[This post is quite lengthy so I suggest you grab a cup of coffee or tea and sit down and read it. The following is not for the faint of heart (or those with a lack of time).]
It’s been amazing to me that I’ve received numerous comments on Zoloft inducing rage. I’m humbled by having a Pittman supporter visit my site and post some comments from the ChristopherPittman.org forums. Read the following:
In my senior year in high school I was diagnosed as being severely depressed and put on medication. The first medication that I was on I took for 5 months and it made me really aggressive. My friends and family noticed the change and I told my doctor about it and she changed my meds. After that I was fine. I am normally a very passive person and will let just about anything fly. But the medication made me really aggravated and aggressive toward my friends and family and it seemed that I wasn’t overcoming my depression. I just got done watching the 48 hours investigation on the Discovery Times Channel and felt a connection with Chris. I felt that I had to write this to let you know that Chris is not the only one out there that had these side effects. I think there should be a study done to see how many people that take antidepressants have increased aggression. The problem is that the pharmaceutical industry has deep pockets and many lobbyists. I hope this helps in some way.
I remember the case when it happened.
At the time I thought, “Zoloft right”.
Let me tell you my physician put me on Zoloft and it took about three weeks for my to become psychotic and I’m a 50 year old woman.
I have three children and I don’t make a lot of money but please let me know if I can do anything for the Pittman boy.
The jury should have been placed on Zoloft before they made they decision. Unless you’ve experience it you simply cannot believe its’ effect.
I did a bit of quick reading/research into Zoloft triggering violence in people who otherwise would have never been violent and it seems that are a few stories out there to support the assertion. I found a few comments on depressionblog.com that mentioned a link between Zoloft and rage fits. A Salon.com article published a story antidepressants inducing rage in 1999. Apparently, Brynn Hartman, the wife of famous comedian Phil Hartman, killed herself and her husband while taking Zoloft. While close friends attribute the sudden behavior on the antidepressant, others attribute it to a combination of the medication with cocaine and alcohol in her system. (Zoloft does have a warning against alcohol use in conjunction with the drug.)
One interesting thing I learned from the article is that this kind of behavior is often labeled under the name akathisia on patient safety guides. Most – if not all – of the major antidepressants list akathisia as a side effect. Here’s the initial description of this condition from Wikipedia:
Akathisia, or acathisia, is an unpleasant subjective sensation of “inner” restlessness that manifests itself with an inability to sit still or remain motionless… Its most common cause is as a side effect of medications, mainly neuroleptic antipsychotics especially the phenothiazines (such as perphenazine and chlorpromazine), thioxanthenes (such as flupenthixol and zuclopenthixol) and butyrophenones (such as haloperidol (Haldol)), and rarely, antidepressants.
Akathisia may range in intensity from a mild sense of disquiet or anxiety (which may be easily overlooked) to a total inability to sit still, accompanied by overwhelming anxiety, malaise, and severe dysphoria (manifesting as an almost indescribable sense of terror and doom).
No real mention of extreme anger or irritability mentioned there. But if you read on…
The 2006 U.K. study by Healy, Herxheimer, and Menkes observed that akathisia is often miscoded in antidepressant clinical trials as “agitation, emotional lability, and hyperkinesis (overactivity)”. The study further points out that misdiagnosis of akathisia as simple motor restlessness occurs, but that this is more properly classed as dyskinesia. Healy, et. al., further show links between antidepressant-induced akathisia and violence, including suicide, as akathisia can “exacerbate psychopathology.” The study goes on to state that there is extensive clinical evidence correlating akathisia with SSRI use, showing that approximately ten times as many patients on SSRIs as those on placebos showed symptoms severe enough to drop out of a trial (5.0% compared to 0.5%).
I checked the Zoloft patient safety information guide and it does warn against increased suicide risk, agitation, and irritability among other negative behavioral changes:
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications… There has been a longstanding concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients. Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders.
Pooled analyses of short-term placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with MDD, OCD, or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal behavior or thinking (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. … No suicides occurred in any of these trials. It is unknown whether the suicidality risk in pediatric patients extends to longer-term use, i.e., beyond several months. It is also unknown whether the suicidality risk extends to adults. All pediatric patients being treated with antidepressants for any indication should be observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. [Pfizer bolded the last two sentences.]
So the average risk of patients feeling suicidal or exhibiting suicidal behavior was twice the risk of placebo. I’m not handy with math, but that would mean out of 100 patients, half of them are at risk for “suicidality.” That’s twice too much. Suicides may not have occurred with patients while enrolled in clinical trials, but of course, Pfizer wouldn’t follow the suicides that may have occurred after patients dropped out.
The company also points out that pediatric patients should be closely monitored for “unusual changes in behavior, especially during the initial few months of a course of drug therapy.” I wonder how many psychiatrists really know that.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric.
Most people – including myself – would take the akathisia parenthetical definition at face value and assume it’s an accurate description of the symptom. If you agree with David Healy et al. above, it’s not.
In these trials, hostile events are found to excess in both adults and children on paroxetine compared with placebo, and are found across indications, and both on therapy and during withdrawal. The rates were highest in children with obsessive-compulsive disorder (OCD), where the odds ratio of a hostile event was 17 times greater (95% confidence interval [CI], 2.22–130.0).
In healthy volunteer studies, hostile events occurred in three of 271 (1.1%) volunteers taking paroxetine, compared with zero in 138 taking placebo. Although not statistically significant, this finding is striking because hostile events are unusual in healthy volunteer trials, and this figure was higher than the rate reported in clinical populations above. GlaxoSmithKline ascribed these episodes to the fact that the volunteers were confined, although this applied to both paroxetine and placebo volunteers. One other healthy volunteer study has reported aggressive behaviour in one volunteer taking sertraline.
Healy goes on at length about the sertraline/violence link:
In data from sertraline paediatric trials submitted by Pfizer, aggression was the joint commonest cause for discontinuation from the two sertraline placebo-controlled trials in depressed children. In these trials, eight of 189 patients randomised to sertraline discontinued for aggression, agitation, or hyperkinesis (a coding term for akathisia), compared with no dropouts for these reasons in 184 patients on placebo (95% CI, 1.72–infinity). When discontinuations for any manifestation of treatment-induced activation (suicidal ideation or attempts, aggression, agitation, hyperkinesis, or aggravated depression) were considered, there were 15 discontinuations on sertraline compared with two on placebo, a relative risk of 7.3 (95% CI, 1.70–31.5; p = 0.0015). The report of these studies does not include an analysis of these data. In the only other placebo-controlled sertraline paediatric trial, undertaken in children and adolescents with OCD, there were ten dropouts out of 92 patients on sertraline, five of whom discontinued for behavioural activation, two for agitation, one for aggression, one for nervousness, and one for emotional lability. In comparison, there was one discontinuation for hyperkinesis out of a total of two dropouts from 95 patients on placebo.
I have no knowledge of confidence intervals and won’t attempt to act like I do, but I’m sure many former Zoloft users and their loved ones wouldn’t be surprised by Healy’s conclusions above. Healy expounds on the vague pharmaceutical labeling of akathisia, which makes the symptom seem like agitation or restlessness rather than increased irritability and behavioral mood swings. He does cite sources, but for the sake of readability, I’ve deleted them. You can feel free to read the article here.
Events such as these in clinical trials of antidepressants have commonly been coded under headings such as agitation, emotional lability, and hyperkinesis (overactivity), and only rarely to akathisia. In clinical practice the term has sometimes been restricted to states of demonstrable motor restlessness, but by definition it cannot be a simple motor disorder or it would be classified as a dyskinesia. There is good evidence that akathisia can exacerbate psychopathology in general and consensus that it can be linked to both suicide and violence. A link between akathisia and violence, including homicide, following antipsychotic use has previously been reported.
The Salon article cites that the Hartman case is “one of more than 170 wrongful death lawsuits filed against the makers of these new antidepressants since Prozac first hit the market 12 years ago.” Stories about violence stemming from antidepressant use have long been documented. Pittman’s case occurred after the following incidents:
But Zoloft and Prozac — along with other similar antidepressants — are being blamed for hundreds of violent deaths, including these:
July 1997: Thirteen-year-old Matthew Miller of Overland Park, Kan., kills himself in his closet one week after he begins taking Zoloft. According to his father, Mark Miller, Matthew had been moody and withdrawn for about nine months — the result, Miller believes, of the family moving to a new neighborhood and Matthew starting at a new school. In June, his parents took him to a psychiatrist. The doctor, accompanied by two medical students in training, talked with Matthew and his parents, but Matthew had little to say. When they met again three weeks later, one thing Matthew did tell him — in response to a question — was that he would never consider suicide. The doctor ruled out attention deficit disorder, but offered no other diagnosis to the Millers. But he did give them a three-week supply of Zoloft to try, and told them to check back in a week. Seven days later, members of Matthew’s family noticed that he seemed agitated. That night, he took his own life.
Feb. 19, 1997: Patricia Williamson, 60, of Beaumont, Texas, stabs and slashes herself more than 100 times in the bathtub while her husband eats breakfast in their kitchen. On the advice of a psychiatrist, she had begun taking Prozac six days earlier to help her through a depression that had arisen just a few months before. Her husband, hearing strange noises in the bathroom, pried open the door and found his wife of 20 years semi-conscious in a pool of her own blood. She died the next day in the hospital. Lawyers for Eli Lilly, the pharmaceutical giant that makes Prozac, recently reached an out-of-court settlement in the case.
March 1996: Daryl Dempsay, 35, stabs his wife and two children at their home in Burlington, Kan., then shoots and kills himself with a .22-caliber rifle. His wife and children survive, and have charged in a recently filed suit against Pfizer that Dempsay’s violent outburst was caused by an adverse reaction to Zoloft, which he had been taking for several weeks.
What interests me about many of these cases – including Pittman’s from what I gather – is that the family members continue to support their loved ones, despite a homicidal act. I’m not one for the “blame game,” but the increasing number of these stories nullifies coincidence. The issue of healthy volunteers becoming hostile during clinical trials is alarming. In the clinical trial date for fluoxetine cited by Healy above, zero patients on placebo exhibited hostile behavior. It sounds pretty damning to me.
Eli Lilly, of course, defended Prozac with a twisted lie:
“This is an old story, it’s gone around and around,” says Jeff Newton, a spokesman for Eli Lilly. “But there’s ample evidence that Prozac is in no way linked to these kinds of violent behavior.” In fact, he added, Prozac reduces aggressive behavior and may lower the risk of suicide.
Prozac’s patient safety guide mentions the following:
In clinical studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults with depression and other psychiatric disorders. … Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.
In a series of 2-month clinical trials, the analyses showed “a tendency toward an increase [in suicidal risk] in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD.” Eleven antidepressants were used for 77,000 patients in 295 trials. (Anyone who can explain the table to the right gets brownie points.)
The highest incidence occurred in those with depression. It’s sad that the drug prescribed specifically for that problem is the same drug that increases the risk of suicidal thoughts and behaviors. While the trial concluded that suicidal risk increased in those 18 and younger, no suicides occurred in that age range. The same could not be said for adults:
There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
Right. It’s dubious how “the number” that wasn’t “sufficient” isn’t mentioned. [It's also worth noting that on the Prozac Web site, the location of the side effect information isn't clear. The patient safety guide is only 2 pages. The prescribing information guide (which most patients wouldn't read) is 35.]
Moving back to Zoloft, Pfizer’s spokesperson also threw the same bullcrap out:
Pfizer representative Celeste Torello rejected the notion that Zoloft had any role in causing suicides or violence. “There’s no scientific or medical evidence that Zoloft causes violent or suicidal behavior,” she told Salon Health. “At this point, there have been over 90 million prescriptions written and there hasn’t been any evidence that it causes anything close to what Brynn Hartman did.”
Please see Zoloft’s own Med Guide above. I admit, this was 1999, but they’re still saying the same thing today. In a May 2007 blog post by the Alliance for Human Research Protection (AHRP), the organization featured a profile on Kim Witczak whose husband, Woody, committed suicide while on Zoloft. She claims that her husband had no history of depression but had been feeling anxious and had trouble sleeping. The profile says that although his doctor did not believe Mr. Witczak suffered from depression, the doctor prescribed Zoloft for Witczak’s insomnia anyway. He committed suicide several weeks later. Bryant Haskins, a spokesperson for Pfizer, essentially delivered Celeste Torello’s line from eight years ago:
“Zoloft has been used safely and beneficially by literally millions of patients since it went on the market more than 14 years ago. The comprehensive medical data, of which there has been a great deal collected over those 14 years since Zoloft was launched in 1992, strongly indicate that allegations linking the medicine to suicide are not supported by scientific fact.”
As of 1999, at least 170 lawsuits can’t be wrong; as of 2007, more are pending.
(Image from Frank’s Reel Reviews)