19 June 2008


A few days ago I discussed Medscape’s parasitic use of professional organizations to embellish its mediocre CME offerings – “highlights” of the closed 2007 ACNP annual meeting, for example. One of the responses to my post called attention to Dr. George D. Lundberg’s video editorial of 13 June 2008, denouncing attacks on commercially sponsored CME activities. Among other claims, Dr. Lundberg, a past editor-in-chief of JAMA, stated that Medscape “follow(s) rules that prevent bias and improper influence.” He went on to boast that Medscape is “the largest single source of CE for health professionals” and that “We are just going to keep doing what we are doing. It is good. We are clean. Our work is transparent…. We welcome analysis and criticism. We function in the best interests of patients …” These words were spoken before Daniel Carlat and I published our critiques of Medscape a few days later (see here and here and here).

There seems to be a right hand – left hand problem at Medscape. Though I take Dr. Lundberg at his word about his intentions, I invite him to defend the products that actually appear under his oversight as editor-in-chief. Let’s look at a case study of an “Expert Interview” published on-line June 9, 2008 under the tagline Medscape Perspectives on the American Psychiatric Association (APA) 161st Annual Meeting, May 3-8, 2008, Washington, DC. A boilerplate legal disclaimer noted, “This activity is not sanctioned by, nor a part of, the American Psychiatric Association. Conference news does not receive grant support and is produced independently.”

The “Expert Interview” for our case study is titled “Pharmacologic Options for Treatment-Resistant Depression…” The featured expert is Charles Nemeroff, chairman of Emory University’s department of psychiatry. Dr. Nemeroff is well known for ethical controversy. In 2003 the Nature Publishing Group revised their policies on disclosure of financial conflicts of interest in the wake of Dr. Nemeroff’s widely publicized nondisclosures. In 2006 Dr. Nemeroff resigned as editor of the journal Neuropsychopharmacology after he failed to disclose conflicts pertinent to a review article he co-authored and placed in his own journal. As is always true of case studies, the devil is in the details if we wish to understand just how sly and subtle was the spinning. Here are some of the issues that arise from Dr. Nemeroff’s Expert Interview on Medscape.

1. Internal contradiction. The legal disclaimer noted above states that there was no grant support and that the conference news items were produced independently. However, Dr. Nemeroff’s featured item prominently acknowledges an unrestricted educational grant from Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc. These two companies jointly market aripiprazole, a member of a drug class highlighted by Dr. Nemeroff in his Expert Interview.

2. Infomercial format. The Expert Interview by Dr. Nemeroff resembles nothing so much as Lindsay Wagner promoting the Select Comfort Sleep Number Bed in television advertisements. Promotional statements are made without scientific backup.

3. Disease mongering. In this interview, Dr. Nemeroff backed away from his earlier strict definition of treatment-resistant depression (TRD), proclaiming that in his current view 40% to 50% of depressed patients have treatment resistance. This sleight of hand naturally expands the market for the agents he later promotes as augmenting agents.

4. The primary care “hook.” Dr. Nemeroff introduced a professional “hook” to primary care physicians, emphasizing the association of depression with cardiovascular disease. This strategy is a component of disease mongering. Dr. Nemeroff’s discussion of this association had approximately zero educational value. Why did Medscape not insist on more substantive content?

5. Inappropriate drug recommendation. In discussing the switch strategy from one antidepressant class to another for resistant depression, Dr. Nemeroff included a recommendation for nefazodone. That drug was withdrawn by Bristol-Myers Squibb Company several years ago because of hepatic toxicity. What kind of “expert” makes such a recommendation? And what kind of editorial oversight by Medscape waves through such an incompetent statement?

6. Uncritical reliance on uncontrolled studies. In discussing switch of antidepressant drugs, Dr. Nemeroff noted that in phase II of the STAR*D trial 25% of patients switched from citalopram to sertraline responded. Dr. Nemeroff’s discussion of that result was inadequate. He invoked a dubiously relevant effect of sertraline on the dopamine transporter (when you are stuck for an answer, invoke neurochemical mythology) but he ignored the default hypothesis that 25% would have been the placebo response rate had STAR*D been designed to include placebo control groups. This default hypothesis assumes that all SSRI drugs are basically similar in terms of efficacy. For an educational item in Medscape or anywhere else, this aspect of the Expert Interview falls short of expected standards.

7. Pushing dangerous drugs. Dr. Nemeroff has been a leader in promoting use of second generation antipsychotic (SGA) drugs as augmenting agents for resistant depression. I have commented previously on his promotion of risperidone for this purpose, here and here. Others have raised serious questions about his reports. Overall, Dr. Nemeroff promotes these drugs by exaggerating their efficacy and glossing over their toxicity in resistant depression.

8. False statements. In this Expert Interview, Dr. Nemeroff leads off his discussion of SGA drugs for TRD with an endorsement of risperidone. The 2 published references to risperidone in TRD have major scientific flaws. Indeed, the study by Rapaport et al (reference 12 in this interview)was retracted. Nevertheless, Dr. Nemeroff still claims this study supports his position on SGA use in TRD. Does Dr. Nemeroff not read the retractions of his own publications (by his own “research team”)? How naïve are Medscape’s editors to be ignorant of these retractions?

9. Talking up the sponsor’s product. In reviewing the toxicity of SGA drugs for TRD, Dr. Nemeroff found something negative to say about the side effects of olanzapine, quetiapine, and risperidone. However, he made no mention of aripiprazole’s side effects, even though he emphasized its recent approval by the FDA for TRD. How convenient, as BMS-Otsuka sponsored his Medscape spot. Where were Medscape’s editors, described by George Lundberg as working to prevent bias and improper influence?

10. Glossing over weak efficacy. Though Dr. Nemeroff endorsed aripiprazole for TRD, he neglected to discuss the weak efficacy of this drug. The Number Needed to Treat for remission with aripiprazole in TRD is a disappointing 10. The studies cited by Dr. Nemeroff only compared aripiprazole against placebo. Dr. Nemeroff surely knows that just beating placebo does not qualify a drug as clinically useful. Dr. Nemeroff neglected to address the comparative efficacy of aripiprazole versus established treatments of TRD, such as lithium augmentation. The available evidence suggests that patients will do better on lithium and that aripiprazole would not be the first line choice, especially in primary care. Where were Medscape’s editors?

11. Reckless promotion of SGAs early in the course of TRD. Dr. Nemeroff emphatically stated he is not opposed to the early use of SGAs for TRD. Here especially he resembled Lindsay Wagner. A conscientious educator would weigh the risks and benefits of the early and broad use of SGA drugs in TRD. Dr. Nemeroff did no such thing. He simply opined. Why did Medscape’s editors allow him to get away with this reckless promotion? There does not appear to have been any effective editorial oversight of this publication.

12. For Dr. Nemeroff to promote early use of SGAs in TRD is reckless because of the serious toxicity associated with these drugs. Where is the discussion of akathisia (26% in the most recent study of aripiprazole in TRD)? Where is the discussion of emergent suicidality associated with akathisia in depression? Where is the discussion of tardive dyskinesia caused by aripiprazole (5% within 12 months in schizophrenia, and quite possibly higher in mood disordered patients)? Where is the discussion of neuroleptic malignant syndrome associated with SGAs like aripiprazole? Where is the discussion of weight gain with aripiprazole in TRD (significantly greater than with placebo)? Where is the overall analysis of risk versus benefit? Where were Medscape’s editors? Who at Medscape was looking out for “the best interests of patients”?

13. Incomplete disclosures. Dr. Nemeroff has a long history of recidivism concerning failure to disclose pertinent financial conflicts of interest. His record in this instance continues that sordid tradition. He failed to disclose that he is currently chairing a national series of CME meetings promoting aripiprazole for TRD, sponsored by, you guessed it, Bristol-Myers Squibb/Otsuka. Perhaps he thinks that because the money is laundered through a Medical Education Communications Company he doesn’t need to disclose it. Tell that to Joseph Biederman, who was called to task last week by Senator Grassley’s Senate Finance Committee for exactly that obfuscation. Dr. Nemeroff also failed to disclose his support from Janssen for studying risperidone in TRD. He failed to disclose his association with CeNeRx, that is developing MAO inhibitors, mentioned favorably in his interview. There is more, but these examples will suffice. Doesn’t Medscape know by now that Dr. Nemeroff cannot be relied on to report his conflicts appropriately? Does Medscape have knowledgeable professionals or ciphers in its editorial office?

So, this sleazy example illustrates many of the systemic problems that Medscape will need to correct if it hopes to remain credible. This documentation gives the lie to Dr. Lundberg’s claims that “We are clean. Our work is transparent.” One suggestion is for Medscape to abandon the degenerate form of scientific journalism exemplified by “Expert Interviews” and News items. In their present formats they cannot be truly educational and balanced items. They do not qualify for CME credit, as I verified with the company. They are simply vehicles for promoting sponsors’ products. And the Medscape staff seem to think their job is to ensure that the spin is firmly in place. Does George Lundberg really intend that?