When a medicine isn't working
It is common for the first antidepressant not to be the right one. There are many next steps, and a provider can help you choose. Here is what the National Institute of Mental Health (NIMH), MedlinePlus, and the U.S. Food and Drug Administration (FDA) drug label say, in plain words.
Talk to your provider before starting, stopping, or changing any medicine.
If you or someone you know is having thoughts of suicide, call or text 988 or chat at 988lifeline.org. In a life-threatening situation, call 911.
Give it time
How long antidepressants usually take
Antidepressants usually take 4 to 8 weeks to work. Sleep, appetite, and concentration often get better before mood lifts.
Giving a medicine a fair chance to work is important before deciding whether it is right for you. Finding the best treatment may take some trial and error.
In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, run by the National Institute of Mental Health, some people felt benefits in the first 6 weeks, but full benefits sometimes took 10 or 12 weeks. The researchers advised doctors to work with patients to adjust doses and to avoid stopping a treatment too early.
National Institute of Mental Health · STAR*D study questions and answers
One antidepressant does not work for everyone. You may need to try two or more medicines before you find one that works for you.
Better or well
What response and remission mean
These words come up when a provider talks about how well a treatment is working. The STAR*D study, the largest and longest study of depression treatment ever done, used them this way.
Response means symptoms have dropped to half or less of where they were at the start. A person who responds feels noticeably better but may still have symptoms.
National Institute of Mental Health · STAR*D study questions and answers
Remission means becoming symptom-free. People who reach remission do better at home and at work, and have a better chance of staying well, than people who only respond.
National Institute of Mental Health · STAR*D study questions and answers
On the first medicine in that study, about one in three people reached remission, and about 10 to 15 percent more responded without reaching remission. Feeling somewhat better is progress, and it is also worth telling your provider if symptoms remain.
National Institute of Mental Health · STAR*D study questions and answers
The study used measurement-based care: symptoms and side effects were measured the same way at every visit with easy-to-use tools, and doses were adjusted based on the results. A self-check and a daily log can help you bring the same kind of information.
National Institute of Mental Health · STAR*D study questions and answers
Next steps
Options a provider may consider
Which option fits depends on your symptoms, side effects, health, and preferences. These are the options the sources describe. Your provider will help decide.
Adjusting the dose or timing. Providers adjust doses to find the right level. For people bothered by side effects, starting low, raising the dose slowly, or changing when or how the medicine is taken (for example, at bedtime or with food) can help.
National Institute of Mental Health · Mental health medications
Switching to a different medicine. In the second step of the study, about 1 in 4 people who switched to a different medicine became symptom-free.
National Institute of Mental Health · STAR*D study questions and answers
Adding a second medicine. In the same step, about 1 in 3 people who added a medicine to the one they were taking became symptom-free.
National Institute of Mental Health · STAR*D study questions and answers
Adding or switching to talk therapy. The STAR*D study offered cognitive therapy either in place of the medicine or added to it.
National Institute of Mental Health · STAR*D study questions and answers
Adding a different type of medicine that may make the antidepressant work better, such as an antipsychotic or an anticonvulsant (seizure medicine). This is one option for treatment-resistant depression.
Brain stimulation therapy. This is an option when other treatments have not worked. The most used types are electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS). ECT may be used earlier when severe depression has become life-threatening.
Treatment-resistant depression
When two medicines have not helped
Treatment-resistant depression means a person has not gotten better after trying at least two antidepressants.
Esketamine is a nasal spray approved by the U.S. Food and Drug Administration (FDA) for treatment-resistant depression. It is given in a doctor's office, clinic, or hospital, often works within a couple of hours, and is usually taken along with an antidepressant pill.
Combining an antidepressant with a different type of medicine and brain stimulation are also options for treatment-resistant depression.
Stopping safely
Why not to stop suddenly
Do not stop a prescribed medicine on your own, even if you feel better. Your provider can lower the dose slowly and safely. Stopping too soon may bring symptoms back.
National Institute of Mental Health · Mental health medications
Never change your dose or stop an antidepressant on your own. If side effects bother you too much, you may need a different antidepressant, and your provider can suggest ways to manage side effects while you wait to see if it works.
Stopping, especially stopping suddenly, has been linked to discontinuation symptoms such as dizziness, irritability, anxiety, headache, trouble sleeping, confusion, low mood, and electric shock-like feelings. They usually go away on their own, but some have been serious. The label for escitalopram (Lexapro), a selective serotonin reuptake inhibitor (SSRI), says these symptoms have been reported with other SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) too, and advises lowering the dose gradually.
Side effects
Side effects to report
Common side effects include upset stomach, headache, and sexual problems. They are generally mild and tend to go away with time.
National Institute of Mental Health · Mental health medications
Call your provider right away if you notice new or worsening symptoms, unusual changes in mood, or acting differently.
Watch for signs of mania or hypomania and report them to the provider. Tell your provider about every medicine you take, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and blood thinners, because some combinations raise the risk of bleeding.
Young people
The boxed warning for children, teens, and young adults
Antidepressant labels carry a boxed warning: in short-term studies, antidepressants increased suicidal thoughts and behaviors in children, teens, and young adults. The label says everyone taking an antidepressant should be closely watched for worsening and for new suicidal thoughts.
People under 25 may have more suicidal thoughts or behavior, especially in the first few weeks after starting a medicine or after a dose change. The FDA advises watching people of all ages closely during the first few weeks.
If this happens, get medical help right away. Call or text 988, or call 911 in an emergency.
For your next visit
Questions to ask
- 1.How long should I take this medicine before we decide whether it is working?Based on: National Institute of Mental Health · Depression
- 2.Am I in remission, or have I only responded? What would remission look like for me?Based on: National Institute of Mental Health · STAR*D study questions and answers
- 3.Should we try a different dose first, or switch, or add a medicine or therapy?Based on: National Institute of Mental Health · STAR*D study questions and answers
- 4.Which side effects are expected, and which ones mean I should call you right away?Based on: MedlinePlus · Antidepressants
- 5.If I stop or switch, how will we lower the dose, and what discontinuation symptoms should I watch for?Based on: DailyMed · Lexapro label
- 6.Do I have treatment-resistant depression? Would esketamine or brain stimulation be an option for me?Based on: National Institute of Mental Health · Depression
- 7.How will we measure my symptoms at each visit?Based on: National Institute of Mental Health · STAR*D study questions and answers
Keep going
Plan the conversation with your provider
See the glossary for any word you are not sure about.