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6 Types of Drugs That Could Cause Depression

Is your medication messing with your mood? More than 200 medications are linked to depression. Here are some of the most common.


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Medications are supposed to help you feel better, but they also have risks, including depression.

In fact, about a third of Americans are taking a prescription medication that could potentially cause depression or increase suicide risk, according to a study published in the journal JAMA.

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Asim Shah, M.D., executive vice chair of psychiatry and behavioral sciences at the Baylor College of Medicine in Texas, says he sees it often in the emergency room where he works:  

“We have had multiple times when someone comes to us and says, ‘Mr. So-and-so was perfectly fine, and then all of a sudden he or she has changed behavior, is acting isolated and withdrawn, isn’t the same as he used to be.’ When we ask what has happened, we come to find out nothing changed except he started on a specific medicine.” 

In general, older adults are more vulnerable to medication side effects, including depression, says Michael Ziffra, M.D., associate professor in the department of psychiatry at Northwestern Feinberg University School of Medicine.

That’s because as you get older, your body is “slower in eliminating medication from your system, so it can build up and cause problems,” Ziffra explains.   

Older adults are also more likely than younger people to be taking multiple medications — and the same JAMA study found that your risk of depression increases for each drug linked to depression.

It can take weeks or months after you start a new medication for a psychological side effect such as depression to emerge, Shah says.

More than 200 drugs are linked to depression. Here are some of the most common:  

1. Steroids (corticosteroids)

These medications, which ease inflammation, can treat short-term flare-ups like allergies, eczema and poison ivy as well as chronic conditions such as rheumatoid arthritis, lupus and multiple sclerosis. Steroids have a “strong reputation” for causing mood changes, Ziffra says. Prednisone is one of the best-known medications in this class.

One review study in Mayo Clinic Proceedings noted that adverse psychiatric events occurred in about a third of patients who were taking corticosteroids. In the short term, euphoria and hypomania were the most common issues, but the authors said long-term therapy “tends to induce depressive symptoms.”

2. Parkinson’s disease medications

Drugs such as carbidopa and levodopa (Sinemet, Rytary, Duopa) that treat Parkinson’s disease affect the brain’s level of dopamine, which is one of the key chemicals involved in regulation of mood, Ziffra says.

Parkinson’s disease is also linked with depression, due to the biological processes associated with the disease, according to the Parkinson’s Foundation. For some patients, antidepressants can help alleviate symptoms. The foundation recommends discussing treatment options with your doctor.  

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3. Hormone replacement therapy

The estrogen and progestin used in birth control methods such as the pill or patch have long been linked to a higher risk of depression.

Some newer research indicates the same association may exist with hormonal replacement therapy, which is prescribed to help with side effects of menopause, including depression.

A 2022 study published in JAMA Network Open of more than 825,000 Danish women who started hormone replacement therapy found they had a higher risk of developing depression, especially if they started the therapy before age 50. The study found that administering hormone replacement therapy locally – through a vaginal cream, for example – had a lower risk of depression.  

Ziffra notes that some patients find that hormone replacement therapy helps with their depression.

4. Benzodiazepines such as Xanax, Valium and Ativan

Benzodiazepines are sedating medications widely prescribed for anxiety and sleep problems. They are also used for seizures or muscle spasms. You may know them by some of their brand names: Xanax, Valium, Ativan, Klonopin or Restoril.

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Because they depress your central nervous system, benzodiazepines can make you feel sleepy and tired, and they tend to reduce cognitive function – factors that may contribute to depression, Ziffra says. “If you’re sleeping most of the day and you’re not engaging in many activities, that can influence mood,” he says.

In addition to the risk of depression, benzodiazepines can be dangerous for older adults for other reasons, according to the National Institutes of Health. They can impair cognition, mobility and driving skills in older people, and they increase the risk of falls. They are also habit-forming, and long-term use can lead to withdrawal symptoms if they’re discontinued.

5. Anti-seizure medications

Drugs such as Keppra (levetiracetam), Topamax (topiramate) and Dilantin (phenytoin) help control seizures caused by epilepsy and other conditions, but they may also be prescribed for conditions such as anxiety, migraines, bipolar disorder, nerve pain, fibromyalgia and restless leg syndrome.  

In 2008, the FDA issued a warning for all types of anti-seizure drugs after a meta-analysis found that they increased the risk of suicidal behavior.

In the years since, questions have been raised about whether all anti-seizure drugs carry an increased risk, and at least one analysis of studies of newer anti-seizure medications did not find a link.  

Ziffra says anti-seizure medications are “very diverse,” and different drugs may either elevate or depress your mood. While no one can predict with certainty how a medicine will affect an individual, the Epilepsy Foundation lists some of the drugs most commonly associated with improved mood, and those linked to worse depression.

6.  Opioids and some other pain medications

Even though opioids are highly addictive, physicians still prescribe them to help patients get through pain from surgery or a traumatic injury, or for painful conditions such as back ailments, sickle cell disease, cancer or rheumatoid arthritis. If you use them for too long, research indicates you may be at an increased risk of depression. 

One study of more than 100,000 patients published in the Annals of Family Medicine found that 1 out of 10 who used the medication for more than a month developed new-onset depression. The researchers speculated that opioids cause changes in the brain regions associated with reward and pleasure, leading to depression.  

Other pain medicines – including over-the-counter drugs such as acetaminophen (Tylenol) and ibuprofen (sold as Advil, Motrin, and Aleve) – also have been linked to depressive side effects with long-term use.

Signs of depression

Talk to your doctor if you have any of the following symptoms of depression. Make sure you mention any medications you started in the past few months. 

  • Feeling sad or anxious often or all the time.
  • Not wanting to do activities that used to be fun.
  • Feeling irritable‚ easily frustrated or restless.
  • Having trouble falling asleep or staying asleep.
  • Waking up too early or sleeping too much.
  • Eating more or less than usual or having no appetite.
  • Experiencing aches, pains, headaches or stomach problems that do not improve with treatment.
  • Having trouble concentrating, remembering details or making decisions.
  • Feeling tired‚ even after sleeping well.
  • Feeling guilty, worthless or helpless.
  • Thinking about suicide or hurting yourself.

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