In an adult without severe liver or kidney disease, uncontrolled substance‑use disorder, pregnancy, or benzodiazepine dependence, what are the optimal PRN medications for anxiety and depressive symptoms?

Best PRN Medications for Anxiety and Depression

There are no optimal PRN medications for anxiety and depression—scheduled antidepressants (SSRIs/SNRIs) combined with psychological interventions are first-line treatment, and benzodiazepines should only be used short-term as a "bridging strategy" while waiting for antidepressants to take effect. 1, 2, 3

Why PRN Anxiolytics Are Not Recommended

The fundamental problem with PRN medication approaches for anxiety and depression is that they treat symptoms rather than underlying pathophysiology:

• Benzodiazepines carry significant risks including abuse potential, dependence, cognitive impairment, and should be time-limited in accordance with psychiatric guidelines 1, 2
• Depression and anxiety require sustained treatment to address neurobiological mechanisms—PRN dosing cannot achieve this 3
• Antidepressants show no compelling evidence for efficacy in depression when used intermittently, with a 2018 Cochrane review finding no difference between antidepressants and placebo at 6-12 weeks in cancer patients 1

The Evidence-Based Treatment Algorithm

Step 1: Rule Out Medical Causes First

Before any psychiatric medication, exclude:

• Thyroid dysfunction (hyperthyroidism commonly mimics anxiety) 4
• Uncontrolled pain, fatigue, electrolyte imbalances, delirium 1, 5
• Hypoglycemia, pheochromocytoma, cardiac arrhythmias 4

Step 2: Assess Severity and Initiate First-Line Treatment

For moderate to severe symptoms:

• Start scheduled SSRI/SNRI therapy: Escitalopram 10-20mg daily, sertraline 50-200mg daily, or venlafaxine 75-225mg daily 2, 5, 3
• Simultaneously refer for psychological intervention: CBT, behavioral activation, structured physical activity, or problem-solving therapy 1
• The combination is superior to monotherapy for moderate-severe presentations 4

For mild symptoms:

• Psychological interventions alone (CBT, behavioral activation, exercise) without pharmacotherapy 1
• Active monitoring with reassessment in 4-6 weeks 4

Step 3: Short-Term Benzodiazepine "Bridging" (If Absolutely Necessary)

Benzodiazepines may be considered only in these specific circumstances:

• As a bridging strategy for acute severe anxiety while waiting 4-8 weeks for antidepressants to take effect 6, 7
• When first-line treatments have failed and the patient has no access to psychological care 1, 5
• Patient preference after informed discussion of risks 1

If benzodiazepines are used:

• Lorazepam 0.5-1mg or alprazolam 0.25-0.5mg up to 2-3 times daily for 2-4 weeks maximum 8, 9
• Warn patients explicitly about sedation, dizziness, abuse potential, dependence, and cognitive impairment 8
• Do not use in patients with substance use history—substitute with atypical antipsychotic augmentation instead 6
• Initiate taper plan immediately once antidepressant effects begin (typically 4-8 weeks), reducing by 0.125-0.25mg every 1-2 weeks 2

Step 4: Alternative Non-Benzodiazepine Options

Buspirone 15-30mg daily (divided doses) may be considered as a non-benzodiazepine anxiolytic when:

• SSRIs are contraindicated or poorly tolerated 5
• Patient requires medication without sedation or abuse potential 5
• However, buspirone has slower onset (2-4 weeks) and is not suitable for true PRN use 3

Critical Pitfalls to Avoid

• Do not prescribe benzodiazepines long-term—they worsen outcomes, cause cognitive decline, and increase mortality risk 1, 2, 8
• Do not use PRN antidepressants—they require daily dosing for 4-12 weeks to achieve therapeutic effect 1, 3
• Do not treat moderate-severe symptoms with monotherapy—combination CBT plus SSRI is superior 4
• Do not discontinue SSRIs before 12 months of remission—continue for 6-12 months after symptom resolution to prevent relapse 4, 3
• Do not trivialize anxiety/depression as "normal stress"—this leads to undertreatment of clinically significant symptoms 5

Monitoring and Follow-Up

• Reassess monthly for medication adherence, adverse effects, and treatment satisfaction 2, 5
• After 8 weeks, if symptoms persist despite good compliance, alter the treatment course: add psychological intervention, change medication, or refer to individual psychotherapy 2, 4, 5
• Proactive follow-up is essential—patients with anxiety commonly avoid following through on referrals due to avoidance behavior 1, 5