Confidence Scale

The confidence ratings in this guide are derived from a systematic review of the literature. The level of confidence is based on the overall quantity and quality of clinical evidence.

HIGH There are consistent results from high quality studies. Further research is very unlikely to change the conclusions.

MEDIUM The findings are supported but further research could change conclusions.

LOW Further research is very likely to change the conclusions.

Acute Phase

• All the medications in this guide work equally well to treat the acute phase of depression.
  LEVEL OF CONFIDENCE:
• All these antidepressants are limited by substantial nonresponse rates. Four of every 10 people will not respond to the first medication prescribed.
• There is no evidence to guide selection of the best initial drug for an individual.

Subsequent Phases

• All the antidepressants in this guide can prevent relapse or recurrence of depression, with the exception of duloxetine, which has not been studied.
  LEVEL OF CONFIDENCE:
• Because most clinical trials have examined only the acute phase of major depression, there is little evidence comparing these medications for the continuation or maintenance phases of depression treatment.

Onset of Action

It takes about 6–8 weeks for most people to begin to get the full therapeutic effect of antidepressants.

• Response rates vary initially but are similar after 4 weeks of treatment with citalopram, fluoxetine, mirtazapine, paroxetine, and sertraline.
  LEVEL OF CONFIDENCE:
• If faster onset is important, consider mirtazapine. It brings greater relief of depression within the first month but is similar to other antidepressants beyond 30 days. The faster onset of action should be balanced with the higher likelihood of weight gain.

Second-Line Agent

Consider switching drugs if the initial antidepressant does not relieve symptoms.

• Usually 1 of every 4 people who do not respond to the first antidepressant tried will respond after switching drugs, according to a recent clinical trial known as the STAR-D trial.
• Evidence is insufficient to determine which drug to choose as a second agent.

Accompanying Symptoms

• For people with symptoms of anxiety that accompany their depression, the antidepressants in this guide work equally well in relieving their anxiety.
  LEVEL OF CONFIDENCE:
• The antidepressants in this guide can relieve symptoms that accompany depression, such as insomnia, pain, somatization, melancholia, and psychomotor symptoms. However, the evidence is insufficient to determine if any particular antidepressant works best for any particular symptoms.

Tolerability

Monitoring an individual’s ability to tolerate an antidepressant is important because up to 15 percent of people discontinue their drugs due to side effects.

• People taking venlafaxine are more likely to discontinue due to side effects than people taking any of the SSRIs (11.5 percent versus 8.5 percent).
  LEVEL OF CONFIDENCE:

Side Effect Profiles

• If sexual dysfunction is a concern, consider bupropion.
• If weight gain is a concern, avoid mirtazapine and paroxetine.
• If diarrhea is a concern, avoid sertraline.

Dose and Cost

Dosing regimens and cost may also influence adherence for some individuals. Drugs and prices are listed in the Dose and Price of Selected Antidepressants table.

Table

Dose & Price of Selected Antidepressants.

Weight Change

• Mirtazapine causes higher weight gain than comparator drugs (citalopram, fluoxetine, paroxetine, and sertraline). The mean range of weight gain with mirtazapine at 6–8 weeks of treatment is about 2–7 lbs. However, the variation in weight gain is large, and some people may gain substantially more weight.
  LEVEL OF CONFIDENCE:
• Paroxetine causes higher average weight gains (about 3.6 percent of body weight, or 5 lbs for someone weighing 150 lbs) than does fluoxetine or sertraline. About 25 percent of people on paroxetine gain more than 7 percent of their body weight.
  LEVEL OF CONFIDENCE:
• Bupropion causes modest weight loss (about 2.5 lbs from baseline) compared with placebo.
  LEVEL OF CONFIDENCE:

Nausea and Vomiting

• Nausea and vomiting are the most common clinical reasons people discontinue an antidepressant during the first 30 days of treatment.
  LEVEL OF CONFIDENCE:
• Nausea and vomiting are 10 percent more common for people taking venlafaxine than for people taking SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline).
  LEVEL OF CONFIDENCE:

Sexual Dysfunction

• Fewer people taking bupropion have sexual problems than do people taking fluoxetine or sertraline.
  LEVEL OF CONFIDENCE:
• More people taking paroxetine have sexual problems than do people taking fluoxetine, fluvoxamine, nefazodone, or sertraline (16 percent for paroxetine versus 6 percent for the others).
  LEVEL OF CONFIDENCE:

Diarrhea

• More people taking sertraline (8 percent more) have diarrhea than do people taking bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, or venlafaxine.
  LEVEL OF CONFIDENCE:

Discontinuation Syndrome

• Discontinuation syndrome (acute headache, dizziness, and nausea) is most common for people who abruptly discontinue paroxetine or venlafaxine.
  LEVEL OF CONFIDENCE:
• Discontinuation syndrome is least common with fluoxetine.
  LEVEL OF CONFIDENCE:

Serotonin Syndrome

These antidepressants carry a risk of serotonin syndrome, a potentially life-threatening condition caused by toxic levels of serotonin. Common symptoms include confusion, shivering, sweating, fever, hypertension, tachycardia, tremor, nausea, and diarrhea. Evidence is insufficient to tell us how these antidepressants compare for the risk of serotonin syndrome.

Adult Suicide

The suicide risk for antidepressants has received considerable attention. The evidence is insufficient to draw conclusions about comparative risks of suicide among adults taking the antidepressants in this guide.

In May 2007, the Food and Drug Administration updated the warning that these antidepressants increase the risk of suicide for young adults. The warning, previously for age 18 and younger, was expanded to include those up to age 24.