Do Antidepressants Work? Everything You Need to Know

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What Do Antidepressants Do?

Depression is one of the most common mental illnesses for Americans of all ages. People who suffer from depression experience sadness, loneliness, emptiness, and hopelessness that interferes with their daily life. In 2019, more than 19.4 million adults1 had a major depressive episode, representing 7.8% of Americans2 aged 18 years or older. 

Antidepressants are medications that help alleviate symptoms of depression. If you suffer from depression and therapy is insufficiently treating your symptoms, your doctor may suggest that you consider an antidepressant medication. 

Different Types of Antidepressants and How They Work

There are several types of antidepressants that are used to treat depression, many of which are reuptake inhibitors. A reuptake inhibitor prevents your presynaptic neurons from reabsorbing the same neurotransmitters that they released. As a result, there are higher concentrations of these neurotransmitters in your brain, and the postsynaptic neurons are able to absorb them instead. This allows your mood to be altered in positive ways at a chemical level. 

Selective Serotonin Reuptake Inhibitors (SSRIs)

Serotonin promotes a good mood and plays a role in your body’s sleep-wake cycle. SSRIs prevent presynaptic neurons from reabsorbing serotonin. As a result, they increase the amount of serotonin in your brain. They can treat a variety of mental illnesses including depression, anxiety, and posttraumatic stress disorder (PTSD)

Commonly prescribed SSRIs include Zoloft (sertraline), Lexapro (escitalopram), and Paxil (paroxetine).

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Similar to SSRIs, SNRIs prevent presynaptic neurons from reabsorbing serotonin, but SNRIs also prevent the reabsorption of norepinephrine. Norepinephrine works with serotonin and other neurotransmitters to help regulate your emotions. SNRIs increase the levels of serotonin and norepinephrine in your brain. They are very effective treatments for depression, as well as anxiety and chronic pain.

Cymbalta (duloxetine) and Effexor (venlafaxine) are two common SNRIs.

Norepinephrine and Dopamine Reuptake Inhibitors (NDRIs)

NDRIs stop neurons from reabsorbing norepinephrine much like SNRIs, but NDRIs also keep your presynaptic neurons from reabsorbing dopamine. Dopamine causes pleasurable feelings, so it is often called the “feel-good hormone.” 

NDRIs allow the levels of both norepinephrine and dopamine to increase in your brain. They effectively treat depression and attention-deficit/hyperactivity disorder (ADHD) in addition to other conditions like Parkinson’s disease. Unlike other antidepressants, NDRIs don’t cause weight gain or decreased libido.

Ritalin (methylphenidate) and Wellbutrin (bupropion) are two of the most common NDRIs available on the market.


Tetracyclics work like SSRIs and prevent the reabsorption of serotonin and norepinephrine in your brain. First introduced in the 1970s, tetracyclics are one of the earliest developed antidepressants. However, they have a host of side effects, so they aren’t commonly prescribed anymore. SSRIs have essentially taken their place.

Remeron (mirtazapine) and Ludiomil (maprotiline) are two tetracyclic antidepressants that are still prescribed today.

Serotonin Antagonist and Reuptake Inhibitor (SARIs)

SARIs work in two ways. They prevent the reabsorption of serotonin by presynaptic neurons, while they also redirect it to bind to nerve receptors that impact your mood by preventing it from binding to undesirable receptors. Not only do SARIs increase levels of serotonin in your brain, they also ensure that this serotonin is used specifically to influence your mood in positive ways. These properties make SARIs a great treatment option for major depressive disorder. 

The main SARIs that doctors prescribe are trazodone and Serzone (nefazodone).

Tricyclics and MAOIs

Tricyclics and monoamine oxidase inhibitors (MAOIs) are some of the oldest antidepressant drugs available. While they have different mechanisms, they both increase the levels of certain neurotransmitters in the brain. They both also have significant side effects that make them less desirable than newer drugs like SSRIs.

Like SSRIs and SNRIs, tricyclics prevent the reabsorption of serotonin. Tricyclics also prevent the reabsorption of epinephrine, making it riskier than other antidepressants. If you have a heart arrhythmia, your doctor will need to closely monitor you while you’re on a tricyclic antidepressant.

MAOIs target monoamine oxidase, an enzyme that consumes serotonin, epinephrine, and dopamine. By preventing monoamine oxidase from breaking down these neurotransmitters, MAOIs increase the levels of serotonin, epinephrine, and dopamine in your brain. These medications can’t be combined with other medications that increase serotonin levels as that can lead to a serious condition called serotonin syndrome, which can be fatal.

Neither tricyclic antidepressants nor MAOIs are usually prescribed for people who respond to SSRIs and other antidepressants with fewer side effects. Common tricyclic medications include Norpramin (desipramine) and Tofranil (imipramine), and available MAOIs include Nardil(phenelzine) and Marplan (isocarboxazid).

The Efficacy of Antidepressants: Do They Work?

Studies that examine the effectiveness of antidepressants are plentiful. Most of them find that placebo treatment and treatment with an antidepressant show positive changes in mood until a certain point at which trial participants on placebos begin to decline. Tricyclics and SSRIs3 are proven to work better than placebos in primary care settings.

Generally, antidepressants are considered effective if patients enter a state of remission for their symptoms. There are a variety of tools that exist to measure the severity of depression, and studies use these to determine a participant’s scores prior to, during, and after the study. 

One such study used the Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR). This study found that a four-step course of treatment brought a total remission rate of 67%4 among study participants. Furthermore, they found that the more steps a treatment requires, the less likely that participants are to reach remission.

If your doctor prescribed antidepressants for you, it’s important that you carefully follow your course of treatment by taking them at the correct dosage and frequency. Antidepressants are less effective when not taken as prescribed.

Additionally, it’s important to note that antidepressant medications are usually prescribed alongside psychotherapy. Therapy and medication typically work better together than relying on medication alone. 

How Long Does It Take for Antidepressants to Work?

The length of time that it takes for antidepressants to work changes on an individual basis, but most doctors will say that they take up to three months to kick in. One study showed that up to 60% of participants5 had fewer symptoms of depression six to eight weeks after beginning an antidepressant. If you’re starting antidepressants, you should ask your doctor what you should expect over the course of your treatment.

Common Side Effects of Antidepressants

There are many possible side effects for antidepressants. These side effects tend to be worse for older medications than their newer counterparts. Possible side effects include:

  • Increased appetite leading to weight gain
  • Decreased libido and inability to achieve erection or orgasm
  • Fatigue and drowsiness
  • Anxiety and agitation
  • Insomnia and restlessness
  • Headaches and dizziness
  • Diarrhea or constipation
  • Tremors and heart arrhythmias
  • Dry mouth
  • Nausea
  • Sweating

What to Do When Antidepressants Don’t Work

Sometimes, antidepressants don’t work, or you build up a tolerance to your current prescription and its benefits begin to wane. Whatever the case, if you feel that your antidepressants aren’t helping you, speak to your doctor and therapist about it before making any changes. Continue to take your antidepressants as prescribed unless and until your doctor tells you otherwise. 

If you’re currently struggling with depression, be sure to check out the therapists in our directory to find someone in your area who can help you through therapy, medication, or some combination of both.If you need immediate support to help you cope with depression symptoms, you can text HOME to 741741 to be connected with a crisis counselor at the Crisis Text Line6.