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Indications for use and efficacy of Xanax

Xanax is a high-potency drug that is the US Food and Drug Administration (FDA)-approved for the treatment of panic disorder and anxiety.

The US FDA’s approval for Xanax based on 2 large, randomized, clinical trials that studied short-term efficacy and clinically acceptable tolerability. A plasma concentration range between 20 and 40 ng/mL has been suggested for targeting symptoms of panic disorder, the higher concentrations were associated with more significant central nervous system depressant effects.

The side effects of Xanax tablets

are likely to be an extension of its pharmacological activity, and most commonly include drowsiness, headache, dizziness, memory impairment, fatigue, dysarthria, and depression.

Xanax is the most widely prescribed and misused benzodiazepine. Xanax can be used effectively and safely when appropriately prescribed, after evaluation of the risks and benefits of treatment. Side effects are common but often downplayed by patients, given their rapid onset of therapeutic action and unique reinforcing properties. Common complaints reported with varying frequency by patients treated with Xanax include fatigue, ataxia, sedation, hypersensitivity, amnesia, slurred speech, poor concentration, and irritability.

All benzodiazepines carry a risk of diversion, misuse, physical dependence, and tolerance. Misuse is more frequently seen in patients with a personal or family history of drug or alcohol misuse. 

Withdrawal symptoms

associated with Xanax discontinuation are more severe than with other benzodiazepines probably due to high potency causing severe rebound anxiety, the short duration of action. Some of the risks listed above could be mitigated with the use of alprazolam extended-release, although little is known about the long-acting formulation, except for one small human laboratory study indicating that lower doses were not as reinforcing as the immediate-release formulation.

Alprazolam is significantly more toxic than other benzodiazepines in cases of overdoses and should be avoided in patients at increased risk of suicide, or who are using, opioids, alcohol, or other sedating drugs. Alprazolam should be prescribed primarily in its extended-release formulation for a short duration to minimize misuse liability and only to those with no prior substance use history. The use of Xanax with opioids doubles the risk of respiratory depression and death and should be avoided. 

Alprazolam should be discontinued slowly,

A reasonable guideline is not to exceed 0.125 mg weekly and over a period of at least 8 weeks. Gabapentin could be beneficial during alprazolam discontinuation to prevent cravings, rebound, and anxiety.

Many providers feel pressurized by their patients to continue prescribing as they try to wean them off benzodiazepines, and more so with alprazolam, given the positive subjective drug effects. Alprazolam should be used as prescribed and don’t increase the dose by yourself, and providers should consider stopping alprazolam if patients are requesting higher doses, as it may be a start for therapeutic tolerance and/or misuse.

Well-designed human studies addressing Xanax’s reinforcing effects and the discontinuation syndrome are needed and must consider important issues such as the selection of appropriate comparison drug, formulation, dose, and population.

Further investigations are required to study the misuse liability of alprazolam extended-release and should attempt to clarify the use of other drugs in the treatment of alprazolam withdrawal syndrome.

Xanax and pregnancy

The US FDA has identified alprazolam and other benzodiazepines as pregnancy category D, which indicates prior evidence of human fetal risk.

21 to 33% of pregnant females are estimated to receive psychotropic drugs, and often these medications are prescribed to treat psychiatric symptoms that predate the pregnancy, Xanax has been reported to cause sedation and withdrawal in the newborn and should be avoided during pregnancy and lactation.