Xanax

It is also available in an extended-release form, Xanax XR, both of which now available in generic form. Alprazolam possesses anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant properties.
Alprazolam may be habit-forming, and long-term use and/or abuse may cause a physical dependence to develop along with withdrawal reactions during abrupt or rapid discontinuation.

In the USA, alprazolam is a schedule IV controlled substance under the Controlled Substances Act.


History
Alprazolam was first synthesized by Upjohn (now a part of Pfizer). Patent 3,987,052, which was filed on October 29, 1969, granted on October 19, 1976 and expired in September 1993.

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.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.
Alprazolam has an exceptional history insofar as soon after its introduction a large 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.
Indications
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 treating 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. However, patients with panic disorder have been treated on an open basis for up to 8 months without apparent loss of benefit.

The physician should periodically reassess the usefulness of the drug for the individual patient.
Anxiety disorder
Alprazolam is indicated for the management of anxiety disorder (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. Alprazolam is recommended for the short-term treatment (2–4 weeks) of severe acute anxiety. Alprazolam should only very rarely be used for longer periods of time – the body becomes rapidly tolerant to the drug's effects, which may translate to decreased efficacy.
Alprazolam is sometimes prescribed for anxiety with associated depression.

There is some evidence for antidepressant treatment of clinical depression in outpatient settings; evidence for inpatients is lacking. The antidepressant effects of alprazolam may be due to its effects on beta-adrenergic receptors. Other benzodiazepines are not known to have antidepressant activity. Studies show that any antidepressant action of alprazolam is questionable and generally weak in comparison to those of antidepressant medications. 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.
Side-effects


Main side effects of alprazolam. More serious effects motivate immediate contact with health care provider.

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. 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.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.
Not all withdrawal effects are evidence of true dependence or withdrawal.

Either of these can occur without the patient's actually being drug-dependent.
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. 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.
In 1992, Romach and colleagues reported that dose escalation is not a characteristic of long-term alprazolam users, and the majority of patients indicated that alprazolam continued to be effective, suggesting that tolerance to the anti-anxiety effect is limited.
If a patient feels the need to end treatment with alprazolam, he/she should consult his/her physician before discontinuing the medication. 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. 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.
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, and one death occurred from withdrawal-related seizures after gradual dose reduction.
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.
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 and method of discontinuation.
Contraindications
Use of alprazolam should be avoided, 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).
Women who are pregnant or are planning on becoming pregnant should avoid starting alprazolam. 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.
Benzodiazepines, including alprazolam are known to be excreted in human milk. Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight. 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.
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. People driving or conducting activities that require vigilance should exercise caution in using alprazolam or any other depressant.
Pharmacology
Alprazolam is classed as a high-potency benzodiazepine and is a triazolobenzodiazepine, that is, a benzodiazepine with a triazole ring attached to its structure. Most of the drug is bound to plasma protein, mainly serum albumin.

Alprazolam may also be insufflated. 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.
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, amphetamines, DXM, and MDMA, along with the related amphetamines). Benzodiazepines are more commonly used recreationally than opiate pharmaceuticals, which accounted for 32% of visits to the emergency department.

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. Alprazolam (Xanax) overdose reflect the central nervous system depression of the brain and may include one or more of the following symptoms:
Somnolence (difficulty staying awake)
Mental confusion
Hypotension
Impaired motor functions
Impaired or absent reflexes
Muscle weakness
Impaired balance
Dizziness

Fainting
Hypoventilation (Respiratory Depression)
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.