Medications are designed to improve health and ease symptoms—but sometimes, they come with unexpected side effects. One particularly serious yet overlooked side effect is depression, which can occur even in people without a history of mental illness.
Depression can happen to anyone, regardless of family background. You don't need a genetic predisposition for medications to affect your mood or mental state. Some people may experience depressive symptoms only while taking certain drugs, with symptoms disappearing once the medication is discontinued. However, you should never stop a medication without speaking to a healthcare provider. Here's what to know about medications commonly linked to depression, and what to do if you start noticing symptoms.
What the Research Says
Both patients and healthcare providers may not always be aware that certain medications can contribute to depression. Research has shown that over a third of adults take at least one prescription drug that lists depression or suicidal thoughts as a possible side effect.
These medications—ranging from antibiotics, birth control, heart medications, and more—are often prescribed for conditions completely unrelated to mental health. Some may influence brain chemicals like dopamine and serotonin, both of which play key roles in regulating mood.
The risk increases when people take multiple medications at once. Studies show that 15% of adults using three or more medications with mood-related side effects reported depression, compared to 5% of people not using any such medications. These patterns persisted even after removing people already being treated for depression or anxiety.
1. Antibiotics
Certain antibiotics, especially levofloxacin and ciprofloxacin (from the fluoroquinolone class), have been associated with depression. Even penicillin has been linked to increased risk, especially after repeated use.
One theory is that antibiotics disrupt the balance of gut bacteria, which may affect brain function and mood, since the gut and brain are closely connected. This highlights the importance of using antibiotics only when absolutely necessary—not just to avoid side effects, but also to help prevent antibiotic resistance.
2. Anticonvulsants
Medications like topiramate and gabapentin—used to treat seizures, nerve pain, and sometimes bipolar disorder—may also be linked to depression. These drugs depress the central nervous system, which may influence mood regulation.
Other CNS depressants, such as benzodiazepines (like Xanax and Valium), may carry similar risks. Fortunately, these symptoms often resolve after discontinuing the medication, and other treatment options are typically available.
3. Beta-Blockers
Commonly used for high blood pressure, chest pain, or irregular heartbeat, beta-blockers like metoprolol and propranolol have long been suspected of contributing to depression.
While recent research has found no direct link, side effects like insomnia and sleep disturbances are common with beta-blockers, and these issues are known contributors to depression. Luckily, newer alternatives may be available that don’t have the same mental health risks.
4. Corticosteroids
Drugs like prednisone, prescribed for asthma, autoimmune conditions, allergies, and even cancer, are known to potentially affect mental health.
Short-term use may lead to mood swings or euphoria, but with long-term use, depression is more likely—even at low doses. If you're concerned about mental side effects while on corticosteroids, consult your provider to weigh risks and explore other options.
5. Heartburn Medications
Drugs like proton pump inhibitors (PPIs)—including omeprazole (Prilosec) and esomeprazole (Nexium)—can reduce your body’s ability to absorb vitamin B12, which plays a key role in mood and cognitive function.
Though depression is not a common side effect, some studies suggest a possible connection with long-term use. Over-the-counter antacids are generally safe but should still be used carefully if taken frequently or in large doses.
6. Hormonal Birth Control
Hormonal contraceptives can cause hormonal shifts, such as lowering testosterone or increasing progesterone, that may contribute to mood changes or depression in some individuals.
However, the effect isn’t universal. Some people don’t experience any mood changes, and others actually report improved mental well-being with birth control. In fact, some studies suggest hormonal birth control may protect against depression later in life by stabilizing hormone levels.
7. Interferon
Interferon, used to treat some cancers and viral infections like hepatitis C, carries a well-documented risk of depression. While it's no longer the standard treatment for hepatitis C, it may still be used in other conditions.
Doctors may recommend starting antidepressants before interferon treatment to reduce the risk of mood-related side effects if interferon is necessary.
8. Opioids
These powerful painkillers are linked to a significant risk of depression—especially with long-term use. A large percentage of people with opioid use disorder (OUD) also experience mental health challenges, including depression.
Extended use of opioids may affect brain chemistry, potentially contributing to treatment-resistant depression.
9. Lipid-Lowering Drugs
Statins, used to lower cholesterol, have produced mixed findings when it comes to depression. Some evidence suggests a potential connection due to impacts on serotonin levels, while other studies have found no increased risk—or even reported benefits for mood regulation.
Further research is needed, but if you're taking statins and notice mood changes, speak with your doctor.
When to Contact a Healthcare Provider
If you notice symptoms like persistent sadness, low energy, loss of interest, or thoughts of self-harm after starting a new medication, contact your healthcare provider immediately.
Do not stop any medication on your own. Your doctor can help determine whether the drug is the cause and guide you through adjusting the dosage, switching medications, or treating depressive symptoms in parallel.
In many cases, medication-induced depression improves once the drug is stopped or replaced.
A Quick Review
Depression can be a side effect of several commonly prescribed medications—especially when taking more than one at a time. If you're experiencing mood changes, always bring it up with your doctor. They can work with you to ensure your treatment supports both your physical and mental health.
