Can hydroxyzine (an antihistamine) cause suicidal ideation?

Hydroxyzine and Suicidal Ideation Risk

Hydroxyzine is not specifically associated with suicidal ideation as a direct side effect, unlike some other medications such as SSRIs that carry black box warnings for this risk.

Mechanism and Risk Profile

Hydroxyzine is an antihistamine with anxiolytic properties that works primarily through H1 receptor antagonism and has additional anticholinergic effects. Unlike medications that directly affect serotonin or other neurotransmitter systems implicated in suicidal behavior, hydroxyzine's mechanism of action doesn't typically lead to suicidal ideation.

The available guidelines and evidence do not specifically identify hydroxyzine as a medication that increases suicidal ideation risk:

• Major psychiatric guidelines focus on SSRIs, benzodiazepines, and certain other medications when discussing medication-induced suicidal ideation 1
• The 2019 VA/DoD guidelines on suicide risk management do not list hydroxyzine among medications associated with increased suicide risk 1
• The 2024 updated VA/DoD guidelines similarly do not mention hydroxyzine as a medication of concern for suicidal ideation 1

Medication Classes Associated with Suicidal Risk

Several medication classes have been associated with increased risk of suicidal ideation:

• SSRIs and other antidepressants carry FDA black box warnings for increased suicidal ideation risk, particularly in children, adolescents, and young adults 1
• Benzodiazepines may cause disinhibition in some individuals, potentially leading to increased suicidal behavior 1
• Phenobarbital and certain other medications that reduce self-control have been associated with increased suicide risk 1

Safety Profile of Hydroxyzine

Hydroxyzine's side effect profile primarily includes:

• Sedation/drowsiness (most common)
• Dry mouth
• Weight gain
• Concentration difficulties

In clinical trials for anxiety, hydroxyzine has demonstrated efficacy without significant reports of suicidal ideation 2, 3. While there is a case report involving hydroxyzine in a suicide case 4, this involved multiple drugs (primarily barbiturates) and doesn't establish hydroxyzine as the causative agent for suicidal behavior.

Monitoring Recommendations

While hydroxyzine itself is not specifically associated with suicidal ideation, prudent clinical practice suggests:

1. Assess baseline suicide risk before starting any psychoactive medication
2. Monitor for any unusual changes in mood, behavior, or thinking during treatment
3. Be particularly vigilant when treating patients with pre-existing risk factors for suicide
4. Consider the patient's overall medication regimen, as drug interactions could potentially affect mental status

Clinical Implications

When choosing between hydroxyzine and other anxiolytics:

• Hydroxyzine may be preferable to benzodiazepines in patients at risk for suicide, as benzodiazepines have been associated with disinhibition and potential increased suicide risk 1
• For patients requiring treatment for both anxiety and depression, an SSRI might be indicated despite the suicidality warning, but would require closer monitoring than hydroxyzine 1

In summary, while all medications should be used cautiously in patients with suicidal risk factors, hydroxyzine does not appear to carry a specific risk for inducing suicidal ideation based on current evidence and guidelines.