Medscape Medical News
May 14, 2009
? Sertraline (Zoloft), one of the oldest selective serotonin-reuptake inhibitors (SSRIs), is superior to a number of other antidepressants in terms of efficacy and tolerability, a new meta analysis shows.
"In the antidepressant literature over the past 20 years, we have been told that all antidepressants are the same," the study's lead author, Andrea Cipriani, MD, from the University of Verona, in Italy, told Medscape Psychiatry. "What we found is that this is not true; there are differences, and these differences are statistically significant."
Despite sertraline doing so well in head-to-head comparisons with other antidepressants, Dr. Cipriani said he is hesitant to conclude that this is a "1-drug-fits-all" agent. Factors such as patient history and clinician comfort level need to be considered in addition to acceptability and efficacy when a physician is prescribing an antidepressant, he said.
A newer SSRI, escitalopram (Lexapro, Forest Laboratories), did well in a separate meta-analysis, although the evidence was not as robust as that for sertraline. Further, unlike the sertraline review, that drug's manufacturer sponsored almost all studies comparing escitalopram with other agents.
Both literature reviews were published in the April 15 issue of the Cochrane Database of Systematic Reviews, a publication of the Cochrane Collaboration, an organization that carries out systematic reviews to critically evaluate medical research.
For the sertraline review, researchers searched several medical databases, including MEDLINE and EMBASE. They included 59 randomized controlled trials allocating a total of 10,000 patients with major depression to sertraline or another antidepressant agent.
Sertraline proved more effective than fluoxetine and more acceptable or tolerable than amitriptyline, imipramine, paroxetine (Paxil, GlaxoSmithKline), and mirtazapine (Remeron, Schering-Plough).
However, the researchers uncovered some differences favoring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion [Wellbutrin, GlaxoSmithKline]). As for adverse effects, sertraline was generally associated with a higher rate of diarrhea.
?I Would Choose Sertraline?
"If I have a patient who responds to another antidepressant, I would not switch to sertraline; however, if I have to prescribe an antidepressant as a first-line treatment for depression, then I would choose sertraline,? said Dr. Cipriani.
Studies in this review looked at efficacy and tolerability, but researchers did not retrieve data about patients' and caregivers' attitude to treatment or patients' ability to return to work and resume normal social functioning.
In the second literature review, researchers searched medical databases for randomized controlled trials comparing escitalopram against any other antidepressant. The reviewers included 22 trials totaling about 4000 participants
The analysis included 14 trials comparing escitalopram with another SSRI and 8 comparing escitalopram with a newer antidepressant agent (venlafaxine [Effexor, Wyeth], bupropion, and duloxetine [Cymbalta, Eli Lilly]). This review found that escitalopram was significantly more effective than citalopram (Celexa, Forest Pharmaceuticals) in achieving acute response and remission. As well, significantly fewer patients taking escitalopram withdrew from trials compared with patients taking duloxetine. The authors concluded that escitalopram appears to be "suitable? as a first-line antidepressant treatment for moderate to severe major depression.
A drawback to this review is that it included studies that compared escitalopram with newer antidepressants but not to older antidepressants such as tricyclics or monoamine oxidase inhibitors (MAOIs), said Dr. Cipriani. "By contrast, we had these kinds of comparisons for the sertraline review."
Cost a Consideration
A major consideration with escitalopram is that it is not yet available in lower-cost generic form. The drug is still under patent and probably will continue to be for another 2 to 3 years, said Dr. Cipriani.
When asked which of the 2 drugs under review he uses more often in his own practice, Dr. Cipriani said: "I usually use sertraline, but if the patient has already tried sertraline, then escitalopram would be a good second choice."
Dr. Cipriani stressed the potential in drug studies for overestimation of treatment effect due to sponsorship bias. Whereas about 40% to 50% of the studies included in the sertraline review were sponsored by the pharmaceutical industry, most studies in the escitalopram review were sponsored by that drug's manufacturer. This, he said, presented "likely" biases.
"Looking at the data we have, escitalopram is a very good antidepressant, but there might be some biases in terms of sponsorship bias and what we call publication bias, where studies with no statistically significant difference favoring the investigational drug may not get published," he said.
Favorable Balance
The results of the Cochrane reviews were supported by another, recent antidepressant meta-analysis carried out by Dr. Cipriani and colleagues (Cipriani A et al. Lancet. 2009;373:746-58). That review found that sertraline might be the best choice for treating moderate to severe major depression because it has the most favorable balance between benefits, acceptability, and cost. That review also found that escitalopram, too, has a favorable profile.
Entirely free of any potential funding bias, the researchers analyzed 117 head-to-head randomized trials that included almost 26,000 patients. The studies examined efficacy (at least 50% symptom reduction at 8 weeks) and acceptability (dropout rates for any reason during the first 8 weeks of treatment).
In addition to sertraline and escitalopram, 2 other drugs ? mirtazapine and venlafaxine ? also emerged as superior in efficacy. Sertraline, along with escitalopram, bupropion, and citalopram, came out ahead in terms of acceptability.
Still More to Do
In an editorial accompanying the Lancet article (Lancet. 2009;373:700-701), Sagar Parikh, MD, from the University of Toronto, in Ontario, said findings such as these have "enormous implications" for practitioners. "Now, the clinician can identify the 4 best treatments, identify individual side-effect profiles, explore costs and patients' preferences, and collaborate in identifying the best treatment for that patient."
He added that a "new gold standard" of reliable information has been compiled for patients to review.
Although these reviews provide clinicians with helpful information to make treatment choices, they do not go far enough, added Dr. Cipriani. "We still don't have any clear and robust rationale to choose 1 drug or another for a generic patient in our outpatient clinic because we don't have any marker that could predict response to 1 treatment or another."
That situation may change. Dr. Cipriani and his colleagues plan to access the "raw" data used in the various studies to help determine individual response to drugs. "If we have individual patient data, we may, for example, analyze and compare response rates for females with depression and males with depression or compare scores in terms of severity of illness."
This has already been done to a certain degree with at least 1 drug. Researchers at Oxford University, in the United Kingdom, have determined that lamotrigine (Lamictal, GlaxoSmithKline), a treatment for bipolar disorder, works better in patients with more severe illness than in those with less severe illness, said Dr. Cipriani.
Cochrane Database Syst Rev. 2009;2:CD006117 Abstract, CD006532. Abstract
May 14, 2009
? Sertraline (Zoloft), one of the oldest selective serotonin-reuptake inhibitors (SSRIs), is superior to a number of other antidepressants in terms of efficacy and tolerability, a new meta analysis shows.
"In the antidepressant literature over the past 20 years, we have been told that all antidepressants are the same," the study's lead author, Andrea Cipriani, MD, from the University of Verona, in Italy, told Medscape Psychiatry. "What we found is that this is not true; there are differences, and these differences are statistically significant."
Despite sertraline doing so well in head-to-head comparisons with other antidepressants, Dr. Cipriani said he is hesitant to conclude that this is a "1-drug-fits-all" agent. Factors such as patient history and clinician comfort level need to be considered in addition to acceptability and efficacy when a physician is prescribing an antidepressant, he said.
A newer SSRI, escitalopram (Lexapro, Forest Laboratories), did well in a separate meta-analysis, although the evidence was not as robust as that for sertraline. Further, unlike the sertraline review, that drug's manufacturer sponsored almost all studies comparing escitalopram with other agents.
Both literature reviews were published in the April 15 issue of the Cochrane Database of Systematic Reviews, a publication of the Cochrane Collaboration, an organization that carries out systematic reviews to critically evaluate medical research.
For the sertraline review, researchers searched several medical databases, including MEDLINE and EMBASE. They included 59 randomized controlled trials allocating a total of 10,000 patients with major depression to sertraline or another antidepressant agent.
Sertraline proved more effective than fluoxetine and more acceptable or tolerable than amitriptyline, imipramine, paroxetine (Paxil, GlaxoSmithKline), and mirtazapine (Remeron, Schering-Plough).
However, the researchers uncovered some differences favoring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion [Wellbutrin, GlaxoSmithKline]). As for adverse effects, sertraline was generally associated with a higher rate of diarrhea.
?I Would Choose Sertraline?
"If I have a patient who responds to another antidepressant, I would not switch to sertraline; however, if I have to prescribe an antidepressant as a first-line treatment for depression, then I would choose sertraline,? said Dr. Cipriani.
Studies in this review looked at efficacy and tolerability, but researchers did not retrieve data about patients' and caregivers' attitude to treatment or patients' ability to return to work and resume normal social functioning.
In the second literature review, researchers searched medical databases for randomized controlled trials comparing escitalopram against any other antidepressant. The reviewers included 22 trials totaling about 4000 participants
The analysis included 14 trials comparing escitalopram with another SSRI and 8 comparing escitalopram with a newer antidepressant agent (venlafaxine [Effexor, Wyeth], bupropion, and duloxetine [Cymbalta, Eli Lilly]). This review found that escitalopram was significantly more effective than citalopram (Celexa, Forest Pharmaceuticals) in achieving acute response and remission. As well, significantly fewer patients taking escitalopram withdrew from trials compared with patients taking duloxetine. The authors concluded that escitalopram appears to be "suitable? as a first-line antidepressant treatment for moderate to severe major depression.
A drawback to this review is that it included studies that compared escitalopram with newer antidepressants but not to older antidepressants such as tricyclics or monoamine oxidase inhibitors (MAOIs), said Dr. Cipriani. "By contrast, we had these kinds of comparisons for the sertraline review."
Cost a Consideration
A major consideration with escitalopram is that it is not yet available in lower-cost generic form. The drug is still under patent and probably will continue to be for another 2 to 3 years, said Dr. Cipriani.
When asked which of the 2 drugs under review he uses more often in his own practice, Dr. Cipriani said: "I usually use sertraline, but if the patient has already tried sertraline, then escitalopram would be a good second choice."
Dr. Cipriani stressed the potential in drug studies for overestimation of treatment effect due to sponsorship bias. Whereas about 40% to 50% of the studies included in the sertraline review were sponsored by the pharmaceutical industry, most studies in the escitalopram review were sponsored by that drug's manufacturer. This, he said, presented "likely" biases.
"Looking at the data we have, escitalopram is a very good antidepressant, but there might be some biases in terms of sponsorship bias and what we call publication bias, where studies with no statistically significant difference favoring the investigational drug may not get published," he said.
Favorable Balance
The results of the Cochrane reviews were supported by another, recent antidepressant meta-analysis carried out by Dr. Cipriani and colleagues (Cipriani A et al. Lancet. 2009;373:746-58). That review found that sertraline might be the best choice for treating moderate to severe major depression because it has the most favorable balance between benefits, acceptability, and cost. That review also found that escitalopram, too, has a favorable profile.
Entirely free of any potential funding bias, the researchers analyzed 117 head-to-head randomized trials that included almost 26,000 patients. The studies examined efficacy (at least 50% symptom reduction at 8 weeks) and acceptability (dropout rates for any reason during the first 8 weeks of treatment).
In addition to sertraline and escitalopram, 2 other drugs ? mirtazapine and venlafaxine ? also emerged as superior in efficacy. Sertraline, along with escitalopram, bupropion, and citalopram, came out ahead in terms of acceptability.
Still More to Do
In an editorial accompanying the Lancet article (Lancet. 2009;373:700-701), Sagar Parikh, MD, from the University of Toronto, in Ontario, said findings such as these have "enormous implications" for practitioners. "Now, the clinician can identify the 4 best treatments, identify individual side-effect profiles, explore costs and patients' preferences, and collaborate in identifying the best treatment for that patient."
He added that a "new gold standard" of reliable information has been compiled for patients to review.
Although these reviews provide clinicians with helpful information to make treatment choices, they do not go far enough, added Dr. Cipriani. "We still don't have any clear and robust rationale to choose 1 drug or another for a generic patient in our outpatient clinic because we don't have any marker that could predict response to 1 treatment or another."
That situation may change. Dr. Cipriani and his colleagues plan to access the "raw" data used in the various studies to help determine individual response to drugs. "If we have individual patient data, we may, for example, analyze and compare response rates for females with depression and males with depression or compare scores in terms of severity of illness."
This has already been done to a certain degree with at least 1 drug. Researchers at Oxford University, in the United Kingdom, have determined that lamotrigine (Lamictal, GlaxoSmithKline), a treatment for bipolar disorder, works better in patients with more severe illness than in those with less severe illness, said Dr. Cipriani.
Cochrane Database Syst Rev. 2009;2:CD006117 Abstract, CD006532. Abstract
