Antidepressants Not Working? 7 Possible Reasons (and What to Do)

August 28, 2023

woman looking at pill bottle

Antidepressants can be life changing. They can help you function better and feel more like yourself again. For more than 13% of adults in the United States, antidepressants offer relief from depression symptoms.

Muaid Ithman, MD
Muaid Ithman, MD

But depression medication doesn’t work for everyone and even when it does, it can become less effective over time, says Dr. Muad Ithman, a MU Health Care interventional psychiatrist specializing in difficult-to-treat mental health conditions. “Studies have shown that 25% to 50% of antidepressants stop working after a long period of being effective,” he adds. More than 60% of people taking antidepressants tend to take them for two years or more. If you’re one of them, you may want to pay closer attention to how well their medication works.

The key is avoiding or identifying things that may counteract your antidepressants whenever possible, according to Dr. Ithman. If you recognize that your medication isn’t working, taking steps to remedy the situation is critical.

Signs Your Antidepressant Isn’t Working

Antidepressants aren’t magic pills — you can still have bad days or feel sad. But if you’re having more bad days than good, your medication may not be doing its job.

Common signs that your medication may not be working or are having a less-than-ideal outcome include:

  • Worsening symptoms of depression or no symptom relief if you’re just starting medicine
  • Upsetting side effects, such as violent mood swings, irritability or not feeling like yourself
  • Sudden surge in energy that may cause impulsive behaviors

“Take a look at whether your mood is suddenly impacting your functionality,” Dr. Ithman says. “Is your depression making you feel like you don’t want to get out of bed? Are you losing interest in activities you typically enjoy? If the answer is yes, don’t hesitate to seek help.” Ignoring the symptoms of depression for too long can impact your overall health.

If you are starting antidepressants, ensure you’ve given the medication adequate time to work. “Antidepressants can take about four to six weeks to take effect,” Dr. Ithman says. “And it takes about 12 weeks to show the full effect.”

Reasons Depression Medication Fails

Drug-resistant depression is a real thing. But often, Dr. Ithman says, there are other underlying reasons your antidepressants may not be working, including:

1. Added stress

If you’re suddenly experiencing more stress than usual, your current antidepressant dosage may not be able to compensate. A job change, move, death of a loved one or getting married/divorced can add excessive stress to your life, throwing your mental health off balance.

2. Aging

An aging body goes through many changes, such as joint pain and menopause. But one difference you don’t often hear about is how age affects how your body absorbs and metabolizes medication. Your medication’s effectiveness might’ve been slowly waning, but now you feel the impact.

3. Another medical condition

Chronic conditions can affect your depression in different ways. The treatment or medication used to treat your chronic condition may trigger depression symptoms. Some conditions, such as diabetes and thyroid disease, make it harder for your body to respond to antidepressants. Other diseases, such as Alzheimer’s disease or multiple sclerosis, can add stress that brings on or worsens depression symptoms.

4. Increased use of drugs, nicotine or alcohol

A recent increase in alcohol or drug use can be a sign you’re depressed. But it can also be the reason you’re feeling that way. Alcohol and some drugs are known depressants, often worsening the symptoms of depression. They can also interfere with how antidepressants work. Alcohol and tobacco both affect how well the body metabolizes some antidepressants.

5. New medication

Whenever you add a new medication to your health regimen, you run the risk of a drug interaction. Most doctors will consider your current medicines and possible drug interactions when prescribing something new. But everyone reacts to medication differently, and any new supplements or prescription medications could affect your antidepressants.

6. Pregnancy

If you are pregnant or planning to become pregnant, it’s always a good idea to talk to your primary care provider about your current medications. Even antidepressants considered safe during pregnancy can be affected by the changes your body goes through. Adjustments in your depression medication may be needed to accommodate the increase in weight and fluids that happens when you’re pregnant.

7. Tachyphylaxis (drug tolerance)

Your body can build a tolerance to antidepressants. Antidepressant tachyphylaxis — a decreasing response to a drug — tends to occur only with selective serotonin reuptake inhibitors (SSRIs). Experts estimate that up to 25% of people treated for depression may experience tachyphylaxis.

What to Do If Your Depression Medication Isn’t Working

Adjusting your lifestyle or medication — under your doctor’s guidance — can help get you back on track. But it could be that your depression simply became resistant to that medication. The good news is that there are many options for treating depression.

“Depression is a treatable condition, and just because one treatment option fails doesn’t mean there isn’t another option that will work,” Dr. Ithman says. “There are numerous ways we can help improve depressive symptoms effectively and allow you to reclaim your life.”

If you’re concerned your antidepressants have stopped working, make an appointment to see your health care provider. Continue taking your medication until that appointment, when your doctor may consider switching the dosage or type of medication. If your drug resistance or depression is severe, they may recommend adding alternative therapies such as TMS or ketamine to help with your symptoms.

Next Steps and Useful Resources



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