What are the effects of long-term use of Alprazolam (Xanax)?

From the Guidelines

Alprazolam (Xanax) should not be used for long-term treatment due to its high risk of dependence, withdrawal symptoms, and other adverse effects. The most recent and highest quality study, published in The Lancet Psychiatry in 2019 1, highlights the risks associated with long-term use of benzodiazepines, including alprazolam. Long-term use can lead to tolerance, dependence, and withdrawal symptoms, as well as cognitive impairment, memory problems, and increased risk of falls, especially in older adults.

Risks of Long-term Use

• Dependence and withdrawal symptoms
• Cognitive impairment and memory problems
• Increased risk of falls, especially in older adults
• Paradoxical reactions, such as increased anxiety or agitation

Safe Discontinuation

If alprazolam has been used long-term, it is essential to taper the dose gradually to avoid severe withdrawal symptoms, including seizures. A commonly used tapering schedule is a reduction of the benzodiazepine dose by 25% every 1–2 weeks, as recommended in the 2016 CDC guideline for prescribing opioids for chronic pain 1. Cognitive behavioral therapy (CBT) can also increase tapering success rates and may be particularly helpful for patients struggling with benzodiazepine taper.

Alternative Treatments

For chronic anxiety disorders, alternative treatments like SSRIs, SNRIs, buspirone, or cognitive behavioral therapy are safer for long-term management. These treatments can help reduce the risk of dependence and withdrawal symptoms associated with long-term alprazolam use. According to the 2016 CDC guideline 1, evidence-based psychotherapies, such as CBT, and/or specific anti-depressants or other nonbenzodiazepine medications approved for anxiety should be offered to patients requiring treatment for anxiety.

From the FDA Drug Label

DRUG ABUSE AND DEPENDENCE Physical and Psychological Dependence Withdrawal symptoms similar in character to those noted with sedative/hypnotics and alcohol have occurred following discontinuance of benzodiazepines, including alprazolam tablets The symptoms can range from mild dysphoria and insomnia to a major syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors and convulsions.

The effects of long-term use of Alprazolam (Xanax) include:

• Physical dependence: Long-term use can lead to physical dependence, and withdrawal symptoms can occur when the drug is discontinued 2.
• Psychological dependence: The risk of psychological dependence is increased with long-term use, especially at doses greater than 4 mg/day, and in patients with a history of alcohol or drug abuse 2.
• Withdrawal symptoms: Withdrawal symptoms can range from mild to severe and include insomnia, dysphoria, abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions 2.
• Increased risk of seizures: The risk of withdrawal seizures may be increased at doses above 4 mg/day, especially in patients with a history of seizures or epilepsy 2 2.
• Difficulty tapering and discontinuing: Some patients may experience considerable difficulty in tapering and discontinuing from alprazolam tablets, especially those receiving higher doses for extended periods 2.

From the Research

Effects of Long-Term Use of Alprazolam

The long-term use of Alprazolam (Xanax) has been associated with several effects, including:

• Dependence and withdrawal symptoms: Studies have shown that long-term use of Alprazolam can lead to dependence and withdrawal symptoms, particularly when discontinued abruptly 3, 4, 5, 6.
• Tolerance: While some studies suggest that Alprazolam may not produce tolerance to its therapeutic effect 3, others indicate that long-term use can lead to tolerance and the need for increased doses 4, 5.
• Cognitive and psychomotor impairment: Alprazolam has been shown to impair performance in various skills, including driving, in healthy volunteers and patients 3, 4.
• Abuse potential: Alprazolam has a high potential for abuse and dependence, particularly in individuals with a history of substance abuse 7, 5.
• Adverse effects: Long-term use of Alprazolam can lead to adverse effects such as drowsiness, sedation, and psychomotor impairment, particularly in the elderly 3, 4.

Recommendations for Use

Based on the available evidence, it is recommended that:

• Alprazolam be used as a second-line treatment option for panic disorder and generalized anxiety disorder, when Selective Serotonin Reuptake Inhibitors (SSRIs) are not effective or well-tolerated 3.
• The use of Alprazolam be limited to short-term treatment (less than 4 weeks) whenever possible, and that dosages be kept minimal 4.
• Patients be carefully selected and monitored for signs of dependence and withdrawal symptoms, particularly when discontinuing treatment 4, 7, 5, 6.
• Alternative pharmacological and non-pharmacological strategies be considered for the treatment of anxiety and insomnia, particularly in individuals with a history of substance abuse 7.