From the Guidelines
Gabapentin is generally considered safer and less neurotoxic than diphenhydramine for long-term PRN use in treating anxiety. Diphenhydramine, an antihistamine, is not recommended for long-term anxiety management due to its anticholinergic properties which can cause cognitive impairment, memory problems, and potentially contribute to dementia risk with prolonged use, as seen in various studies 1. It also commonly causes sedation, dry mouth, blurred vision, and constipation.
Key Considerations
- Gabapentin, while originally developed as an anti-seizure medication, has a more favorable long-term safety profile for anxiety, with fewer cognitive effects and less potential for tolerance or dependence compared to benzodiazepines.
- Typical gabapentin dosing for anxiety starts at 100-300mg once daily, gradually increasing as needed to 300-600mg three times daily, though individual needs vary, and should be guided by a healthcare provider.
- Side effects may include dizziness, fatigue, and mild edema, particularly when starting treatment, as noted in studies such as 1.
- Any medication decision should be made with a healthcare provider who can consider your specific medical history, as gabapentin requires kidney function monitoring and has its own set of precautions, including careful discontinuation to avoid withdrawal symptoms, as highlighted in the 2023 ACC expert consensus decision pathway 1.
Important Precautions
- Kidney insufficiency requires dosage adjustment for gabapentin, and psychiatric disease or addiction history may increase the risk of euphoria.
- The choice between gabapentin and other medications like pregabalin, tricyclic antidepressants, or selective serotonin–noradrenaline reuptake inhibitors should be based on individual patient factors and medical history, considering the potential risks and benefits of each option, as discussed in the context of neuropathic pain management 1.
From the Research
Comparison of Diphenhydramine and Gabapentin for Long-term PRN Use
- There are no direct studies comparing the safety and neurotoxicity of Diphenhydramine and Gabapentin for long-term PRN use for anxiety.
- However, studies have reported on the safety and efficacy of Gabapentin and its related compounds, such as Pregabalin, for anxiety treatment 2, 3, 4.
- Gabapentinoids have been associated with risks of tolerance, dependence, addiction, and withdrawal, similar to benzodiazepines 2.
- Pregabalin, a gabapentinoid, has been shown to be effective for generalized anxiety disorder, but its use is not without risks, including dizziness, somnolence, and weight gain 3.
- The potential for abuse of Gabapentin is a concern, particularly when used off-label for conditions such as alcohol use disorder 5.
Safety Considerations for Long-term PRN Use
- A systematic review of PRN medicines management for psychotropic medications in long-term care settings highlighted the need for improved guidelines to prevent harm and ensure safety 6.
- Long-term pharmacological treatments for anxiety disorders, including Gabapentin and Pregabalin, require careful consideration of potential risks and benefits 4.
- The lack of evidence on the optimal length and dosage of medications to minimize relapse risk and potential cognitive side-effects is a concern for long-term treatment 4.