Maintenance Medications for Depression

Medically Reviewed by Smitha Bhandari, MD on July 20, 2023
4 min read

Antidepressants are some of the best treatments we have for depression. But these drugs don't cure depression in the way that antibiotics cure infections. Instead, they can help ease the symptoms.

You will probably need to continue medication even after you feel better. The American Psychiatric Association recommends that people keep taking their medicine for four to five months after they recover from a first episode of depression and often longer (sometimes even indefinitely) for people who have had multiple previous depressions. This helps reduce the risk of relapse.

Depression can sometimes be like other chronic illnesses, like diabetes or heart disease, that need ongoing treatment. This is called maintenance treatment.

Here is a rundown of some of the most common medicines used to treat depression and prevent it from coming back.

  • Newer antidepressants. In the past two decades, many new types of antidepressants have become available, each working in slightly different ways:

Selective serotonin reuptake inhibitors (SSRIs) affect the activity of a chemical in your brain called serotonin. This class of antidepressants include citalopram (Celexa), escitalopram (Lexapro ), fluoxetine (Prozac ), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft). vilazodone (Viibryd) and vortioxetine (Trintellix, former called Brintellix) are newer medicines that bind to the serotonin reuptake receptor (the same one as with SSRIs as well as other types of serotonin receptors that may have unique effects. Side effects of most SSRIs are generally mild. They include stomach upset, sexual problems, insomnia, dizziness, weight change, and headaches.

Serotonin and norepinephrine reuptake inhibitors (SNRIs) affect the action of both serotonin and another brain chemical, norepinephrine. This class includes desvenlafaxine (Khedezla or Pristiq), duloxetine (Cymbalta), levomilnacipran (Fetzima), and or venlafaxine (Effexor). Side effects are usually mild. They include upset stomach, sleep problems, sexual problems, headache, anxiety, and dizziness, and weakness.

Norepinephrine and dopamine reuptake inhibitors (NDRIs) affect norepinephrine and a different chemical in the brain, dopamine. This class of drugs includes bupropion (Wellbutrin). Side effects are usually mild, and include upset stomach, headache, sleep problems, tremor, and anxiety. Wellbutrin may be less likely to cause sexual side effects or weight gain than other antidepressants. You cannot take this medication if you have had seizures before.

Noradragenic and specific serotonergic antidepressants (NaSSAs) also affect serotonin and norepinephrine in your brain. This class of drugs includes mirtazapine (Remeron). Side effects are usually mild, and include upset stomach, sleepiness, weight gain, anxiety, and dizziness.

  • Older antidepressants

Some of the first medicines used to treat depression were tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs). Both types affect the availability of certain neurotransmitters (chemicals in the brain) that are thought to play a role in depression. While these medicines can be very effective in some forms of depression, doctors usually no longer use them as first-line treatments because of concerns about side effects. They can have more severe safety risks due to certain drug or food interactions and also can be very dangerous in overdose. However, they are still the right choice for some people with depression -- especially if newer antidepressants don't help.

  • Other medicines
    Other drugs that are not actually antidepressants can also help. For instance, some people recovering from depression will benefit from drugs for anxiety or insomnia. In addition, certain atypical antipsychotics -- (primarily used for schizophrenia or bipolar disorder) such as aripiprazole (Abilify), brexipiprazole (Rexulti), caripiprazole (Vraylar), or quetiapine (Seroquel XR) -- have been shown to enhance the effect of antidepressant medicines for depression when an antidepressant alone isn't fully effective.
  • While not classified as a medication by the FDA, l-methylfolate (Deplin) has proven successful in treating depression. Considered a medical food or nutriceutical, it is a prescription strength form of the vitamin B known asfolate and helps regulate the neurotransmitters that control moods. It has been effective in treating treatment resistant depression.

Unfortunately, finding the right medicine and the right dose isn't always simple. People have very different reactions to these drugs. There's no way for your doctor to predict how well a medicine will work for you. You may even find that a medicine that used to help just doesn't anymore.

You may have to put up with some trial and error. While antidepressants usually begin to show significant effects within a few weeks, it can take several months before you feel the full effects of a new drug, so don't give up. Over time, your doctor may want to increase or decrease the dose, depending on how you're doing.

If you've given a depression drug a chance and it still isn't helping, talk to your doctor. Your doctor may recommend that you try another antidepressant. With time, you should be able to find a medicine or a combination of medicines that helps.

Don't ever stop taking a medicine without your doctor's approval, even if you're feeling better. Stopping a medicine suddenly can trigger a relapse or, with some antidepressants, flu-like symptoms and nausea or dizziness caused by sudden discontinuation of the drug.

Your doctor will want you to check in on a regular basis, especially soon after starting a new medicine, to see how you're doing and monitor the effects of medication. Take advantage of these appointments to talk about any issues you have with your medication.