Does Hydroxyzine interact with Zoloft? (3+ side effects)

In this article, we will discuss the interactions between Zoloft and Hydroxyzine. We will also discuss what side effects one may experience by combining these two medications and what are the alternatives to Hydroxyzine while taking Zoloft.

Does Hydroxyzine interact with Zoloft?

Yes, Hydroxyzine does interact with Zoloft in terms of side effects. Hydroxyzine is a first-generation antihistamine which is sedative in nature. Sertraline (Zoloft), on the other hand, is one of the most commonly prescribed antidepressants. It is not suitable to take Hydroxyzine and Zoloft together because of the potential health risks.

Hydroxyzine, a piperazine derivative, is sometimes used to treat anxiety. Because of drowsiness and sedative effects, it is often used as a short-term solution for anxiety or insomnia (1).

It is important to note that individuals respond differently to antidepressants. Therefore, individuals who experience sedation as a side effect of Zoloft are more vulnerable to increased dizziness and drowsiness when combining Hydroxyzine with Zoloft.

What are the potential risks of taking Hydroxyzine and Zoloft together?

Combined use of Hydroxyzine and Zoloft can increase the risk of certain side effects, primarily related to central nervous system (CNS) depression. Since both these medications can cause dizziness and sedation, their combined use can intensify the risk of these side effects.

Additionally combining these medications may also cause dry mouth, difficulty urination, headache and impaired cognitive and motor skills.

There are some common side effects of Zoloft and Hydroxyzine that patients may experience due to drug-patient interaction rather than Zoloft and Hydroxyzine interaction.

Common side effects of Hydroxyzine include (2):

  • Drowsiness
  • Dizziness
  • Dry mouth
  • Blurred vision
  • Constipation
  • Weight gain

Common side effects of Zoloft include (3):

Risk of serotonin syndrome

The risk of serotonin syndrome is generally higher when multiple medications that affect CNS are used together like Zoloft and Hydroxyzine. It is a life-threatening condition characterized by excess serotonin in the brain resulting in symptoms such as agitation, confusion, muscle rigidity and high blood pressure.

If you experience any of such symptoms while taking Zoloft and Hydroxyzine together, reach out to your healthcare provider.

What are the potential benefits of taking Zoloft and Hydroxyzine together?

Patients experiencing insomnia due to Zoloft may find relief by using Hydroxyzine, for allergy symptoms, as its sedative effects could potentially counter the sleep disturbances leading to improved sleep quality.

However, you should always discuss such drug combinations with your doctor before you start taking them. People are different and they can have different factors affecting their health.

What to do if you have taken Hydroxyzine and Zoloft together? 

If you have taken the two medications together once or twice, it will most likely not harm you. The concomitant use of these medications for a long time can produce side effects related to central nervous system depression.

If you experience severe side effects or any other concerning symptoms while taking these medications together, contact your healthcare provider immediately. They may adjust the dosages or recommend alternative treatments if necessary. Always report any side effects to your healthcare provider to ensure safety and well-being during treatment.

If you are struggling to fall asleep, especially during the early course of treatment with Zoloft, talk to your healthcare provider if it is safe for you to take Hydroxyzine for sleep.

Alternatives to Hydroxyzine while taking Zoloft

If you are taking Zoloft for depression and need an alternative to Hydroxyzine for allergy relief, there are alternative medications you may consider having fewer side effects. They include:

Second-generation antihistamines: Use second-generation antihistamines like Claritin (Loratadine) and Zyrtec (Cetirizine) as they are considered safer options to manage allergy symptoms without causing significant drowsiness (4).

Saline nasal rinses: Using saline solution for nasal irrigation can help relieve congestion and nasal irritation without any drug interactions.

Natural remedies: Some people find relief from allergy symptoms with natural remedies like local honey and steam inhalation.


Individuals undergoing dual therapy with Hydroxyzie and Zoloft should establish a routine of periodic check-ups and communicate with their healthcare provider. They may suggest alternative treatments or medications if there is a concern about interactions.

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