For many people, finding the right depression treatment is a trial-and-error process. An antidepressant may work well for one person but not at all for someone else — and experts don’t yet have ways to predict this.

In other cases, a person may start to feel better on an antidepressant, but the side effects are too bothersome for them to keep taking it.

One review assessed previous studies of 21 antidepressant medications and concluded that although these drugs are an effective treatment for depression, some work better than others, and some are better tolerated by the body than others.

One way to improve your chances of finding the depression medication that works best for you is to look for the following signs that your antidepressant isn’t working well enough or is no longer working the way it should.

1. You Feel Better Right Away, but It Doesn’t Last

Exactly how antidepressants work is still a mystery. The effects are thought to be related to changes in neurochemicals in your brain, such as serotonin, dopamine, and norepinephrine — changes that usually take 2 to 12 weeks to set in, with a peak at 6 to 8 weeks. So, if you feel different immediately after starting a depression treatment, it could be a placebo effect, says Joseph Hullett, MD, medical director of behavioral health services at Molina Healthcare in San Juan Capistrano, California.

Sometimes that placebo effect wears off, and the actual effect of the antidepressant kicks in. Other times, the placebo just wears off, and the intended effects of the antidepressant are never felt. In this second case, it isn’t that the medication stopped working — it’s that the medication (beyond the placebo effect) just didn’t work for you in the first place.

2. You Skipped a Dose — or Several

It’s a common situation — busy people often miss doses or take their medication at irregular intervals. The trouble is, not taking an antidepressant medication consistently can prevent it from working as well as it should — or prevent it from working at all, Dr. Hullett cautions. This can cause people to abandon what otherwise might be a very effective treatment.

3. You Can’t Sleep Well

“Antidepressants can make you feel more sleepy, less sleepy, and affect your libido and sex life, which can affect your sleep,” says Karen Lim, MD, a double board-certified psychiatrist at Prairie Health, a telepsychiatry platform based in California.

“Some people are also surprised to know that antidepressants can cause vivid dreams, myoclonus (sudden jerking of limbs especially at night and when tired), and, rarely, seizures,” Dr. Lim adds. She says the following tweaks to your bedtime routine can be enough to correct some of these issues:

Try relaxation techniques, such as deep breathing.
Exercise during the day rather than at night.
Listen to calming sounds and music, or watch calming videos.
Talk to your doctor about taking an over-the-counter sleep aid like melatonin.

You may also want to consider additional tweaks, including:

Avoid caffeine for at least six hours before bedtime.
Make your bedroom a screen-free zone (no TV, smart phone, tablet or computer).
Avoid any alcohol for at least four hours before bed.
Go to bed at the same time each night, and set an alarm to wake up at the same time each morning.
Keep your bedroom dark and cool.

4. Your Mood Is Still Low After a Few Months

According to the Cleveland Clinic, you may not see the full benefits of an antidepressant for two to three months after you begin taking it. If that doesn’t seem to be happening, discuss this with the healthcare provider who prescribed it, as you might need to try a different antidepressant or have the dosage changed.

5. You Feel More Energetic — but Still Feel Blue

“If you feel more physical energy after starting an antidepressant, but you still have depression, that’s good and bad news,” says Gabriela Cora, MD, a psychiatrist in Miami. “It means the depression medication is starting to work but not in the right way.” Increased physical energy combined with depression is a bad combination that can make you act out or increase your risk of suicide, she explains. “So report these symptoms to your doctor right away,” urges Dr. Cora.

6. You’re Experiencing Unpleasant Side Effects

Deciding which depression medication is best for you often comes down to side effects, says Hullett. If you gain weight or have sexual problems on one antidepressant, for example, you may want to switch to one without those side effects, he advises.

7. You Show Symptoms of Serotonin Syndrome

Although antidepressants are meant to help you feel better, in some cases, an antidepressant may combine with other medications you are taking or foods you are eating and lead to serotonin syndrome, an uncommon condition involving an overabundance of serotonin in the body, the Cleveland Clinic states.

Symptoms to watch out for, Lim says, include fever, aches, shakes, sweats, fatigue, irritability, a bad headache, confusion, agitation, restlessness, dizziness, difficulty seeing or walking, muscle twitching, muscle tension, or jaw clenching.

Typically, serotonin syndrome happens within days or weeks of starting an antidepressant or after a dose increase, says Lim. The most common factors that affect your risk of serotonin syndrome, per the Cleveland Clinic, are:

Too much of one medication that affects your serotonin levels
Multiple medications that affect your serotonin levels at the same time

8. Your Antidepressant Doesn’t Pack the Same Punch

“If you’ve been on an antidepressant for a long time, your body may develop a tolerance,” notes Hullett. As a result, a medication that once worked well at quelling your sadness, anxiety, and other symptoms no longer has that power. Sometimes, Hullett says, increasing the dose under supervision by your doctor may help. “If you’ve been taking 10 milligrams (mg) of Prozac (fluoxetine), for example, your physician may increase the dose to 20 mg,” he says. In other cases, trying a different medication or treatment is helpful.

9. Your Depression Worsens

“If your depression symptoms get worse as soon as you start taking an antidepressant, or they get better and then very suddenly get worse, it’s a sign that the depression medication isn’t working properly, and you should see your healthcare professional right away,” Hullett says. Specific warning signs to watch for include feeling agitated or restless, pacing or constant movement, hand wringing, or feeling generally out of control.

10. Your Mood Has Improved, but You’re Still Not Yourself

If you experience some relief on an antidepressant, but it’s not the relief you hoped for, talk to your doctor about other treatments, or perhaps even a combination of treatments. Options may include trying another depression medication or the addition of counseling, psychotherapy, mood-boosting cardio exercise, or light therapy to your treatment regimen. And research has shown that adding psychotherapy to medication treatment produced better outcomes for people with depression than just medication alone, notes Harvard Health Publishing.

11. Your Mood or Energy Improves — but Too Much

“Depression medications can sometimes cause mood swings, especially in people who have a tendency toward bipolar disorder — depression and mania,” Hullett says. If you feel unusually elated or you become very terse with your spouse, feel noticeably more irritable, or have an uncharacteristic bout of road rage, you probably need to change your antidepressant, he advises.

The Bottom Line

While taking an antidepressant can be very helpful for managing depression, you might not find the right one for you on the first try.

If your medication isn’t meeting your expectations, don’t give up. Consider talking to a doctor who specializes in treating mood disorders if you aren’t already seeing one. And be on the lookout for — and tell your doctor about — any worrisome symptoms you experience while you’re taking any antidepressant, Lim advises. Manic episodes, serotonin syndrome, suicidal thoughts, and seizures, for example, need to be evaluated by a doctor ASAP.

Additional reporting by Michelle Pugle.

Editorial Sources and Fact-Checking

Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.

Resources

Cipriani A, Furukawa TA, Salanti G, et al. Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults With Major Depressive Disorder: A Systematic Review and Network Meta-Analysis. The Lancet. April 7, 2018.
Clinical Depression (Major Depressive Disorder). Cleveland Clinic. November 30, 2022.
Serotonin Syndrome. Cleveland Clinic. March 24, 2022.
Medication or Therapy for Depression? Or Both? Harvard Health Publishing. May 26, 2020.

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