Hydroxyzine for Patients with Anxiety and/or Anxiety with Comorbid Insomnia 7/23/2020

Although hydroxyzine is by no means considered to be a first line medication in treating anxiety symptoms, it has great potential to be of benefit for many patients who suffer with persistent anxiety.

While not a cure all, there can be many benefits in using hydroxyzine, a medicine that has been around for sixty years! It often can be helpful for patients with crippling symptoms of anxiety, is affordable, and has a low risk of abuse/diversion/dependence. Hydroxyzine has a low propensity of toxicity and it has a fast onset of action compared to SSRI medications.

With a unique mechanism of action hydroxyzine targets anxiety without serotonin reuptake inhibition and without effect on GABA. It also does not have the muscarinic anticholinergic side effects that most anti histamines since those receptors aren’t impacted significantly.

Biochemically, most of hydroxyzine’s anxiolytic effect is by reverse antagonism of H1, histamine receptors. The molecule has a favorable effect on serotonin levels. Like trazodone, another medication that has been around for decades, it has 5HT2A antagonistic effects that increase drowsiness and may for many, improve the quality of sleep that results. To a far smaller degree this medicine can promote physical relaxation by affecting both dopamine and norepinephrine. If used as an adjunct to an SSRI, it might therefore magnify the therapeutic effect on these monoamines in reduction of anxiety.

With those anxious patients who prove refractory to all SSRI medication trials or those who cannot tolerate them even at miniscule doses, hydroxyzine may be an appropriate therapeutic choice. This medicine may be offered as an adjunct to ongoing treatment regimens of an SSRI, most typically with a PRN recommendation to aid with peaks times or anxiety but if effective in that context, switching to a standing regular administration regimen may be quite appropriate and helpful.

In contrast to SSRI medications and benzodiazepines, the discontinuation of this antihistamine is typically not difficult for patients in terms of withdrawal symptoms as discontinuation is not associated with rebound anxiety reactions. In fact, some studies have shown that the anxiolytic effects of hydroxyzine may linger after discontinuation. In this context, use of hydroxyzine availability as an alternate to prescribing a benzodiazepine has obvious desirability, particularly in the context of avoiding medication dependence or risk of misuse and diversion.

Untoward effects of hydroxyzine are typically minor but may include the drowsiness, fatigue and cognitive impairment that is characteristic of antihistamines. In order to reduce those dose related side effects, the dose could be lowered but then it may come at the cost of losing its anxiolytic efficacy. More significant side effect issues are unusual but use of hydroxyzine in pregnant patients is discouraged and it should be used with caution with individuals with serious cardiac concerns as it may contribute to QT interval prolongation if used in higher dosing ranges. Care should be used with patients with glaucoma and unstable seizure disorders.

Unfortunately some individuals report tolerance to this medicine which is a drawback for prescribers, who may find themselves prescribing at the maximum daily dose with diminishing returns.
Dosing guideline are as follows: for children (10-25mg per dose with max daily dose of 50-100mg); for adults 25-50mg with maximum daily dose of 250-300mg with careful monitoring suggested at the higher dose ranges. Attention to potential drug-drug interactions is recommended.

1. Mental Health Daily.com/2016/01/04/hydroxyzine-vistaril-atarax-for anxiety-disorders/
2. www.ncbi.nlm.nih.gov/pubmed/23616706
3. www.ncbi.nlm.nih.gov/pubmed/9035982
4. www.ncbi.nlm.nih.gov/pubmed/7875114

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