Posted by SLS on February 5, 2007, at 7:08:58
In reply to Re: Lamictal... is it truly effective at anything? » psychobot5000, posted by River1924 on February 5, 2007, at 0:15:56
McMan's Depression and Bipolar Report
Research and News
Jan 20, 2007 Vol 9 No 3
Lead Story
The answer is Lamictal. The question is why?
Also in This Issue
New Orleans, Quiz, The internet, rTMS, BP relapse risk, Omega-3, DSM, BP meds use, Brain science, Wellbutrin in Europe, Zyprexa settlement, Seroquel misstatements, Art Buchwald, William Styron, Final Word, About McMan's Report, About McMan, My Book, McMan's Web, My Blog, McMan Interviewed, My Upcoming San Diego Talk, Donations.
The Bipolar Depression Indication That Isn’t
Report 9#1 reported on seven unpublished phase II and III clinical trials that found that Lamictal (lamotrigine), failed to outperform the placebo in each of the studies. The trials in question tested Lamictal across a spectrum of depressions in the acute (initial) phase of treatment, including two for recurrent depression and four for bipolar depression. All but one of the seven trials involved at least two hundred patients.
All of these studies were conducted by GSK, makers of Lamictal, with a view to an FDA indication. Not surprisingly, GSK never sought approval for bipolar depression. Despite this, GSK is running advertisements that say: "Have you taken more than one antidepressant and still feel depressed?" The ads conclude with, "Say something to your healthcare provider."
With seven failed studies? What is GSK basing this on?
In 2003, the FDA granted Lamictal an indication for bipolar maintenance, based on two (published) trials that found the drug delayed relapses into bipolar depression over 18 months. In other words, Lamictal may help keep you well, but get you well? Surely, the psychiatric profession would see through this. Um, well, read on …
What the Treatment Guidelines Say
This Report reviewed six major bipolar treatment guidelines, all prepared by leading psychiatrists, with input from many more leading psychiatrists. All but one of the guidelines purports to be "evidence-based." The other relies on "expert consensus." In practice, most, if not all, are hybrid documents.
The four North American guidelines give Lamictal an overwhelming thumbs-up for acute (initial) phase bipolar depression. The American Psychiatric Association’s (APA) Practice Guideline published in 2002 advises: "The first-line pharmacological treatment for bipolar depression is the initiation of either lithium or lamotrigine."
The latest edition of the Texas Implementation of Medication Algorithms (TIMA, formerly TMAP), put out by the state of Texas in 2005 goes one better. For treating acute bipolar depression, the algorithm recommends Lamictal (either alone or with an antimanic agent) as its ONLY first choice.
The Canadian Network of Mood and Anxiety Treatment (CANMAT) Guidelines, issued around the same time as TIMA’s latest version, also recommends Lamictal as a first option for treating acute bipolar depression, but includes other choices, as well.
The 2004 Expert Consensus Guidelines, in its Patients and Families Guide, advises that Lamictal is "sometimes considered an antidepressant agent" and that "antidepressants treat symptoms of depression."
Exhibit A in the evidence line-up for these guidelines is the one GSK Lamictal study that produced an encouraging result. The reason everyone knows about this study is because this is the one that GSK published (in 1999). All four of the guidelines above site this study as evidence of Lamictal’s apparent efficacy, though there are two important caveats:
The APA did note that the study only succeeded using the MADRS scale as a measure (which happened to be the secondary endpoint) rather than the primary one (the HAM-D). In other words, the FDA probably would have thrown this study out.
The editors of the Expert Consensus Guideline did note that enthusiasm for the drug among the 47 psychiatrists it surveyed was rather surprising in light of only one published study.
What about all those failed studies? Nary a mention. Almost. The APA did manage to put a positive spin on one of the failed studies by way of an indirect citation from a review article. In addition, the APA (and TIMA and CANMAT) turned to Exhibit B in the form of a small study comparing Lamictal to Neurontin. The APA also cited an open label study in which most of the patients were on other meds.Time to hear from the English.
The British Association for Psychopharmacology (BAP), in its 2003 Guidelines, citing "limited evidence," recommends Lamictal as a first choice in the acute phase only for "less severe" depression.
The National Institute of Health and Clinical Excellence (NICE) is far less charitable. Its 2006 Guideline states: "The following treatments should not be routinely used for acute depressive episodes in people with bipolar disorder: lamotrigine …"
NICE cites GSK’s 1999 published study as "inconclusive" for efficacy and "unclear" for risk-benefit. The slow dosing schedule for Lamictal (six weeks to get up to full strength) is also an issue with NICE.
In another section, NICE explains its skepticism for industry-sponsored studies: "Such studies are more likely to report results that favor the sponsor’s product than are independent studies. This may reflect publication bias or design bias."
Publication bias? Talk about understatement.
Conclusion
In science, the object of an experiment is to prove one’s hypothesis wrong. In eight clinical trials – seven failures and one partial success - GSK admirably succeeded beyond its wildest expectations.
As expected, GSK was far too modest to broadcast the results. That, of course, is the job of psychiatry.
Which leads to the crunch question: With my illness, a serious depression is not a matter of if, but when. When that time comes, I expect my psychiatrist to recommend the best treatment to meet my needs. This will probably involve a medication of some sort. I do not expect to be handed what amounts to a placebo with side effects. My life may be riding on the outcome and one wrong choice may prove fatal. The problem is, with the best minds in psychiatry getting it wrong, with the APA itself getting it wrong, how on earth can I trust my psychiatrist to get it right?
Reminder
Lamictal is FDA-approved for bipolar maintenance, with demonstrated efficacy for delaying relapses into bipolar depression. As a mood stabilizer, there is also evidence that it helps against rapid-cycling. There may be occasion for your psychiatrist to recommend Lamictal for other uses, including ones that run counter to study evidence. But once again, the problem remains: How well do you trust your psychiatrist?
poster:SLS
thread:729516
URL: http://www.dr-bob.org/babble/20070201/msgs/729899.html