How reliable are studies of medicines used to treat psychiatric conditions such as anxiety, panic or depression? A quick count of popular antidepressants reveals that more than 40 million Americans filled over 200 million prescriptions for such medications. Another 6 million people filled over 30 million prescriptions for just two anti-anxiety agents, alprazolam (Xanax) and clonazepam (Klonopin). Most doctors pride themselves for practicing “evidence-based medicine (EBM). How good is the evidence for these psych drugs? Do conflicts of interest influence scientific publications promoting alprazolam effectiveness or antidepressant risks?
Alprazolam Effectiveness Against Panic?
It is an article of faith that the very popular anti-anxiety drug alprazolam is the go-to drug to treat panic disorder. How good is the evidence to support that belief?
An article in Psychological Medicine, Oct. 19, 2023 suggests that publication bias may have led to overestimation of the benefits of the anti-anxiety medicine alprazolam. The title of this analysis:
“Unpublished trials of alprazolam XR and their influence on its apparent efficacy for panic disorder”
This benzodiazepine is better known by its brand name Xanax.
The authors of the latest study note that:
“…the consensus view appears to be that benzodiazepines are ‘highly effective’ and ‘efficacious for the short- and long-term treatment of anxiety disorders.'”
The authors note that there have been meta-analyses of published studies demonstrating effectiveness for anxiety disorders.
However, they note:
“…few have searched for unpublished trial data…To our knowledge, no studies have formally investigated publication bias with benzodiazepines by searching for unpublished benzodiazepine trial data in regulatory documents and reassessing their efficacy.”
That is what these investigators did!
The Oregon Health and Science University provided this news release on Oct. 19, 2023:
“They found that five trials had been conducted, but only three of them had been published in medical journals. Further, when the FDA reviewed the drug company’s trial results on how well the drug performed compared with a placebo, Turner said they determined that only one of the five trials had a clearly positive outcome.”
The FDA does not require a drug company to submit or publish data that demonstrate drug disappointments. Think about that for a moment.
Imagine a championship basketball game is down to the last 10 seconds and the score is tied. Someone gets fouled and has two “free throws.” Both miss…but the team requests two more chances and this time they go in and the team wins the game.
Would anyone agree to such a deal? Of course not! And yet the FDA permits additional studies even though the first or second trials fail. What’s worse, neither health care providers nor the public get to see the data from the failed clinical trials if they are not published. What drug company wants to allow publication of a failed trial?
The Skinny on Alprazolam Effectiveness from the Data:
Here is what the authors of the study in Psychological Medicine discovered:
“We found that alprazolam XR may be less effective than the published literature would suggest. According to the published literature, every trial of alprazolam XR found it to be effective. By contrast, according to the FDA, only one of five trials was positive. Consequently, the effect size derived from FDA data (0.33) was substantially lower than the effect size derived from the published literature (0.47)…These findings arguably alter the risk-benefit ratio for the prescribing of this benzodiazepine, especially in the light of recent attention to their contribution to the opioid crisis and the availability of safer alternatives.
“This study brings to light unpublished trial data and provides a more balanced and realistic view of the efficacy of alprazolam XR, compared to what has been previously reported.”
In our opinion, all data submitted to the FDA should be available for public review, including negative studies! Actually, correct that. Especially negative studies!
It’s Not Just Alprazolam Effectiveness…What About Antidepressants and Suicide?
Another study was published on psych drugs that raises concerns about publication bias and conflict of interest. This study was published in the Journal of Clinical Epidemiology, Oct. 2023. The title:
“Observational studies of antidepressant use and suicide risk are selectively published in psychiatric journals”
- “• Based on a systematic review and meta-analysis of 27 observational studies reporting associations between antidepressant use and risk of suicidal behavior, we found that studies with favorable results for antidepressant use (i.e., reduced suicide risk or no effect) are more often published in psychiatric journals than studies with unfavorable results (i.e., increased suicide risk).
- “• Lead-authors with financial conflicts of interest (fCOI) published more favorable results than lead-authors without ties to the pharmaceutical industry, and we found strong evidence of selective publication of studies conducted by lead-authors with fCOI.”
The Authors Offer This Conclusion:
“Studies reporting unfavorable results (increased suicide risk with antidepressant exposure) are less likely to be published in psychiatric journals. Lead authors with fCOI report more favorable results, and their studies are published in the most prestigious psychiatric journals. This may create a biased evidence base and an unbalanced dissemination and appraisal of findings within psychiatry.”
Final Words About Alprazolam Effectiveness and Antidepressants:
If you go back to the top of this article you will see that I reported 46 million Americans are taking antidepressants and/or anti-anxiety agents called benzodiazepines. And that is not a true tally. I did not include benzos like diazepam, lorazepam or temazepam or all the antidepressants that are on the market. My guess is that over 50 million Americans are taking such medications.
Many of these people have not been told that such drugs may be hard to stop. You can listen to our nationally syndicated public radio show interview with a psychiatrist and a patient titled:
Please share your thoughts about publication bias and conflicts of interest in the comment section below. You may also find our article “Benzodiazepine Dependence | A Hard Habit to Kick” of some value.