What is the treatment for psychomotor agitation without depression?

Treatment of Psychomotor Agitation Without Depression

For psychomotor agitation without depression, SSRIs are first-line pharmacologic treatment for chronic mild-to-moderate agitation, while benzodiazepines (lorazepam 2-4 mg) combined with antipsychotics (haloperidol 5 mg or ziprasidone 20 mg IM) are preferred for acute severe agitation requiring immediate control. 1, 2, 3

Acute Severe Agitation (Immediate Control Needed)

First-Line Approach

• Always attempt verbal de-escalation first when there is no immediate danger to patient or others 2, 4
• Combination therapy is superior to monotherapy: Lorazepam 2-4 mg plus haloperidol 5 mg IM demonstrates higher improvement rates than either agent alone, with lower extrapyramidal side effects 3
• Alternative combination: Lorazepam 2-4 mg plus ziprasidone 20 mg IM is highly effective with notably absent movement disorders and decreases restraint time 3

Critical Pre-Treatment Assessment

• Rule out anticholinergic or sympathomimetic drug ingestions first, as antipsychotics can paradoxically worsen agitation in these scenarios 3
• Check capillary glucose immediately, as hypoglycemia is rapidly reversible and potentially fatal 2
• Obtain vital signs to identify fever, tachycardia, hypertension, or respiratory compromise indicating specific etiologies 2

Monotherapy Options (When Combination Not Feasible)

• For non-psychotic agitation: Lorazepam 0.05-0.1 mg/kg PO/IM/IV is preferred 2
• For psychotic agitation: Haloperidol 5-10 mg IM or olanzapine 10 mg IM 2, 5
• Ziprasidone 20 mg IM shows significant calming effects emerging 30 minutes after administration 6, 7

Contraindications to Avoid

• Benzodiazepines are contraindicated in patients with respiratory compromise or significant CNS depression 2
• Antipsychotics are contraindicated in delirium or anticholinergic intoxication, and use with extreme caution in elderly patients with dementia 2
• Ziprasidone should not be used in patients with known QTc interval-associated conditions 6

Chronic Mild-to-Moderate Agitation (Non-Acute Setting)

First-Line Pharmacologic Treatment

• SSRIs are considered first-line treatments for agitation, as serotonergic antidepressants significantly improved overall neuropsychiatric symptoms, agitation, and depression in individuals with vascular cognitive impairment, both with and without major depressive disorder at baseline 1
• SSRIs as a class significantly reduce overall neuropsychiatric symptoms, while non-SSRIs did not, though both drug classes reduced agitation 1

Alternative Pharmacologic Options

• Trazodone is useful for chronic mild-to-moderate agitation, particularly when insomnia is present, as it addresses both agitation and sleep disturbances 8
• Trazodone should NOT be used for acute severe agitation requiring immediate control due to delayed onset of action 8
• Use trazodone with extreme caution in patients with premature ventricular contractions or cardiovascular disease 8

Non-Pharmacologic Interventions (Dementia-Related Agitation)

• Simulated presence therapy using audio/video recordings of positive past experiences can reduce agitation in severe dementia 1
• Massage therapy, animal-assisted interventions, and personally tailored interventions have been shown to help agitation 1

Special Population: Dementia-Related Agitation

Antipsychotic Use (Last Resort Only)

• Both typical and atypical antipsychotics can reduce agitation in Alzheimer's disease or vascular dementia with neuropsychiatric symptoms 1
• Antipsychotics should be used with extreme caution because they increase the risk of death, probably from cardiac toxicities 1
• Trazodone is positioned as an alternative to antipsychotics for severe agitated, repetitive, and combative behaviors, particularly when antipsychotics are not tolerated or contraindicated 8

Critical Pitfalls to Avoid

• Never use trazodone for acute agitation—onset is too slow; use benzodiazepines or antipsychotics instead 8, 2
• Never use benzodiazepines for chronic agitation due to risk of paradoxical rage reactions and dependence 3
• Never use trazodone or any antidepressant alone in bipolar patients without mood stabilizer coverage, as antidepressants can destabilize mood or trigger manic episodes 8
• Do not use antipsychotics in anticholinergic toxicity—they will worsen agitation 3

Monitoring After Acute Treatment

• Monitor vital signs, level of sedation, and respiratory status closely after medication administration 2
• Evaluate orthostatic hypotension before subsequent doses of olanzapine IM 2
• Patients over 50 years may experience deeper and more prolonged sedation with lorazepam 2
• Transition to oral formulation of the same agent once acute agitation diminishes 6, 7