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Harvard Commentaries
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School

Minding Your Mind Minding Your Mind

Which Antidepressant Is Right for You?

January 10, 2012

By Michael Craig Miller M.D.

Harvard Medical School

Depression is one of the most common medical problems in the world. It affects at least one out of every six adults in the United States at some point during a person's life. Psychotherapy and medication are both good treatments for depression. Sometimes both are used in combination. But, if you decide to include medication in your treatment program, how should you and your doctor decide which one to try first?

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All Antidepressants Are Not Created Equal

All antidepressants are roughly equal in how well they treat depression. But, because every individual responds differently to these medications, choosing the right one can be challenging.

Let's say, hypothetically, that scientists are testing how Drug A compares to Drug B. They give Drug A to 100 people who are depressed, and it might help 65 of them. The scientists might then offer those same people Drug B. It also helps 65 people, but not the same 65 people. That is, some people are helped by both drugs, some are helped by only A or B, and some get no relief at all.

It gets even more complicated when you consider that there are dozens of medications available for treating depression — not just two.

Unfortunately, it's impossible to predict in advance which drug (or which combination of drugs) might work best for you. In the future, we may have tests that help us choose. For now, we have to let other principles guide us.

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Are Some Antidepressants Better Than Others?

The first generation of antidepressants, which were discovered about 50 years ago, were the tricyclics and monoamine oxidase inhibitors. They have side effects that are a little harder to tolerate than the newer antidepressants. These newer, second-generation medicines like the selective serotonin reuptake inhibitors (SSRIs) and the serotonin and norepinephrine reuptake inhibitors (SNRIs), have fewer side effects and therefore tend to be more popular today.

Scientists have been trying to figure out if any of the antidepressants that are "roughly equal" stand out by even the smallest margin. Scientists in Italy and England reviewed many studies to see if they could discover any important trends. They published their analysis in January 2009. They evaluated how well several antidepressants worked (defined as at least a 50% reduction in symptoms according to a rating scale) and how well patients tolerated the different drugs (determined by how many patients continued to take the drug).

The authors concluded that escitalopram (Lexapro) and sertraline (Zoloft) show a slight edge over the rest in terms of how well they worked and how well they were tolerated. They recommended that clinicians and patients use one of these drugs first.

The analysis had limitations. Some of the studies may have been too short — shorter than the 12 to 14 weeks that some patients need to experience relief. In some studies, the doses may have been too low. Also, many of the studies included in the meta-analysis were funded by pharmaceutical companies, raising questions about their reliability.

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Side Effects -- A Sensible Way To Choose

Meanwhile, treatment guidelines published in November 2008 by the American College of Physicians (ACP) took a different approach. The authors noted that patients often stop taking medications because of side effects, even when they are mild. Because individual responses to antidepressants are so varied and unpredictable, finding the right drug is often a matter of trial and error.

As a practical matter, the ACP suggested considering a person's preferences regarding side effects when choosing a drug. For example, one person may have a particular concern about weight gain while another person may have an issue with sexual dysfunction.

Here are side effects that are associated with particular antidepressant drugs, based on a review of antidepressant studies.

  • Nausea and vomiting – Although usually classified as "mild" side effects, nausea and vomiting were the most common reason patients stopped taking a medication. About 33% of patients taking venlafaxine (Effexor) became nauseated or vomited, compared with 22% taking other drugs.
  • Diarrhea – Approximately 11% of patients taking sertraline experienced diarrhea, compared with 8% taking any of the eight other antidepressants tested.
  • Weight gain – Mirtazapine (Remeron) and paroxetine (Paxil) were more likely to cause weight gain than sertraline, venlafaxine or trazodone. In the studies involving mirtazapine, the mean weight gain ranged from 0.8 to 3 kg (roughly 2 to 6.5 pounds) after six to eight weeks of drug treatment. Data on paroxetine weight gain were not reported.
  • Sexual side effects – Sexual problems include trouble reaching orgasm or difficulty getting an erection. Patients taking bupropion (Wellbutrin) were less likely to experience sexual dysfunction than those taking fluoxetine (Prozac), paroxetine or sertraline. In head-to-head studies, about 16% of patients taking paroxetine experienced sexual difficulties, compared with 6% of patients taking fluoxetine, fluvoxamine (Luvox) or sertraline. Sometimes people are embarrassed to tell their doctor about sexual problems, so these side effects may actually occur more often than the studies show.

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Challenges and Clinical Guidance

The evidence that antidepressant medications help some but not all patients with depression only gets stronger. According to the ACP research, initial antidepressant treatment reduced symptoms in many patients, but fewer than 50% achieved complete relief or remission.

The ACP guidelines recommend that clinicians and patients take the following steps to get the most benefits from antidepressant treatment.

  • Assess response and side effects regularly. One to two weeks after starting therapy, determine if the symptoms are improving and if there side effects. Pay particular attention to signs of suicidal thoughts or behavior.
  • Modify treatment in some way if symptoms are still bothersome six to eight weeks after starting drug therapy. Increase the antidepressant dose or add psychotherapy. Other options are to boost the first medication by adding another drug or switching to a new drug.
  • Continue drug treatment for four to nine months. This period of time reduces the risk of relapse after a patient's mood has improved or depression symptoms have been relieved. Patients who have had two or more episodes of major depression may have to continue drug therapy even longer.

The real challenge, of course, is that depression has so many causes that we cannot predict, with certainty, which patients will respond to a particular drug and what side effects they may experience. But the information from these studies gives patients and clinicians a systematic way to make individual treatment choices.

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Michael Craig Miller, M.D. is editor-in-chief of the Harvard Mental Health Letter and an assistant professor of psychiatry at Harvard Medical School. Dr. Miller has an active clinical practice and has been on staff at Beth Israel Deaconess Medical Center for more than 25 years.

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