Alprazolam, sold as the trade name Xanax among others, is a short-acting benzodiazepine—a minor tranquilizer. It is most commonly used as a treatment for anxiety disorders, specifically panic disorder or generalized anxiety disorder (GAD). Other uses include chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is available by mouth.
Common side effects include sleepiness, depression, headaches, feeling tired, dry mouth, and memory problems. Some of the sedation and tiredness may improve within a few days. Due to concerns of abuse, some do not recommend alprazolam as an initial treatment of panic disorder. Withdrawal or rebound symptoms may occur if use is suddenly decreased. Other risks include suicide, possibly due to loss of inhibition. Gradually decreasing the dose over weeks or months may be required. Alprazolam, like other benzodiazepines, binds to the GABAA receptor through which it acts.
Alprazolam was approved for medical use in 1981. In 2013, more than 48 million prescriptions were filled in the United States making it the most prescribed psychiatric medication. Overall in 2010, it was the 12th most prescribed medicine in the United States. Alprazolam is a Schedule IV controlled substance and is a very common drug of abuse. It is available as a generic medication. The wholesale cost in the United States is less than 0.03 USD per dose as of 2018.
Medical Uses
Alprazolam 0.5mg pills
Alprazolam is mostly used to treat anxiety disorders, panic disorders, and nausea due to chemotherapy. Alprazolam may also be indicated for the treatment of generalized anxiety disorder, as well as for the treatment of anxiety conditions with co-morbid depression. The FDA label advises that the physician should periodically reassess the usefulness of the drug.
Panic disorder
Alprazolam is effective in the relief of moderate to severe anxiety and panic attacks. However, it is not a first line treatment since the development of selective serotonin reuptake inhibitors. Alprazolam is no longer recommended in Australia for the treatment of panic disorder due to concerns regarding tolerance, dependence, and abuse. Most evidence shows that the benefits of alprazolam in treating panic disorder last only 4 to 10 weeks. However, people with panic disorder have been treated on an open basis for up to 8 months without apparent loss of benefit.
In the United States, alprazolam is FDA-approved for the treatment of panic disorder with or without agoraphobia. Alprazolam is recommended by the World Federation of Societies of Biological Psychiatry (WFSBP) for treatment-resistant cases of panic disorder where there is no history of tolerance or dependence.
Anxiety disorders
Anxiety associated with depression is responsive to alprazolam. Clinical studies have shown that the effectiveness is limited to 4 months for anxiety disorders. However, the research into antidepressant properties of alprazolam is poor and has only assessed its short-term effects against depression. In one study, some long-term, high-dosage users of alprazolam developed reversible depression. In the US, alprazolam is FDA-approved for the management of anxiety disorders (a condition corresponding most closely to the APA Diagnostic and Statistical Manual DSM-IV-TR diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. In the UK, alprazolam is recommended for the short-term treatment (2–4 weeks) of severe acute anxiety.
Nausea due to chemotherapy
Alprazolam may be used in combination with other medications for chemotherapy-induced nausea and vomiting.
Contraindications
Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals. Particular care should be taken in pregnant or elderly people, people with a substance abuse history (particularly alcohol dependence), and people with comorbid psychiatric disorders. The use of alprazolam should be avoided or carefully monitored by medical professionals in individuals with: myasthenia gravis, acute narrow-angle glaucoma, severe liver deficiencies (e.g., cirrhosis), severe sleep apnea, pre-existing respiratory depression, marked neuromuscular respiratory, acute pulmonary insufficiency, chronic psychosis, hypersensitivity or allergy to alprazolam or other benzodiazepines, and borderline personality disorder (where it may induce suicidality and dyscontrol).
Like all central nervous system depressants, alprazolam in larger-than-normal doses can cause significant deterioration in alertness and increase drowsiness, especially in those unaccustomed to the drug's effects.
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.
Adverse effects
Side effects from alprazolam
Sedative drugs, including alprazolam, have been associated with an increased risk of death.
Possible side effects include:
Anterograde amnesia and concentration problems
Ataxia, slurred speech
Disinhibition
Drowsiness, dizziness, lightheadedness, fatigue, unsteadiness, and impaired coordination, vertigo
Dry mouth (infrequent)
Hallucinations (rare)
Jaundice (very rare)
Skin rash, respiratory depression, constipation
Suicidal ideation or suicide
Urinary retention (infrequent)
Paradoxical reactions
Although unusual, the following paradoxical reactions have been shown to occur:
Aggression
Mania, agitation, hyperactivity, and restlessness
Rage, hostility
Twitches and tremor
Food and drug interactions
Alprazolam is primarily metabolized via CYP3A4. Combining CYP3A4 inhibitors such as cimetidine, erythromycin, norfluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene, and ritonavir delay the hepatic clearance of alprazolam, which may result in its accumulation and increased severity of its side effects.
Imipramine and desipramine have been reported increase an average of 31% and 20% respectively by the concomitant administration of alprazolam tablets. Combined oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation.
Alcohol is one of the most common interactions; alcohol and 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 took, the worse the interaction. Combination of alprazolam with the herb kava can result in the development of a semi-comatose state. Plants in the genus Hypericum (including St. John's wort) conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.
Pregnancy and breastfeeding
Benzodiazepines cross the placenta, enter the fetus, and are also excreted in breast milk. Chronic administration of diazepam, another benzodiazepine, to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.
The use of alprazolam during pregnancy is associated with congenital abnormalities, and use in the last trimester may cause fetal drug dependence and withdrawal symptoms in the post-natal period as well as neonatal flaccidity and respiratory problems. However, in long-term users of benzodiazepines, abrupt discontinuation due to concerns of teratogenesis has a high risk of causing extreme withdrawal symptoms and a severe rebound effect of the underlying mental health disorder. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications, including benzodiazepines.
Overdose
Xanax: 0.25, 0.5, and 1 mg scored tablets
Main article: Benzodiazepine overdose
Overdoses of alprazolam can be mild to severe depending on the quantity ingested and if other drugs are taken in combination.
Alprazolam overdoses cause excess central nervous system (CNS) depression and may include one or more of the following symptoms:
Coma and death if alprazolam is combined with other substances.
Fainting
Hypotension (low blood pressure)
Hypoventilation (shallow breathing)
Impaired motor functions
Dizziness
Impaired balance
Impaired or absent reflexes
Muscle weakness
Orthostatic hypotension (fainting while standing up too quickly)
Somnolence (drowsiness)
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