A recently published guideline on the recognition and management of mixed depression fails to meet standards of trustworthiness and of disclosure of conflicts of interest by the majority of the authors, raising serious concerns, say three researchers who took a deep dive into the guideline.
The guideline was published in the April 2017 issue of CNS Spectrums, which was a theme issue devoted to mixed features in mental disorders.
As reported by Medscape Medical News at that time, the guideline writers conclude that one third or more of adults who are diagnosed with major depression have depression with mixed features and probably would derive more benefit by taking an antipsychotic than an antidepressant.
But the guideline raised red flags with Lisa Cosgrove, PhD, of the University of Massachusetts, Boston, Allen Shaughnessy, PharmD, of Tufts University School of Medicine, Boston, and Terrence Shaneyfelt, MD, of the University of Alabama, Birmingham.
When they got into “the weeds” of the guideline, they found that four of the seven studies put forth as evidence for recommending antipsychotics for mixed depression were post hoc analyses.
“That’s a big no-no. Post hoc analyses should only be used to generate hypotheses for future research — they should not be used as evidence of the efficacy of an intervention,” Dr Cosgrove told Medscape Medical News.
The report was published online January 25 in BMJ Evidenced-Based Medicine.
A Public Health Issue
The researchers are also concerned about the guideline’s frontline recommendation for lurasidone (Latuda, Sunovion Pharmaceuticals) and asenapine (Saphris, Actavis) for mixed depression.
“These are very expensive on-patent drugs, and when we looked at the clinical trial data more closely, it was clear that there weren’t enough data to support the recommendation that was made for second-generation antipsychotics for mixed depression,” said Dr Cosgrove.
The guideline also runs the risk of widening diagnostic boundaries and unnecessarily exposing people to treatment, the researchers conclude.
The guideline expands the diagnostic criteria for depression with mixed features by including criteria that do not appear in the Diagnostic and Statistical of Mental Disorders, Fifth Edition (DSM-5). However, the guideline fails to provide “adequate empirical support for their significant expansion of these criteria,” the researchers write.
“Our main concern is the potential for overdiagnosis and therefore overtreatment when you expand diagnostic criteria, which this guideline does, in terms of what constitutes mixed symptoms,” Dr Cosgrove said.
The three researchers also worry that the guideline contains no description of the process used to develop the recommendations, no report of a systematic review of the evidence being used, and no report on how evidence was evaluated for quality (evidence was not graded, and there was no rating of the strength of recommendations). In addition, there does not appear to have been any external review of the guideline prior to publication.
They are also concerned that some of the symptoms that the guideline suggests are indicative of mixed depression, such as insomnia, irritability, and rumination, are classic symptoms of unipolar depression. The guideline also encourages clinicians to look for evidence of subthreshold symptoms and emphasizes that mixed depression is significantly underdiagnosed in clinical practice and is especially common in children and adolescents.
“When you dig into the details, it becomes more apparent how the language in the guideline could really lead to overdiagnosis and overtreatment, particularly in children and adolescents. To us, this is really a public health issue,” said Dr Cosgrove.
Guideline or Industry-Friendly Opinion Piece?
In addition, the researchers note, potential financial conflicts of interest (FCOI) abound in this guideline. More than half of the authors disclosed ties to drug companies that manufacture antipsychotic medications recommended in the guideline, and there was no information about the management of FCOI, they point out. Five of the guideline authors served on speakers’ bureaus, including the lead author, who serves on the speakers’ bureau for Sunovion, the manufacturer of lurasidone.
“While any financial arrangement is considered to be a conflict of interest, participation on speakers’ bureaus — an extension of the marketing departments of manufacturers — is widely recognized to constitute a significant conflict of interest,” they write.
The lead author of the guideline is Stephen M. Stahl, MD, PhD, University of California, San Diego, and chairman of Neuroscience Education Institute in Carlsbad, California. Medscape Medical News reached out to Dr Stahl for comment and was told through his assistant that he was unavailable because he was out of town.
Dr Cosgrove and her colleagues believe it’s time for the United States to consider adopting a national guideline assessment process. Consolidating guideline development efforts would likely improve guidelines, they say.
“We do not need multiple guidelines [often recommending different things] on the same topic developed by multiple groups. Guideline development needs to be prioritized for those diseases with significant practice variability and for which a valid evidence base can guide recommendations. Guideline development should be commissioned to panels with demonstrated technical and clinical expertise.”
To achieve this, they say guideline development should be centralized under the guidance of the Agency for Healthcare Research and Quality in the United States or similar organizations in other countries. “Until this happens, we will continue to see the proliferation of industry-friendly opinion pieces, not genuine guidelines, developed by conflicted experts,” they conclude.
Dr Cosgrove, Dr Shaughnessy, and Dr Shaneyfelt have disclosed no relevant financial relationships.
Evid Based Med. Published online January 25, 2018. Full text
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