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Unimpressive Results For Atyp Antip In Depression

Posted by Phillipa on March 19, 2013, at 21:19:47

Seems the use of atypical antipsychotics for major depression is more risk than benefit with almost no improvement noted. Phillipa


Medscape Medical News > Psychiatry

'Unimpressive' Evidence Base for Antipsychotics in Depression

Megan Brooks
Mar 18, 2013




Adding an atypical antipsychotic to an antidepressant provides a small to moderate improvement in depressive symptoms in adults, new research suggests.

The meta-analysis also shows that the benefits of adjunctive antipsychotics in terms of quality of life and improved functioning are small to nonexistent, and according to investigators, there is "abundant evidence of potential treatment-related harm."

"The rapidly increasing use of atypical antipsychotics for treatment-resistant depression is based on a rather unimpressive evidence base," study author Glen Spielmans, PhD, associate professor, Department of Psychology, Metropolitan State University in St. Paul, Minnesota, who worked on the review, told Medscape Medical News.

"It is likely wise to carefully examine options linked to fewer adverse events before considering use of an atypical antipsychotic for treating depression," he added.

The study was published online March 12 in PLoS Medicine.

Small to Moderate Effect

For the analysis, the researchers identified 14 randomized controlled trials that compared adjunctive antipsychotic medications (aripiprazole, olanzapine/fluoxetine combination [OFC], quetiapine, or risperidone) to placebo in the treatment of depression unresponsive to antidepressant medication alone. The trials lasted from 4 to 12 weeks.

All 4 antipsychotics had statistically significant albeit small to moderate effects on remission, with odds ratios ranging from 1.42 to 2.37. Remission was usually defined as a score of less than 8 at the study end point on the Montgomery-Ǻsberg Depression Rating Scale. The researchers note that the number needed to treat (NNT) for 1 patient to achieve remission was 19 for OFC and 9 for all other drugs.

All of the antipsychotic medications except OFC also significantly improved response rates (defined as a 50% improvement in depression rating score), with odds ratios ranging from 1.53 to 2.07. The NNT for 1 patient to achieve a response was 7 with aripiprazole, 8 with risperidone, and 10 with quetiapine.

However, the medications provided little or no benefit in terms of functioning and quality of life, except for risperidone, which had a small to moderate effect on quality of life (Hedges g = 0.49).


Dr. Glen Spielmans

Adjunctive treatment with atypical antipsychotic medications was linked to several adverse effects, "although the drugs varied in their adverse event profiles somewhat," Dr. Spielmans said.

Common side effects included weight gain (for all 4 drugs), akathisia (with aripiprazole), sedation (with quetiapine, OFC, and aripiprazole), and abnormal metabolic laboratory results (with quetiapine and OFC).

The researchers say "shortcomings in study design and data reporting, as well as use of post hoc analyses, may have inflated the apparent benefits of treatment and reduced the apparent incidence of adverse events."

Dr. Spielmans pointed out that long-term efficacy and safety of these agents are "unknown" and that "no research has compared atypical antipsychotics to other options for treatment-resistant depression, such as switching antidepressants or adding psychotherapy."

Uncertain Risk-Benefit Ratio

"It's just not certain that these drugs have a favorable benefit-to-risk profile, and they really do need to be compared against other existing standards and alternatives," Michael Thase, MD, professor of psychiatry at the University of Pennsylvania Perelman School of Medicine in Philadelphia, who was not involved in the study, told Medscape Medical News.

The results of this new meta-analysis basically show that the benefits of these antipsychotics for depression are "modest and that each of these drugs has particular tolerability that are fairly clear," Dr. Thase added.



Information from Industry

He also noted that this new meta-analysis has a "somewhat more cautionary, less upbeat spin" on this topic than 2 prior meta-analyses (Nelson et al, Am J Psychiatry 2009;166:980-991, and Papakostas et al, J Clin Psychiatry 2007;68:826-831). He said the basic findings of the 3 meta-analyses are "pretty much the same; the major difference is interpretive."

At the end of the day, clinicians "are very careful and should be very careful in using these medications," Dr. Thase said.

Dr. Spielmans is a member of Healthy Skepticism and holds shares of less than $10,000 in a mutual fund (Vanguard Health Care) that invests in pharmaceutical firms. A complete list of author disclosures is given in the article. Dr. Thase has disclosed no relevant financial relationships.

PLoS Med. Published online March 2013

 

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