What is a suitable non-benzodiazepine (nonbenzo) medication for a patient with anxiety, considering a history of substance abuse or dependence, that can be prescribed on an as-needed (prn) basis?

Non-Benzodiazepine PRN Anxiety Medication

Buspirone is the only non-benzodiazepine medication with established efficacy for anxiety that can be used in patients with substance abuse history, but it requires 2-4 weeks to become effective and therefore cannot function as a true PRN medication. 1, 2

Critical Limitation: No True PRN Non-Benzodiazepine Exists

The fundamental problem is that effective non-benzodiazepine anxiolytics require continuous dosing to achieve therapeutic effect—they are not suitable for as-needed use. 1, 3, 4

• Buspirone takes 2-4 weeks to become effective and must be dosed 2-3 times daily on a scheduled basis, not PRN. 1, 2
• SSRIs/SNRIs (sertraline, escitalopram, venlafaxine, duloxetine) require 4-8 weeks for full therapeutic effect and continuous daily dosing. 2
• Pregabalin/gabapentin are not FDA-approved for anxiety and carry their own abuse potential (Schedule V controlled substance). 5

The Substance Abuse History Dilemma

Benzodiazepines remain the only truly effective PRN anxiolytics, but traditional teaching discourages their use in patients with substance abuse history. However, this position may lack strong empirical justification. 6

Evidence Challenging the Absolute Contraindication:

• Most benzodiazepine abusers concurrently abuse other substances; a history of substance abuse (particularly non-benzodiazepine substances) is not necessarily a major risk factor for future benzodiazepine abuse. 6
• Benzodiazepines do not appear to induce relapse of other substance abuse in patients with remote histories. 6
• Few cases of addiction arise from legitimate medical use of benzodiazepines—intentional abusers typically have polysubstance abuse patterns. 7
• The 2002 stimulant guidelines note that patients with histories of using alcohol, opiates, or sedatives may still receive controlled medications for legitimate indications with appropriate monitoring. 1

When Benzodiazepines Might Be Considered Despite History:

If the substance abuse history involves alcohol, opiates, or stimulants (not benzodiazepines or sedatives), short-acting benzodiazepines may be cautiously prescribed with:

• Lorazepam 0.5-1 mg PRN (maximum 2 mg/24 hours in elderly; standard dosing in younger adults). 1, 2
• Strict quantity limits (e.g., 10-15 tablets per month). 2
• Regular monitoring for signs of misuse (dose escalation, early refill requests, drug-seeking behavior). 5
• Documented informed consent discussion about addiction risk. 7

Absolute contraindication remains if: 1

• Recent benzodiazepine or sedative abuse/dependence
• Active polysubstance abuse
• Patient requests benzodiazepines specifically or exhibits drug-seeking behavior

Practical Algorithm for This Clinical Scenario

Step 1: Clarify the Nature of Anxiety

• Chronic/generalized anxiety → Requires scheduled medication (buspirone, SSRI/SNRI), not PRN therapy. 2, 3
• Situational/episodic anxiety → True PRN need, but options are extremely limited without benzodiazepines. 1

Step 2: Assess Substance Abuse History Details

• What substance(s)? Benzodiazepine/sedative history = absolute contraindication. 1
• How recent? Active use = absolute contraindication; remote history (>5 years) = relative contraindication. 6
• Pattern of use? Polysubstance abuse = higher risk. 7

Step 3: Choose Treatment Strategy

For patients who CANNOT receive benzodiazepines:

• Transition to scheduled buspirone 5 mg twice daily, titrate to 20 mg three times daily over 2-4 weeks. 1, 2
• Add SSRI (sertraline 25-50 mg daily or escitalopram 5-10 mg daily) for long-term management. 2
• Hydroxyzine 25-50 mg PRN may provide mild anxiolysis through antihistamine effects, though evidence is limited and anticholinergic burden is concerning in elderly. 1
• Cognitive behavioral therapy should be offered as first-line non-pharmacologic intervention. 2

For patients who MIGHT receive benzodiazepines (remote non-benzodiazepine substance history):

• Lorazepam 0.5-1 mg PRN with strict limits and monitoring. 1, 2
• Concurrent initiation of scheduled anxiolytic (buspirone or SSRI) to transition away from PRN benzodiazepine use. 2

Common Pitfalls to Avoid

• Do not prescribe buspirone "PRN"—it has no acute anxiolytic effect and requires continuous dosing for 2-4 weeks. 1, 2
• Do not use trazodone PRN for anxiety—it is sedating but not specifically anxiolytic, and is better suited for agitation in dementia or insomnia. 1
• Do not assume all substance abuse history equally contraindicates benzodiazepines—the type and recency of abuse matter significantly. 6, 7
• Do not use antipsychotics (haloperidol, olanzapine) for primary anxiety—they are reserved for severe agitation, psychosis, or when other options have failed. 1
• Avoid pregabalin/gabapentin as first-line—they are Schedule V controlled substances with their own abuse potential and lack FDA approval for anxiety. 5

The Uncomfortable Truth

There is no ideal non-benzodiazepine PRN anxiolytic for patients with substance abuse history. The choice is between:

1. Accepting that PRN treatment is not feasible and transitioning to scheduled therapy (buspirone, SSRI/SNRI). 2, 3
2. Carefully reconsidering benzodiazepines in select patients with remote, non-benzodiazepine substance histories under strict monitoring. 6, 7
3. Using hydroxyzine PRN as a weak alternative with limited evidence and significant anticholinergic concerns. 1

The safest approach prioritizes scheduled anxiolytic therapy over PRN dosing in this population. 2, 7