What medication regimen is recommended for a patient with irritability, agitation, and low mood?

Medication Management for Irritability, Agitation, and Low Mood

For a patient presenting with irritability, agitation, and low mood, initiate an SSRI (sertraline 25-50 mg/day or citalopram 10 mg/day) as first-line pharmacological treatment, reserving antipsychotics only for severe, dangerous agitation after behavioral interventions have failed. 1, 2

Initial Assessment: Rule Out Reversible Medical Causes

Before prescribing any psychotropic medication, systematically investigate and treat:

• Infections: urinary tract infections, pneumonia, and other occult sources that commonly precipitate behavioral symptoms 1, 2
• Metabolic disturbances: hypoxia, dehydration, electrolyte abnormalities, hyperglycemia 1, 2
• Pain: a major contributor to behavioral disturbances in patients who cannot verbally communicate discomfort 2
• Constipation and urinary retention: both significantly contribute to restlessness and agitation 1, 2
• Medication review: identify and discontinue anticholinergic agents (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen confusion and agitation 1, 2

Non-Pharmacological Interventions (Mandatory First-Line)

Implement these strategies before any medication:

• Environmental modifications: ensure adequate lighting, reduce excessive noise, provide predictable daily routines 1, 2
• Communication strategies: use calm tones, simple one-step commands, gentle touch for reassurance, allow adequate processing time 1, 2
• Activity-based interventions: at least 30 minutes of daily sunlight exposure, increased supervised physical and social activities 2
• Caregiver education: explain that behaviors are symptoms of the underlying condition, not intentional actions 2

Pharmacological Treatment Algorithm

For Chronic Irritability, Agitation, and Low Mood (First-Line)

SSRIs are the preferred first-line pharmacological option because they significantly reduce overall neuropsychiatric symptoms, agitation, and depression 2:

• Sertraline: start 25-50 mg/day, maximum 200 mg/day 1, 2

  • Well tolerated with minimal drug interactions 2
  • Less effect on metabolism of other medications 1

• Citalopram: start 10 mg/day, maximum 40 mg/day 1, 2

  • Well tolerated though some patients experience nausea and sleep disturbances 1

Dosing principles: Begin with 50% of the adult starting dose in elderly patients, titrate slowly using increments of the initial dose every 5-7 days, allow 4-8 weeks for full therapeutic trial 2

Monitoring: Assess response within 4 weeks using quantitative measures (Cohen-Mansfield Agitation Inventory or NPI-Q); if no clinically significant response after 4 weeks at adequate dose, taper and withdraw 1, 2

For Severe Agitation with Imminent Risk of Harm (Second-Line)

Antipsychotics should only be used when:

• Patient is severely agitated, distressed, or threatening substantial harm to self or others 1, 2
• Behavioral interventions have been thoroughly attempted and documented as insufficient 1, 2
• Emergency situations with imminent risk of harm 2

Acute severe agitation:

• Haloperidol 0.5-1 mg orally or subcutaneously, maximum 5 mg/day in elderly patients 1, 2
  • Preferred over benzodiazepines except for alcohol/benzodiazepine withdrawal 1
  • Has the largest evidence base with 20 double-blind studies since 1973 1

Chronic severe agitation with psychotic features:

• Risperidone: start 0.25 mg once daily at bedtime, target 0.5-1.25 mg daily 1, 2

  • Extrapyramidal symptoms increase significantly above 2 mg/day 1, 2

• Quetiapine: start 12.5 mg twice daily, maximum 200 mg twice daily 1, 2

  • More sedating with risk of orthostatic hypotension 2

Critical Safety Warnings

All antipsychotics increase mortality risk 1.6-1.7 times higher than placebo in elderly patients with dementia 2. Before initiating any antipsychotic, discuss with the patient (if feasible) and surrogate decision maker:

• Increased mortality risk 2
• Cardiovascular effects: QT prolongation, dysrhythmias, sudden death, hypotension 1, 2
• Falls risk 2
• Metabolic changes 2
• Extrapyramidal symptoms 1, 2

Use the lowest effective dose for the shortest possible duration, with daily in-person evaluation and attempt to taper within 3-6 months 2

What NOT to Use

Avoid benzodiazepines as first-line treatment for agitation (except alcohol/benzodiazepine withdrawal) because they:

• Increase delirium incidence and duration 1, 2
• Cause paradoxical agitation in approximately 10% of elderly patients 1, 2
• Risk tolerance, addiction, cognitive impairment, respiratory depression 1, 2

Avoid typical antipsychotics (haloperidol, fluphenazine, thiothixene) as first-line therapy due to 50% risk of tardive dyskinesia after 2 years of continuous use in elderly patients 1, 2

Common Pitfalls to Avoid

• Do not add medications without first treating reversible medical causes (pain, infection, metabolic disturbances) 2
• Do not continue antipsychotics indefinitely; review need at every visit and taper if no longer indicated 2
• Do not use antipsychotics for mild agitation or behaviors like unfriendliness, poor self-care, repetitive questioning, or wandering—these are unlikely to respond to psychotropics 2
• Do not combine high-dose benzodiazepines with antipsychotics due to risk of fatal respiratory depression 3