Alprazolam abuse

Ciraulo DA, Sands BE, Shader RI Critical review of liability for benzodiazepine abuse among alcoholics. Am J Psychiatry 145 1501-1506, 1988b Ciraulo DA, Barnhill JG, Ciraulo AM, et al Parental alcoholism as a risk factor in benzodiazepine abuse a pilot smdy. Am J Psychiatry 146 1333-1335, 1989 Ciraulo DA, Antal EJ, Smith RB, et al The relationship of alprazolam dose to steady-state plasma concentrations. J Clin Psychopharmacol 10 27—32, 1990 Ciraulo DA, Sarid-Segal O, Knapp C, et al Liability to alprazolam abuse in daughters of alcoholics. Am J Psychiatry 153 956-958, 1996 Ciraulo DA, Barnhill JG, Ciraulo AM, et al Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. J Clin Pharmacol 37 64-73, 1997... 

The benzodiazepines currently available for clinical use vary substantially in pharmacokinetics, acute euphoriant effects, and frequency of reported dependence. It is likely, therefore, than not all benzodiazepines have the same potential for abuse. Diazepam, lorazepam, and alprazolam may have greater abuse potential than chlordiazepoxide and clorazepate (Wolf et al. 1990). Similarly, oxazepam has been reported to produce low levels of abuse (Eliding 1978). Jaffe et al. (1983) found that in recently detoxified alcoholic patients, halazepam produces minimal euphoria even at a supratherapeutic dosage. The development of partial agonist and mixed agonist/antagonist compounds at the benzodiazepine receptor complex may offer an advantage over approved benzodiazepines for use in alcoholic patients. 

Ciraulo DA, Nace EP Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Am J Addict 9 276—284, 2000 Ciraulo DA, Barnhill JG, Greenblatt DJ, et al Abuse liability and clinical pharmacokinetics of alprazolam in alcoholic men. J Clin Psychiatry 49 333—337, 1988a... 

Klein E, Uhde TW, Post RM Preliminary evidence for the utility of carbamazepine in alprazolam withdrawal. Am J Psychiatry 143 235—236, 1986 Kouyanou K, Pither CE, Wessely S Medication misuse, abuse and dependence in chronic pain patients. J Psychosom Res 43 497-304, 1997 Kryspin-Exner K [Misuse of bezodiazepine derivatives in alcoholics] (German). Br J Addict Alcohol Other Drugs 61 283-290, 1966 Kryspin-Exner K, Demel 1 The use of tranquilizers in the treatment of mixed drug abuse. Int J Clin Pharmacol Biopharm 12 13-18, 1973... 

Mumford GK, Evans SM, Fleishaker JC, et al Alprazolam absorption kinetics affects abuse liability. Clin Pharmacol Ther 57 356—365, 1995a... 

The most commonly ingested BZs by individuals seen in emergency rooms are alprazolam and clonazepam, but lorazepam and diazepam are also commonly abused. 

Agents with rapid onset of action (e.g., diazepam, alprazolam) have higher abuse potential because of their reinforcing effects. Chlordiazepoxide or oxazepam are less likely to be abused. 

Because Rohypnol is banned in the United States, there is an emerging trend for young people to start abusing two other Rohypnol-like drugs that are still legal in the United States clonazepam (Klonopin ) and alprazolam (Xanax). Both Klonopin and Xanax are benzodiazepines that are used for the treatment of anxiety and insomnia. Although they are less potent than Rohypnol, they can produce similar effects when mixed with alcohol and also have been reported to enhance the effects of heroin. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

American Psychiatric Association Benzodiazepine Dependence, Toxicity, and Abuse A Task Force Report of the American Psychiatric Association. Washington, DC, American Psychiatric Association, 1990 Cohn JB, Wilcox CS Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients a double-blind study. J Clin Psychiatry 47 409 12, 1986 Dolovich LR, Addis A, Vaillancourt JM, et al Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and case-control studies. BMJ 317 839-843, 1998 Goldberg HL, Finnerty RJ The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 136 1184—1187, 1979 Kupfer DJ, Reynolds CF 111 Management of insomnia. N Engl J Med 336 341-346, 1997... 

Anxiolytics and Sedative-Hypnotics. Because of their large therapeutic index, measurement of anxiolytic or sedative-hypnotic serum concentrations is not usually necessary in clinical practice, unless abuse, overdose, or inadvertent toxicity are suspected. Some data indicate that plasma alprazolam levels of 40 ng/mL may be required to manage panic disorder ( 51) (see the sections Adverse Effects of Anxiolytics and Adverse Effects of Sedative-Hypnotics in Chapter 12). 

Alprazolam has been researched more extensively than any other benzodiazepine in panic disorder, and is very effective. Because of its short duration of action, it generally must be administered in three to five daily doses. Clonazepam, which has a longer duration of action than alprazolam, has also been investigated in panic disorder. It can generally be administered twice a day. Clonazepam is reported to have less abuse potential than alprazolam and to be easier to taper during discontinuation owing to its longer half-life. 

Risk of seizure is greatest during the first 3 days after discontinuation of alprazolam, especially in those with prior seizures, head injuries, or withdrawal from drugs of abuse... 

Slower rises in plasma drug levels for alprazolam XR have the potential to reduce euphoria/abuse liability, but this has not been proven... 

If clonazepam can be considered a long-acting alprazolam-like anxiolytic , then alprazolam XR can be considered an even longer-acting clonazepam-like anxiolytic with the potential of improved tolerability features in terms of less euphoria, abuse, dependence, and withdrawal problems, but this has not been proven... 

For the acute relief of anxiety or panic attacks, benzodiazepines are often useful, usually on an as-needed basis. Many clinicians are reluctant to prescribe these medications for an extended period of time (due to risks associated with physiologic dependence, withdrawal, or abuse), but for the relief of acute symptoms, benzodiazepines are a valuable therapeutic modality. Although a wide variety of benzodiazepines are currently available, they are all qualitatively similar in terms of their pharmacologic effects and side effect potential. Clonazepam and alprazolam are the two benzodiazepines used most commonly to treat anxiety disorders. 

Another consideration in the choice of benzodiazepine is their potential for abuse. Individuals with addictive disorders prefer certain agents to others. Agents with rapid onset of action, such as diazepam or alprazolam, demonstrate higher abuse potential because of their reinforcing effects. Those with slower onset of action, such as chlor-diazepoxide, oxazepam, and halazepam, are less likely to be abused. This consideration may be relevant in an outpatient setting or for patients with a history of benzodiazepine or other substance abuse. ... 

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