Popularity Doesn't Necessarily Make Prozac Best Antidepressant Choice

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The review also compared the tolerability of fluoxetine and several other often-prescribed antidepressants. Patients found fluoxetine more tolerable than both Elavil or Endep (amitryptilline) and Tofranil (imipramine).

Cipriani, a psychiatrist at the University of Verona in Italy, said in an e-mail, "Fluoxetine, the most widely studied SSRI, has progressively replaced amitriptyline and imipramine as the standard of comparison for newer medications. We chose fluoxetine because of its long-time position as the market leader and because it has been often used as a reference compound for newer [antidepressants]."

Psychiatrist Xavier Amador, a member of the board of directors for the National Alliance for the Mentally Ill, said, "Prozac was available years before other SSRIs. Since, as a group, the SSRIs were far safer than [earlier antidepressants] the first one, Prozac, became hugely popular. It has tremendous name recognition for this reason."

The review appeared in the latest issue of the Cochrane Library. The Cochrane Library is a publication of The Cochrane Collaboration, an independent international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The review pooled data from 132 published randomized controlled trials, with effectiveness data on 9,311 participants and of tolerability data on 14,391 participants, both inpatients and outpatients diagnosed with depression, without other ongoing medical problems.

The researchers looked at SSRIs, tricyclic and heterocyclic antidepressants, and newer antidepressants. The researchers analyzed participants' scores on several diagnostic scales for depression, comparing measurements on Prozac with other antidepressants.

Results were mixed: Prozac was found less effective than Prothiaden (dothiepin), Zoloft, Remeron (mirtazapine) and Effexor but more effective than the antidepressants ABT-200 and milnacipran. Prozac was better tolerated than tricyclic antidepressants as a group and with other individual antidepressants.

"Although the better effectiveness profile of sertraline and venlafaxine over fluoxetine seems meaningful, it needs further investigation," Cipriani said, noting that studies were short, usually eight weeks or less. "This limits the ability of the studies to show clinically meaningful differences," he said. "We need more robust and pragmatic evidence, free from industry influence."

According to Cipriani, fluoxetine's huge success has occurred despite the fact that "results from randomized clinical trials did not clearly indicate that it offered substantial benefits over conventional agents." Many studies have compared fluoxetine with other antidepressants, but he said a major problem with some of these studies is "that they have analyzed the SSRIs as a group and evidence applicable to this group of drugs might not be entirely applicable to fluoxetine alone."

Until additional, robust, unbiased evidence becomes available, Cipriani said that clinicians ought to base their selection upon considerations of drug toxicity, patient acceptability and cost.

"The great majority of randomized controlled trials have been sponsored by pharmaceutical industry and data have shown a possible relationship between industry sponsorship and trial outcomes," said Cipriani, "We need further analyses on the possible confounding role of sponsorship and new tools to improve the quality of evidence."

The review notes that one of its co-authors has received fees for speaking and research grants from pharmaceutical companies that market antidepressants, and another has received funding and support from two companies that manufacture SSRIs.

Center for the Advancement of Health