Investigating the Link: Can Restasis Cause Migraines?

October 9, 2025 •

4 min read

Studies show that people with migraine headaches may have at least a 20% higher chance of having dry eye disease [1.4.1]. This raises the question for many: can Restasis cause migraines, or is there a different connection at play?

Quick Summary

While headache is listed as a less common side effect of Restasis, the connection to migraines is complex. The underlying dry eye condition itself is strongly associated with migraines due to shared inflammatory pathways.

Key Points

Headache as a Side Effect: Headache is listed as a less common side effect of Restasis (cyclosporine ophthalmic), though it was not reported in some major clinical trials [1.2.3, 1.3.4, 1.5.2].
Dry Eye and Migraine Link: There is a strong, scientifically documented association between dry eye disease and migraines, with migraine sufferers having a higher risk of dry eye [1.4.1].
Shared Pathways: Dry eye and migraines may share common underlying mechanisms, including inflammation and activation of the trigeminal nerve, which can cause facial and head pain [1.4.2, 1.4.5].
Most Common Side Effect: The most frequently reported side effect of Restasis is a temporary burning sensation in the eyes, affecting about 17% of users [1.3.7].
Alternative Medications: Other dry eye medications, such as Xiidra and Cequa, also list headache as a potential side effect [1.5.2].
Symptom Confusion: It can be difficult to determine if a headache is a side effect of the medication or a symptom related to the underlying dry eye condition itself [1.4.2].
Consult a Doctor: Patients experiencing new or worsening headaches while using Restasis should consult their healthcare provider before stopping the medication [1.6.3].

Understanding Restasis and Its Purpose

Restasis (cyclosporine ophthalmic emulsion) is a prescription medication designed to treat chronic dry eye, a condition that may be caused by inflammation [1.3.3]. Unlike artificial tears which provide temporary lubrication, Restasis is an immunomodulator that helps to increase the eyes' natural ability to produce tears [1.3.3, 1.2.9]. It works by reducing underlying inflammation that can prevent tear glands from functioning properly [1.2.5]. Patients are typically instructed to instill one drop in each eye twice a day, approximately 12 hours apart [1.3.2]. The therapeutic effects are often not immediate, with noticeable improvement sometimes taking three to six months [1.2.5]. The most common side effect reported in clinical trials is a temporary burning sensation in the eye, experienced by about 17% of users [1.3.7].

The Direct Question: Can Restasis Cause Migraines or Headaches?

The connection between Restasis and headaches is not straightforward. While some sources state that headache is not an expected side effect because very little of the drug reaches the rest of the body, others list it as a less common adverse reaction [1.2.2, 1.2.3]. MedlinePlus and the Mayo Clinic both include headache in their lists of potential side effects of cyclosporine eye drops [1.3.1, 1.3.4]. User-reported data also shows that a small percentage of patients (around 1.3%) mention headaches as a side effect [1.2.1].

It's important to differentiate between a general headache and a migraine. Migraines are a neurological condition often characterized by severe, throbbing head pain, frequently accompanied by symptoms like nausea, vomiting, and extreme sensitivity to light and sound. The official prescribing information for Restasis does not specifically list migraine as a side effect, but reports of "headache" can be found [1.3.7]. Some patients have anecdotally reported experiencing headaches and nausea the day after applying the drops [1.2.1]. However, clinical studies for Restasis did not report headache as a side effect, whereas studies for oral cyclosporine do list severe, throbbing headache as a more common side effect [1.2.2, 1.2.8].

The Dry Eye and Migraine Connection

A more significant factor may be the strong association between the condition Restasis treats—dry eye disease (DED)—and migraines. Several studies have highlighted this link:

Increased Prevalence: Research indicates that people with migraines are more likely to have DED than the general population [1.4.1, 1.4.2]. A large 2018 study found that individuals with migraines had at least a 20% higher odds of also having DED [1.4.1, 1.4.7].
Shared Pathways: Experts theorize that both DED and migraines may involve shared mechanisms, such as inflammation and activation of the trigeminal nerve [1.4.2, 1.4.5]. The trigeminal nerve supplies sensation to the face and eyes, and its overstimulation due to corneal irritation in DED can trigger pain signals that the brain interprets as a headache [1.4.4].
Common Symptoms: Photophobia, or extreme light sensitivity, is a hallmark symptom of both migraines and DED. In DED, an unstable tear film can improperly scatter light entering the eye, causing discomfort that can trigger or worsen a headache [1.4.2].
Symptom Severity: One study noted that migraine attacks in people with DED may be longer and more severe [1.4.5]. Another found that as dry eye symptoms worsen, the negative impact on quality of life for migraine sufferers increases significantly [1.4.6].

Given this strong correlation, it's possible for a person starting Restasis to mistakenly attribute a new or worsening migraine to the medication, when it may actually be related to the underlying dry eye disease itself. In fact, some research suggests that effectively treating DED might help reduce migraine severity [1.4.8].

Comparing Prescription Dry Eye Medications

Restasis is not the only prescription treatment for dry eye. Other common medications include Xiidra and Cequa. While they all aim to treat DED, their side effect profiles differ.


Feature	Restasis (cyclosporine 0.05%)	Xiidra (lifitegrast)	Cequa (cyclosporine 0.09%)
Common Side Effects	Eye burning (most common, ~17%), redness, discharge, watery eyes, eye pain, itching, stinging, blurred vision [1.3.7, 1.5.3]	Eye irritation, unusual taste sensation (dysgeusia), blurred vision [1.5.3]	Instillation site pain (most common, ~22%), conjunctival hyperemia (redness) [1.3.2]
Headache Reported?	Listed as a less common side effect; not reported in some clinical trials [1.2.3, 1.5.2]	Yes, reported in 1-5% of patients in studies [1.2.7]	Yes, can cause headache [1.5.2]
Unique Side Effects	Sensation of something in the eye, stinging [1.5.1]	Unusual taste, sinusitis [1.2.6, 1.5.1]	Swollen eyelid, UTI [1.5.1]

Managing Side Effects and Making Decisions

If you experience headaches or migraines while using Restasis, it's crucial not to stop the medication without consulting a healthcare provider [1.6.3]. An eye doctor can help determine if the symptom is a side effect of the drug, related to the underlying dry eye, or coincidental. They may suggest strategies to manage side effects, such as:

Refrigerating the Drops: Some clinicians suggest that refrigerating Restasis can help reduce the burning sensation upon instillation [1.2.5].
Punctal Occlusion: Gently pressing on the corner of the eye near the nose for about 30 seconds after instilling the drop can help keep the medication in the eye and prevent it from draining into the nasal passages and throat, which may reduce systemic side effects [1.2.5].
Lifestyle Adjustments: Managing environmental factors by using a humidifier, wearing wraparound sunglasses, and taking breaks from digital screens can help alleviate dry eye symptoms that may be contributing to headaches [1.6.1, 1.4.2].

Conclusion

So, can Restasis cause migraines? While headache is a possible but uncommon side effect of Restasis, a direct causal link to migraines is not clearly established in clinical trials [1.2.2, 1.2.3]. The powerful association between dry eye disease and migraines provides a more likely explanation for why a person might experience both conditions [1.4.1, 1.4.3]. The inflammation and nerve activation common to both disorders suggest a complex relationship where one can influence the other [1.4.5]. Patients experiencing headaches while using Restasis should consult their eye doctor and neurologist to explore the cause, discuss management strategies, and determine the best course of treatment for both their dry eyes and their migraines.

For more information from the manufacturer, visit the official Restasis website.

Frequently Asked Questions

No, headache is not a common side effect of Restasis. The most common side effect is a temporary burning sensation in the eye [1.3.7]. Headache is considered a less common adverse reaction [1.2.3, 1.3.4].

Yes, there is a strong link between dry eye disease and migraines. The strain, inflammation, and nerve activation associated with dry eyes can trigger or worsen headaches and migraines [1.4.2, 1.4.4].

You should speak with your eye doctor or primary care physician. They can help determine the cause of the headache and recommend appropriate management strategies. Do not stop taking your prescribed medication without consulting a doctor first [1.6.3].

Yes, both Xiidra and Cequa list headache as a potential side effect. In clinical studies for Xiidra, headache occurred in 1% to 5% of patients [1.2.7, 1.5.2].

Some research suggests that effectively treating dry eye symptoms may lead to a reduction in migraine frequency and severity, though more studies are needed. This is likely due to the shared inflammatory and nerve pathways between the two conditions [1.4.8].

Local side effects like burning or stinging typically occur immediately upon instillation of the drops [1.3.3]. Systemic side effects like headache have been anecdotally reported to occur the day after application, but the timing can vary [1.2.1].

Yes. Because Restasis is an eye drop, very little of the drug is absorbed systemically, so side effects like headache are not expected as frequently [1.2.2]. Oral cyclosporine has a higher rate of systemic side effects, including severe, throbbing headaches [1.2.8].