Furious Seasons

February 06, 2009

FDA Links Neuroleptic Malignant Syndrome To Anti-Depressants

UPDATE, 10.50 a.m., Feb. 6, 2009. Below the FDA responds to my overnight query of what prompted the label changes and how many cases the agency is seeing. Thankfully, NMS does appear to be rare, but it is intertwined with serotonin syndrome, which is more prevalent.

This is major stuff. Yesterday, the FDA ordered that makers of several anti-depressants change their labels to warn patients and doctors that the drugs can cause neuroleptic malignant syndrome. So far, the only press I've seen on this is on the Los Angeles Times' "Booster Shots" blog. I'd not known before of a connection between anti-depressants and NMS, which has largely been linked to antipsychotics in the past.

NMS involves muscle rigidity, fever and can cause delirium. While I don't know the details of what prompted the FDA's ruling, one assumes the agency must've been receiving adverse events reports. According to the LAT's post, NMS seems to be cropping up in the first few weeks of anti-depressant use and upon dose changes. I'll try to find out more of what's going on from the agency later today.

Keep in mind that 30 million people take anti-depressants each day in this country, so this obviously could effect a lot people. NMS is generally uncommon, but it sure is a worry as it can be fatal in extreme cases. Isn't it interesting that drugs marketed as safe and touted by doctors as side-effect free, especially back in the early-1990s, have turned out to have so many side effects and problems? It's all kind of stunning for the most-prescribed class of drugs in America.

Drugs covered by the change include Cymbalta, Effexor, Prozac, Paxil, Zoloft, Celexa and Lexapro. Most of the notices only cover brand name versions of the drugs, but one assumes the generic versions will be covered as well. Wellbutrin is not affected by the change.

You can read the FDA's letter to Eli Lilly, maker of Cymbalta and Prozac, here. You can read the new labeling for Cymbalta here. The letters to other drugmakers are likely the same. On the new label, it states on page 7:

"Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including Cymbalta treatment, but particularly with concomitant use of serotonergic drugs (including triptans [migraine medications]) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms."

On a personal level, this bit of news is certainly making me think back over my experiences with and reactions to anti-depressants over the years. I don't like what I'm thinking.

Updated with FDA response:

"The labeling changes regarding neuroleptic malignant syndrome (NMS) for the SSRIs and SNRIs were based on 28 U.S. adverse event reports and several literature reports for these 8 drugs. These labels already had language regarding the occurrence of serotonin syndrome for these drugs, and the labeling change was done to clarify that event, very much like NMS that is seen with many antipsychotic drugs, can be seen with these drugs as well, sometimes with the drug alone and sometimes in combination with an antipsychotic drug. The new labeling language makes clear that these two events, i.e., serotonin syndrome, especially in its most severe form, and NMS are overlapping with regard to the findings seen, and may not be distinguishable."

Posted by Philip Dawdy at February 6, 2009 12:05 AM

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Comments

To: Marcie
Cc: World

I am a regular reader of Furious Seasons as well as a professional educator, technologist, and phd student at Columbia's School of Journalism. I rely on Philip's superb journalism in my research, as he is one of the few professional journalists with the courage, tenacity, and ethical integrity to cover one of the most important issues of our time.

I am writing to you in support of Phillip, and to implore you to consider the multi-faceted complexities of the issues the Furious Seasons community explores. I am startled by your allegation that his readers are "desperate need of neuropsychological evaluations and suffer from neuropsychiatric brain disorders - OR - you are the ones who are members of a cult called - scientology.." and that we are "narrow-minded and contentious."

I personally do not suffer from any brain disorders, nor am I a Scientologist. Rather, I am trying to judge reality in a world of mis/over-information that seems to have gone quite mad.

I urge you to read my open letter to the FDA and to try to keep an open, compassionate mind when it comes to learning about alternate perspectives around madness, and to be a bit more critical of the political economy driving the corruption in the pharmaceutical industry.

http://alchemicalmusings.org/2008/09/11/open-letter-to-the-fda/

The evidence is mounting that a scandal is brewing that will rival Big Tobacco's.

I appreciate your efforts to fight for the human rights and parity laws, and wish your son the best of luck in life and love.

warm regards,
/Jonah

Posted by: Jonah at February 5, 2009 09:23 PM

I'm thinking it's time to get some legal opinions.

Posted by: Lilly NC at February 6, 2009 07:33 AM

At least, in spite of Big Tobacco's lies & manipulation, the average age of death for smokers is 71.9 years. However, the "mentally ill" who are medicated to the hilt have only an average lifespan of 57 years. This is evil.

Yet, those who worked to get the FDA Black Box warning on antidepressants for youth 24 and under - they saw how the medical establishment fought them at every turn, how the APA manipulated figures to make it appear as though the Black Box warning was wrong, etc.

Also, at www.SSRIstories.com there are close to 2,900 cases of antidepressant suicides, murders, murder-suicides, 47 school shootings, women school teachers molesting their young male students, all kinds of bizarre behavior, etc.

Recently added to www.SSRIstories.com/index.php was an article which showed that in January, 2009, there were 16 combat deaths in Iraq/ Afghanistan and 24 suicides among soldiers. In this article, some are beginning to look at the excessive use of antidepressants and the Black Box warning for those 18 to 24 which includes most of the soldiers.

Here is the article in its entirety.

Paragraph 9 reads: "But Platoni said she sees the multiple deployments, stigma associated with seeking treatment and the excessive use of anti-depressants as ongoing concerns for mental-health professionals who work with soldiers."

Paragraph 13 reads: "The anti-depressants prescribed to soldiers can have side effects that include suicidal thoughts. Those side effects reportedly are more common in people 18 to 24."

Paragraphs 2 through 6 read: "If reports of suicides are confirmed, more soldiers will have taken their lives in January than died in combat."

"The Army said 24 soldiers are believed to have committed suicide in January alone -- six times as many as killed themselves in January 2008, according to statistics released Thursday."

"The Army said it already has confirmed seven suicides, with 17 additional cases pending that it believes investigators will confirm as suicides for January."

"If those prove true, more soldiers will have killed themselves than died in combat last month. According to Pentagon statistics, there were 16 U.S. combat deaths in Afghanistan and Iraq in January."

"'This is terrifying,' an Army official said. "We do not know what is going on."

http://www.cnn.com/2009/US/02/05/army.suicides/

WASHINGTON (CNN) -- One week after the U.S. Army announced record suicide rates among its soldiers last year, the service is worried about a spike in possible suicides in the new year.

If reports of suicides are confirmed, more soldiers will have taken their lives in January than died in combat.

The Army said 24 soldiers are believed to have committed suicide in January alone -- six times as many as killed themselves in January 2008, according to statistics released Thursday.

The Army said it already has confirmed seven suicides, with 17 additional cases pending that it believes investigators will confirm as suicides for January.

If those prove true, more soldiers will have killed themselves than died in combat last month. According to Pentagon statistics, there were 16 U.S. combat deaths in Afghanistan and Iraq in January.

"This is terrifying," an Army official said. "We do not know what is going on."

Col. Kathy Platoni, chief clinical psychologist for the Army Reserve and National Guard, said that the long, cold months of winter could be a major contributor to the January spike.

"There is more hopelessness and helplessness because everything is so dreary and cold," she said.

But Platoni said she sees the multiple deployments, stigma associated with seeking treatment and the excessive use of anti-depressants as ongoing concerns for mental-health professionals who work with soldiers.

Those who are seeking mental-health care often have their treatment disrupted by deployments. Deployed soldiers also have to deal with the stress of separations from families.

"When people are apart you have infidelity, financial problems, substance abuse and child behavioral problems," Platoni said. "The more deployments, the more it is exacerbated."

Platoni also said that while the military has made a lot of headway in training leaders on how to deal with soldiers who may be suffering from depression or post-traumatic stress disorder, "there is still a huge problem with leadership who shame them when they seek treatment."

The anti-depressants prescribed to soldiers can have side effects that include suicidal thoughts. Those side effects reportedly are more common in people 18 to 24.

Concern about last month's suicide rate was so high, Congress and the Army leadership were briefed. In addition, the Army took the rare step of releasing data for the month rather than waiting to issue it as part of annual statistics at the end of the year.

In January 2008, the Army recorded two confirmed cases of suicides and two other cases it was investigating.

Last week, in releasing the report that showed a record number of suicides in 2008, the Army said it soon will conduct servicewide training to help identify soldiers at risk of suicide.

The program, which will run February 15 through March 15, will include training to recognize behaviors that may lead to suicide and instruction on how to intervene. The Army will follow the training with another teaching program, from March 15 to June 15, focused on suicide prevention at all unit levels.

The 2008 numbers were the highest annual level of suicides among soldiers since the Pentagon began tracking the rate 28 years ago. The Army said 128 soldiers were confirmed to have committed suicide in 2008, and an additional 15 were suspected of having killed themselves. The statistics cover active-duty soldiers and activated National Guard and reserves.

The Army's confirmed rate of suicides in 2008 was 20.2 per 100,000 soldiers. The nation's suicide rate was 19.5 per 100,000 people in 2005, the most recent figure available, Army officials said last month.

Suicides for Marines were also up in 2008. There were 41 in 2008, up from 33 in 2007 and 25 in 2006, according to a Marines report.

In addition to the new training, the service has a program called Battlemind, intended to prepare soldiers and their families to cope with the stresses of war before, during and after deployment. It also is intended to help detect mental-health issues before and after deployments.

The Army and the National Institute of Mental Health signed an agreement in October to conduct research to identify factors affecting the mental and behavioral health of soldiers and to share strategies to lower the suicide rate. The five-year study will examine active-duty, National Guard and reserve soldiers and their families.

CNN's Adam Levine contributed to this report.