous to alprazolam.
And perhaps alprazolam: inhibits stress-induced ACTH release; enhances vasopressin release (in various brain regions); and/or decreases cortisol levels – analogous to temazepam. That said, it appears as though both temazepam and alprazolam treatment reduces HPA (hypothalamic-pituitary-adrenal) axis activation.
Moreover, it has also been hypothesized that temazepam, alprazolam, and other benzodiazepines function as modulators of voltage-gated ion channels. Though neither temazepam nor alprazolam have been specifically shown to modulate voltage-gated ion channels in research, other benzodiazepines, including diazepam (the parent chemical of temazepam), inhibit voltage-gated sodium channels in rats.
Even subtle disparities between temazepam and alprazolam in GABAA receptor subunit binding and/or potentiation – and/or secondary neurochemical actions could account for differences in: tolerance development (rate of onset and/or likelihood); therapeutic properties (e.g. sleep enhancement, anxiety reduction, etc.); and/or tolerability (severity and/or incidence of side effects). In summary, the mechanisms of action associated with temazepam and alprazolam are extremely similar.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/16395302
- Source: https://www.ncbi.nlm.nih.gov/pubmed/8944402
- Source: https://www.ncbi.nlm.nih.gov/pubmed/9600648
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074285/
- Source: https://www.ncbi.nlm.nih.gov/pubmed/2450203
Metabolism & Half-Life
Pharmacokinetic studies indicate that both temazepam and Xanax (alprazolam) are subject to metabolism within the liver prior to elimination. That said, unlike alprazolam, temazepam: (1) is solely metabolized via conjugation and demethylation prior to excretion; (2) is not subject to significant first-pass metabolism; and (3) is not metabolized via hepatic enzymes.
The chief metabolites of temazepam include: its major O-conjugate metabolite (90%) and its minor N-desmethyl metabolite (7%) – each of which are biologically-inactive. Unlike temazepam, alprazolam undergoes first-pass metabolism facilitated by the hepatic CYP3A4 (cytochrome P450 3A4) enzyme and forms multiple bioactive metabolites including: alpha-OHALP (alpha-hydroxy alprazolam) and 4-OHALP (4-hydroxy alprazolam).
The bioavailability of orally-administered temazepam is around 96% – and the bioavailability of orally-administered alprazolam is around 90%. The elimination half-life of temazepam is estimated to fall within the range of 3.5 to 18.4 hours (~8.8 hours) – and the elimination half-life of alprazolam is estimated to fall within the range of 9 to 16 hours (~12 hours).
In the domain of metabolism, it’s reasonable to suggest that temazepam is favorable over alprazolam. Temazepam is not subject to enzymatic metabolism and is therefore less likely than alprazolam to trigger pharmacokinetically-mediated adverse reactions when administered concurrently with other substances.
More specifically, since temazepam doesn’t interact with hepatic CYP450 enzymes (via induction or inhibition), it’s unlikely to affect plasma concentrations of a concurrently-administered agent (and vice-versa) – to trigger an adverse reaction. Because alprazolam is known to interact with CYP3A4 enzymes, any concurrently-administered substance that interacts with CYP3A4 enzymes increases puts users at risk of: (1) experiencing adverse reactions and/or (2) deriving insufficient therapeutic benefit from either substance.
Also worth underscoring is the fact that persons with genetic abnormalities may exhibit atypical CYP3A4 expression whereby the metabolism, bioavailability, and efficacy of alprazolam differ from the general population – thus affecting treatment outcomes. Because temazepam isn’t subject to enzymatic metabolism via hepatic enzymes, its metabolism, bioavailability, and efficacy are relatively consistent among users regardless of gene expression.
Though Restoril (temazepam) and Xanax (alprazolam) were introduced to the United States pharmaceutical market in 1981, alprazolam is significantly more popular than temazepam in both medical and recreational (non-medical) settings. According to prescribing data compiled by ClinCalc DrugStats database, approximately 3.7 million prescriptions were filled for temazepam throughout 2015 – making it the 174th most-prescribed pharmaceutical medication.
In comparison, approximately 27 million prescriptions were filled for generic Xanax (alprazolam) in 2015 – making it the 23rd most-prescribed pharmaceutical medication and most-prescribed benzodiazepine. It is unclear as to why temazepam is significantly less popular than alprazolam, however, there are a variety of possible explanations.
Differences in the popularity of temazepam and alprazolam might be attributable to things like: (1) marketing efforts; (2) approved medical uses; (3) average durations of use; and/or (4) available formats. Perhaps the marketing of Xanax (alprazolam) was historically superior to that of Restoril (temazepam) such that consumers and/or medical doctors developed a preference for using alprazolam over temazepam.
Furthermore, alprazolam is approved to treat 2 medical conditions (generalized anxiety disorder and panic disorder) with no restriction on duration of use – whereas temazepam is solely approved to treat 1 medical condition (insomnia) for a short-term (7 to 10 days). The medical conditions for which alprazolam is approved and/or the recommendation that temazepam solely be administered for a short-term – might be reasons as to why alprazolam is more popular than temazepam.
Lastly, there are a greater number of available alprazolam formats than temazepam formats – some of which offer alternative administration modalities for the sake of convenience and/or extend its duration of effect. It’s possible that formatting differences also contributed to alprazolam becoming more popular than temazepam.
The most common temazepam side effects (according to FDA Access Data) include: drowsiness, headache, fatigue, nervousness, lethargy, and dizziness. The most common Xanax (alprazolam) side effects (according to FDA Access Data) include: drowsiness, lightheadedness, dry mouth, depression, headache, constipation, and diarrhea.
Considering the most common side effects of temazepam and alprazolam (according to FDA Access Data), it appears as though temazepam and alprazolam are both likely to cause: drowsiness and headache. However, it seems as though temazepam may be more likely than alprazolam to cause: fatigue, nervousness, lethargy, and dizziness – and that alprazolam may be more likely than temazepam to cause: lightheadedness, dry mouth, depression, constipation, and diarrhea – as common side effects.
Perhaps differences in common side effects for temazepam and alprazolam are attributable to disparities in: (1) chemical structure and composition; (2) metabolism; and/or (3) secondary neurochemical actions. That said, it’s possible that suspected differences in rates and/or magnitudes of side effects based upon existing trial data might be less significant than some might expect or clinically insignificant.
Because temazepam and alprazolam each function primarily as GABAA receptor positive allosteric modulators to induce CNS depression, users of each medication tend to experience similar CNS depression-related side effects. Examples of CNS depression-related side effects among temazepam and alprazolam users include: sedation, cognitive impairment, psychomotor dysfunction, muscle weakness, incoordination, and slurred speech.
In summary, when administered in accordance with medical instruction, both temazepam and alprazolam generally well-tolerated. Moreover, because large-scale trials haven’t directly compared the side effects and tolerability of temazepam and alprazolam, neither medication should be regarded as more tolerable relative to the other.
Complete cessation of Restoril (temazepam) or Xanax (alprazolam) treatment can provoke severe withdrawal symptoms, especially among high-dose and/or long-term users and/or following abrupt discontinuation. Furthermore, a subset of temazepam and alprazolam users may endure post-acute withdrawal syndrome (PAWS) in which discontinuation symptoms persist for a protracted duration (e.g. months) following the date of cessation.
Withdrawal symptoms associated with temazepam, alprazolam, and other benzodiazepines are hypothesized to occur as a result of neurophysiologic compensatory responses and recalibration in the aftermath of drug cessation. As a result, former users of temazepam or alprazolam may experience disconcerting physical and/or psychological symptoms as neurochemistry transitions from a benzodiazepine-adapted state to homeostasis (pre-medication functioning).
If temazepam or alprazolam are administered regularly for a moderate term (e.g. months), neurochemistry adapts to the positive allosteric modulation facilitated by each substance at GABAA receptor subunits. Eventually neurochemistry adapts to benzodiazepine-mediated GABA modulation and compensatory reactions might occur.
Examples of hypothesized compensatory reactions include: modified mRNA transcription for GABA receptor subunits; degradation of GABA receptor subunits in endoplasmic reticulum; reduced production of GABAA receptor-associated helper proteins; modified endocytosis of GABAA receptor subtypes; fluctuations in perisynaptic or extrasynaptic localization of GABAA receptors; changes in functioning of the glutamate system; and abnormal production of neurotrophic factors.
As a consequence of the compensatory reactions accrued throughout treatment, the neurochemistry of former temazepam or alprazolam users can become drastically imbalanced following medication discontinuation. Despite the fact that neurochemistry should eventually transition back to homeostasis from the benzodiazepine-adapted state, the complete transition process may require weeks or months.
Until the transition from benzo-adapted to homeostasis is complete, users may experience numerous unpleasant withdrawal symptoms such as: dizziness, insomnia, sweating, lightheadedness, shortness of breath, tremor, palpitations, high anxiety, panic attacks, muscle tension, cognitive impairment, frequent urination, hypertension, seizures, and others – some of which may be life-threatening. Due to the severity of discontinuation symptoms, it is recommended that users only discontinue treatment with the guidance of a medical professional.
Since no large-scale, well-designed studies have directly compared the respective difficulties of temazepam and alprazolam discontinuation, it’s unknown as to whether there are significant differences in withdrawal difficulty, duration, and/or symptoms between the two substances. Knowing that temazepam and exhibit similar mechanisms of action and elimination half-life times, it’s reasonable to suspect that withdrawal presentations would be similar among users.
That said, because temazepam is only approved for short-term use (7 to 10 days) whereas alprazolam is commonly used for extended terms (e.g. months or years), withdrawal should be less severe among temazepam users than alprazolam users. Moreover, the average dose of temazepam is less potent than the average dose of alprazolam – and temazepam is generally administered less frequently (once before bed) than alprazolam (1 to 4 times per day).
Due to the lower potency of temazepam and/or its less frequent administration (on average), temazepam users are probably less prone to tolerance onset – or experience tolerance onset at a slower rate than alprazolam users. For this reason, it’s logical to suspect that temazepam users would experience fewer severe withdrawal symptoms than alprazolam users.
However, if we hypothetically assume that the: (1) dosage of temazepam and alprazolam is equally potent; (2) duration of administration is similar; and (3) frequency of administration is similar – there are unlikely to be significant differences in withdrawal symptoms or severities – between users of alprazolam versus users of temazepam. The lack of significant difference in discontinuation symptoms between temazepam and alprazolam [in the aforementioned hypothetical scenario] would probably be attributable to similarities in the pharmacodynamics and elimination half-life of each medication.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/7841856
- Source: https://www.ncbi.nlm.nih.gov/pubmed/24337417
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321276/
Similarities (Summary): Temazepam vs. Xanax
Included below is a list of noteworthy similarities between Restoril (temazepam) and Xanax (alprazolam). Temazepam and alprazolam are similar in the following aspects: abuse potential; drug classification; efficacy; legal status; mechanism of action; side effects; and withdrawal.
- Abuse potential: There’s no significant difference in the abuse liabilities of temazepam and alprazolam. Both substances have a modest-to-moderate abuse potential due to reinforcing properties. The reinforcing properties of temazepam and alprazolam are attributable to: (1) rapid onsets of action (post-ingestion) and (2) stimulation of reward pathways within the brain (via dopamine secretion as a downstream consequence of GABAA receptor modulation).
- Drug classification: Both temazepam and alprazolam are generally classified as “benzodiazepines” in medical settings. Temazepam is a traditional benzodiazepine in that its chemical structure contains a benzene ring fused to a diazepine ring. Alprazolam is technically a triazolo-benzodiazepine in that its chemical structure contains a triazole ring along with a benzene ring fused to a diazepine ring.
- Efficacy: There are no data suggesting that either temazepam or alprazolam is more effective than the other for any specific medical condition. Temazepam and alprazolam are considered efficacious treatment options for insomnia (temazepam) and anxiety disorders (alprazolam). Large-scale randomized controlled trials indicate that temazepam is significantly more effective than a placebo for the treatment of insomnia (over a short-term) – and that alprazolam is significantly more effective than a placebo for the treatment of anxiety disorders.
- Generic availability: Because Restoril and Xanax have been on the pharmaceutical market since 1981, the patents for each medication have long-expired. As a result, consumers can attain generic Restoril for a low cost under its chemical name “temazepam” – and generic Xanax for a low cost under its chemical name “alprazolam.”
- Legal status: The legal status of temazepam and alprazolam does not significantly differ in the United States. Both medications are classified as “Schedule IV” substances, indicating that they: (1) carry lower abuse liability than Schedule III substances; (2) can be used to treat medical conditions; (3) might induce physical and/or psychological dependence when abused.
- Mechanism of action: Temazepam and alprazolam exhibit nearly identical mechanisms of action. Both medications allosterically bind to GABAA receptor subunits to bolster endogenous GABA (gamma-aminobutyric acid) binding upon GABAA receptors. Increased GABA binding to GABAA receptors alters chloride ion flow to induce neuronal hyperpolarization, and ultimately, depressed CNS function.
- Side effects: Because temazepam and alprazolam are similar in chemical structure and primary mechanism of action, their side effect profiles are similar. Both “drowsiness” and “headache” are listed as common side effects for temazepam and alprazolam. Moreover, each medication may cause side effects due to the induction of CNS depression, including: fatigue, cognitive impairment, weakness, incoordination, slurred speech, dizziness, lethargy, lightheadedness, and depression.
- Withdrawal: In the event that temazepam is administered: (1) at a lower-potency dose; (2) less frequently; and/or (3) for a shorter duration – than alprazolam, then temazepam withdrawal should be easier to manage than alprazolam withdrawal. However, assuming there are no differences in potency of dosage; administration frequency; and/or duration of use – withdrawal symptoms (severities and duration) should be similar between temazepam and alprazolam due to their similar mechanisms of action and elimination half-lives.
Differences (Summary): Temazepam vs. Xanax
Included below is a list of noteworthy differences between Restoril (temazepam) and Xanax (alprazolam). Temazepam and alprazolam are different in aspects such as: available formats; cost; duration of effect; elimination half-life; approved medical uses; popularity; and potency.
- Available formats: The standard formatting for both temazepam and alprazolam is “immediate-release.” That said, temazepam immediate-release is manufactured in capsules and alprazolam immediate-release is manufactured in tablets. Though temazepam is solely available in immediate-release format, alprazolam is available in additional formats such as: orally-disintegrating tablet (ODT); extended-release tablet (ER or XR); and oral solution.
- Cost: Although generic Restoril (temazepam) and generic Xanax (alprazolam) can be attained for a low price at most pharmacies, generic alprazolam is generally less expensive. A standard alprazolam tablet costs between $0.11 and $0.35 (on average) – whereas a standard temazepam capsule costs between $0.28 and $6.60 (on average). Moreover, brand name Restoril is typically 2-to-7-fold more expensive than brand name Xanax.
- Duration of effect: The estimated duration of effect for standard temazepam is 6 to 10 hours, whereas the estimated duration of effect for standard alprazolam is 4 to 6 hours. Although standard temazepam exerts a longer-lasting effect than standard alprazolam, the extended-release version of alprazolam exerts an effect of 10 to 12 hours – exceeding the duration of effect associated with standard temazepam.
- Half-life: Research suggests that the elimination half-life of temazepam ranges from 3.5 to 18.4 hours (8.8-hour average) – and that the elimination half-life of alprazolam ranges from 9 to 16 hours (12-hour average). More specifically, the elimination half-life of temazepam is ~3.2 hours faster than alprazolam on average.
- Ingredients: Temazepam is the active chemical ingredient in the brand name medication Restoril – and alprazolam is the active chemical ingredient in the brand name medication Xanax. Temazepam is a traditional benzodiazepine comprised of a benzene ring fused to a diazepine ring – and alprazolam is a triazolo-benzodiazepine comprised of a benzene ring fused to a diazepine ring plus a triazole ring.
- Manufacturers: Despite the fact that temazepam and alprazolam were introduced to the pharmaceutical market during the same year (1981), the original manufacturers for each medication differed. Temazepam was originally manufactured by Sandoz (a company acquired by Novartis) and alprazolam was originally manufactured by Upjohn (a company acquired by Pfizer).
- Medical uses: Approved medical uses for temazepam and alprazolam differ significantly. Temazepam is medically-approved for the short-term (7 to 10 day) treatment of insomnia – whereas alprazolam is medically-approved for the treatment of generalized anxiety disorder and panic disorder. In brief, temazepam and alprazolam do not share any official medical indications.
- Metabolism: Though temazepam and alprazolam are each metabolized in the liver, the metabolism of each substance significantly differs. Temazepam is minimally metabolized via conjugation and demethylation prior to excretion, forms no bioactive metabolites – and is not subject to metabolism via hepatic enzymes. Alprazolam is extensively metabolized by the hepatic enzyme CYP3A4 (cytochrome P450 3A4) – and forms bioactive metabolites.
- Popularity: The popularity of temazepam is significantly less than the popularity of alprazolam. Differences in popularity may be attributable to disparities in: marketing; approved medical uses; available formats; and/or medically-recommended durations of use. As of 2015, around 3.7 million prescriptions were filled for temazepam – whereas over 27 million prescriptions were filled for alprazolam.
- Potency (per mg): On a “per milligram” basis, temazepam is markedly less potent than alprazolam. Benzodiazepine equivalence charts suggest that alprazolam is nearly 40-fold more potent “per milligram” than temazepam. The 4 standard dosages of temazepam (7.5 mg, 15 mg, 22.5 mg, 30 mg) are respectively 1.3-fold, 1.3-fold, 1.7-fold, and 2.66 fold less potent than the 4 standard dosages of alprazolam (0.25 mg, 0.5 mg, 1 mg, 2 mg).
Which medication is “better”? (Temazepam or Xanax)
There’s no evidence to suggest that temazepam is “better” than alprazolam (or vice-versa) for the treatment of any specific medical condition. Temazepam hasn’t been extensively evaluated as a treatment for anxiety disorders – and alprazolam hasn’t been extensively evaluated as a treatment for insomnia. For this reason, it’s impossible to definitively state that temazepam is more effective than alprazolam for the treatment of insomnia – and/or that alprazolam is more effective than temazepam for the treatment of anxiety disorders.
Nevertheless, because temazepam is medically-approved to treat short-term insomnia (whereas alprazolam is not), it’s reasonable to suggest that temazepam would be the better “medication choice” for persons with insomnia (relative to alprazolam). Similarly, because alprazolam is medically-approved to treat generalized anxiety disorder and panic disorder (whereas temazepam is not), it’s reasonable to suggest that alprazolam would be the better “medication choice” for persons with anxiety disorders (relative to temazepam).
Still, it’s important to avoid conflating the concept of better “medication choice” with clinical efficacy, tolerability, and/or safety. Future studies may reveal that temazepam is equally as effective as alprazolam for the treatment of anxiety disorders – and/or that alprazolam is equally as effective as temazepam as a short-term treatment for insomnia.
Understand that temazepam is only the better medication choice (relative to alprazolam) as a short-term treatment for insomnia because there’s strong evidence supporting its efficacy among patients with insomnia – (there’s no strong evidence supporting the efficacy of alprazolam for insomnia). Additionally, alprazolam is only the better medication choice (relative to temazepam) as a treatment for anxiety disorders because there’s strong evidence supporting its efficacy among patients with anxiety disorders – (there’s no strong evidence supporting the efficacy of temazepam for anxiety disorders).
Furthermore, because temazepam and alprazolam exhibit similar mechanisms of action and elimination half-lives, it’s logical to suspect that the effectiveness of these medications probably does not significantly differ for any specific medical condition. In other words, alprazolam (extended-release) might be as useful as temazepam for insomnia – and temazepam might be as useful as alprazolam for anxiety disorders.
In categories such as: abuse liability; bioavailability; mechanism of action (pharmacodynamics); onset of action; tolerability; and withdrawal – there are unlikely significant differences between temazepam and alprazolam. Modest differences between temazepam and alprazolam may exist in bioavailability (~96% temazepam vs. ~90% alprazolam) and onset of action (20 to 90 minutes – temazepam vs. 20 to 40 minutes – alprazolam).
The aspect in which temazepam may be superior to alprazolam is metabolism. Unlike alprazolam, temazepam is not subject to metabolism via hepatic CYP450 enzymes and (1) is unlikely to provoke pharmacokinetic interactions with concurrently-administered CYP450 inducers/inhibitors (2) and its peak plasma concentrations won’t be altered by atypical gene expression among users.
Because alprazolam is metabolized via hepatic CYP3A4 enzymes: (1) concurrently-administered CYP450 inducers/inhibitors may provoke adverse reactions (2) and/or atypical gene expression among users might alter its peak plasma concentrations. In other words, the tolerability and/or therapeutic effect of temazepam may be more consistent across patients than the tolerability and/or therapeutic effect of alprazolam.
Although temazepam is favorable over alprazolam in the aspect of metabolism, alprazolam is favorable over temazepam in the aspects of: cost; formatting; and potency. In terms of cost, Alprazolam is generally lower-priced than temazepam (regardless of dosage) and brand name Xanax is significantly lower-priced than brand name Restoril.
In terms of formatting, there are 4 available formats of Xanax (alprazolam) including: immediate-release (IR) tablet; extended-release (ER or XR) tablet; orally-disintegrating tablet (ODT); and oral solution – and only 1 available format (immediate-release capsules) of Restoril (temazepam). Even if we solely compared the standard formats, one might regard alprazolam as better than temazepam based on the fact that the “tablets” can be easily split for dosage adjustments – whereas the “capsules” of temazepam cannot.
Furthermore, the variety of alprazolam formats: (1) might be more convenient for certain users to administer (e.g. orally-disintegrating tablets and oral solution); (2) allow medical doctors and/or patients to conveniently adjust its duration of effect (e.g. using extended-release tablets). Also worth noting is that alprazolam is around 40-fold more potent than temazepam on a “per milligram” basis.
In conclusion, temazepam is a better treatment option than alprazolam for insomnia – and alprazolam is a better treatment option than temazepam for anxiety disorders. Temazepam is superior over alprazolam with regard to metabolism, but alprazolam is superior to temazepam in its lower average cost and variety of available formats.
Assuming dosage potency, administration frequency, and duration of treatment are identical among temazepam and alprazolam users – there will likely be no significant differences in: efficacy, tolerability, safety, abuse potential, tolerance onset, and withdrawal symptoms. That said, certain users might report one medication as being more effective and/or tolerable than the other.
A unique combination of: genetic and/or epigenetic expression, baseline neurochemistry, medical status, concurrently-administered substances – likely explain why certain individuals may respond better to one medication versus the other. If you’re having difficulty determining whether you’d be better off using temazepam or alprazolam, it is recommended to consult a medical doctor.
Which medication do you prefer: Temazepam or Xanax?
If you have used both temazepam and alprazolam, separately, as treatments for anxiety, insomnia, or another medical condition – feel free to share your experience in the comments section. Additionally, mention some similarities and/or differences that you noticed between temazepam and alprazolam.
In your experience, was temazepam or alprazolam more efficacious than the other as a treatment for your medical condition(s)? Assuming you found one medication to be more efficacious than the other, have you considered that the difference in perceived efficacy could be related to disparities in: dosage potency; formatting; frequency of treatment; length of use; and/or concurrently-administered substances?
Have you further considered the possibility that atypical gene expression might alter CYP3A4 enzyme function to account for differences in perceived effectiveness? (For example, if you are a poor CYP3A4 metabolizer, you might find alprazolam to be of suboptimal efficacy at standard doses).
If you had the choice between temazepam and alprazolam for your medical condition – would you have a strong preference for using one medication over the other? If you have a preference for temazepam over alprazolam, or vice-versa, share specific reasons as to why you’ve developed this preference such as: quicker onset of action; superior formatting; duration of effect; cost; slower tolerance onset; fewer adverse reactions; and/or fewer withdrawal symptoms.
To help others accurately understand your respective experiences with temazepam and alprazolam, document specifics such as: (1) the dosages and formats utilized; (2) frequency and duration of treatment; (3) concomitant substance use; and (4) the medical diagnosis for which these agents were prescribed.