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Depression Treatment

Depression Treatment

Medications for Depression

The most commonly prescribed medications for depression are referred to as antidepressants. Most antidepressants prescribed today are both safe and effective when taken as directed by your physician or psychiatrist. Although most antidepressants in the U.S. are prescribed by family doctors or general practitioners, you should nearly always seek out a psychiatrist for the best treatment of depression with medications.

A class of antidepressants called selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for depression today. Prozac (fluoxetine), Paxil (paroxetine), Zoloft (sertraline) and Luvox (fluvoxamine) are the most commonly prescribed brand names. SSRI medications should not be prescribed in conjunction with the older MAOIs (more popular in Europe than in the U.S.). SSRIs work on increasing the amount of serotonin in the brain. Researchers are not sure why an increase in serotonin helps relieve depression (there’s little evidence of support for the serotonin theory of depression), but decades’ worth of studies suggest such medications nonetheless help improve mood.

SSRI antidepressant medications were once thought to have lesser side effects than other antidepressants, but research in the past decade suggests differently. While SSRI antidepressants appear to be safe, most people will experience side effects while taking them, such as nausea, diarrhea, agitation, insomnia, or headache. For most people, these initial side effects will go away within 3 to 4 weeks.

Many people taking an SSRI complain of sexual side effects, such as decreased sexual desire (decreased libido), delayed orgasm, or an inability to have an orgasm. Some people also experience tremors with SSRIs. Serotonin syndrome is a rare but serious neurological condition associated with the use of SSRIs. It is characterized by high fevers, seizures, and heart-rhythm disturbances.

Long-term side effects of taking SSRI medications for more than a year include sleep disturbance, sexual dysfunction, and weight gain.

The large-scale, multi-clinic government research study called STAR*D found that people with depression who take medication often need to try different brands and be patient before they find one that works for them. The effects of medications will usually be felt within 6 to 8 weeks of taking an antidepressant, but not everyone feels better on the first medication tried. You may have to try 2 or 3 different medications before finding the one that works for you.

Results from the STAR*D study indicate that if a first treatment with one SSRI fails, about one in four people who choose to switch to another medication will get better, regardless of whether the second medication is another SSRI or a medication of a different class. And if people choose to add a new medication to the existing SSRI, about one in three people will get better. It appears to make some — but not much — difference if the second medication is an antidepressant from a different class (e.g., bupropion) or if it is a medication that is meant to enhance the SSRI (e.g., buspirone). Because the switch group and the add-on group cannot be directly compared to each other, it is not known whether patients are more likely to get better by switching medications or by adding another medication.

Results from one of the findings of the study apply to those who do not get better after two medication treatment steps. At this stage, by switching to a different antidepressant medication, about one in seven people will get better, and by adding a new medication to the existing one, about one in five people will get better. Finally, for patients with the most treatment-resistant depression, additional results suggest that tranylcypromine is limited in its tolerability and that up to 10 percent may benefit from the combination of venlafaxine-XR/mirtazapine.

An overall analysis of the ground-breaking STAR*D results indicates that patients with difficult-to-treat depression can get well after trying several treatment strategies, but the odds of beating the depression diminish with every additional treatment strategy needed. In addition, those who become symptom-free have a better chance of remaining well than those who experience only symptom improvement. And those who need to undergo several treatment steps before they become symptom-free are more likely to relapse during the follow-up period. Those who required more treatment levels tended to have more severe depressive symptoms and more co-existing psychiatric and general medical problems at the beginning of the study than those who became well after just one treatment level.

Other medications may also be of help. Atypical antidepressants are often prescribed when a person hasn’t improved with a common SSRI. Such medications include nefazodone (Serzone), trazodone (Desyrel), and bupropion (Wellbutrin). Abilify (aripiprazole) is also an aytpical antipsychotic that is approved for the use in the treatment of depression. It is the first medication approved by the U.S. Food and Drug Administration for “add-on treatment.” That is, your doctor can prescribe it to you even if you’re already taking an antidepressant. In clinical studies, when Abilify was added to an antidepressant treatment, many people experienced significant improvement of their depressive symptoms.

Ketamine is the newest treatment for severe forms of this condition. Ketamine is not FDA-approved for treatment of major depressive episodes, but has been approved for other uses. Ketamine clinics have appeared, offering off-label prescription of ketamine infusion treatment. Because it is not an FDA-approved treatment, insurance companies rarely cover the costs of this treatment. An initial set of treatment sessions of ketamine infusion runs anywhere from $4,000 – $8,000, with regular booster treatments needed every month or two. While apparently effective in many people who try it, treatment appears to be life-long, while long-term effects of such treatment have yet to be studied.


John M. Grohol, Psy.D.

Dr. John Grohol is the founder, Editor-in-Chief & CEO of Psych Central. He is an author, researcher and expert in mental health online, and has been writing about online behavior, mental health and psychology issues -- as well as the intersection of technology and human behavior -- since 1992. Dr. Grohol sits on the editorial board of the journal Computers in Human Behavior and is a founding board member and treasurer of the Society for Participatory Medicine. He writes regularly and extensively on mental health concerns, the intersection of technology and psychology, and advocating for greater acceptance of the importance and value of mental health in today's society. You can learn more about Dr. John Grohol here.

APA Reference
Grohol, J. (2019). Depression Treatment. Psych Central. Retrieved on March 18, 2019, from
Scientifically Reviewed
Last updated: 10 Jan 2019
Last reviewed: By a member of our scientific advisory board on 10 Jan 2019
Published on Psych All rights reserved.