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===Panic disorder===
===Panic disorder===
Alprazolam is [[Food and Drug Administration (United States)|FDA studied and approved]] for the treatment of [[panic disorder]]. Alprazolam is effective in the relief of moderate to severe [[anxiety]] and [[panic attacks]]. Physicians should be aware that continued efficacy has not been systematically demonstrated beyond 8 weeks' use. The physician who elects to use alprazolam for longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient.<ref>{{cite web |url = http://www.fda.gov/cder/foi/label/2003/21434_xanax_lbl.pdf |title = Fda approved labeling for xanax xr |accessdate = 2 August 2007 |date=23rd |year = 2003 |month = January |author = FDA |format = PDF |publisher = Federal Drug Administration |page = 4 |quote = The longer-term efficacy of XANAX XR has not been systematically evaluated. Thus, the physician that elects to use this drug for periods longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient. |archiveurl = http://web.archive.org/web/20070204134224/http://www.fda.gov/cder/foi/label/2003/21434_xanax_lbl.pdf |archivedate = February 4, 2007}}</ref><ref name=xcppdmm>{{cite web | url = http://www.rxlist.com/xanax-drug.htm | title = Xanax (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList | author = First DataBank | year = 2008 | month = July | publisher = RxList }}</ref> Alprazolam is recommended for treatment resistant cases of panic disorder where there is no history of [[drug tolerance|tolerance]] or [[drug dependence|dependence]].<ref>{{Cite journal | last1 = Bandelow | first1 = B. | last2 = Zohar | first2 = J. | last3 = Hollander | first3 = E. | last4 = Kasper | first4 = S. | last5 = Möller | first5 = HJ. | title = World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders. | journal = World J Biol Psychiatry | volume = 3 | issue = 4 | pages = 171–99 | month = Oct | year = 2002 | pmid = 12516310 | doi = 10.3109/15622970209150621 | author6 = World Federation of Societies of Biological Psychiatry Task Force on Treatment Guidelines for Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders }}</ref>
Alprazolam is FDA-approved for the short-term treatment (up to 8 weeks) of panic disorder, with or without agoraphobia {{http://www.mahalo.com/alprazolam/}}</ref>. Alprazolam is effective in the relief of moderate to severe [[anxiety]] and [[panic attacks]]. Physicians should be aware that continued efficacy has not been systematically demonstrated beyond 8 weeks' use. The physician who elects to use alprazolam for longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient.<ref>{{cite web |url = http://www.fda.gov/cder/foi/label/2003/21434_xanax_lbl.pdf |title = Fda approved labeling for xanax xr |accessdate = 2 August 2007 |date=23rd |year = 2003 |month = January |author = FDA |format = PDF |publisher = Federal Drug Administration |page = 4 |quote = The longer-term efficacy of XANAX XR has not been systematically evaluated. Thus, the physician that elects to use this drug for periods longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient. |archiveurl = http://web.archive.org/web/20070204134224/http://www.fda.gov/cder/foi/label/2003/21434_xanax_lbl.pdf |archivedate = February 4, 2007}}</ref><ref name=xcppdmm>{{cite web | url = http://www.rxlist.com/xanax-drug.htm | title = Xanax (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList | author = First DataBank | year = 2008 | month = July | publisher = RxList }}</ref> Alprazolam is recommended for treatment resistant cases of panic disorder where there is no history of [[drug tolerance|tolerance]] or [[drug dependence|dependence]].<ref>{{Cite journal | last1 = Bandelow | first1 = B. | last2 = Zohar | first2 = J. | last3 = Hollander | first3 = E. | last4 = Kasper | first4 = S. | last5 = Möller | first5 = HJ. | title = World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders. | journal = World J Biol Psychiatry | volume = 3 | issue = 4 | pages = 171–99 | month = Oct | year = 2002 | pmid = 12516310 | doi = 10.3109/15622970209150621 | author6 = World Federation of Societies of Biological Psychiatry Task Force on Treatment Guidelines for Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders }}</ref>


===Anxiety disorders===
===Anxiety disorders===

Revision as of 13:36, 25 July 2011

Alprazolam
Clinical data
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80–90%
MetabolismHepatic, via Cytochrome P450 3A4
Elimination half-lifeImmediate release: 11.2 hours,[2]
Extended release: 10.7–15.8 hours[3]
ExcretionRenal
Identifiers
  • 8-chloro-1-methyl-6-phenyl-4H-
    [1,2,4]triazolo[4,3-a][1,4]benzodiazepine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.044.849 Edit this at Wikidata
Chemical and physical data
FormulaC17H13ClN4
Molar mass308.765 g·mol−1
3D model (JSmol)
  • Clc3cc2\C(=N/Cc1nnc(n1c2cc3)C)c4ccccc4
  • InChI=1S/C17H13ClN4/c1-11-20-21-16-10-19-17(12-5-3-2-4-6-12)14-9-13(18)7-8-15(14)22(11)16/h2-9H,10H2,1H3 checkY
  • Key:VREFGVBLTWBCJP-UHFFFAOYSA-N checkY
  (verify)

Alprazolam (/[invalid input: 'icon']ælˈpræzəˌlæm/; trade name Xanax, among others) is a potent short-acting drug of the benzodiazepine class. Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor. It is primarily used to treat moderate to severe anxiety disorders (e.g., social anxiety disorder) and panic attacks.[4] It is available in an immediate-release and an extended-release (Xanax XR) preparation, both of which are available under several generic names. Alprazolam possesses anxiolytic, sedative, hypnotic, skeletal muscle relaxant, anticonvulsant, and amnestic properties.[5]

Alprazolam has a fast onset of symptom relief (within the first week). It is unlikely to produce dependency or abuse. No tolerance has been reported, but withdrawal and rebound symptoms necessitate a gradual reduction in dosage to minimize withdrawal effects when discontinuing.[6][7] It is a C IV controlled substance by the DEA. Based on findings in the US from the Treatment Episode Data Set (TEDS), an annual compilation of patient characteristics in substance abuse treatment facilities in the United States, admissions due to "primary tranquilizer" (including, but not limited to, benzodiazepine-type) drug use increased 79% from 1992 to 2002. Thus, the DAWN and TEDS data sets demonstrate clearly that the misuse of these sedative/hypnotics is on the rise, and cause for concern.[8]

Alprazolam is the most prescribed[9] and the most abused benzodiazepine in the US.[10]

Medical uses

Alprazolam is primarily used to treat anxiety disorders, panic disorders, and nausea due to chemotherapy.[11]

Panic disorder

Alprazolam is FDA-approved for the short-term treatment (up to 8 weeks) of panic disorder, with or without agoraphobia Template:Http://www.mahalo.com/alprazolam/</ref>. Alprazolam is effective in the relief of moderate to severe anxiety and panic attacks. Physicians should be aware that continued efficacy has not been systematically demonstrated beyond 8 weeks' use. The physician who elects to use alprazolam for longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient.[12][13] Alprazolam is recommended for treatment resistant cases of panic disorder where there is no history of tolerance or dependence.[14]

Anxiety disorders

Alprazolam is indicated by the FDA for the management of Panic Disorder with and without agoraphobia (a condition corresponding most closely to the APA Diagnostic and Statistical Manual DSM-III-R diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. Anxiety associated with depression is responsive to XANAX. [15]

In the UK Alprazolam is recommended for the short-term treatment (2–4 weeks) of severe acute anxiety.[13][16][17]

Long term users of alprazolam may develop depression.[18]

Nausea due to chemotherapy

Alprazolam may be used in combination with other medications for chemotherapy-induced nausea and vomiting.[11]

Pregnancy and lactation

Benzodiazepines cross the placenta and enter into the fetus and also penetrate into breast milk. The use of benzodiazepines during pregnancy or lactation should be weighed against the potential risks. Alprazolam should not be used during pregnancy and lactation as it is believed to be associated with congenital abnormalities. In general benzodiazepines should not be used during pregnancy. If a benzodiazepine is needed during pregnancy diazepam or chlordiazepoxide are recommended as these benzodiazepines have a better safety profile than alprazolam.

Women who are pregnant or are planning on becoming pregnant should avoid starting alprazolam.[19] Possible adverse effects on the fetus include spontaneous abortion, congenital disorder, intrauterine growth retardation, functional neurological deficit, carcinogenesis, and mutagenesis.[clarification needed] Use in the last trimester may cause fetal drug dependence and withdrawal symptoms on the post-natal period.[20] Also, neonatal flaccidity and respiratory problems have been reported in children born of mothers that have been receiving benzodiazepines.[21] However, in long-term users of benzodiazepines or antidepressants, abrupt discontinuation due to concerns of teratogenic effects of the medications is more likely to do harm than good. Abrupt withdrawal has a high risk of causing extreme withdrawal symptoms including suicidal ideation and a severe rebound effect of the underlying mental health disorder. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications including benzodiazepines. Many physicians are not aware of the severe consequences of abrupt withdrawal from psychotropic medications such as benzodiazepines or antidepressants.[22]

Benzodiazepines, including alprazolam, are known to be excreted in human milk.[23] Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.[24][25] As a general rule, nursing should not be undertaken by mothers who use alprazolam.

Contraindications

Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals. Particular care should be taken in pregnant or elderly patients, patients with substance abuse history, particularly alcohol dependence and patients with comorbid psychiatric disorders.[26] Use of alprazolam should be avoided or carefully monitored by medical professionals in individuals with the following conditions: myasthenia gravis, acute narrow-angle glaucoma, severe liver deficiencies (e.g., cirrhosis), severe sleep apnea, pre-existing respiratory depression, marked neuromuscular respiratory weakness including unstable myasthenia gravis, acute pulmonary insufficiency, chronic psychosis, hypersensitivity or allergy to alprazolam or other drugs in the benzodiazepine class, borderline personality disorder (may induce suicidality and dyscontrol).[27][28][29][30]

Like all central nervous system depressants, including alcohol, alprazolam in larger-than-normal doses can cause significant deterioration in alertness, combined with increased feelings of drowsiness, especially in those unaccustomed to the drug's effects.[31] People driving or conducting activities that require vigilance should exercise caution in using alprazolam or any other depressant.

Elderly individuals should be cautious in the use of alprazolam due to the possibility of increased susceptibility to side-effects, especially loss of coordination and drowsiness.[24]

Adverse effects

Xanax 2 mg tablets (AU)

Although the side-effect profile of alprazolam is, in general, benign, side-effects may occur in some patients and are more likely the higher the dosage taken. Some side-effects may disappear with continued treatment. If signs of an allergic reaction occur - such as hives; difficulty breathing; swelling of face, lips, tongue, or throat - medical attention should be sought immediately. Medical attention should also be sought immediately if signs of jaundice appear: yellowing of the skin or eyes. Other side-effects that may occur are as follows:

Paradoxical reactions

Although unusual, if the following paradoxical reactions occur, the prescribing physician or other healthcare professional should be alerted and the medication gradually discontinued:

Dependence and withdrawal

Xanax 0.25, 0.5 and 1 mg tablets (US)
See also: Benzodiazepine withdrawal syndrome

Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor. When bound to these sites, which are referred to as benzodiazepine receptors, it modulates the effect of GABA A receptors and, thus, GABAergic neurons. Long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to stimulation and less powerful in their effects.[51]

Not all withdrawal effects are evidence of true dependence or withdrawal. Recurrence of symptoms such as anxiety may simply indicate that the drug was having its expected anti-anxiety effect and that, in the absence of the drug, the symptom has returned to pretreatment levels. If the symptoms are more severe or frequent, the patient may be experiencing a rebound effect due to the removal of the drug. Either of these can occur without the patient's actually being drug-dependent.[51]

Alprazolam and other benzodiazepines may also cause the development of physical dependence, tolerance, and benzodiazepine withdrawal symptoms during rapid dose reduction or cessation of therapy after long-term treatment.[52][53] There is a higher chance of withdrawal reactions if the drug is administered in a higher dosage than recommended, or if a patient stops taking the medication altogether without slowly allowing the body to adjust to a lower-dosage regimen.[54][55][56]

In 1992, Romach and colleagues reported that dose escalation is not a characteristic of long-term alprazolam users, and that the majority of long-term alprazolam users change their initial pattern of regular use to one of symptom control only when required.[57]

If a patient feels the need to end treatment with alprazolam, he/she should consult his/her physician before discontinuing the medication. Some common symptoms of alprazolam discontinuation include tachycardia, dysphoria, dry mouth, loss of appetite, insomnia, anxiety, dizziness, tremors, nausea, cramps, vomiting, diarrhea, panic attacks, mood swings, heart palpitations, memory loss. Less common and more severe reactions can occur, including hallucinations, seizures or fever[58]

Patients taking a dosing regimen larger than 4 mg per day have an increased potential for dependence. This medication may cause withdrawal symptoms upon abrupt withdrawal or rapid tapering, which in some cases have been known to cause seizures. The discontinuation of this medication may also cause a reaction called rebound anxiety. Other withdrawal effects anecdotally reported from discontinuing alprazolam therapy include homicidal ideation (very rare), rage reactions, hyperalertness, vivid dreams, and intrusive thoughts in eight patients with combat-induced post traumatic stress disorder.[59] Grand mal seizures have occurred after abrupt withdrawal after only short-term use. Therefore, even short-term users of alprazolam should taper off of their medication slowly to avoid serious withdrawal reactions including seizures.[60][61]

Alprazolam should never be abruptly stopped if taken regularly for any length of time because severe withdrawal symptoms may occur. Delirium and seizures have been anecdotally reported in the medical literature from abrupt alprazolam discontinuation,[62][63] and one death has anecdotally been reported after suspected alprazolam-related seizures after gradual dose reduction.[63]

In a 1983 study of patients that had taken long-acting benzodiazepines, e.g., clorazepate, for extended periods, the medications were stopped abruptly under double-blind conditions (that is, patients were receiving either placebo or the same drug they had been taking). Only 5% of patients that had been taking the drug for less than 8 months demonstrated withdrawal symptoms, but 43% of those that had been taking them for more than 8 months did, whereas, with alprazolam - a short-acting benzodiazepine - taken for 8 weeks, 35% of patients experienced significant rebound anxiety. To some degree, these older benzodiazepines are self-tapering.[64]

The benzodiazepines diazepam (Valium) and oxazepam (Serepax) have been found to produce fewer withdrawal reactions than alprazolam (Xanax), temazepam (Restoril/Normison), or lorazepam (Temesta/Ativan). Factors that determine the risk of psychological dependence or physical dependence and the severity of the benzodiazepine withdrawal symptoms experienced during dose reduction of alprazolam include: dosage used, length of use, frequency of dosing, personality characteristics of the individual, previous use of cross-dependent/cross-tolerant drugs (alcohol or other sedative-hypnotic drugs), current use of cross-dependent/-tolerant drugs, use of other short-acting, high-potency benzodiazepines,[65][66] and method of discontinuation.[67]

Food and drug interactions

Alprazolam is primarily metabolised via CYP3A4.[68] Combining CYP3A4 inhibitors with alprazolam can lead to profound sedating effects.[69] Cimetidine, erythromycin, fluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene, and ritonavir all interact with alprazolam leading to a delayed clearance of alprazolam, which may result in excessive accumulation of alprazolam. This may result in excessive sedation and other adverse effects associated with excessive intake of alprazolam.[70][71]

Imipramine and desipramine have been reported to be increased an average of 31% and 20%, respectively, by the concomitant administration of alprazolam tablets in doses up to 4 mg/day.[72] Combined oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation.[73]

Alcohol is one of the most important and common interactions. Alcohol and benzodiazepines such as alprazolam taken in combination have a synergistic effect on one another, which can cause severe sedation, behavioral changes, and intoxication. The more alcohol and alprazolam taken the worse the interaction.[34] Combination of alprazolam with the herb kava can result in the development of a semi-comatose state.[74] Hypericum conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.[75][76][77]

Overdose

Main article: Benzodiazepine overdose

Overdoses of alprazolam can be mild to severe depending on how much of the drug is taken and if any other depressants have been taken. Combined overdose with tricyclic antidepressants, alcohol, or opiates, or overdoses of alprazolam in the elderly, significantly increases the likelihood for severe toxicity and possible fatality.[78] Alprazolam (Xanax) overdose reflect the central nervous system depression of the brain and may include one or more of the following symptoms:[37]

About 50% of the cases of death involving alprazolam were attributed to combined drug toxicity of alprazolam and another drug, most often cocaine and methadone. Only 1% of such deaths were attributed to alprazolam alone, indicating that alprazolam has a very high therapeutic index and that mortality is extremely rare when alprazolam is the only drug taken.[79][80]

Detection in body fluids

Alprazolam may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest or to assist in a medicolegal death investigation. Blood or plasma alprazolam concentrations are usually in a range of 10-100 μg/L in persons receiving the drug therapeutically, 100-300 μg/L in those arrested for impaired driving and 300-2000 μg/L in victims of acute overdosage. Most commercial immunoassays for the benzodiazepine class of drugs will cross-react with alprazolam, but confirmation and quantitation is usually performed using chromatographic techniques.[81][82][83]

Pharmacology

Alprazolam is classed as a high-potency benzodiazepine and is a triazolobenzodiazepine more specifically[84][85]–a benzodiazepine with a triazole ring attached to its structure. Benzodiazepines produce a variety of therapeutic and adverse effects by binding to the benzodiazepine receptor site on the GABAA receptor and modulating the function of the GABA receptor, the most prolific inhibitory receptor within the brain. The GABA chemical and receptor system mediates inhibitory or calming effects of alprazolam on the nervous system. The GABAA receptor is made up of 5 subunits out of a possible 19, and GABAA receptors made up of different combinations of subunits have different properties, different locations within the brain, and, importantly, different activities with regard to benzodiazepines.[40][86] Benzodiazepines and in particular alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. The therapeutic properties of alprazolam are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic[87] and amnesic.[88]

Pharmacokinetics

Alprazolam is readily absorbed from the gastrointestinal tract with a bioavailability of 80–100%. The peak plasma concentration is achieved in 1–2 hours. Most of the drug is bound to plasma protein, mainly serum albumin. Alprazolam is hydroxylated in the liver to α-hydroxyalprazolam, which is also pharmacologically active but much less so than the parent compound. This and other metabolites are later excreted in urine as glucuronides. Some of the drug is also excreted in unchanged form. The elderly clear alprazolam more slowly than younger adults.[70]

Chemistry

Alprazolam is a chemical analog of triazolam that differs by the absence of a chlorine atom in the o-position of the 6-phenyl ring. The same scheme that was used to make triazolam can be used to make alprazolam, with the exception that it begins with 2-amino-5-chlorobenzophenone.[89][90][91] However, a non-standard way of making alprazolam has been suggested, which comes from 2,6-dichloro-4-phenylquinoline, the reaction of which with hydrazine gives 6-chloro-2-hydrazino-4-phenylquinoline. Boiling this with triethyl orthoacetate in xylene leads to the heterocyclization into a triazole derivative. The resulting product undergoes oxidative cleavage using sodium periodate and ruthenium dioxide in an acetone–water system to give 2-[4-(3′-methyl-1,2,4-triazolo)]-5-chlorobenzophenone.[92][93][94] Oxymethylation of the last using formaldehyde and subsequent substitution of the resulting hydroxyl group by phosphorus tribromide,gives 2-[4-(3′-methyl-5′-bromomethyl-1,2,4-triazolo)]-5-chlorobenzophenone. Substitution of the bromine atom with an amino group using ammonia and the spontaneous, intermolecular heterocyclization following that reaction gives alprazolam.

History

Alprazolam was first released by Upjohn (now a part of Pfizer). It is covered under U.S. patent 3,987,052, which was filed on October 29, 1969, granted on October 19, 1976, and expired in September 1993. Alprazolam was released in 1981.[95][96] The first approved indication was panic disorder. Upjohn took this direction at the behest of a young psychiatrist, David Sheehan. Sheehan's suggestion was to use the new distinction the DSM-III created in the classification of anxiety disorders between generalized anxiety disorder (GAD) and panic disorder in order to market alprazolam specifically for the latter.[clarification needed] Panic disorder was, at that point, perceived to be rare and treatable only with tricyclic antidepressants; benzodiazepines were thought to be ineffective.

However, from his clinical experience, Sheehan knew panic disorder to be both widespread among the populace and responsive to benzodiazepines. He suggested to Upjohn that marketing alprazolam for panic disorder would both cover new diagnostic territory and emphasize the unique potency of this drug. Sheehan describes the first group of patients treated by alprazolam as so impressed by its action that the company knew outright that the drug was going to be a hit. A few of those patients actually pooled their money and purchased stock in Upjohn. Several months later, when alprazolam was approved by the United States Food and Drug Administration, they sold out and made a profit.[97][clarification needed]

Soon after its introduction a number of case reports were published in the medical literature of severe withdrawal symptoms, including psychoses, seizures and intense rebound anxiety, upon discontinuation of alprazolam.[65] Several studies found that initial treatment of panic disorder with alprazolam was significantly superior but after 8 weeks of use alprazolam lost its effectiveness and was no more effective than placebo.[citation needed] It was found[by whom?] that behavioral therapy and the drug imipramine however, proved superior to both placebo and alprazolam. It has been argued[by whom?] that placebo is superior than alprazolam after 8 weeks of use due to lack of rebound withdrawal effects and side effects. Controversy exists in that there are allegations that the drug manufacturer suppressed these negative findings regarding lack of sustained efficacy.[98][99]

Society and culture

Recreational use

Generic alprazolam 2 mg tablets (US)
See also: Benzodiazepine drug misuse

Alprazolam has a relatively high potential for recreational use[100] and is one of the most commonly misused benzodiazepine in the United States.[7] Injection of alprazolam, though extremely rare, is considered especially dangerous by medical professionals[101] because, when crushed in water it will not fully dissolve (40 µg/ml of H2O at pH 7[102]), potentially causing severe damage to arteries if not filtered properly. While it is somewhat soluble in alcohol, the combination of the two, particularly when injected, has the potential to cause a serious, and potentially fatal, overdose. Alprazolam may also be snorted,[103] although this is a highly inefficient method of delivery, as the drug is hardly soluble in water[104] and does not readily cross the nasal membranes, resulting in reduced bioavailability. However, most prescribed alprazolam users do not use their medication recreationally, and long-term use of benzodiazepines does not usually result in notable dose escalation.[105]

Alprazolam is sometimes used with other recreational drugs to relieve the panic or distress of dysphoric ("bad trip") reactions to psychedelic drugs such as LSD, and also to promote sleep in the "come-down" period following use of recreational drugs with stimulant or insomniac properties (such as amphetamines (e.g. MDMA), LSD, cocaine, methylphenidate, and DXM). It is also often used in conjunction with alcohol, marijuana or heroin and other opiates to potentiate the relaxing effect.[106][107][108][109][110] Due to the low weight of a dose, alprazolam in one case was found to be distributed on blotter paper in a manner similar to LSD.[111]

A large-scale nationwide U.S. government study conducted by SAMHSA found that, in the U.S., benzodiazepines are recreationally the most frequently used pharmaceutical due to their widespread availability, with these substances accounting for 35% of all drug-related visits to hospital emergency and urgent care facilities. Benzodiazepines are more commonly used recreationally than opioid pharmaceuticals, which accounted for 32% of visits to emergency departments. No other pharmaceutical is more commonly used recreationally than benzodiazepines; however, benzodiazepines remain in Schedule IV of the Controlled Substances Act, whereas opioids are much more strictly controlled due to their higher abuse potential. Men use benzodiazepines recreationally as commonly as women. The report found that alprazolam is the most common benzodiazepine for recreational use followed by clonazepam, lorazepam, and diazepam.[10]

At a particularly high risk for misuse and dependence are people with a history of alcoholism (including a family history of alcoholism), or drug abuse and/or dependence[112][113][114][115][116] and people with borderline personality disorder.[117]

Availability

Alprazolam instant release (IR) is available in 0.125 mg, 0.25 mg, 0.5 mg, 1 mg and 2 mg strength regular and orally disintegrating tablets.[118] Alprazolam Extended Release (XR) is available in 0.5 mg, 1 mg, 2 mg, and 3 mg strength oral.

Alprazolam is available in English-speaking countries under the following brand names:[119]

In the United States, alprazolam is a prescription drug and is assigned to Schedule IV of the Controlled Substances Act by the Drug Enforcement Administration.[120] Under the UK drug misuse classification system benzodiazepines are class C drugs (Schedule 4).[121] In the UK alprazolam is not available on the NHS and can only be obtained on private prescription.[122] Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[123] In Ireland, alprazolam is a Schedule 4 medicine.[124] In Sweden, alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[125] In the Netherlands, alprazolam is a List 2 substance of the Opium Law and is available for prescription.

See also

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ First DataBank (2008). "Xanax (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList". RxList. {{cite web}}: Unknown parameter |month= ignored (help)
  3. ^ First DataBank (2008). "Xanax XR (Alprazolam) clinical pharmacology - prescription drugs and medications at RxList". RxList. {{cite web}}: Unknown parameter |month= ignored (help)
  4. ^ Work Group on Panic Disorder (January 2009). "APA Practice Guideline for the Treatment of Patients With Panic Disorder, Second Edition" (PDF). Retrieved 07/12/09. {{cite web}}: Check date values in: |accessdate= (help)
  5. ^ Mandrioli R, Mercolini L, Raggi MA (2008). "Benzodiazepine metabolism: an analytical perspective". Curr. Drug Metab. 9 (8): 827–44. doi:10.2174/138920008786049258. PMID 18855614. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Verster JC, Volkerts ER. (2004). "Clinical pharmacology, clinical efficacy, and behavioral toxicity of alprazolam: a review of the literature". CNS Drug Rev. 10 (1): 45–76. doi:10.1111/j.1527-3458.2004.tb00003.x. PMID 14978513.
  7. ^ a b Galanter, Marc (1 July 2008). The American Psychiatric Publishing Textbook of Sustance Abuse Treatment (American Psychiatric Press Textbook of Substance Abuse Treatment) (American Psychiatric ... Press Textbook of Substance Abuse Treatment) (4 ed.). American Psychiatric Publishing, Inc. p. 222. ISBN 978-1-58562-276-4.
  8. ^ Licata, SC; Rowlett, JK (January 12, 2008). "Abuse and dependence liability of benzodiazepine-type drugs: GABA(A) receptor modulation and beyond". Pharmacology Biochemistry and Behavior. 90 (1): 74–89. PMID 18295321.
  9. ^ Forbes. "The most prescibed drugs in the US". Retrieved 9 February 2009.
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