Professional Documents
Culture Documents
org/wiki/Alprazolam
1 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
2 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
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]
3 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
Panic disorder
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:
4 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
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:
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
5 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
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]
6 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
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.
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 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
7 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
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]
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
8 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
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]
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]
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]
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]
9 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
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.
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.
10 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
Benzodiazepine
Benzodiazepine dependence
Benzodiazepine withdrawal syndrome
Long term effects of benzodiazepines
1. ^ First DataBank (July 2008). "Xanax (Alprazolam) "APA Practice Guideline for the Treatment of
clinical pharmacology - prescription drugs and Patients With Panic Disorder, Second Edition"
medications at RxList" (http://www.rxlist.com/xanax- (http://www.psychiatryonline.com/pracGuide
drug.htm#cp) . RxList. http://www.rxlist.com/xanax- /loadGuidelinePdf.aspx?file=PanicDisorder_2e_Prac
drug.htm#cp. ticeGuideline) (PDF).
2. ^ First DataBank (July 2008). "Xanax XR http://www.psychiatryonline.com/pracGuide
(Alprazolam) clinical pharmacology - prescription /loadGuidelinePdf.aspx?file=PanicDisorder_2e_Prac
drugs and medications at RxList" ticeGuideline. Retrieved 07/12/09.
(http://www.rxlist.com/xanax-xr-drug.htm#cp) . 8. ^ a b United States Government; U.S.
RxList. http://www.rxlist.com/xanax-xr-drug.htm#cp. DEPARTMENT OF HEALTH AND HUMAN
3. ^ Mandrioli R, Mercolini L, Raggi MA (October SERVICES (2006). "Drug Abuse Warning Network,
2008). "Benzodiazepine metabolism: an analytical 2006: National Estimates of Drug-Related
perspective" (http://www.benthamdirect.org/pages Emergency Department Visits"
/content.php?CDM/2008/00000009/00000008 (http://dawninfo.samhsa.gov/files/ed2006
/0009F.SGM) . Curr. Drug Metab. 9 (8): 827–44. /DAWN2k6ED.htm) . Substance Abuse and Mental
doi:10.2174/138920008786049258 (http://dx.doi.org Health Services Administration.
/10.2174%2F138920008786049258) . http://dawninfo.samhsa.gov/files/ed2006
PMID 18855614 (http://www.ncbi.nlm.nih.gov /DAWN2k6ED.htm. Retrieved 9 February 2009.
/pubmed/18855614) . http://www.benthamdirect.org 9. ^ Cynthia Cotts (November 19, 2007). "Xanax
/pages/content.php?CDM/2008/00000009/00000008 junkies" (http://thephoenix.com
/0009F.SGM. /article_ektid51411.aspx) . Boston, USA: The
4. ^ a b Verster JC, Volkerts ER. (2004). "Clinical Phoenix. http://thephoenix.com
pharmacology, clinical efficacy, and behavioral /article_ektid51411.aspx.
toxicity of alprazolam: a review of the literature". 10. ^ Walker, Sydney (3 December 1996). A dose of
CNS Drug Rev. 10 (1): 45–76. PMID 14978513 sanity: mind, medicine, and misdiagnosis
(http://www.ncbi.nlm.nih.gov/pubmed/14978513) . (http://books.google.com/?id=1H_jx9XO4dcC&
5. ^ a b Galanter, Marc (1 July 2008). The American pg=PA65) . New York: John Wiley & Sons.
Psychiatric Publishing Textbook of Sustance Abuse pp. 64–65. ISBN 978-0-471-19262-6.
Treatment (American Psychiatric Press Textbook of http://books.google.com/?id=1H_jx9XO4dcC&
Substance Abuse Treatment) (American Psychiatric pg=PA65.
... Press Textbook of Substance Abuse Treatment) 11. ^ Healy, David (2000). The Psychopharmacologists,
(http://books.google.com/?id=6wdJgejlQzYC) (4 Vol. III: Interviews. London: Arnold. pp. 479–504.
ed.). American Psychiatric Publishing, Inc.. p. 222. ISBN 0-340-761105.
ISBN 978-1-58562-276-4. http://books.google.com 12. ^ a b Wolf B, Griffiths RR (December 1991).
/?id=6wdJgejlQzYC. "Physical dependence on benzodiazepines:
6. ^ McIntosh A, Cohen A, Turnbull N et al. (2004). differences within the class"
"Clinical guidelines and evidence review for panic (http://linkinghub.elsevier.com/retrieve
disorder and generalised anxiety disorder" /pii/0376-8716(91)90044-Y) . Drug Alcohol Depend
(http://www.nice.org.uk/nicemedia 29 (2): 153–6. doi:10.1016/0376-8716(91)90044-Y
/pdf/cg022fullguideline.pdf) (PDF). National (http://dx.doi.org
Collaborating Centre for Primary Care. /10.1016%2F0376-8716%2891%2990044-Y) .
http://www.nice.org.uk/nicemedia PMID 1686752 (http://www.ncbi.nlm.nih.gov
/pdf/cg022fullguideline.pdf. Retrieved 2009-06-16. /pubmed/1686752) . http://linkinghub.elsevier.com
7. ^ Work Group on Panic Disorder (January 2009). /retrieve/pii/0376-8716(91)90044-Y.
11 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
13. ^ Walker, Sydney (3 December 1997). A dose of beta-adrenergic receptors in the antidepressant
sanity: mind, medicine, and misdiagnosis activity of alprazolam.". Research communications
(http://books.google.com/?id=1H_jx9XO4dcC) . in chemical pathology and pharmacology 36 (2):
New York: Wiley Sons. pp. 65–74. 329–32. PMID 6285432
ISBN 978-0-471-19262-6. http://books.google.com (http://www.ncbi.nlm.nih.gov/pubmed/6285432) .
/?id=1H_jx9XO4dcC. 22. ^ Lader, Mh (9 December 1985). "Treatment of
14. ^ J. McNally, Richard (1994). Panic disorder: a affective disorders."
critical analysis (http://books.google.com (http://www.pubmedcentral.nih.gov
/?id=SlUl5oTQIHoC) . New York: Guilford Press. /articlerender.fcgi?tool=pmcentrez&artid=1463505)
pp. 93–99. ISBN 978-0-89862-263-8. (Free full text). British journal of clinical
http://books.google.com/?id=SlUl5oTQIHoC. pharmacology 19 (Suppl 1): 29S–30S.
15. ^ FDA (23rd). "FDA APPROVED LABELING FOR PMID 2859875 (http://www.ncbi.nlm.nih.gov
XANAX XR" (http://www.fda.gov/cder/foi/label /pubmed/2859875) .
/2003/21434_xanax_lbl.pdf) (pdf). Federal Drug 23. ^ Johnson, Da (9 December 1985). "The use of
Administration. pp. 4. http://www.fda.gov/cder/foi benzodiazepines in depression."
/label/2003/21434_xanax_lbl.pdf. Retrieved 2 (http://www.pubmedcentral.nih.gov
August 2007. "The longer-term efficacy of XANAX /articlerender.fcgi?tool=pmcentrez&artid=1463500)
XR has not been systematically evaluated. Thus, the (Free full text). British journal of clinical
physician that elects to use this drug for periods pharmacology 19 (Suppl 1): 31S–35S.
longer than 8 weeks should periodically reassess the PMID 2859876 (http://www.ncbi.nlm.nih.gov
usefulness of the drug for the individual patient." /pubmed/2859876) .
16. ^ a b First DataBank (July 2008). "Xanax 24. ^ Kostowski W, Malatyńska E, Płaźnik A, Dyr W,
(Alprazolam) clinical pharmacology - prescription Danysz W (1986). "Comparative studies on
drugs and medications at RxList" antidepressant action of alprazolam in different
(http://www.rxlist.com/xanax-drug.htm) . RxList. animal models". Pol J Pharmacol Pharm 38 (5-6):
http://www.rxlist.com/xanax-drug.htm. 471–81. PMID 2883637
17. ^ Bandelow, B.; Zohar, J.; Hollander, E.; Kasper, S.; (http://www.ncbi.nlm.nih.gov/pubmed/2883637) .
Möller, HJ.; World Federation of Societies of 25. ^ Srisurapanont, M; Boonyanaruthee, V (March
Biological Psychiatry Task Force on Treatment 1997). "Alprazolam and standard antidepressants in
Guidelines for Anxiety, Obsessive-Compulsive and the treatment of depression: a meta-analysis of the
Posttraumatic Stress Disorders (Oct 2002). "World antidepressant effect.". Journal of the Medical
Federation of Societies of Biological Psychiatry Association of Thailand = Chotmaihet thangphaet
(WFSBP) guidelines for the pharmacological 80 (3): 183–8. PMID 9175386
treatment of anxiety, obsessive-compulsive and (http://www.ncbi.nlm.nih.gov/pubmed/9175386) .
posttraumatic stress disorders.". World J Biol 26. ^ Brasfield, Kh (September 1991). "Practical
Psychiatry 3 (4): 171–99. psychopharmacologic considerations in depression.".
doi:10.3109/15622970209150621 (http://dx.doi.org The Nursing clinics of North America 26 (3):
/10.3109%2F15622970209150621) . 651–63. PMID 1891399
PMID 12516310 (http://www.ncbi.nlm.nih.gov (http://www.ncbi.nlm.nih.gov/pubmed/1891399) .
/pubmed/12516310) . 27. ^ Hubain, Pp; Castro, P; Mesters, P; De, Maertelaer,
18. ^ NetDoctor (October 1, 2006). "Xanax" V; Mendlewicz, J (January 1990). "Alprazolam and
(http://www.netdoctor.co.uk/medicines amitriptyline in the treatment of major depressive
/100002807.html) . netdoctor.co.uk. disorder: a double-blind clinical and sleep EEG
http://www.netdoctor.co.uk/medicines study.". Journal of affective disorders 18 (1):
/100002807.html. Retrieved 2 August 2007. 67–73. doi:10.1016/0165-0327(90)90118-R
19. ^ The British National Formulary (2007). (http://dx.doi.org
"Alprazolam" (http://www.bnf.org/bnf/bnf /10.1016%2F0165-0327%2890%2990118-R) .
/53/3173.htm) . BNF. http://www.bnf.org/bnf/bnf PMID 2136871 (http://www.ncbi.nlm.nih.gov
/53/3173.htm. Retrieved 2 August 2007. /pubmed/2136871) .
20. ^ Warner MD; Peabody CA, Whiteford HA, 28. ^ Lydiard, Rb; Laraia, Mt; Ballenger, Jc; Howell, Ef
Hollister LE (April 1988). "Alprazolam as an (May 1987). "Emergence of depressive symptoms in
antidepressant". J Clin Psychiatry 49 (4): 148–50. patients receiving alprazolam for panic disorder.".
PMID 3281931 (http://www.ncbi.nlm.nih.gov The American journal of psychiatry 144 (5): 664–5.
/pubmed/3281931) . PMID 3578580 (http://www.ncbi.nlm.nih.gov
21. ^ Sethy, Vh; Hodges, Dh, Jr (May 1982). "Role of /pubmed/3578580) .
12 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
13 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
14 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
15 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
16 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
17 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
PMID 9754450 (http://www.ncbi.nlm.nih.gov 114. ^ Fraser AD, Bryan W. Evaluation of the Abbott
/pubmed/9754450) . ADx and TDx serum benzodiazepine immunoassays
107. ^ Ciraulo, Da; Sarid-Segal, O; Knapp, C; Ciraulo, for analysis of alprazolam. J. Anal. Toxicol. 15:
Am; Greenblatt, Dj; Shader, Ri (July 1996). 63-65, 1991.
"Liability to alprazolam abuse in daughters of 115. ^ R. Baselt, Disposition of Toxic Drugs and
alcoholics.". The American journal of psychiatry Chemicals in Man, 8th edition, Biomedical
153 (7): 956–8. PMID 8659624 Publications, Foster City, CA, 2008, pp. 45-48.
(http://www.ncbi.nlm.nih.gov/pubmed/8659624) . 116. ^ Merck Manual; Davis-Drug-Guide (5 February
108. ^ Ciraulo, Da; Barnhill, Jg; Greenblatt, Dj; Shader, 2009). "alprazolam"
Ri; Ciraulo, Am; Tarmey, Mf; Molloy, Ma; Foti, Me (http://www.unboundmedicine.com/merckmanual
(September 1988). "Abuse liability and clinical /ub/view/Davis-Drug-Guide/51030/8/alprazolam) .
pharmacokinetics of alprazolam in alcoholic men.". Unbound Medicine.
The Journal of clinical psychiatry 49 (9): 333–7. http://www.unboundmedicine.com/merckmanual
PMID 3417618 (http://www.ncbi.nlm.nih.gov /ub/view/Davis-Drug-Guide/51030/8/alprazolam.
/pubmed/3417618) . Retrieved 10 March 2009.
109. ^ Vorma, H; Naukkarinen, Hh; Sarna, Sj; 117. ^ "Benzodiazepine Names" (http://www.non-
Kuoppasalmi, Ki (2005). "Predictors of benzodiazepines.org.uk/benzodiazepine-names.html)
benzodiazepine discontinuation in subjects . non-benzodiazepines.org.uk. http://www.non-
manifesting complicated dependence.". Substance benzodiazepines.org.uk/benzodiazepine-names.html.
use & misuse 40 (4): 499–510. doi:10.1081/JA- Retrieved 2008-10-31.
200052433 (http://dx.doi.org/10.1081%2FJA- 118. ^ "DEA, Drug Scheduling" (http://www.usdoj.gov
200052433) . PMID 15830732 /dea/pubs/scheduling.html) . DEA.
(http://www.ncbi.nlm.nih.gov/pubmed/15830732) . http://www.usdoj.gov/dea/pubs/scheduling.html.
110. ^ Isbister GK, O'Regan L, Sibbritt D, Whyte IM Retrieved 2008-10-31.
(July 2004). "Alprazolam is relatively more toxic 119. ^ UK Gov (1991). "Misuse of Drugs Act 1971 (c.
than other benzodiazepines in overdose" 38)" (http://www.statutelaw.gov.uk
(http://www.pubmedcentral.nih.gov /content.aspx?LegType=All+Primary&
/articlerender.fcgi?tool=pmcentrez&artid=1884537) . PageNumber=56&NavFrom=2&
Br J Clin Pharmacol 58 (1): 88–95. parentActiveTextDocId=1367412&
doi:10.1111/j.1365-2125.2004.02089.x activetextdocid=1367464) . The UK Statute Law
(http://dx.doi.org database. http://www.statutelaw.gov.uk
/10.1111%2Fj.1365-2125.2004.02089.x) . /content.aspx?LegType=All+Primary&
PMID 15206998 (http://www.ncbi.nlm.nih.gov PageNumber=56&NavFrom=2&
/pubmed/15206998) . parentActiveTextDocId=1367412&
111. ^ Wolf BC, Lavezzi WA, Sullivan LM, Middleberg activetextdocid=1367464.
RA, Flannagan LM (2005). "Alprazolam-related 120. ^ British Medical Association, Royal Pharmaceutical
deaths in Palm Beach County". Am J Forensic Med Society of Great Britain (March 2009). "4.1.2:
Pathol 26 (1): 24–7. Anxiolytics". British National Formulary (BNF 57).
doi:10.1097/01.paf.0000153994.95642.c1 United Kingdom: BMJ Group and RPS Publishing.
(http://dx.doi.org p. 190. ISBN 9780853698456.
/10.1097%2F01.paf.0000153994.95642.c1) . 121. ^ International Narcotics Control Board (August
PMID 15725773 (http://www.ncbi.nlm.nih.gov 2003). "List of psychotropic substances under
/pubmed/15725773) . international control" (http://www.incb.org/pdf/e
112. ^ Rogers, Wo; Hall, Ma; Brissie, Rm; Robinson, Ca /list/green.pdf) (PDF). incb.org. http://www.incb.org
(January 1997). "Detection of alprazolam in three /pdf/e/list/green.pdf. Retrieved 7 December 2008.
cases of methadone/benzodiazepine overdose.". 122. ^ "Misuse Of Drugs (Amendment) Regulations"
Journal of forensic sciences 42 (1): 155–6. (http://www.irishstatutebook.ie/1993/en/si/0342.html)
PMID 8988593 (http://www.ncbi.nlm.nih.gov . Irish Statute Book. Office of the Attorney General.
/pubmed/8988593) . 1993. http://www.irishstatutebook.ie/1993/en
113. ^ Jones AW, Holmgren A, Kugelberg FC. /si/0342.html.
Concentrations of scheduled prescription drugs in 123. ^ ____284.aspx Narkotikaklassade läkemedel
blood of impaired drivers: considerations for (http://www.lakemedelsverket.se/Tpl/NormalPage) ,
interpreting the results. Ther. Drug Monit. 29: Läkemedelsverket
248-260, 2007.
18 of 19 8/12/2010 8:15 PM
Alprazolam - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Alprazolam
19 of 19 8/12/2010 8:15 PM