Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.
Finding the best depression treatment for you can sometimes seem like a series of science experiments that fail to yield positive results.
After trying an initial antidepressant for two months, you still feel worn out, “brain fogged,” hopeless and restless. So your healthcare professional suggests switching to another option. That one also fails to satisfactorily resolve your symptoms, so you change your treatment plan again.
“Different people respond to different medicines and treatments. No one knows for sure why one treatment works for one person but not for another,” says Simon Kung, M.D., an associate professor of psychiatry at Mayo Clinic College of Medicine and Science.
Because of this trial-and-error process, it can sometimes take many months to find a depression treatment — or combination of treatments — that works for you. To reduce frustration as you wait, it helps to know what to expect.
Antidepressants: What happens during the first month
During the first few days of taking a new depression medication, you may notice side effects like nausea, headache, dry mouth, insomnia or loose stools. According to Dr. Kung, most, if not all, of these problems may naturally go away as your body adjusts to the medicine.
If you’re still experiencing severe side effects after several days, contact your healthcare professional. Together, you may decide to stay on a lower dose of your medicine for longer, giving your body more time to get used to the drug.
Once you’re taking a full dose of an antidepressant, it takes several weeks or more before your brain responds to the medicine. You may notice some improvement in symptoms in the first month and full benefits by the end of the second month.
When to try a new antidepressant
If side effects persist or your depression symptoms fail to resolve within two months, your healthcare professional will likely recommend a medication adjustment.
If side effects aren’t a problem but the antidepressant isn’t having the full desired effect, you may benefit from a higher dose of medication than is usually prescribed. If that doesn’t work, your healthcare professional may suggest switching to another antidepressant.
“There are different classes of medicines, and it’s always worth trying different ones,” says Dr. Kung. “Stay on each medicine for at least two months and at a good dose. Try not to give up on a new medicine too soon.”
Some of the standard medicine classes include:
Selective serotonin reuptake inhibitors (SSRIs): These medicines treat depression by increasing levels of serotonin in the brain. Examples include citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft).
Serotonin and norepinephrine reuptake inhibitors (SNRIs): These antidepressants ease depression by increasing serotonin and norepinephrine in the brain. Examples include venlafaxine (Effexor XR), desvenlafaxine (Pristiq), duloxetine (Cymbalta) and levomilnacipran (Fetzima).
Atypical antidepressants. These antidepressants are called atypical because they don’t fit neatly into other antidepressant categories. Examples include bupropion (Forfivo XL, Wellbutrin SR), mirtazapine (Remeron), vilazodone (Viibryd) and vortioxetine (Trintellix).
Read more: Antidepressants: Selecting to one that’s right for you.
Your healthcare professional may initially recommend trying a second medicine from the same class. For example, if escitalopram doesn’t work for you, you might try sertraline next.
Alternatively, your healthcare provider may suggest that you switch to a medicine that affects the brain differently. For example, instead of trying yet another SSRI, you might switch to an SNRI or an atypical antidepressant.
To make the switch, you gradually reduce the dose of your current medication. Once you’re no longer taking the initial medicine, you begin the new one and gradually increase the dose.
This slow shift from one medicine to another often takes 2 to 3 months. Talk with your health professional or therapist about coping with depression symptoms as you wait for the new antidepressant to take effect.
When to add booster medicine
If you’ve tried two or three antidepressants without success, it might be time to explore combination therapy, says Dr. Kung. This involves either pairing two antidepressants or taking an antidepressant and another medicine not typically used to treat depression, like an antipsychotic.
Adding a second antidepressant
By combining two different classes of antidepressants, you may be able to affect a broader range of brain chemicals linked to mood. For example, your healthcare professional might recommend pairing an SSRI like fluoxetine with an atypical antidepressant like bupropion.
Adding other medications
Several medications are thought to augment or boost the effect of antidepressants. They include antipsychotics, mood stabilizers and the thyroid hormone liothyronine (Cytomel).
When to try other depression treatments
For some people, the search for an effective antidepressant can take many months or years.
“That’s why we get a lot of patients who are frustrated,” says Dr. Kung.
However, several treatments may help shorten that wait.
If several medicines have failed to bring depression into remission, Dr. Kung recommends talking to your healthcare professional about whether the following options make sense for you.
Ketamine
Intravenous (IV) ketamine is an FDA-approved anesthetic for surgical and medical procedures. In recent years, ketamine has increasingly been used off-label as an antidepressant for treatment-resistant depression (TRD). It’s thought to work by increasing glutamate in the brain. “Like serotonin, the glutamate system is another important set of chemicals in the brain that is involved with depression,” says Dr. Kung. The treatment may also help create more connections, also called synapses, between brain cells.
A typical treatment lasts 1.5 to 2 hours including prep time, the infusion and the post-infusion recovery.
“During the infusion, people can feel discombobulated,” says Dr. Kung. “They may have some dissociation and see colors.”
About 60% of people feel better swiftly, within a day or two. Because the effect wears off, repeat doses are given every few weeks.
Transcranial magnetic stimulation (TMS)
This procedure uses magnetic fields to stimulate nerve cells in the brain. During a session, a healthcare professional places an electromagnetic coil against the scalp. This coil delivers magnetic pulses thought to change areas of the brain that are associated with depression.
People who receive TMS undergo five treatments weekly for 4 to 6 weeks. Each treatment ranges from 3.5 to 37 minutes, depending on the machine. Like ketamine, these treatments help about 60% of people feel better, with relief typically taking place after several weeks.
Electroconvulsive therapy (ECT)
Done under general anesthesia, this procedure involves using electricity to cause a generalized seizure. It causes changes in brain chemistry that can quickly reverse depression symptoms. It’s used for people with severe TRD.
Much of the stigma attached to ECT is based on early treatments in which high doses of electricity were administered without anesthesia, leading to memory loss and other serious side effects. Today, ECT is done at lower doses and with advanced anesthesia techniques, making it much safer.
ECT treatments are generally given 2 to 3 times weekly for 3 to 4 weeks. Many people notice improvements within six treatments.
Read more: What happens during electroconvulsive therapy.
For best results, pair medicine with lifestyle changes
If you’ve spent years trying many drugs and treatments to no avail, the problem may not completely center on your brain chemistry. Instead, there may be a larger behavioral or environmental component.
Consider whether you:
- Consistently put your therapist’s advice into practice.
- Get enough sleep, exercise regularly, manage stress, participate in social activities and consume a well-balanced diet.
- Abstain from alcohol, cannabis and other drugs.
Also address toxic relationships, job stress or other situations that can contribute to depression.
Though the search for an effective treatment can take time, know that many depression treatments are available. With time, effort and patience, chances are you’ll be able to find a treatment approach that works well for you.
Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.
Relevant reading
Mayo Clinic Guide to Better Vision, Third Edition
Mayo Clinic Guide to Better Vision, Sophie J. Bakri, M.D., walks readers through the diagnoses and treatment options associated with common eye issues, as well as preventive measures for protecting your eyes.
