Can hydroxyzine (an antihistamine) cause depression, particularly in individuals with a history of mood disorders?

Does Hydroxyzine Cause Depression?

Hydroxyzine does not directly cause depression as a primary adverse effect, but it can produce CNS depressant effects including drowsiness, cognitive impairment, and paradoxical CNS stimulation that may be confused with or exacerbate mood symptoms in vulnerable individuals.

Primary CNS Effects of Hydroxyzine

The FDA label and clinical guidelines identify the following CNS effects of hydroxyzine that are distinct from depression 1, 2:

• Drowsiness and sedation occur in many patients, with performance impairment that can exist without subjective awareness 2
• Cognitive deficits including decreased alertness, impaired concentration, and reduced work performance 2
• Paradoxical CNS stimulation may occur, particularly in children, manifesting as irritability or hyperactivity rather than depression 2
• Confusion and oversedation especially in elderly patients 1

Depression vs. CNS Depression: Important Distinction

The term "CNS depressant" refers to hydroxyzine's sedating pharmacological effects, not psychiatric depression 1. The FDA label emphasizes that hydroxyzine potentiates other CNS depressants (narcotics, barbiturates, alcohol), requiring dose reduction when used concomitantly 1.

Considerations in Patients with Mood Disorders

While hydroxyzine is not contraindicated in depression, several clinical considerations apply:

• Stimulant guidelines note that medications can produce dysphoria in vulnerable patients, and caution is warranted when prescribing sedating agents to patients with unstable mood disorders 3
• Sedation may mimic or worsen depressive symptoms through decreased energy, motivation, and cognitive function, particularly in patients already experiencing these symptoms 2
• Elderly patients are at higher risk for confusion and cognitive impairment that could be misinterpreted as worsening depression 1

Clinical Evidence on Anxiety Treatment

Research demonstrates hydroxyzine's efficacy in generalized anxiety disorder without reports of inducing depression 4, 5, 6:

• Hydroxyzine 50 mg/day showed significant anxiolytic effects from week one through four weeks without rebound anxiety or withdrawal symptoms upon discontinuation 5
• The most common side effect was transient sleepiness (28% vs 14% placebo), not depression 5
• Hydroxyzine demonstrated cognitive improvement in anxiety treatment, suggesting it does not impair mood when used appropriately 6

High-Risk Scenarios to Monitor

Be vigilant for mood changes in these situations:

• Patients with pre-existing depression taking hydroxyzine may experience worsening fatigue and apathy due to sedation, which could be mistaken for depression progression 2, 1
• Concurrent use with other CNS depressants (antidepressants, benzodiazepines, alcohol) significantly enhances sedation and cognitive impairment 1, 2
• Elderly patients are more sensitive to psychomotor impairment and confusion, which may present as pseudo-dementia or depressive symptoms 1
• Neonatal withdrawal from maternal hydroxyzine use includes irritability and hyperactivity, not depression 2

Practical Management Algorithm

When prescribing hydroxyzine to patients with mood concerns:

1. Start with low doses (10-25 mg) rather than standard 50 mg, especially in elderly or those with mood disorders 7, 1
2. Use bedtime dosing to minimize daytime sedation that could be confused with depressive symptoms 7
3. Monitor for excessive sedation that persists beyond the first week, as this may impact mood and function 5
4. Avoid combining with other sedating medications including antidepressants with sedating properties 1, 8
5. Reassess if mood symptoms worsen, distinguishing between medication-induced sedation and true depression progression 3

Common Pitfall to Avoid

Do not confuse hydroxyzine's sedating "CNS depressant" effects with psychiatric depression. The drowsiness, decreased alertness, and cognitive slowing from hydroxyzine are pharmacological effects, not mood disorder symptoms, though they may overlap phenomenologically and require clinical judgment to distinguish 2, 1.