What is the next best treatment for a patient with increased anxiety who is currently taking hydroxyzine (antihistamine) four times a day?

Next Best Treatment for Inadequately Controlled Anxiety on Hydroxyzine

For a 30-year-old female with inadequately controlled anxiety despite taking hydroxyzine four times daily, transition to an SSRI (selective serotonin reuptake inhibitor) as first-line pharmacotherapy, as SSRIs are the guideline-recommended treatment for generalized anxiety disorder while hydroxyzine lacks strong evidence as a reliable first-line agent. 1, 2

Why Transition Away from Hydroxyzine

• Hydroxyzine is not recommended as a reliable first-line treatment for generalized anxiety disorder due to high risk of bias in supporting studies, small sample sizes, and limited evidence base 2
• While hydroxyzine showed superiority over placebo in some trials, the Cochrane review concluded it cannot be recommended as first-line therapy despite its historical use 2
• The fact that she requires four-times-daily dosing suggests inadequate symptom control and the need for a more effective maintenance treatment 2, 3

Recommended First-Line Pharmacotherapy

SSRIs should be initiated as the primary treatment:

• SSRIs are the guideline-recommended first-line pharmacotherapy for anxiety disorders in adults, with strong evidence supporting their efficacy 1
• The Japanese Society of Anxiety and Related Disorders/Japanese Society of Neuropsychopharmacology specifically recommends SSRIs as first-line treatment (GRADE 2C recommendation) 1
• SSRIs provide sustained anxiolytic effects without the tolerance, dependence, or sedation issues associated with antihistamines 3, 4

Practical Implementation Strategy

Start with a low "test dose" and titrate gradually:

• Begin with a subtherapeutic dose to minimize initial anxiety or agitation, which can be an early adverse effect of SSRIs 1
• Increase the dose in small increments at 1-2 week intervals for shorter half-life SSRIs (sertraline, citalopram) or 3-4 week intervals for longer half-life SSRIs (fluoxetine) 1
• Continue titration until optimal benefit-to-harm ratio is achieved and remission occurs 1

During the transition period:

• Hydroxyzine can be continued temporarily while initiating the SSRI, as SSRIs typically require 2-4 weeks to demonstrate anxiolytic effects 2, 5
• Gradually taper hydroxyzine once the SSRI reaches therapeutic effect to avoid abrupt discontinuation 5

Alternative Pharmacotherapy Options

If SSRIs are contraindicated or not tolerated:

• Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine are recommended as an alternative first-line option 1
• SNRIs have demonstrated efficacy comparable to SSRIs for anxiety disorders 1

Important Caveats and Monitoring

Watch for discontinuation syndrome with shorter-acting SSRIs:

• Paroxetine, fluvoxamine, and sertraline can cause withdrawal symptoms (vertigo, sensory disturbances, paresthesias, anxiety, irritability, agitation) if doses are missed or abruptly discontinued 1
• This makes adherence counseling particularly important 1

Consider combination therapy if monotherapy fails:

• While the evidence is primarily in pediatric populations, combination treatment with CBT plus an SSRI showed superior outcomes compared to either treatment alone 1
• This approach may be considered for adults with severe or treatment-resistant anxiety 1

Avoid benzodiazepines as routine next-step:

• Although benzodiazepines like lorazepam are mentioned in some guidelines for acute anxiety management 6, 7, they carry risks of dependence and tolerance that make them inappropriate for chronic anxiety management in a young adult 3, 4
• Reserve benzodiazepines only for acute exacerbations or bridging therapy during SSRI initiation 3