Is hydroxyzine (an antihistamine) effective for treating anxiety symptoms in post-traumatic stress disorder (PTSD)?

Hydroxyzine for Anxiety Symptoms in PTSD

Hydroxyzine is not recommended as a first-line treatment for anxiety symptoms in post-traumatic stress disorder (PTSD) due to lack of specific evidence supporting its efficacy for this indication. 1

Evidence for Hydroxyzine in Anxiety Disorders

• Hydroxyzine is FDA-approved for "symptomatic relief of anxiety and tension associated with psychoneurosis," but its effectiveness for long-term use (beyond 4 months) has not been assessed by systematic clinical studies 1
• While hydroxyzine has shown efficacy in generalized anxiety disorder (GAD) compared to placebo in several studies, the evidence has significant limitations including high risk of bias, small sample sizes, and short duration 2
• Hydroxyzine at 50 mg/day has demonstrated anxiolytic effects beginning in the first week of treatment for GAD, with effects maintained throughout 4-week treatment periods 3, 4

PTSD-Specific Treatment Recommendations

• First-line pharmacological treatments for PTSD are selective serotonin reuptake inhibitors (SSRIs), specifically sertraline and paroxetine, which are FDA-approved for PTSD 5
• Cognitive behavioral therapy (CBT), particularly prolonged exposure therapy, is recommended as a first-line psychological treatment for PTSD 6
• WHO guidelines do not recommend benzodiazepines for PTSD, and evidence suggests they may actually worsen PTSD outcomes 6
• Contrary to expectations, one small study found that 63% of participants receiving benzodiazepines (clonazepam or alprazolam) met criteria for PTSD at 6 months post-trauma compared to only 23% in the placebo group 6

Limited Evidence for Hydroxyzine in PTSD

• There is a notable absence of controlled clinical trials specifically examining hydroxyzine for PTSD 5, 2
• One case report described using hydroxyzine in combination with ziprasidone and propranolol for acute PTSD exacerbation with panic, suicidality, and agitation, but this represents very low-quality evidence 7
• The authors of this case report noted that an extensive literature search did not reveal any use of this combination for PTSD, and there were few studies about each medication individually for PTSD 7

Treatment Algorithm for Anxiety in PTSD

1. First-line treatments:

   • SSRIs (sertraline or paroxetine) for pharmacological management 5
   • Cognitive behavioral therapy, particularly prolonged exposure therapy 6

2. Second-line treatments:

   • Serotonin-potentiating non-SSRIs (venlafaxine, nefazodone, trazodone, mirtazapine) 5

3. Third-line treatments:

   • Tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) 5

4. Adjunctive treatments:

   • Atypical antipsychotics may be considered where paranoia or flashbacks are prominent 5
   • Anticonvulsants may be considered where impulsivity and anger predominate 5

Important Caveats

• Hydroxyzine's most common side effect is transient sleepiness/drowsiness (28% vs. 14% with placebo), which may limit its utility in PTSD patients 4
• Benzodiazepines should be avoided in PTSD due to potential depressogenic effects and the possibility they may promote or worsen PTSD 5, 6
• If hydroxyzine is used in PTSD, it should be considered as a short-term adjunctive treatment for acute anxiety symptoms rather than as a primary treatment for the disorder itself 1, 7