Alprazolam
| Evidence Level: L3 | Predicted Indications: 3 |
Table of Contents
Alprazolam: From Anxiety and Panic Disorders to Insomnia
One-Sentence Summary
Alprazolam is a benzodiazepine marketed in the US as oral tablets (immediate-release, extended-release and orally disintegrating). The literature in this pack places its established use in anxiety and panic disorder. The TxGNN model predicts it may be effective for insomnia, with 6 retrieved clinical trials and 18 retrieved publications. None of the trials is confirmed to test alprazolam for insomnia, and only a few publications address it directly. The prediction is therefore supported mainly by class pharmacology, not by direct clinical evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the supplied US license records; the literature in the pack describes anxiety and panic disorder |
| Predicted New Indication | Insomnia |
| TxGNN Prediction Score | 99.81% |
| Evidence Level | L3 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 license records (NDA and ANDA generics) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the record. Based on known class pharmacology, alprazolam is a positive allosteric modulator of GABA-A receptors. It enhances inhibitory neurotransmission, which gives a plausible sedative-hypnotic effect. Other benzodiazepines are already used for insomnia, and anxiety-related insomnia is a possible subgroup.
Anxiety and insomnia often occur together, so a drug proven for anxiety and panic may plausibly help sleep. The very high TxGNN score is a graph-based prediction, not clinical evidence.
Two limits apply. Dependence, falls and cognitive effects, especially in the elderly, limit how far this can be pursued. The mechanistic link is also inferred from class pharmacology, not from the supplied record.
Two other predictions in the pack are worth noting:
- Agoraphobia (score 99.56%, L2) is essentially an extension of alprazolam’s known panic-disorder use and is supported by several controlled studies.
- Benign paroxysmal torticollis of infancy (score 99.61%) has no supporting trials or publications and raises major safety concerns in infants.
Clinical Trial Evidence
None of these trials is confirmed to test alprazolam for insomnia.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02648776 | N/A (cohort) | Unknown | 1400 | Prospective cohort on risks and benefits of hypnotics in elderly patients in Taiwan. Useful for the safety signal, but observational and may not isolate alprazolam |
| NCT01584440 | Phase 2 | Completed | 220 | Randomized, placebo-controlled study of AVP-923 for agitation in Alzheimer’s disease. The intervention is not confirmed to be alprazolam and the target is not insomnia; verify before counting toward L2 |
| NCT03327506 | Phase 4 | Unknown | 128 | Hypnosis versus alprazolam premedication for perioperative anxiety. The outcome is anxiety, not insomnia |
| NCT00266409 | Phase 4 | Completed | 418 | Open-label trial of Niravam (an alprazolam orally disintegrating tablet) plus SSRI/SNRI versus SSRI/SNRI alone in generalized anxiety or panic disorder. Anxiety outcome, not insomnia |
| NCT04572750 | N/A | Completed | 170 | Self-management packet for benzodiazepine cessation in Veterans. Relevant to dependence, not efficacy |
| NCT01893632 | Phase 2 | Terminated | 2 | Gabapentin for benzodiazepine dependence, stopped with 2 participants. No efficacy information for insomnia |
NCT01146600 (clarithromycin for hypersomnia) was also retrieved but involves a different drug and the opposite sleep phenotype, so it is not listed.
Literature Evidence
No randomized trial of alprazolam for insomnia was retrieved.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33403184 | 2020 | Comparative clinical study | Cureus | Alprazolam versus melatonin for sleep disturbances in hemodialysis patients. This is the most direct study in the set; the results are not in the supplied excerpt |
| 39183410 | 2024 | Retrospective observational | Medicine | 116 patients with coronary heart disease and insomnia. Alprazolam was the control arm against moxibustion plus ear acupuncture, so it is not a test of alprazolam itself |
| 36692463 | 2023 | Meta-analysis (observational) | Acta Pharm | Tranquilizers in elderly patients with chronic non-communicable diseases, assessing dose, outcomes and adverse effects |
| 35041261 | 2022 | RCT (different drug) | Brain Behav | Eszopiclone for sleep quality and cognition in Alzheimer’s patients. Indirect: not alprazolam |
| 37984023 | 2024 | Predictive/economic model | Value Health Reg Issues | Benzodiazepine use trends and burden in Croatia. Notes memory loss, dependence, falls and accident risk with long-term use |
| 35493764 | 2022 | Cohort | JHEP Rep | Deprescribing zolpidem reduces falls and fractures in cirrhosis. Safety context for sedative-hypnotics |
| 37801512 | 2023 | Preclinical (mouse) | Aging | Repeated alprazolam causes mitochondrial dysfunction and impaired hippocampus-dependent memory consolidation |
| 15341891 | 2004 | Prescription-pattern study | Sleep Med | Hypnotic prescribing patterns in a managed-care population |
| 25532388 | 2014 | Real-world cross-sectional | Zhongguo Zhong Yao Za Zhi | Concurrent diseases and medicine use among patients with insomnia |
| 38363887 | 2024 | Cross-sectional | Medicine | Insomnia among COVID-19 survivors. Background only, not about alprazolam |
US Market Information
Approved indication text was not supplied in the license records. Dosage forms on the US market are oral tablet, extended-release tablet and orally disintegrating tablet.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| NDA018276 | Alprazolam | Tablet | Mylan Pharmaceuticals Inc. |
| ANDA074342 | Alprazolam | Tablet | Bryant Ranch Prepack |
| ANDA203346 | Alprazolam | Tablet | NuCare Pharmaceuticals, Inc. |
| ANDA203346 | Alprazolam | Tablet | Direct_Rx |
Safety Considerations
Please refer to the package insert for safety information. The FDA package insert warnings and contraindications are missing from the record and are a blocking gap.
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence is at L3: the literature is observational or indirect, and none of the retrieved trials is confirmed to test alprazolam for insomnia. Package insert safety data is missing, and dependence, falls and cognitive concerns in the elderly weigh against pursuing this indication.
To proceed, the following is needed:
- FDA package insert warnings and contraindications (blocking gap)
- Detailed mechanism of action data from DrugBank
- Full text and results of PMID 33403184 (alprazolam vs melatonin), and confirmation of the intervention in NCT01584440
- A search for randomized trials of alprazolam specifically for insomnia, including anxiety-related insomnia
- A safety plan covering dependence, withdrawal, falls and cognitive effects in older adults
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.