Are Drug Interaction Warnings Influenced by Drug Company Promotion? An Interview with Dr. Jeffrey Mattes

Last updated: August 28, 2018

 

Dr. Jeffrey Mattes, psychiatrist in Princeton, New Jersey speaks about drug interaction warnings that appear during electronic prescribing and how these warnings may be influenced by drug company promotion.

This interview is part of a series covering the 2018 ASCP Annual Meeting.

Here is the summary of this interview:

  • Drug interaction warnings are issued by drug compendia, which claim to be independent of drug company influence. However, this has been recently questioned and there are examples that point to drug warnings being motivated by drug company promotion.
  • Clinicians should meet these warnings with skepticism and be aware of this potential.

Transcript

Hello everyone, welcome to the Psychopharmacology Institute Podcast. I’m your host, Dr. Wegdan Rashad. Today we are covering yet another interesting topic from the 2018 American Society of Clinical Psychopharmacology Annual Meeting.

We met with Dr Jeffrey Mattes, who is a psychiatrist practicing in Princeton, New Jersey. He shared with us his poster entitled:  Are Drug Interaction Warnings Influenced by Drug Company Promotion?

This thought-provoking interview addresses some evidence that may suggest that the drug warnings that we, as clinicians receive and read about are not entirely transparent.

Dr Mattes speaks about the warnings of serotonin syndrome with the concomitant use of lithium and SSRIs and how it relates to atypical antipsychotic promotion, how drug companies use educational campaigns and research to promote their drugs indirectly and finally some insight from Dr Mattes about what we can do about it.

Dr Rashad: Dr Mattes, what initiated your interest in this subject?

Dr Mattes: Well, the poster was instigated by my prescribing psychotropic medication using electronic prescribing and getting all sorts of warnings which seem to be unnecessary and fallacious. So for example, there’s a warning prescribing lithium with SSRI antidepressants, a warning of interaction that could cause serotonin syndrome. So of course, lithium and antidepressants have been used together for 30 years and there were no reports of this interaction.

When I noticed this warning of lithium and SSRIs causing this major interaction, at the time there was promotion for atypical antipsychotics to be used to augment antidepressants. Adding an atypical antipsychotic given all the side effects that they have would not normally be a first choice, but the drug companies making atypical antipsychotics did studies to get their drug FDA approved to augment antidepressants.

Abilify, for example, could advertise that they were the first and only drug approved to augment antidepressants even though other drugs have been used for many years to augment antidepressants, but they weren’t studied enough to get FDA approval because they were generic. By then, there was no financial incentive to do those studies. So I wondered whether the drug companies making atypicals might somehow be instigating these warnings about using lithium with antidepressants.

Dr Rashad:  Who develops these drug warnings? And in particular for this lithium-SSRI warning you mentioned.

Dr Mattes: So these interaction warnings are developed by drug compendium which provides a considerable amount of information about drugs. And I tried to find out where this warning about lithium and SSRIs came from. Most drug compendia don’t provide any detailed information about where their warnings come from. The only one that provides information is Micromedex and they provide a short summary. Although they had a number of references, only one of the references was to a controlled study using lithium to augment antidepressants. And that study did not show evidence of it causing a serotonin syndrome. The only thing that showed evidence of a serotonin syndrome was some case reports. But case reports in a situation like this are not very meaningful partly because lithium and SSRIs have been used by thousands of patients for many years and they’ve been used in many controlled studies. The validity of a case report is questionable, especially with something like the serotonin syndrome which is a very nebulous diagnosis.

Dr Rashad: Could it be that drug companies really do influence the warnings issued by drug compendia?

Dr Mattes: The drug compendia all say that they have independent boards, assessors and that they’re independent of drug company influence. But there was a paper by a group of researchers from Duke which was commissioned by the Center for Medicaid and Medicare which indicated some reason for concern that drug compendia may be influenced by drug company promotion. They gave a couple of examples but what they found is that the drug compendia seemed to be somewhat selective in its use of references and that their conclusions didn’t seem always to be based on the best evidence available and that it may have been biased towards what would profit the drug companies rather than being an objective evaluation.

So I can’t prove that the drug companies initiated this concern about an interaction between lithium and SSRIs but there is evidence that drug companies do this sort of thing.

Dr Rashad: Interesting. You also mentioned in your poster that drug companies may even promote their drug through highlighting the side effects that a competitor has. Can you elaborate more on this?

Dr Mattes: There were some papers published online when Lilly was being sued for Zyprexa promotion. Those papers showed that Lilly was considering an educational campaign regarding QT prolongation when Geodon was marketed. Now, Geodon was made by another drug company, Pfizer, which was going to compete with Lilly’s Zyprexa. One weakness in regard to Geodon was that it prolonged the QT interval. So Lilly was going to provide education about QT prolongation without directly linking it to Geodon or to Zyprexa but just as an educational effort but the effort really was to encourage Zyprexa use and to discourage Geodon use. So I knew that drug companies do make efforts to publicize side effects from competitors.

Dr Rashad: Can you share with us another example of how drug companies can use research for their own advantage?

Dr Mattes: Well, one other thing, there was a hypnotic, a sleeping pill marketed, Lunesta. When Lunesta marketed, the company that made Lunesta, Sepracor, funded a study, a paper reviewing the evidence that trazodone works for insomnia. Now, trazodone is an old antidepressant. It’s very sedating. So it is actually used more for its sedation. So there are many studies and many reports of using trazodone for sedation but trazodone’s use for sedation became evident pretty much after the drug lost patent protection. It was generic so there were not enough studies with it to get FDA approval for sedation but it’s widely used. Sepracor came out with Lunesta. And they evidently thought it would be in their interest to try to discourage use of trazodone. So they paid someone to write a paper which could be expected that there wasn’t much evidence that trazodone worked for insomnia. Well, there is no evidence. It hasn’t been studied because there was no financial motivation to do so. So it’s no surprise to find out that there wasn’t a lot of good evidence. But that was sort of irrelevant because it’s widely used for insomnia and it has advantages over most sleeping pills because it’s not a controlled drug. It’s not addictive. But that part was not in the paper. The paper just said well, there’s not much evidence it works implying that it shouldn’t be used very much.

Dr Rashad: If drug warnings are indeed influenced by drug companies; Is there anything clinicians can do about this?

Dr Mattes: Yes. Well, I think that clinicians already don’t pay that much attention to drug warnings because many of the drug warnings don’t seem to be accurate. I think in terms of what they can do it’s hard to say. I mean, it’s possible that if more people are concerned about this it might motivate the drug compendia to be a little more transparent, a little more careful about what warnings they include in their databases. Perhaps, it will motivate the FDA to do something, to look at this type of promotion.

But for the average clinician, if they see a warning and they say “Well, should I prescribe lithium or an atypical to augment an antidepressant?” and they get a warning with one and not with the other, they may be inclined to use the atypical even though atypical have a lot side effects that are not really ideal. There are many options like mirtazapine that would really be better but everybody’s worried about being sued. And I can tell clinicians well, they shouldn’t worry so much about the warnings, but it is a warning.

Key Points

  • Drug Interaction warnings are issued by drug compendia which claim to be independent of drug company influence. However, this seems questionable and there are examples that point to drug warnings being motivated by drug company promotion. Clinicians should meet these warnings with skepticism and be aware of this potential.
  • The following people participated in this episode: Dr. Flavio Guzman as the general editor, Andy Rhode as the audio engineer, Pamela Gonzalez as the project manager and myself Dr. Wegdan Rashad as the host and of course, Dr Jeffery Mattes for joining us today.

Thank you for joining us in today’s podcast until the next episode, good bye!

References

  • Mattes J D. (2018): Are Drug Interaction Warnings Influenced by Drug Company Promotion? Conference poster. American Society of Clinical Psychopharmacology Annual Meeting, 2018.
  • McKinney R et al. (2009): Potential Conflict Of Interest in the Production of Drug Compendia. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Apr.

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