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Alprazolam

Alprazolam is a drug which is a benzodiazepine derivative. It is classified as short-acting, and is used to treat anxiety disorders and insomnia. more...

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Pharmacology

Alprazolam is a triazolobenzodiazepine, that is, a benzodiazepine with a triazolo-ring attached to its structure. Alprazolam binds to the GABAA subtype of the GABA receptor, increasing inhibitory effects of GABA within the central nervous system. The binding site for benzodiazepines is distinct from the binding site for GABA on the GABA receptor.

Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.

Pharmacokinetics

The mechanism of action is not fully understood; However, Alprazolam is readily absorbed from the gastrointestinal tract. The peak plasma concentration is achieved in 1-2 hours. Most of the drug is bound to plasma protein, mainly albumin. Alprazolam is hydroxylated in the liver to α-hydroxyalprazolam, which is also pharmacologically active. This and other metabolites are later excreted in urine as glucuronides. Some of the drug is also excreted in unchanged form.

Indications

The main medical uses for alprazolam include:

  • Treatment of panic disorder, with or without agoraphobia.
    Alprazolam is very effective in preventing panic attacks. However, despite its efficacy, many psychiatrists are reluctant to use alprazolam for this condition because of the possibility of dependence and interdose anxiety due to its short-acting nature. An extended-release formulation of alprazolam known as Xanax XR® was introduced in 2001 and is often preferred.
  • Treatment of panic attacks.
    Alprazolam is taken as needed (PRN); 4 to 6 doses per month are the acceptable limit. If dependence seems to develop and/or the limit is exceeded, therapy may be reconsidered and/or discontinued.
  • Long-term treatment of severe generalized anxiety disorders.
    Alprazolam may be used for long-term treatment of anxiety if other therapies either do not work or are contraindicated. Duration of therapy in this case is often four months or longer. The decision to use alprazolam for this purpose must be carefully made by a specialized psychiatrist, taking into account the individual's suffering, quality of life, loss of social performance and risk of dependence.
  • Adjunctive treatment of depression.
    Alprazolam is sometimes used together with SSRIs such as paroxetine, sertraline, or fluoxetine to alleviate initial SSRI-induced anxiety while waiting for the antidepressant to begin working. However, clinical experience has shown that SSRIs may actually provoke panic attacks in otherwise healthy individuals, and cause sexual dysfunction. In these cases, a tricyclic antidepressant may be used instead. Buspirone may also be useful in conjunction with alprazolam in cases of generalized anxiety disorder.
  • Other uses.
    Alprazolam may be used by specialists to treat severe cases of Borderline Personality Disorder. Some studies have shown positive results.

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Use of alprazolam in premenstrual syndrome - Tips from Other Journals
From American Family Physician, 12/1/93

Alprazolam, a benzodiazepine, has been studied as a possible treatment for the anxiety- and depression-like components of premenstrual syndrome, but the results of these studies have been inconclusive. Schmidt and colleagues performed a randomized, double-blind, placebo-controlled crossover trial of alprazolam in women with prospectively confirmed premenstrual syndrome.

Women were recruited by newspaper advertisements or physician referral. Twenty women completed the study. A diagnosis of premenstrual syndrome was confirmed through the use of daily self-rating symptom checklists. The women were randomized to receive alprazolam or placebo from day 16 of the menstrual cycle until the onset of menses. Over four menstrual cycles, the alprazolam dose was increased from 0.25 mg to 0.75 mg three times a day. The women completed checklists daily and a battery of psychiatric screening questionnaires twice monthly. Results of these measures in placebo and alprazolam months were then compared.

No differences were found in self-rating scores between alprazolam months and placebo months. Results of psychiatric screening also did not differ between treatment and placebo months, except for a statistically, but not clinically significant, improvement in depression scores during alprazolam treatment.

The authors conclude that no uniform improvement in symptoms of premenstrual syndrome occurs in patients receiving alprazolam, although patients with strong depressive symptoms may have some benefit. (Archives of General Psychiatry, June 1993, vol. 50, p. 467)

COPYRIGHT 1993 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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