Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.

org/wiki/Alprazolam

From Wikipedia, the free encyclopedia

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Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam

Alprazolam (trade name Xanax, among others) is a potent

Alprazolam
short-acting drug of the benzodiazepine class. It is primarily
used to treat moderate to severe anxiety disorders (e.g., social
anxiety disorder) and panic attacks, and is used as an
adjunctive treatment for anxiety associated with moderate
depression. It is available in an instant release and an
extended-release (Xanax XR) preparation, both of which are
available under several generic names. Alprazolam possesses
anxiolytic, sedative, hypnotic, anticonvulsant, and muscle
relaxant properties.[3]

Alprazolam has a fast onset of symptom relief (within the first

week). It is the most commonly misused benzodiazepine;
however, the majority of prescribed users do not develop a
substance use disorder.[4][5] Tolerance to the therapeutic
effects of alprazolam is controversial with one view being
that alprazolam is ineffective with long term use[6] and the
other view being that tolerance to the therapeutic effects does
not occur.[7] A physical dependence commonly occurs as a
result of alprazolam treatment, typified by a withdrawal and
rebound symptoms necessitating a gradual reduction in Systematic (IUPAC) name
dosage to minimize withdrawal effects when discontinuing.[4] 8-chloro-1-methyl-6-phenyl-4H-
Withdrawal symptoms similar in character to those noted [1,2,4]triazolo[4,3-a][1,4]benzodiazepine
with sedative-hypnotics and alcohol have occurred following
discontinuance of benzodiazepines, including alprazolam. The Identifiers
symptoms can range from mild dysphoria and insomnia to a CAS number 28981-97-7
major syndrome that may include anxiety, abdominal pain, ATC code N05BA12
muscle cramps, vomiting, depression, sweating, tremors and
PubChem CID 2118
in very rare cases suicidal ideation or suicide itself.[8]
DrugBank APRD00280
ChemSpider 2034
Chemical data
Formula C17H13ClN4
1 History Mol. mass 308.765
2 Indications
SMILES eMolecules & PubChem
2.1 Panic disorder
2.2 Anxiety disorders Pharmacokinetic data

3 Side effects Bioavailability 80–90%

3.1 Paradoxical reactions Metabolism Hepatic, via Cytochrome P450 3A4
4 Physical dependence and withdrawal Half-life Immediate release: 11.2 hours;[1]
5 Contraindications Extended release: 10.7–15.8
5.1 Pregnancy and lactation
hours[2]
6 Pharmacology Excretion Renal
7 Pharmacokinetics
8 Food and drug interactions Therapeutic considerations
9 Recreational use Pregnancy cat. D(US)
Legal status POM (UK) Schedule IV (US)

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9.1 Patients at a high risk for misuse and Routes Oral

addiction
(what is this?) (verify) (http://en.wikipedia.org
10 Overdose /w/index.php?&diff=cur&oldid=321790496)
10.1 Detection in body fluids
11 Availability
12 Legal status
13 See also
14 References
15 External links

Alprazolam was first released by Upjohn (now a part of Pfizer). It is covered under U.S. Patent 3,987,052
(http://www.google.com/patents?vid=3987052) , which was filed on October 29, 1969, granted on October 19,
1976 and expired in September 1993. Alprazolam was released in 1981.[9][10] 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.
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 that the
first group of patients treated by alprazolam was 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.[11]

Alprazolam has an exceptional history insofar as soon after its introduction a number of case reports were
published in the medical literature of severe withdrawal symptom-related case reports of psychoses, seizures,
and intense rebound anxiety upon discontinuation of alprazolam.[12] 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. It was found that behavioural therapy and the drug
imipramine however, proved superior to both placebo and alprazolam. It has been argued 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.[13][14]

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The main medical uses for alprazolam include:

Panic disorder

Alprazolam is FDA-approved for the short-term treatment (up to 8

weeks) of panic disorder, with or without agoraphobia. Alprazolam
is very effective in the short-term symptomatic relief of moderate to
severe anxiety, essential tremor, and panic attacks. Physicians that
elect to prescribe alprazolam for longer than 8 weeks should be
aware that continued efficacy has not been systematically
demonstrated beyond 8 weeks' use, as tolerance to alprazolam's
effects may occur after 8 weeks and necessitate discontinuation or
physician-directed dose escalation.[15] The physician should
periodically reassess the usefulness of the drug for the individual
patient.[16] Alprazolam is recommended for treatment resistant
cases of panic disorder where there is no history of tolerance or Xanax 2 mg tri-score tablets (AU)
dependence.[17]

Anxiety disorders

Alprazolam is indicated for the management of anxiety disorders (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.[16] Alprazolam is recommended for the short-term treatment (2–4 weeks) of
severe acute anxiety.[18][19]

Alprazolam is sometimes prescribed for anxiety with associated depression. There is some evidence that it has
antidepressant effects in treating clinical depression in outpatient settings; evidence for inpatients is lacking.[20]
The antidepressant effects of alprazolam may be due to its effects on beta-adrenergic receptors.[21] Other
benzodiazepines are not known to have antidepressant activity.[22][23] Studies show that any antidepressant
action of alprazolam is questionable and generally weak in comparison to those of antidepressant medications.
[24][25][26][27]
In contrast, while alprazolam in acute or short-term treatment may have some antidepressant
properties, there is evidence that up to a third of long-term users of alprazolam may develop depression.[28]

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:

drowsiness, dizziness, lightheadedness, fatigue, unsteadiness and impaired coordination, vertigo[29][30]

skin rash, respiratory depression, constipation[29][30]
disinhibition[31]
suicidal ideation (rare)[32][33]
urinary retention (infrequent)[34]

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hallucinations (rare)[35]
ataxia, slurred speech[36]
short-term memory loss and impairment of memory functions, particular the memory that the user
experienced during the time of inxication[37]
anterograde amnesia[38] and concentration problems
Change in libido[39]
xerostomia (infrequent)[40]
disorientation (when medicating in excess, such as to induce intoxication for recreational purposes)[41]
increase in appetite[42]
jaundice (very rare)[43]

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:

Fasciculations and tremor[44]

aggression[45]
rage, hostility[31]
mania, agitation, hyperactivity and restlessness[46][47][48]

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, GABAnergic neurons. Long-term use causes adaptive changes in the
benzodiazepine receptors, making them less sensitive to stimulation and less powerful in their effects.[49]

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.[49]

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.[50][51] 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.[52][53][54]

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.[55]

If a patient feels the need to end treatment with alprazolam, he/she should consult his/her physician before

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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[56]

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 reported from discontinuing alprazolam therapy include homicidal
ideation (very rare), rage reactions, hyperalertness, vivid dreams, and intrusive thoughts.[57] 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.[58][59]

Alprazolam should never be abruptly stopped if taken regularly for any length of time because severe
withdrawal symptoms may occur. Severe psychosis and seizures have been reported in the medical literature
from abrupt alprazolam discontinuation,[60][61] and one death occurred from withdrawal-related seizures after
gradual dose reduction.[61]

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.[62]

The benzodiazepines diazepam (Valium) and oxazepam (Serepax) have been found to produce fewer
withdrawal reactions than alprazolam (Xanax) 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/cross-tolerant drugs (alcohol or other
sedative-hypnotic drugs), use of other short-acting, high-potency benzodiazepines[12][63] and method of
discontinuation.[64]

Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals.[65]
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).[66][67][68][69]

Women who are pregnant or are planning on becoming pregnant should avoid starting alprazolam.[70] It should
be considered that the child born of a mother receiving benzodiazepines may be at risk of developing withdrawal
reactions during the postnatal period. Also, neonatal flaccidity and respiratory problems have been reported in
children born of mothers that have been receiving benzodiazepines.[71]

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Benzodiazepines, including alprazolam, are known to be excreted in human milk.[72] Chronic administration of
diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.
[73][74]
As a general rule, nursing should not be undertaken by mothers who use alprazolam.

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.[74]

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.[75] People driving or conducting activities that require vigilance should
exercise caution in using alprazolam or any other depressant.

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. Possible adverse effects to the fetus include abortion, malformation, intrauterine growth retardation,
functional deficits, carcinogenesis, and mutagenesis. Use in the last trimester may cause fetal drug dependence
and withdrawal symptoms.[76] 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. In general physicians are not aware
of the severe consequences of abrupt withdrawal of psychotropic medications such as benzodiazepines or
antidepressants.[77]

Alprazolam is classed as a high-potency benzodiazepine and is a triazolobenzodiazepine,[78][79] that is, a

benzodiazepine with a triazole ring attached to its structure. Benzodiazepines produce a variety of therapeutic
and adverse effects by binding to the benzodiazepine 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 from 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, what is significant, different
activities with regard to benzodiazepines.[38][80] 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[81] and amnesics.[82]

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

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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.[83]

Alprazolam is primarily metabolised via CYP3A4.[84] Combining CYP3A4 inhibitors with alprazolam can lead
to profound sedating effects.[85] 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.[83][86]

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.[87] Combined oral contraceptive
pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and
accumulation.[88]

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.[31] Combination of
alprazolam with the herb kava can result in the development of a semi-comatose state.[89] Hypericum
conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.[90][91][92]

See also: Benzodiazepine drug misuse

Alprazolam has a relatively high potential for recreational use[93]

and is the most commonly misused benzodiazepine.[5] Injection of
alprazolam, though extremely rare, is considered especially
dangerous by medical professionals[94] because, when crushed in
water it will not fully dissolve (40 µg/ml of H2O at pH 7, and
12 mg/mL at pH 1.2[95]), 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. Sandoz generic 2 mg alprazolam tablets
[96]
Alprazolam may also be insufflated. Snorting alprazolam is
highly inefficient, as it is insoluble in water and does not readily cross the nasal membranes, resulting in reduced
bioavailability. However, long-term use of benzodiazepines does not usually result in notable dose escalation,
and most prescribed alprazolam users do not use their medication recreationally.[97]

Alprazolam is sometimes used with other recreational drugs to relieve the panic or distress of dysphoric
reactions to psychedelics 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 LSD, cocaine, amphetamine and other related
amphetamines, DXM, and MDMA). It is also often used in conjunction with marijuana or heroin to potentiate
the relaxing effect.[98][99][100][101][102] Due to the low weight of a dose, alprazolam in one case was found to

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be distributed on blotter paper in a manner similar to LSD.[103]

A large-scale nationwide USA government study conducted by SAMHSA found that, in the USA,
benzodiazepines are recreationally the most frequently-used pharmaceutical due to their widespread availability,
with 35% of drug-related visits to the Emergency Department involving them. Benzodiazepines are more
commonly used recreationally than opioid pharmaceuticals, which accounted for 32% of visits to the emergency
department. 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.[8]

Patients at a high risk for misuse and addiction

At a particularly high risk for misuse and dependence are patients with a history of alcoholism (including a
family history of alcoholism) or drug abuse and/or dependence[104][105][106][107][108] and patients with
borderline personality disorder.[109]

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. Alprazolam is significantly more toxic in overdose having higher rates of fatalities
compared to other benzodiazepines. A study in New Zealand found that alprazolam is almost 8 times more likely
to result in death in overdose than other sedative hypnotics as a group, with higher rates of intensive-care unit
admissions and mechanical ventilation. 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.[110] Alprazolam (Xanax) overdose reflect the central nervous system depression of the brain and may
include one or more of the following symptoms:[34]

Somnolence (sleepy state)

Hypotension (low blood pressure)
Hypoventilation (shallow breathing)
Impaired motor functions
Dizziness
Impaired balance
Muscle weakness
Impaired or absent reflexes
Fainting
Coma
Death

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.[111][112]

Detection in body fluids

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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.[113][114][115]

Alprazolam instant release (IR) is available in 0.25 mg, 0.5 mg, 1 mg and 2 mg strength regular and orally
disintegrating tablets.[116] Alprazolam Extended Release (XR) is available in 0.5 mg, 1 mg and 2 mg 3 mg
strength oral.

Alprazolam is available in English-speaking countries under the following brand names:[117]

Alganax
Alzolam
Alprax
Alprox
Alzam
Anxirid
Apo-Alpraz
Azor
Calmax
Gerax
Helex
Kalma
Nervin
Niravam
Novo-Alprazol
Nu-Alpraz
Tafil
Texidep
Trika
Xanax
Xanor
Zamhexal
Zopax

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.[118] Under the UK drug misuse classification system
benzodiazepines are class C drugs;[119] alprazolam itself is not available on the NHS and can only be obtained
on private prescription.[120] Internationally, alprazolam is included under the United Nations Convention on
Psychotropic Substances as Schedule IV.[121] In Ireland, alprazolam is a Schedule 4 medicine.[122] In Sweden,
alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[123] In the
Netherlands, alprazolam is a List 2 substance of the Opium Law and is available for prescription.

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Benzodiazepine
Benzodiazepine dependence
Benzodiazepine withdrawal syndrome
Long term effects of benzodiazepines
1. ^ First DataBank (July 2008). "Xanax (Alprazolam)
clinical pharmacology - prescription drugs and
medications at RxList" (http://www.rxlist.com/xanax-
drug.htm#cp) . RxList. http://www.rxlist.com/xanax-
drug.htm#cp.
2. ^ First DataBank (July 2008). "Xanax XR
(Alprazolam) clinical pharmacology - prescription
drugs and medications at RxList"
(http://www.rxlist.com/xanax-xr-drug.htm#cp) .
RxList. http://www.rxlist.com/xanax-xr-drug.htm#cp.
3. ^ Mandrioli R, Mercolini L, Raggi MA (October
2008). "Benzodiazepine metabolism: an analytical
perspective" (http://www.benthamdirect.org/pages
/content.php?CDM/2008/00000009/00000008
/0009F.SGM) . Curr. Drug Metab. 9 (8): 827–44.
doi:10.2174/138920008786049258 (http://dx.doi.org
/10.2174%2F138920008786049258) .
PMID 18855614 (http://www.ncbi.nlm.nih.gov
/pubmed/18855614) . http://www.benthamdirect.org
/pages/content.php?CDM/2008/00000009/00000008
/0009F.SGM.
4. ^ a b 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. PMID 14978513
(http://www.ncbi.nlm.nih.gov/pubmed/14978513) .
5. ^ 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)
(http://books.google.com/?id=6wdJgejlQzYC) (4
ed.). American Psychiatric Publishing, Inc.. p. 222.
ISBN 978-1-58562-276-4. http://books.google.com
/?id=6wdJgejlQzYC.
6. ^ McIntosh A, Cohen A, Turnbull N et al. (2004).
"Clinical guidelines and evidence review for panic
disorder and generalised anxiety disorder"
(http://www.nice.org.uk/nicemedia
/pdf/cg022fullguideline.pdf) (PDF). National
Collaborating Centre for Primary Care.
http://www.nice.org.uk/nicemedia
/pdf/cg022fullguideline.pdf. Retrieved 2009-06-16.
7. ^ Work Group on Panic Disorder (January 2009).
11 of 19
http://en.wikipedia.org/wiki/Alprazolam
"APA Practice Guideline for the Treatment of
Patients With Panic Disorder, Second Edition"
(http://www.psychiatryonline.com/pracGuide
/loadGuidelinePdf.aspx?file=PanicDisorder_2e_Prac
ticeGuideline) (PDF).
http://www.psychiatryonline.com/pracGuide
/loadGuidelinePdf.aspx?file=PanicDisorder_2e_Prac
ticeGuideline. Retrieved 07/12/09.
8. ^ a b United States Government; U.S.
DEPARTMENT OF HEALTH AND HUMAN
SERVICES (2006). "Drug Abuse Warning Network,
2006: National Estimates of Drug-Related
Emergency Department Visits"
(http://dawninfo.samhsa.gov/files/ed2006
/DAWN2k6ED.htm) . Substance Abuse and Mental
Health Services Administration.
http://dawninfo.samhsa.gov/files/ed2006
/DAWN2k6ED.htm. Retrieved 9 February 2009.
9. ^ Cynthia Cotts (November 19, 2007). "Xanax
junkies" (http://thephoenix.com
/article_ektid51411.aspx) . Boston, USA: The
Phoenix. http://thephoenix.com
/article_ektid51411.aspx.
10. ^ Walker, Sydney (3 December 1996). A dose of
sanity: mind, medicine, and misdiagnosis
(http://books.google.com/?id=1H_jx9XO4dcC&
pg=PA65) . New York: John Wiley & Sons.
pp. 64–65. ISBN 978-0-471-19262-6.
http://books.google.com/?id=1H_jx9XO4dcC&
pg=PA65.
11. ^ Healy, David (2000). The Psychopharmacologists,
Vol. III: Interviews. London: Arnold. pp. 479–504.
ISBN 0-340-761105.
12. ^ a b Wolf B, Griffiths RR (December 1991).
"Physical dependence on benzodiazepines:
differences within the class"
(http://linkinghub.elsevier.com/retrieve
/pii/0376-8716(91)90044-Y) . Drug Alcohol Depend
29 (2): 153–6. doi:10.1016/0376-8716(91)90044-Y
(http://dx.doi.org
/10.1016%2F0376-8716%2891%2990044-Y) .
PMID 1686752 (http://www.ncbi.nlm.nih.gov
/pubmed/1686752) . http://linkinghub.elsevier.com
/retrieve/pii/0376-8716(91)90044-Y.
8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia
13. ^ Walker, Sydney (3 December 1997). A dose of
sanity: mind, medicine, and misdiagnosis
(http://books.google.com/?id=1H_jx9XO4dcC) .
New York: Wiley Sons. pp. 65–74.
ISBN 978-0-471-19262-6. http://books.google.com
/?id=1H_jx9XO4dcC.
14. ^ J. McNally, Richard (1994). Panic disorder: a
critical analysis (http://books.google.com
/?id=SlUl5oTQIHoC) . New York: Guilford Press.
pp. 93–99. ISBN 978-0-89862-263-8.
http://books.google.com/?id=SlUl5oTQIHoC.
15. ^ FDA (23rd). "FDA APPROVED LABELING FOR
XANAX XR" (http://www.fda.gov/cder/foi/label
/2003/21434_xanax_lbl.pdf) (pdf). Federal Drug
Administration. pp. 4. http://www.fda.gov/cder/foi
/label/2003/21434_xanax_lbl.pdf. Retrieved 2
August 2007. "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."
16. ^ a b First DataBank (July 2008). "Xanax
(Alprazolam) clinical pharmacology - prescription
drugs and medications at RxList"
(http://www.rxlist.com/xanax-drug.htm) . RxList.
http://www.rxlist.com/xanax-drug.htm.
17. ^ Bandelow, B.; Zohar, J.; Hollander, E.; Kasper, S.;
Möller, HJ.; World Federation of Societies of
Biological Psychiatry Task Force on Treatment
Guidelines for Anxiety, Obsessive-Compulsive and
Posttraumatic Stress Disorders (Oct 2002). "World
Federation of Societies of Biological Psychiatry
(WFSBP) guidelines for the pharmacological
treatment of anxiety, obsessive-compulsive and
posttraumatic stress disorders.". World J Biol
Psychiatry 3 (4): 171–99.
doi:10.3109/15622970209150621 (http://dx.doi.org
/10.3109%2F15622970209150621) .
PMID 12516310 (http://www.ncbi.nlm.nih.gov
/pubmed/12516310) .
18. ^ NetDoctor (October 1, 2006). "Xanax"
(http://www.netdoctor.co.uk/medicines
/100002807.html) . netdoctor.co.uk.
http://www.netdoctor.co.uk/medicines
/100002807.html. Retrieved 2 August 2007.
19. ^ The British National Formulary (2007).
"Alprazolam" (http://www.bnf.org/bnf/bnf
/53/3173.htm) . BNF. http://www.bnf.org/bnf/bnf
/53/3173.htm. Retrieved 2 August 2007.
20. ^ Warner MD; Peabody CA, Whiteford HA,
Hollister LE (April 1988). "Alprazolam as an
antidepressant". J Clin Psychiatry 49 (4): 148–50.
PMID 3281931 (http://www.ncbi.nlm.nih.gov
/pubmed/3281931) .
21. ^ Sethy, Vh; Hodges, Dh, Jr (May 1982). "Role of
12 of 19
http://en.wikipedia.org/wiki/Alprazolam
beta-adrenergic receptors in the antidepressant
activity of alprazolam.". Research communications
in chemical pathology and pharmacology 36 (2):
329–32. PMID 6285432
(http://www.ncbi.nlm.nih.gov/pubmed/6285432) .
22. ^ Lader, Mh (9 December 1985). "Treatment of
affective disorders."
(http://www.pubmedcentral.nih.gov
/articlerender.fcgi?tool=pmcentrez&artid=1463505)
(Free full text). British journal of clinical
pharmacology 19 (Suppl 1): 29S–30S.
PMID 2859875 (http://www.ncbi.nlm.nih.gov
/pubmed/2859875) .
23. ^ Johnson, Da (9 December 1985). "The use of
benzodiazepines in depression."
(http://www.pubmedcentral.nih.gov
/articlerender.fcgi?tool=pmcentrez&artid=1463500)
(Free full text). British journal of clinical
pharmacology 19 (Suppl 1): 31S–35S.
PMID 2859876 (http://www.ncbi.nlm.nih.gov
/pubmed/2859876) .
24. ^ Kostowski W, Malatyńska E, Płaźnik A, Dyr W,
Danysz W (1986). "Comparative studies on
antidepressant action of alprazolam in different
animal models". Pol J Pharmacol Pharm 38 (5-6):
471–81. PMID 2883637
(http://www.ncbi.nlm.nih.gov/pubmed/2883637) .
25. ^ Srisurapanont, M; Boonyanaruthee, V (March
1997). "Alprazolam and standard antidepressants in
the treatment of depression: a meta-analysis of the
antidepressant effect.". Journal of the Medical
Association of Thailand = Chotmaihet thangphaet
80 (3): 183–8. PMID 9175386
(http://www.ncbi.nlm.nih.gov/pubmed/9175386) .
26. ^ Brasfield, Kh (September 1991). "Practical
psychopharmacologic considerations in depression.".
The Nursing clinics of North America 26 (3):
651–63. PMID 1891399
(http://www.ncbi.nlm.nih.gov/pubmed/1891399) .
27. ^ Hubain, Pp; Castro, P; Mesters, P; De, Maertelaer,
V; Mendlewicz, J (January 1990). "Alprazolam and
amitriptyline in the treatment of major depressive
disorder: a double-blind clinical and sleep EEG
study.". Journal of affective disorders 18 (1):
67–73. doi:10.1016/0165-0327(90)90118-R
(http://dx.doi.org
/10.1016%2F0165-0327%2890%2990118-R) .
PMID 2136871 (http://www.ncbi.nlm.nih.gov
/pubmed/2136871) .
28. ^ Lydiard, Rb; Laraia, Mt; Ballenger, Jc; Howell, Ef
(May 1987). "Emergence of depressive symptoms in
patients receiving alprazolam for panic disorder.".
The American journal of psychiatry 144 (5): 664–5.
PMID 3578580 (http://www.ncbi.nlm.nih.gov
/pubmed/3578580) .
8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia
29. ^ a b Rawson NS, Rawson MJ (1999). "Acute
adverse event signalling scheme using the
Saskatchewan Administrative health care utilization
datafiles: results for two benzodiazepines". Can J
Clin Pharmacol 6 (3): 159–66. PMID 10495368
(http://www.ncbi.nlm.nih.gov/pubmed/10495368) .
30. ^ a b "Alprazolam – Complete medical information
regarding this treatment of anxiety disorders on
MedicineNet.com" (http://www.medicinenet.com
/alprazolam/article.htm) . medicinenet.com.
http://www.medicinenet.com/alprazolam/article.htm.
Retrieved 2 August 2007.
31. ^ a b c Michel L, Lang JP (2003). "[Benzodiazepines
and forensic aspects (http://www.masson.fr/masson
/MDOI-
ENC-12-2003-29-6-0013-7006-101019-ART2) "] (in
French). Encephale 29 (6): 479–85. PMID 15029082
(http://www.ncbi.nlm.nih.gov/pubmed/15029082) .
http://www.masson.fr/masson/MDOI-
ENC-12-2003-29-6-0013-7006-101019-ART2.
32. ^ Kravitz HM, Fawcett J, Newman AJ (October
1993). "Alprazolam and depression: a review of
risks and benefits". J Clin Psychiatry 54 (Suppl):
78–84; discussion 85. PMID 8262892
(http://www.ncbi.nlm.nih.gov/pubmed/8262892) .
33. ^ Hori A (February 1998). "Pharmacotherapy for
personality disorders"
(http://www3.interscience.wiley.com/resolve
/openurl?genre=article&sid=nlm:pubmed&
issn=1323-1316&date=1998&volume=52&issue=1&
spage=13) . Psychiatry Clin. Neurosci. 52 (1): 13–9.
doi:10.1111/j.1440-1819.1998.tb00967.x
(http://dx.doi.org
/10.1111%2Fj.1440-1819.1998.tb00967.x) .
PMID 9682928 (http://www.ncbi.nlm.nih.gov
/pubmed/9682928) .
http://www3.interscience.wiley.com/resolve
/openurl?genre=article&sid=nlm:pubmed&
issn=1323-1316&date=1998&volume=52&issue=1&
spage=13.
34. ^ a b "alprazolam Side Effects, Interactions and
Information - Drugs.com" (http://www.drugs.com
/alprazolam.html) . drugs.com. http://www.drugs.com
/alprazolam.html. Retrieved 2 August 2007.
35. ^ "Complete Alprazolam information from
Drugs.com" (http://alprazolam.drugs.com/) .
drugs.com. http://alprazolam.drugs.com/. Retrieved 2
August 2007.
36. ^ Cassano GB, Toni C, Petracca A, et al. (March
1994). "Adverse effects associated with the
short-term treatment of panic disorder with
imipramine, alprazolam or placebo". Eur
Neuropsychopharmacol 4 (1): 47–53.
doi:10.1016/0924-977X(94)90314-X
13 of 19
http://en.wikipedia.org/wiki/Alprazolam
(http://dx.doi.org
/10.1016%2F0924-977X%2894%2990314-X) .
PMID 8204996 (http://www.ncbi.nlm.nih.gov
/pubmed/8204996) .
37. ^ Münte TF, Gehde E, Johannes S, Seewald M,
Heinze HJ (1996). "Effects of alprazolam and
bromazepam on visual search and verbal recognition
memory in humans: a study with event-related brain
potentials". Neuropsychobiology 34 (1): 49–56.
doi:10.1159/000119291 (http://dx.doi.org
/10.1159%2F000119291) . PMID 8884760
(http://www.ncbi.nlm.nih.gov/pubmed/8884760) .
38. ^ a b Barbee, Jg (October 1993). "Memory,
benzodiazepines, and anxiety: integration of
theoretical and clinical perspectives.". The Journal
of clinical psychiatry 54 (Suppl): 86–97; discussion
98–101. PMID 8262893
(http://www.ncbi.nlm.nih.gov/pubmed/8262893) .
39. ^ "ALPRAZOLAM - ORAL (Xanax) side effects,
medical uses, and drug interactions."
(http://www.medicinenet.com/alprazolam-
oral/article.htm) . medicinenet.com.
http://www.medicinenet.com/alprazolam-
oral/article.htm. Retrieved 2 August 2007.
40. ^ Elie R, Lamontagne Y (June 1984). "Alprazolam
and diazepam in the treatment of generalized
anxiety". J Clin Psychopharmacol 4 (3): 125–9.
doi:10.1097/00004714-198406000-00002
(http://dx.doi.org
/10.1097%2F00004714-198406000-00002) .
PMID 6145726 (http://www.ncbi.nlm.nih.gov
/pubmed/6145726) .
41. ^ http://doublecheckmd.com
/EffectsDetail.do?dname=Xanax&sid=1327&
eid=2974
42. ^ Evans SM, Foltin RW, Fischman MW (June 1999).
"Food "cravings" and the acute effects of alprazolam
on food intake in women with premenstrual
dysphoric disorder" (http://linkinghub.elsevier.com
/retrieve/pii/S0195-6663(98)90222-7) . Appetite 32
(3): 331–49. doi:10.1006/appe.1998.0222
(http://dx.doi.org/10.1006%2Fappe.1998.0222) .
PMID 10336792 (http://www.ncbi.nlm.nih.gov
/pubmed/10336792) . http://linkinghub.elsevier.com
/retrieve/pii/S0195-6663(98)90222-7.
43. ^ Noyes R, DuPont RL, Pecknold JC, et al. (May
1988). "Alprazolam in panic disorder and
agoraphobia: results from a multicenter trial. II.
Patient acceptance, side effects, and safety". Arch.
Gen. Psychiatry 45 (5): 423–8. PMID 3358644
(http://www.ncbi.nlm.nih.gov/pubmed/3358644) .
44. ^ Béchir M, Schwegler K, Chenevard R, et al. (July
2007). "Anxiolytic therapy with alprazolam increases
muscle sympathetic activity in patients with panic
disorders" (http://linkinghub.elsevier.com/retrieve
8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia
/pii/S1566-0702(07)00008-2) . Auton Neurosci 134
(1-2): 69–73. doi:10.1016/j.autneu.2007.01.007
(http://dx.doi.org/10.1016%2Fj.autneu.2007.01.007)
. PMID 17363337 (http://www.ncbi.nlm.nih.gov
/pubmed/17363337) . http://linkinghub.elsevier.com
/retrieve/pii/S1566-0702(07)00008-2.
45. ^ Rapaport, M; Braff, Dl (January 1985).
"Alprazolam and hostility.". The American journal
of psychiatry 142 (1): 146. PMID 2857070
(http://www.ncbi.nlm.nih.gov/pubmed/2857070) .
46. ^ Arana, Gw; Pearlman, C; Shader, Ri (March 1985).
"Alprazolam-induced mania: two clinical cases.".
The American journal of psychiatry 142 (3): 368–9.
PMID 2857534 (http://www.ncbi.nlm.nih.gov
/pubmed/2857534) .
47. ^ Strahan A, Rosenthal J, Kaswan M, Winston A
(July 1985). "Three case reports of acute paroxysmal
excitement associated with alprazolam treatment"
(http://ajp.psychiatryonline.org
/cgi/pmidlookup?view=long&pmid=2861755) . Am J
Psychiatry 142 (7): 859–61. PMID 2861755
(http://www.ncbi.nlm.nih.gov/pubmed/2861755) .
http://ajp.psychiatryonline.org
/cgi/pmidlookup?view=long&pmid=2861755.
48. ^ Reddy J, Khanna S, Anand U, Banerjee A (August
1996). "Alprazolam-induced hypomania". Aust N Z J
Psychiatry 30 (4): 550–2.
doi:10.3109/00048679609065031 (http://dx.doi.org
/10.3109%2F00048679609065031) . PMID 8887708
(http://www.ncbi.nlm.nih.gov/pubmed/8887708) .
49. ^ a b Stahl, Stephen (1996). Essential Pharmacology:
Neuroscientific Basis and Practical Applications.
Cambridge: Cambridge University Press.
ISBN 0-521-42620-0.
50. ^ Juergens, Sm; Morse, Rm (May 1988).
"Alprazolam dependence in seven patients.". The
American journal of psychiatry 145 (5): 625–7.
PMID 3258735 (http://www.ncbi.nlm.nih.gov
/pubmed/3258735) .
51. ^ Klein, E (2002). "The role of extended-release
benzodiazepines in the treatment of anxiety: a
risk-benefit evaluation with a focus on extended-
release alprazolam.". The Journal of clinical
psychiatry 63 (Suppl 14): 27–33. PMID 12562116
(http://www.ncbi.nlm.nih.gov/pubmed/12562116) .
52. ^ Professor Heather Ashton (2002). "The Ashton
Manual – Benzodiazepines: How They Work and
How to Withdraw" (http://www.benzo.org.uk
/manual/) . benzo.org.uk. http://www.benzo.org.uk
/manual/. Retrieved 2008-10-31.
53. ^ Dr JG McConnell (May 2007). "The
Clinicopharmacotherapeutics of Benzodiazepine and
Z drug dose Tapering Using Diazepam"
(http://www.bcnc.org.uk/whyvalium.html) . bcnc.
http://www.bcnc.org.uk/whyvalium.html. Retrieved
14 of 19
http://en.wikipedia.org/wiki/Alprazolam
2008-10-31.
54. ^ Closser, Mh; Brower, Kj (July 1994). "Treatment
of alprazolam withdrawal with chlordiazepoxide
substitution and taper.". Journal of substance abuse
treatment 11 (4): 319–23.
doi:10.1016/0740-5472(94)90042-6 (http://dx.doi.org
/10.1016%2F0740-5472%2894%2990042-6) .
PMID 7966502 (http://www.ncbi.nlm.nih.gov
/pubmed/7966502) .
55. ^ Romach MK, Somer GR, Sobell LC, Sobell MB,
Kaplan HL, Sellers EM (October 1992).
"Characteristics of long-term alprazolam users in the
community". J Clin Psychopharmacol 12 (5):
316–21. doi:10.1097/00004714-199210000-00004
(http://dx.doi.org
/10.1097%2F00004714-199210000-00004) .
PMID 1479048 (http://www.ncbi.nlm.nih.gov
/pubmed/1479048) .
56. ^ Fyer AJ; Liebowitz MR, Gorman JM, Campeas R,
Levin A, Davies SO, Goetz D, Klein DF (March
1987). "Discontinuation of Alprazolam Treatment in
Panic Patients" (http://www.benzo.org.uk
/alprazolam.htm) . Am J Psychiatry (benzo.org.uk)
144 (3): 303–8. PMID 3826428
(http://www.ncbi.nlm.nih.gov/pubmed/3826428) .
http://www.benzo.org.uk/alprazolam.htm. Retrieved
10 December 2008.
57. ^ Risse SC; Whitters A, Burke J, Chen S, Scurfield
RM, Raskind MA. (1990). "Severe withdrawal
symptoms after discontinuation of alprazolam in
eight patients with combat-induced posttraumatic
stress disorder". The Journal of clinical psychiatry.
51 (5): 206–9. PMID 2335496
(http://www.ncbi.nlm.nih.gov/pubmed/2335496) .
58. ^ Breier, A; Charney, Ds; Nelson, Jc (December
1984). "Seizures induced by abrupt discontinuation
of alprazolam.". The American journal of psychiatry
141 (12): 1606–7. PMID 6150649
(http://www.ncbi.nlm.nih.gov/pubmed/6150649) .
59. ^ Noyes R, Perry PJ, Crowe RR, et al. (January
1986). "Seizures following the withdrawal of
alprazolam". J. Nerv. Ment. Dis. 174 (1): 50–2.
doi:10.1097/00005053-198601000-00009
(http://dx.doi.org
/10.1097%2F00005053-198601000-00009) .
PMID 2867122 (http://www.ncbi.nlm.nih.gov
/pubmed/2867122) .
60. ^ Levy AB (1984). "Delirium and seizures due to
abrupt alprazolam withdrawal: case report". J Clin
Psychiatry 45 (1): 38–9. PMID 6141159
(http://www.ncbi.nlm.nih.gov/pubmed/6141159) .
61. ^ a b Haque W, Watson DJ, Bryant SG (1990).
"Death following suspected alprazolam withdrawal
seizures: a case report". Tex Med 86 (1): 44–7.
PMID 2300914 (http://www.ncbi.nlm.nih.gov
8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia
/pubmed/2300914) .
62. ^ Schatzberg, Alan; DeBattista, Charles (2003).
Manual of Clinical Psychopharmacology.
Washington, DC: American Psychiatric Pub..
pp. 328–331. ISBN 1-58562-209-5.
63. ^ Higgitt, A; Fonagy, P; Lader, M (1988). "The
natural history of tolerance to the benzodiazepines.".
Psychological medicine. Monograph supplement 13:
1–55. doi:10.1017/S0264180100000412
(http://dx.doi.org/10.1017%2FS0264180100000412)
. PMID 2908516 (http://www.ncbi.nlm.nih.gov
/pubmed/2908516) .
64. ^ Professor Heather Ashton (August 2002). "The
Ashton Manual - Benzodiazepines: How They Work
and How to Withdraw" (http://www.benzo.org.uk
/manual/) . http://www.benzo.org.uk/manual/.
65. ^ Authier, N.; Balayssac, D.; Sautereau, M.;
Zangarelli, A.; Courty, P.; Somogyi, AA.; Vennat, B.;
Llorca, PM. et al. (November 2009).
"Benzodiazepine dependence: focus on withdrawal
syndrome.". Ann Pharm Fr 67 (6): 408–13.
doi:10.1016/j.pharma.2009.07.001 (http://dx.doi.org
/10.1016%2Fj.pharma.2009.07.001) .
PMID 19900604 (http://www.ncbi.nlm.nih.gov
/pubmed/19900604) .
66. ^ Hori A. (February 1998). "Pharmacotherapy for
personality disorders". Psychiatry and clinical
neurosciences. 52 (1): 13–9.
doi:10.1111/j.1440-1819.1998.tb00967.x
(http://dx.doi.org
/10.1111%2Fj.1440-1819.1998.tb00967.x) .
PMID 9682928 (http://www.ncbi.nlm.nih.gov
/pubmed/9682928) .
67. ^ Gardner DL, Cowdry RW (January 1985).
"Alprazolam-induced dyscontrol in borderline
personality disorder". Am J Psychiatry 142 (1):
98–100. PMID 2857071
(http://www.ncbi.nlm.nih.gov/pubmed/2857071) .
68. ^ "Alprazolam" (http://www.bnf.org/bnf/bnf
/53/3173.htm) . British National Formulary. 2007.
http://www.bnf.org/bnf/bnf/53/3173.htm. Retrieved 3
August 2007.
69. ^ mentalhealth.com (2007). "Alprazolam"
(http://www.mentalhealth.com/drug/p30-x01.html) .
http://www.mentalhealth.com/drug/p30-x01.html.
Retrieved 3 August 2007.
70. ^ "Xanax (Alprazolam) Drug Information: Uses, Side
Effects, Drug Interactions and Warnings at RxList"
(http://www.rxlist.com/xanax-drug.htm#wcp) . USA:
RxList.com. July 2008. pp. 4. http://www.rxlist.com
/xanax-drug.htm#wcp.
71. ^ García-Algar O; López-Vílchez MA, Martín I, Mur
A, Pellegrini M, Pacifici R, Rossi S, Pichini S.
(2007). "Confirmation of gestational exposure to
alprazolam by analysis of biological matrices in a
15 of 19
http://en.wikipedia.org/wiki/Alprazolam
newborn with neonatal sepsis". Clinical toxicology
(Philadelphia, Pa.). 45 (3): 295–8.
doi:10.1080/15563650601072191 (http://dx.doi.org
/10.1080%2F15563650601072191) .
PMID 17453885 (http://www.ncbi.nlm.nih.gov
/pubmed/17453885) .
72. ^ Oo CY; Kuhn RJ, Desai N, Wright CE, McNamara
PJ. (September 1995). "Pharmacokinetics in lactating
women: prediction of alprazolam transfer into milk"
(http://www.pubmedcentral.nih.gov
/articlerender.fcgi?tool=pmcentrez&artid=1365102) .
British journal of clinical pharmacology. 40 (3):
231–6. PMID 8527284 (http://www.ncbi.nlm.nih.gov
/pubmed/8527284) .
73. ^ DataBank, Inc (July 2008). "Xanax (Alprazolam)
Drug Information: Uses, Side Effects, Drug
Interactions and Warnings at RxList"
(http://www.rxlist.com/cgi/generic/alpraz_wcp.htm) .
RxList. pp. 8. http://www.rxlist.com/cgi/generic
/alpraz_wcp.htm. Retrieved 7 December 2008.
74. ^ a b "ALPRAZOLAM - ORAL (Xanax) side effects,
medical uses, and drug interactions"
(http://www.medicinenet.com/alprazolam-
oral/article.htm) . MedicineNet. July 2005.
http://www.medicinenet.com/alprazolam-
oral/article.htm. Retrieved 7 December 2008.
75. ^ Kozená L; Frantik E, Horváth M. (May 1995).
"Vigilance impairment after a single dose of
benzodiazepines". Psychopharmacology (Berl). 119
(1): 39–45. doi:10.1007/BF02246052
(http://dx.doi.org/10.1007%2FBF02246052) .
PMID 7675948 (http://www.ncbi.nlm.nih.gov
/pubmed/7675948) .
76. ^ Iqbal, MM.; Sobhan, T.; Ryals, T. (Jan 2002).
"Effects of commonly used benzodiazepines on the
fetus, the neonate, and the nursing infant."
(http://ps.psychiatryonline.org/cgi/content/full/53
/1/39) . Psychiatr Serv 53 (1): 39–49.
doi:10.1176/appi.ps.53.1.39 (http://dx.doi.org
/10.1176%2Fappi.ps.53.1.39) . PMID 11773648
(http://www.ncbi.nlm.nih.gov/pubmed/11773648) .
http://ps.psychiatryonline.org/cgi/content/full/53
/1/39.
77. ^ Einarson A, Selby P, Koren G (January 2001).
"Abrupt discontinuation of psychotropic drugs during
pregnancy: fear of teratogenic risk and impact of
counselling" (http://www.cma.ca/multimedia
/staticContent/HTML/N0/l2/jpn/vol-26/issue-
1/pdf/pg44.pdf) (PDF). J Psychiatry Neurosci 26
(1): 44–8. PMID 11212593
(http://www.ncbi.nlm.nih.gov/pubmed/11212593) .
PMC 1408034 (http://www.pubmedcentral.gov
/articlerender.fcgi?tool=pmcentrez&artid=1408034) .
http://www.cma.ca/multimedia/staticContent
/HTML/N0/l2/jpn/vol-26/issue-1/pdf/pg44.pdf.
8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia
78. ^ Skelton KH; Nemeroff CB, Owens MJ (October
20, 2004). "Spontaneous withdrawal from the
triazolobenzodiazepine alprazolam increases cortical
corticotropin-releasing factor mRNA expression". J
Neurosci 24 (42): 9303–12.
doi:10.1523/JNEUROSCI.1737-04.2004
(http://dx.doi.org
/10.1523%2FJNEUROSCI.1737-04.2004) .
PMID 15496666 (http://www.ncbi.nlm.nih.gov
/pubmed/15496666) .
79. ^ Chouinard G (2004). "Issues in the clinical use of
benzodiazepines: potency, withdrawal, and rebound"
(http://article.psychiatrist.com
/?ContentType=START&ID=10000770) . J Clin
Psychiatry 65 (Suppl 5): 7–12. PMID 15078112
(http://www.ncbi.nlm.nih.gov/pubmed/15078112) .
http://article.psychiatrist.com
/?ContentType=START&ID=10000770.
80. ^ White, G; Gurley, Da (February 1995). "Alpha
subunits influence Zn block of gamma 2 containing
GABAA receptor currents.". Neuroreport 6 (3):
461–4. doi:10.1097/00001756-199502000-00014
(http://dx.doi.org
/10.1097%2F00001756-199502000-00014) .
PMID 7766843 (http://www.ncbi.nlm.nih.gov
/pubmed/7766843) .
81. ^ Arvat, E.; Giordano, R.; Grottoli, S.; Ghigo, E.
(Sep 2002). "Benzodiazepines and anterior pituitary
function.". J Endocrinol Invest 25 (8): 735–47.
PMID 12240908 (http://www.ncbi.nlm.nih.gov
/pubmed/12240908) .
82. ^ Mandrioli, R.; Mercolini, L.; Raggi, MA. (Oct
2008). "Benzodiazepine metabolism: an analytical
perspective.". Curr Drug Metab 9 (8): 827–44.
doi:10.2174/138920008786049258 (http://dx.doi.org
/10.2174%2F138920008786049258) .
PMID 18855614 (http://www.ncbi.nlm.nih.gov
/pubmed/18855614) .
83. ^ a b Greenblatt, Dj; Wright, Ce (June 1993).
"Clinical pharmacokinetics of alprazolam.
Therapeutic implications.". Clinical
pharmacokinetics 24 (6): 453–71.
doi:10.2165/00003088-199324060-00003
(http://dx.doi.org
/10.2165%2F00003088-199324060-00003) .
PMID 8513649 (http://www.ncbi.nlm.nih.gov
/pubmed/8513649) .
84. ^ Otani, K. (2003). "[Cytochrome P450 3A4 and
Benzodiazepines]". Seishin Shinkeigaku Zasshi 105
(5): 631–42. PMID 12875231
(http://www.ncbi.nlm.nih.gov/pubmed/12875231) .
85. ^ Dresser, GK.; Spence, JD.; Bailey, DG. (Jan
2000). "Pharmacokinetic-pharmacodynamic
consequences and clinical relevance of cytochrome
P450 3A4 inhibition.". Clin Pharmacokinet 38 (1):
16 of 19
http://en.wikipedia.org/wiki/Alprazolam
41–57. doi:10.2165/00003088-200038010-00003
(http://dx.doi.org
/10.2165%2F00003088-200038010-00003) .
PMID 10668858 (http://www.ncbi.nlm.nih.gov
/pubmed/10668858) .
86. ^ Wang JS, DeVane CL (2003). "Pharmacokinetics
and drug interactions of the sedative hypnotics"
(http://www.medworksmedia.com
/psychopharmbulletin/pdf/12
/010-029_PB%20W03_Wang_final.pdf) (PDF).
Psychopharmacol Bull 37 (1): 10–29.
PMID 14561946 (http://www.ncbi.nlm.nih.gov
/pubmed/14561946) .
http://www.medworksmedia.com
/psychopharmbulletin/pdf/12
/010-029_PB%20W03_Wang_final.pdf.
87. ^ "FDA SPL Approved Application Filing for NDC
Code 0228-3083 (Alprazolam by Actavis Elizabeth
LLC)". AD535DF9-6361-460D-
9648-450A0A6F61CD.xml.
88. ^ Back DJ; Orme ML. (June 1990).
"Pharmacokinetic drug interactions with oral
contraceptives". Clin Pharmacokinet. 18 (6):
472–84. doi:10.2165/00003088-199018060-00004
(http://dx.doi.org
/10.2165%2F00003088-199018060-00004) .
PMID 2191822 (http://www.ncbi.nlm.nih.gov
/pubmed/2191822) .
89. ^ Izzo, AA.; Ernst, E. (2001). "Interactions between
herbal medicines and prescribed drugs: a systematic
review.". Drugs 61 (15): 2163–75.
doi:10.2165/00003495-200161150-00002
(http://dx.doi.org
/10.2165%2F00003495-200161150-00002) .
PMID 11772128 (http://www.ncbi.nlm.nih.gov
/pubmed/11772128) .
90. ^ Izzo, AA. (Mar 2004). "Drug interactions with St.
John's Wort (Hypericum perforatum): a review of the
clinical evidence.". Int J Clin Pharmacol Ther 42
(3): 139–48. PMID 15049433
(http://www.ncbi.nlm.nih.gov/pubmed/15049433) .
91. ^ Madabushi, R.; Frank, B.; Drewelow, B.;
Derendorf, H.; Butterweck, V. (Mar 2006).
"Hyperforin in St. John's wort drug interactions.".
Eur J Clin Pharmacol 62 (3): 225–33.
doi:10.1007/s00228-006-0096-0 (http://dx.doi.org
/10.1007%2Fs00228-006-0096-0) . PMID 16477470
(http://www.ncbi.nlm.nih.gov/pubmed/16477470) .
92. ^ Izzo, AA.; Ernst, E. (2009). "Interactions between
herbal medicines and prescribed drugs: an updated
systematic review.". Drugs 69 (13): 1777–98.
doi:10.2165/11317010-000000000-00000
(http://dx.doi.org
/10.2165%2F11317010-000000000-00000) .
PMID 19719333 (http://www.ncbi.nlm.nih.gov
8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia
/pubmed/19719333) .
93. ^ Griffiths RR, Wolf B (August 1990). "Relative
abuse liability of different benzodiazepines in drug
abusers". J Clin Psychopharmacol 10 (4): 237–43.
doi:10.1097/00004714-199008000-00002
(http://dx.doi.org
/10.1097%2F00004714-199008000-00002) .
PMID 1981067 (http://www.ncbi.nlm.nih.gov
/pubmed/1981067) .
94. ^ Eric C; Wang, Felix S, Chew. (2006). "MR
Findings of Alprazolam Injection into the Femoral
Artery with Microembolization and Rhabdomyolysis"
(http://www.radiologycasereports.net/index.php
/rcr/article/viewPDFInterstitial/33/187) (pdf).
Radiology Case Reports 1 (3).
http://www.radiologycasereports.net/index.php
/rcr/article/viewPDFInterstitial/33/187.
95. ^ "DB00404 (Alprazolam)"
(http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin
/getCard.cgi?CARD=APRD00280) . Canada:
DrugBank. August 26, 2008.
http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin
/getCard.cgi?CARD=APRD00280.
96. ^ Sheehan MF, Sheehan DV, Torres A, Coppola A,
Francis E (1991). "Snorting benzodiazepines". Am J
Drug Alcohol Abuse 17 (4): 457–68.
doi:10.3109/00952999109001605 (http://dx.doi.org
/10.3109%2F00952999109001605) . PMID 1684083
(http://www.ncbi.nlm.nih.gov/pubmed/1684083) .
97. ^ Soumerai SB, Simoni-Wastila L, Singer C, et al.
(July 2003). "Lack of relationship between long-term
use of benzodiazepines and escalation to high
dosages" (http://ps.psychiatryonline.org
/cgi/pmidlookup?view=long&pmid=12851438) .
Psychiatr Serv 54 (7): 1006–11.
doi:10.1176/appi.ps.54.7.1006 (http://dx.doi.org
/10.1176%2Fappi.ps.54.7.1006) . PMID 12851438
(http://www.ncbi.nlm.nih.gov/pubmed/12851438) .
http://ps.psychiatryonline.org
/cgi/pmidlookup?view=long&pmid=12851438.
98. ^ Walker, Bm; Ettenberg, A (April 2003). "The
effects of alprazolam on conditioned place
preferences produced by intravenous heroin.".
Pharmacology, biochemistry, and behavior 75 (1):
75–80. doi:10.1016/S0091-3057(03)00043-1
(http://dx.doi.org
/10.1016%2FS0091-3057%2803%2900043-1) .
PMID 12759115 (http://www.ncbi.nlm.nih.gov
/pubmed/12759115) .
99. ^ MARCIA LANE (29 September 2006). "Xanax,
alcohol mix kills 2" (http://staugustine.com/stories
/092906/news_4113407.shtml) . USA: St. Augustine
Record. http://staugustine.com/stories/092906
/news_4113407.shtml. Retrieved 10 December 2008.
100. ^ Wright State University and the University of
17 of 19
http://en.wikipedia.org/wiki/Alprazolam
Akron (January 2008). "OSAM - O- GRAM
Highlights of Statewide Drug Use Trends"
(http://www.odadas.state.oh.us/WebManager
/UltimateEditorInclude/UserFiles/WebDocuments
/Planning/Jan05ExecSummry.pdf) (PDF). USA: Ohio
Government. http://www.odadas.state.oh.us
/WebManager/UltimateEditorInclude/UserFiles
/WebDocuments/Planning/Jan05ExecSummry.pdf.
Retrieved 10 December 2008.
101. ^ Detective Eladio M. Paez (15 June 2008).
"STATEMENT ON RAVES AND CLUB DRUGS
TO THE SUBCOMMITTEE ON CRIME,
CONGRESS OF THE UNITED STATES, HOUSE
OF REPRESENTATIVES"
(http://judiciary.house.gov/Legacy/paez0615.htm) .
USA: GOV House Judiciary.
http://judiciary.house.gov/Legacy/paez0615.htm.
Retrieved 10 December 2008.
102. ^ "SURVEILLANCE OF DRUG ABUSE TRENDS
IN THE STATE OF OHIO - A Report Prepared for
the Ohio Department of Alcohol and Drug Addiction
Services" (http://www.odadas.ohio.gov
/GD/DocumentManagement
/DocumentDownload.aspx?DocumentID=225) .
USA: The Ohio Substance Abuse Monitoring
Network. 31 July 2001. http://www.odadas.ohio.gov
/GD/DocumentManagement
/DocumentDownload.aspx?DocumentID=225.
Retrieved 10 December 2008.
103. ^ "Microgram bulletin" (http://www.justice.gov
/dea/programs/forensicsci/microgram/mg0508
/mg0508.html) . US DEA. http://www.justice.gov
/dea/programs/forensicsci/microgram/mg0508
/mg0508.html.
104. ^ Ballenger, Jc (December 1984).
"Psychopharmacology of the anxiety disorders.". The
Psychiatric clinics of North America 7 (4): 757–71.
PMID 6151647 (http://www.ncbi.nlm.nih.gov
/pubmed/6151647) .
105. ^ Evans, Sm; Levin, Fr; Fischman, Mw (June 2000).
"Increased sensitivity to alprazolam in females with a
paternal history of alcoholism.".
Psychopharmacology 150 (2): 150–62.
doi:10.1007/s002130000421 (http://dx.doi.org
/10.1007%2Fs002130000421) . PMID 10907668
(http://www.ncbi.nlm.nih.gov/pubmed/10907668) .
106. ^ Streeter, Cc; Ciraulo, Da; Harris, Gj; Kaufman, Mj;
Lewis, Rf; Knapp, Cm; Ciraulo, Am; Maas, Lc;
Ungeheuer, M; Szulewski, S; Renshaw, Pf (May
1998). "Functional magnetic resonance imaging of
alprazolam-induced changes in humans with familial
alcoholism.". Psychiatry research 82 (2): 69–82.
doi:10.1016/S0925-4927(98)00009-2
(http://dx.doi.org
/10.1016%2FS0925-4927%2898%2900009-2) .
8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia
PMID 9754450 (http://www.ncbi.nlm.nih.gov
/pubmed/9754450) .
107. ^ Ciraulo, Da; Sarid-Segal, O; Knapp, C; Ciraulo,
Am; Greenblatt, Dj; Shader, Ri (July 1996).
"Liability to alprazolam abuse in daughters of
alcoholics.". The American journal of psychiatry
153 (7): 956–8. PMID 8659624
(http://www.ncbi.nlm.nih.gov/pubmed/8659624) .
108. ^ Ciraulo, Da; Barnhill, Jg; Greenblatt, Dj; Shader,
Ri; Ciraulo, Am; Tarmey, Mf; Molloy, Ma; Foti, Me
(September 1988). "Abuse liability and clinical
pharmacokinetics of alprazolam in alcoholic men.".
The Journal of clinical psychiatry 49 (9): 333–7.
PMID 3417618 (http://www.ncbi.nlm.nih.gov
/pubmed/3417618) .
109. ^ Vorma, H; Naukkarinen, Hh; Sarna, Sj;
Kuoppasalmi, Ki (2005). "Predictors of
benzodiazepine discontinuation in subjects
manifesting complicated dependence.". Substance
use & misuse 40 (4): 499–510. doi:10.1081/JA-
200052433 (http://dx.doi.org/10.1081%2FJA-
200052433) . PMID 15830732
(http://www.ncbi.nlm.nih.gov/pubmed/15830732) .
110. ^ Isbister GK, O'Regan L, Sibbritt D, Whyte IM
(July 2004). "Alprazolam is relatively more toxic
than other benzodiazepines in overdose"
(http://www.pubmedcentral.nih.gov
/articlerender.fcgi?tool=pmcentrez&artid=1884537) .
Br J Clin Pharmacol 58 (1): 88–95.
doi:10.1111/j.1365-2125.2004.02089.x
(http://dx.doi.org
/10.1111%2Fj.1365-2125.2004.02089.x) .
PMID 15206998 (http://www.ncbi.nlm.nih.gov
/pubmed/15206998) .
111. ^ Wolf BC, Lavezzi WA, Sullivan LM, Middleberg
RA, Flannagan LM (2005). "Alprazolam-related
deaths in Palm Beach County". Am J Forensic Med
Pathol 26 (1): 24–7.
doi:10.1097/01.paf.0000153994.95642.c1
(http://dx.doi.org
/10.1097%2F01.paf.0000153994.95642.c1) .
PMID 15725773 (http://www.ncbi.nlm.nih.gov
/pubmed/15725773) .
112. ^ Rogers, Wo; Hall, Ma; Brissie, Rm; Robinson, Ca
(January 1997). "Detection of alprazolam in three
cases of methadone/benzodiazepine overdose.".
Journal of forensic sciences 42 (1): 155–6.
PMID 8988593 (http://www.ncbi.nlm.nih.gov
/pubmed/8988593) .
113. ^ Jones AW, Holmgren A, Kugelberg FC.
Concentrations of scheduled prescription drugs in
blood of impaired drivers: considerations for
interpreting the results. Ther. Drug Monit. 29:
248-260, 2007.
18 of 19
http://en.wikipedia.org/wiki/Alprazolam
114. ^ Fraser AD, Bryan W. Evaluation of the Abbott
ADx and TDx serum benzodiazepine immunoassays
for analysis of alprazolam. J. Anal. Toxicol. 15:
63-65, 1991.
115. ^ R. Baselt, Disposition of Toxic Drugs and
Chemicals in Man, 8th edition, Biomedical
Publications, Foster City, CA, 2008, pp. 45-48.
116. ^ Merck Manual; Davis-Drug-Guide (5 February
2009). "alprazolam"
(http://www.unboundmedicine.com/merckmanual
/ub/view/Davis-Drug-Guide/51030/8/alprazolam) .
Unbound Medicine.
http://www.unboundmedicine.com/merckmanual
/ub/view/Davis-Drug-Guide/51030/8/alprazolam.
Retrieved 10 March 2009.
117. ^ "Benzodiazepine Names" (http://www.non-
benzodiazepines.org.uk/benzodiazepine-names.html)
. non-benzodiazepines.org.uk. http://www.non-
benzodiazepines.org.uk/benzodiazepine-names.html.
Retrieved 2008-10-31.
118. ^ "DEA, Drug Scheduling" (http://www.usdoj.gov
/dea/pubs/scheduling.html) . DEA.
http://www.usdoj.gov/dea/pubs/scheduling.html.
Retrieved 2008-10-31.
119. ^ UK Gov (1991). "Misuse of Drugs Act 1971 (c.
38)" (http://www.statutelaw.gov.uk
/content.aspx?LegType=All+Primary&
PageNumber=56&NavFrom=2&
parentActiveTextDocId=1367412&
activetextdocid=1367464) . The UK Statute Law
database. http://www.statutelaw.gov.uk
/content.aspx?LegType=All+Primary&
PageNumber=56&NavFrom=2&
parentActiveTextDocId=1367412&
activetextdocid=1367464.
120. ^ British Medical Association, Royal Pharmaceutical
Society of Great Britain (March 2009). "4.1.2:
Anxiolytics". British National Formulary (BNF 57).
United Kingdom: BMJ Group and RPS Publishing.
p. 190. ISBN 9780853698456.
121. ^ International Narcotics Control Board (August
2003). "List of psychotropic substances under
international control" (http://www.incb.org/pdf/e
/list/green.pdf) (PDF). incb.org. http://www.incb.org
/pdf/e/list/green.pdf. Retrieved 7 December 2008.
122. ^ "Misuse Of Drugs (Amendment) Regulations"
(http://www.irishstatutebook.ie/1993/en/si/0342.html)
. Irish Statute Book. Office of the Attorney General.
1993. http://www.irishstatutebook.ie/1993/en
/si/0342.html.
123. ^ ____284.aspx Narkotikaklassade läkemedel
(http://www.lakemedelsverket.se/Tpl/NormalPage) ,
Läkemedelsverket
8/12/2010 8:15 PM
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