Treating depression related to lupus is a balancing act. On average, about 30 percent of people with systemic lupus erythematosus (SLE) — the most common type of lupus — have depression. For people who want to treat their depression with an antidepressant, it’s essential to know what other lupus medications they take.

Hydroxychloroquine (HCQ), sold as Plaquenil, is a medication used to treat lupus and other rheumatic diseases. A type of antimalarial drug, HCQ can help relieve pain and inflammation and prevent flares. People living with lupus usually take HCQ for their entire lives. Taking HCQ with other medications is fairly common — and it needs to be done carefully.

Members of MyLupusTeam sometimes discuss the relationship between HCQ and antidepressants. “Recently prescribed Zoloft for bad anxiety and so fearful of taking it. I take Plaquenil as well so I’m worried about the adverse effects or just the effects of Zoloft itself,” wrote one member.

Here are four things to know when considering taking antidepressants along with lupus treatments.

1. Effects of Antidepressants Can Worsen Lupus Symptoms

People living with lupus typically have multiple chronic symptoms. Antidepressants can potentially worsen certain lupus symptoms, such as dry eyes and dry mouth. This effect is especially important to consider in people with Sjögren’s syndrome (dry eye and mouth syndrome). Sjögren’s syndrome commonly occurs along with other autoimmune conditions, like lupus and rheumatoid arthritis.

Though rare, antidepressants can also sometimes worsen feelings of depression and suicidal thoughts. This is more common in early treatment with antidepressants, during a dose change, or in people younger than 25.

(Note: If you or someone you know needs help, you can contact the 988 Suicide & Crisis Lifeline by calling or texting 988 or chatting online.)

2. Some Antidepressants Interact With Hydroxychloroquine

A drug interaction refers to a change in how a drug affects the body when it’s taken with another drug. This reaction may increase or decrease the effects of a drug or lead to additional side effects.

HCQ can interact with antidepressants. According to the National Institutes of Health, the most commonly prescribed antidepressants are:

• Serotonin reuptake inhibitors (SSRIs) including citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) including venlafaxine (Effexor) and duloxetine (Cymbalta)
• Bupropion (Wellbutrin)

SSRIs and SNRIs work by increasing the amount of serotonin and norepinephrine in the brain, which can help improve symptoms of depression, including depressed mood, low energy, and lack of motivation. The way bupropion works is not fully understood, but it does increase norepinephrine and dopamine levels in the brain. Dopamine is another brain chemical that improves mood.

Several of these antidepressants interact with HCQ by decreasing the amount of the drug that’s broken down by the body. Less breakdown means that more HCQ will stay in the blood, causing the drug to have a greater effect or increasing risk of toxicity (side effects).

When taken with HCQ, several antidepressants can increase your risk of abnormal heart rhythm, including escitalopram, fluoxetine, sertraline, and venlafaxine. Bupropion, when taken with HCQ, can increase a person’s seizure risk. Paroxetine can increase your risk for other HCQ side effects.

Common side effects of HCQ include:

• Diarrhea
• Headache
• Nausea
• Stomach pain
• Vomiting

The heart rhythm effects of HCQ taken in combination with antidepressants are serious. The arrhythmia (abnormal heart rhythm) caused by HCQ is called QT prolongation — an abnormal electrical signal between heartbeats that can lead to a life-threatening rapid heartbeat.

Importantly, the body can’t break down the antidepressant sertraline as well when it’s taken with HCQ, increasing the risk for toxicity. Side effects of sertraline include:

• Nausea
• Diarrhea
• Constipation
• Low sex drive
• Trouble sleeping

3. Certain Factors Affect Drug Interactions

Certain factors may increase a person’s risk of drug interactions, including:

• Their age
• The number of drugs they’re taking
• Which other drugs they’re taking
• How they take the medications
• Whether they have a history of drug interactions
• Whether they’re taking medication at high doses
• Other medical conditions they may have

Older people who take several medications and have multiple medical conditions are at the highest risk of experiencing a drug interaction. Having these risk factors increases the likelihood that a person will have difficulty breaking down medications, increasing the risk of side effects. For example, QT prolongation is a more common side effect of HCQ in people with other heart conditions.

The type of medication someone takes can also affect the risk of drug interactions. For example, HCQ commonly interacts with diabetes medications (including insulin and glipizide) and seizure medications (including carbamazepine and phenytoin).

Someone who takes both HCQ and diabetes medication faces a higher risk of side effects if they add an antidepressant to the medication regimen. Combining antidepressants with HCQ can increase your risk of hypoglycemia (low glucose, or blood sugar), which is especially important to know for people who also have diabetes.

To reduce the chance of drug interaction, it’s important to take medications as recommended by a health care professional — specifically a rheumatologist in the case of lupus treatment. Care should be taken with over-the-counter medication and dietary supplement instructions as well.

4. Always Discuss Medication Issues With a Health Care Provider

Anytime you have medication concerns, you should seek medical advice from your rheumatologist. Given the side effects that can develop with antidepressants in combination with HCQ, this treatment plan may not work.

If you want to stop taking an antidepressant, it’s important to talk to a doctor first. They’ll help you with decreasing the medication slowly and safely. Stopping antidepressants suddenly can cause what’s called discontinuation syndrome, which can cause side effects including nausea, dizziness, lethargy (very low energy), and fever. It can also cause severe depressive symptoms, including thoughts of suicide.

This rule applies to treatment of lupus as well. If you or your loved one is thinking of changing lupus medications, talk first with your rheumatologist.

Connect With Others Who Understand

MyLupusTeam is the social network for people with lupus and their loved ones. On MyLupusTeam, more than 223,000 members come together to ask questions, give advice, and share their stories with others who understand life with lupus.

Are you living with lupus and depression? Have you taken antidepressants with hydroxychloroquine? Share your experience in the comments below, or start a conversation by posting on your Activities page.