What medication can be added to the treatment of a patient with Major Depressive Disorder (MDD) and aggression, currently on sertraline (Selective Serotonin Reuptake Inhibitor) 50mg daily and Abilify (aripiprazole) 5mg daily, with prn (as needed) hydroxyzine 50mg and Zyprexa (olanzapine) 5mg, who is experiencing extreme high anxiety?

Recommended Medication Addition for Extreme Anxiety

Add lorazepam 0.25-0.5 mg orally PRN (as needed) up to four times daily, with a maximum of 2 mg in 24 hours, as the most appropriate medication for this patient's extreme anxiety. 1

Rationale for Lorazepam Selection

Lorazepam is the preferred benzodiazepine for PRN anxiety management because it has a short half-life, lacks active metabolites, and demonstrates predictable pharmacokinetics, making it particularly suitable for managing acute anxiety episodes. 1 This is especially important given that the patient already has PRN hydroxyzine and olanzapine available but continues to experience extreme anxiety, suggesting these agents are insufficient.

Why Lorazepam Over Current PRN Medications

• The patient's existing PRN regimen (hydroxyzine 50mg and olanzapine 5mg) has not adequately controlled the extreme anxiety, indicating need for a more potent anxiolytic agent. 1
• For anxiety without delirium, lorazepam 0.25-0.5mg orally PRN is the first-line recommendation according to current guidelines. 1
• Lorazepam provides rapid onset of action for acute anxiety relief, which is critical when a patient verbalizes "extreme high anxiety." 2

Specific Dosing Protocol

• Start with lorazepam 0.25-0.5 mg orally every 4-6 hours as needed, with a strict maximum of 2 mg total in 24 hours. 1, 3
• Begin at the lower end of the dosing range (0.25 mg) if the patient has any frailty, COPD, or is elderly, to minimize risks. 1
• The medication can be given orally or sublingually if swallowing is difficult. 3

Critical Safety Considerations and Monitoring

Monitor closely for paradoxical agitation, which occurs in approximately 10% of patients taking benzodiazepines, and can actually worsen anxiety rather than improve it. 1, 3

Drug Interaction Warnings

• Exercise extreme caution when combining lorazepam with the patient's PRN olanzapine 5mg, as concomitant use of benzodiazepines with high-dose antipsychotics has been associated with reported fatalities. 1, 3
• When both medications are needed, use the lowest effective doses and avoid administering them simultaneously. 1
• Monitor for oversedation when combining benzodiazepines with the patient's standing aripiprazole and PRN olanzapine. 1

Additional Safety Monitoring

• Assess for increased fall risk, as benzodiazepines significantly increase this risk, particularly when combined with antipsychotics. 1
• Monitor for cognitive impairment, as regular benzodiazepine use can lead to tolerance, addiction, depression, and cognitive decline. 1, 3
• Evaluate the patient daily with in-person examination to determine ongoing need for PRN anxiolytic medication. 4

Duration of Treatment

• Limit lorazepam use to the shortest possible duration, ideally no more than 2-4 weeks of regular use. 3, 2
• Consider this a bridge therapy while optimizing the patient's standing antidepressant (sertraline) and antipsychotic (aripiprazole) regimen, which may take several weeks to achieve full therapeutic effect. 2
• If anxiety persists beyond 2-4 weeks, reassess the underlying treatment plan rather than continuing long-term benzodiazepine therapy. 2

Alternative Considerations if Lorazepam is Contraindicated

If lorazepam cannot be used due to contraindications (severe pulmonary insufficiency, severe liver disease, myasthenia gravis), consider:

• Increasing the standing aripiprazole dose from 5mg to 10mg daily, as aripiprazole has demonstrated efficacy for anxiety in mood disorders. 5
• Optimizing sertraline dosing by increasing from 50mg to therapeutic doses (typically 100-200mg daily) for better anxiety control in MDD. 6
• Using quetiapine 25mg orally as needed as a second-line PRN option, though this carries risks of orthostatic hypotension and dizziness. 1

Common Pitfalls to Avoid

• Do not use benzodiazepines as monotherapy for delirium-related agitation, as they may worsen confusion—ensure the extreme anxiety is not actually delirium before prescribing. 1
• Do not prescribe long-acting benzodiazepines (such as diazepam or clonazepam) in this context, as they accumulate and cause prolonged sedation. 1
• Do not combine lorazepam with other sedatives beyond what is already prescribed, as this significantly increases respiratory depression risk. 3
• Avoid writing open-ended prescriptions—specify maximum daily doses and duration of therapy on the prescription. 3