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Dr. Block was just told by his nurse that Mr. Green had been “squeezed” into his schedule at lunchtime tomorrow. This is Mr. Green’s fifth visit in 9 weeks. Mr. Green is a 54-year-old high school football coach who is being treated for major depression. His wife called, very upset, to make the appointment and told the nurse that “his medicine is just not working, and he is really bad.” Mr. Green has tried two different types of antidepressant drugs before the currently prescribed medication. One was changed after 14 days because of intolerable side effects, and the second was changed after 3 weeks because of a combination of side effects and lack of improvement. Dr. Block reviewed Mr. Green’s record and pondered what to do next. During a previous discussion about potential treatment options, Mr. Green said that he does not believe in counseling because “he tried it when he lived in Michigan and it does not work.”

Dr. Block must consider the advantages and disadvantages of the available treatment options for this patient: (1) switch to another antidepressant, (2) augment the current antidepressant with a second agent, (3) try to persuade the patient to get counseling in addition to medication, (4) consider electroconvulsive therapy (ECT), or (5) refer him for repeated transcranial magnetic stimulation (r-TMS) treatment. What to do? Then he remembers having seen some recent reports on advances in depression treatment, and he decides to search for evidence on the comparative effectiveness (CE) of the approaches that he is considering for Mr. Green.

To find a summary of the evidence, he first searches the website of the Agency for Healthcare Research and Quality (AHRQ). He finds a list of Clinician Research Summaries, including one on “Non-pharmacologic Interventions for Treatment-Resistant Depression in Adults” (AHRQ Clinician Research Summaries, 2012). Great, he thinks, my problem is solved. That is until he sees that the summary identifies a number of important gaps in the knowledge in the studies reviewed, including (1) information on quality of life is substantially missing from the studies; (2) few studies compare nonpharmacologic interventions with each other or with pharmacologic interventions or combinations of treatments; (3) there is almost no evidence on how the CE might differ for patient subgroups defined by age or sex; and (4) the studies use inconsistent measures of treatment resistance, clinical outcomes, and adverse events and have short follow-up periods.

When he retrieves the full research report (, he finds that most of the studies were published before 2008 and thus are 6 or more years old and not clearly relevant to his current patient. Shaking his head at the clear lack of external validity and relevance of these studies to his clinical problem, he gives up and decides he will have to spend some time doing more detailed searches for evidence tonight after dinner.

This physician is ...

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