Applied Evidence

Answers to your questions about SSRIs

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Which SSRI is best? What drug interactions should you be most concerned about? The authors provide evidence-based answers to 7 frequently asked questions.


 

References

PRACTICE RECOMMENDATIONS

Avoid prescribing a highly activating SSRI, such as fluoxetine, for patients for whom agitation is a presenting symptom. B

Consider citalopram and escitalopram, which have less potential for drug interactions and less complex dose titration compared with other SSRIs, as first-line agents for depressed patients with complex medication profiles. C

For patients with sexual side effects caused by SSRIs, consider augmentation therapy with bupropion or mirtazapine; for male sexual dysfunction, a trial of a phosphodiesterase inhibitor is another alternative. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Shortly after the US Food and Drug Administration (FDA) approved fluoxetine for the treatment of major depression nearly a quarter of a century ago, Prozac became a household name. And, as a handful of additional selective serotonin reuptake inhibitors (SSRIs) were approved, the popularity of this category of antidepressant continued to grow.1 In 2008, 5 of the 6 SSRIs on the US market (fluvoxamine was the exception) were among the 200 most frequently dispensed prescription drugs.2

While much has been written about the properties of SSRIs, uncertainty about many features of particular agents and what should be considered in selecting an antidepressant for a particular patient remains. To help clear up the confusion, we’ve addressed 7 questions about SSRIs that we are often asked. Although there are no simple answers, the evidence presented, both in the answers and in the tables that follow, will help primary care physicians make more informed choices for patients who require antidepressant therapy.

1. Which is the best SSRI to start a patient on?

A recent meta-analysis of 117 head-to-head studies assessed the efficacy and acceptability of 12 newer antidepressants, including all 6 SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline).3 The researchers found 2 SSRIs, sertraline and escitalopram, to be superior to the other medications studied on both counts. A choice between sertraline or escitalopram may be a reasonable starting point in many cases, but it is impossible to recommend 1 or 2 SSRIs that are effective for all patients. There are several reasons for this.

The first is addressed by the Cipriani meta-analysis. The researchers assessed the efficacy of initial antidepressant therapy at 8 weeks, so the results cannot be extrapolated to long-term response rates or acceptability. (For a detailed review of the meta-analysis, see “Try these 2 drugs first for depression,” J Fam Pract. 2009;58:365-369.)

A second reason is the substantial publication bias associated with studies of antidepressants. Turner et al assessed 74 studies registered with the FDA, determined whether the results were positive or negative, and categorized the studies based on publication status.4 Their conclusions: 97% of studies with positive findings (n=38) were published.

The majority of the remaining studies, all of which were determined to have negative findings, were either not published or published in a manner that suggested a positive outcome. When these additional studies are taken into account, the percentage of published studies with a positive response drops to 51%.4 In addition, the effect size of each agent is reduced when all the studies are included.

There are many confounding variables associated with publication, so Turner and his colleagues were unable to definitively determine the reason for the disparity. Nonetheless, their evaluation raises questions about the reported effectiveness, not only of SSRIs, but of antidepressants in general.

A recent Cochrane review of SSRIs for treatment of depression in children and adolescents (a topic covered in greater detail in the answer to Question 6) raised similar concerns. The reviewers cited study methodology and recruitment methods as potential sources of the conflicting results they found.5

Finally, individual differences, such as age, comorbidities, and medication history, require an individualized approach to SSRI treatment.

2. Which side effects are common to all SSRIs, and which can be resolved by switching agents?

As a class, SSRIs are well tolerated, but they do have some common adverse effects, most notably gastrointestinal (GI) problems, sexual dysfunction, and sleep disturbances. There are also considerable differences in SSRI profiles and a few adverse effects that a switch to another SSRI may alleviate or resolve.

Compared with other SSRIs, for example, sertraline has a higher risk of diarrhea, but this adverse event does not usually lead to medication discontinuation. If it is bothersome to the patient or does not resolve with continued therapy, a change to another agent might eliminate this adverse effect.

Weight gain has been found to be more significant with paroxetine than with fluoxetine or sertraline, which may be due to the anticholinergic action of the drug.6 For someone who is particularly concerned about extra weight, avoiding paroxetine in the first place, or changing a patient who’s already taking it to fluoxetine or sertraline, might be an effective treatment strategy.

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