Review Articles of the Month–Emphasis Psychiatry

Like most physicians, I subscribe to several medical education and CME sites.  One of my favorites is Primary Care Medical Abstracts.  PCMA chooses 30 papers a month of interest to primary care physicians and then these papers are reviewed by two physicians (usually Rick Bukata and Jerry Hoffman).  The reviews are insightful and funny and pretty fun to listen to.  These guys have no problem calling B.S. when they review certain papers.  I like that!  (By the way, I have no affiliation with PCMA).

Each month, I find that of the 30 articles reviewed, maybe half have applicability to correctional medicine.  That is enough to keep me listening!  This month’s issue reviewed three psychiatry papers in a row that I thought were quite interesting and which I want to summarize here.  You can click on the titles below to go to the article abstracts in Pubmed.

The Efficacy and Safety of Alprazolam versus other Benzodiazepines in the Treatment of Panic Disorder, Moylan, S., et al, J Clin Psychopharm 31(5):647, October 2011

Despite the fact that published guidelines and psychiatric textbooks call for SSRIs and TCAs to be used as the primary agents for the treatment of anxiety and panic disorder, and for benzodiazepines to be used second line and rarely chronically, in actual clinical practice, benzodiazepines are really the most prescribed first line agents, and Xanax is prescribed most of all.  In fact, I was surprised to learn that Xanax is the number one prescribed psychotropic agent in the US!  This paper reviewed eight trials that compared alprazolam with other benzodiazepines in the treatment of panic disorder and anxiety.  Their conclusion is that alprazolam offers no benefits over other benzodiazepines but that it does cause more problems.  Patients using alprazolam compared to other benzodiazepines have an increased risk of abuse, are more prone to withdrawal and dependence, and are particularly prone to rebound anxiety.  The authors also note that alprazolam is more toxic in overdose than other benzos.

Hopefully, none of use uses alprazolam in our correctional facilities, but we certainly see plenty of patients come into our care taking this agent.

Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-label Uses in Adults:  A Systematic Review and Meta-analysis, A.R., et al, JAMA 306(12):1359, September 28, 2011

This is a big study published in JAMA that reviewed 162 studies of off-label use of antipsychotics.  The original authors of this study found 14 out of 162 studies that showed some benefit of atypical antipsychotics in certain situations although they admit that this benefit is inconsistent across all of the studies.  The PCMA reviewers argue that the reported benefit was “tiny” and likely a statistical phenomenon rather than real clinical benefit; i.e., if you do 162 studies, a few are going to show benefit just by chance alone.  On the other hand, the paper documents ample evidence of real harm caused by the atypicals, especially in the elderly.  As one example, elderly patients taking atypical antipsychotics have an increased risk of death and stroke; the  Number Needed to Harm was 87 for death and 54 for stroke.  If you take all patients (young and old) and all harms, including weight gain, extrapyramidal symptoms, etc. the Number Needed to Harm is one in ten.  The PCMA authors conclude that the reported risks far outweigh the reported benefits.

Antidepressant Use and Risk of Adverse Outcomes in Older People:  Population Based Cohort Study, Coupland, C., et al, Br Med J 343:d4551, August 23, 2011

In Britain, 10-15% of people older than 65 are prescribed antidepressants for depression.  This study followed more than sixty thousand of these patients over 10+ years and compared them with a group not taking antidepressants.  This was a big study.  The group taking antidepressants had a much increased risk of several serious adverse events including suicide, death (from all causes), falls, fractures and, weirdly, GI bleeds (I didn’t see that one coming).  But the risk for each of these bad events varied widely depending on what antidepressants were being used.  patients taking SSRIs and mirtazepine/venlafaxine were much more likely to die than those taking TCAs.  (Here are the absolute numbers.  Remember that these were elderly patients.  If you were taking no antidepressant, your chance of dying within any given year was 7.04%.  If you were taking a TCA, this risk went up to 8.12%.  For SSRIs, it rose to 10.61% and for mirtazepine/venlafaxine, the chance of dying within one year was 11.43%.  I find this astounding.  I would have thought that the SSRIs would be the “safest” antidepressants.  Of note also is that the TCAs themselves are not equal.  Trazodone has a mortality risk at least as bad as the SSRIs and the “others.”  (Note the comparison chart at the beginning of the article).

Here is where it gets even more interesting.  Patients taking SSRIs were at increased risk for having heart attacks compared to those taking no anti-depressant–but patients taking Tricyclics or “Other” antidepressants (mirtazepine and venlafaxine) had no increased risk of heart attacks.  Patients taking SSRIs and “other” antidepressants had increased risk of stokes, but not those taking TCAs.

Anyway, quite an interesting article.  It would appear that, in the elderly at least, SSRIs have more adverse effects than do TCAs.

Any comments?  I would love to hear your opinion.

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9 thoughts on “Review Articles of the Month–Emphasis Psychiatry

  1. Aldo Torrente

    I think that all these studies have to be taken with a grain of salt.
    Every medication has a potential for doing harm, but that does not mean that we are not going to rule out its use.
    Therefore, I believe that, as in every situation, we have to balance pros and cons, and even do a trial to see the results.
    More and more the medical studies around the world are becoming a shameful charade in the quest of their authors to obtain research money.
    Consequently, I am more and more leery every day about the results of medical research.
    Money taints every thing!
    Aldo Torrente, PA-C

    Reply
    1. Jeffrey Keller Post author

      Hi Aldo,
      Don’t throw in the towel yet! Like most things, there are good studies and bad studies and everything in between. It’s OK to take these studies with a grain of salt but it is important to recognize that at least half of what we were taught is wrong–we just don’t know which half–and the good studies are what expose this. In my career, I have noticed a definite trend, though. When new drugs are introduced, they are touted and marketed as wonderfully efficacious with little in the way of adverse effects. But as time goes on, and the drugs are studied more and more, the benefit shrinks and the negative effects grow larger. So I am not surprised anymore when that happens yet again!

      Reply
  2. Roger S Buck MD

    Regarding SSRI use, especially in the elderly, there was a 50% increase risk for bleeding when taken with either aspirin or plavix, versus taking either anti-platelet drug alone. This was reported in Journal Watch 12/15/2011, referencing a study published in CMAJ 2011 Nov8; 183:1835.

    Reply
    1. Jeffrey Keller Post author

      Interesting, Roger! Nobody would have predicted that. It just goes to show us that medications have all sorts of side effects that we are not aware of. They tend not to be noticed in the initial trials because obody looked for them. who would ever think that the SSRIs might affect platelets?

      Reply
  3. Tim Burbach

    I’m curious about alprazolam being more toxic than other benzos in overdose. Is this in comparison with other short-acting benzos? I was under the impression that its shorter half-life allowed quicker elimination and clearance, and therefore less toxicity. Could you comment on this?

    Reply
    1. Jeffrey Keller Post author

      The statement that alprazolam has greater toxicity in overdose than other benzos was made in the “Background” section of the paper. That is also where the authors state that alprazolam has a greater risk of dependency and withdrawal. I assume that the authors referenced these assertions, but I will have to run over to the medical library to look up what those references were. I’ll get back to you!

      Reply
        1. Jeffrey Keller Post author

          Hi Tim: Here is the reference for the statement that alprazolam is more toxic in overdose than the other benzos:

          Isbister G, O’Regan L, Sibbritt D, et al. Alprazolam is relatively more
          toxic than other benzodiazepines in overdose. Br J Clin Pharmacol.
          2004;58:88Y95.

          Reply
  4. Pingback: Inappropriate Drugs in Jails and Prisons–Continued! | Jail Medicine

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