SSRIs may cause personality change --Archives of General Psychiatry (Dec 2009)

From: Can SSRIs Change Your Personality?

Patients taking a SSRI antidepressant to treat depression may experience changes in their personality separate from the alleviation of depressive symptoms, according to a report in the December 2009 issue of Archives of General Psychiatry.

“Patients taking paroxetine reported 6.8 times as much change on neuroticism and 3.5 times as much change on extraversion as placebo patients matched for depression improvement,” the authors write.

The findings provide evidence against a theory known as the state effect hypothesis, which proposes that any personality changes during SSRI treatment occur only as a result of alleviating depressive symptoms, the authors note. Several alternative explanations could be considered. “One possibility is that the biochemical properties of SSRIs directly produce real personality change,” they write. “Furthermore, because neuroticism is an important risk factor that captures much of the genetic vulnerability for major depressive disorder, change in neuroticism (and in neurobiological factors underlying neuroticism) might have contributed to depression improvement.”

Poll: Scientific American readers trust what scientists say about "depression drugs" least, second to only "flu pandemics"

Interesting poll here by the Scientific American: In Science We Trust

The basic point of the article and poll is to see how trustworthy a selection Nature and Scientific American readers thought scientists were in the wake of "climategate" and hyperbolic swine flu epidemic predictions.

The more interesting thing for this blog is how much the respondents trusted scientists in a breakdown of selected subjects.

Flu Pandemics is dead last at 3.19

Depression Drugs is just a few ticks above that at 3.21

And strangely, both pharmaceutical related. Hmm.

I realize that this isn't a scientific poll, but I still find this interesting.

"Antidepressants Under Scrutiny Over Efficacy" --WSJ January 2008

Antidepressants Under Scrutiny over Efficacy -- Wall Street Journal, Jan 2008

More evidence that (surprise, surprise) drug manufacturers attempt to present their products in the best possible light. And why not... if they happen to get called on fraud they just settle for a couple hundred million... peanuts.

A total of 74 studies involving a dozen antidepressants and 12,564 patients were registered with the FDA from 1987 through 2004. The FDA considered 38 of the studies to be positive. All but one of those studies was published, the researchers said.

The other 36 were found to have negative or questionable results by the FDA. Most of those studies -- 22 out of 36 -- weren't published, the researchers found. Of the 14 that were published, the researchers said at least 11 of those studies mischaracterized the results and presented a negative study as positive.

...

Dr. Turner, who once worked at the FDA reviewing data on psychotropic drugs, said the idea for the study was triggered in part by colleagues who questioned the need for further clinical drug trials looking at the effectiveness of antidepressants.

"There is a view that these drugs are effective all the time," he said. "I would say they only work 40% to 50% of the time," based on his reviews of the research at the FDA, "and they would say, 'What are you talking about? I have never seen a negative study.'" Dr. Turner, said he knew from his time with the agency that there were negative studies that hadn't been published.

...

In this week's study, the researchers found that failing to publish negative findings inflated the reported effectiveness of all 12 of the antidepressants studied, which were approved between 1987 and 2004. The researchers used a measurement called effect size. The larger the effect size, the greater the impact of a treatment.

Effexor's estimated effect size was 27% (XR) and 28% in the study. Zoloft 64%. Paxil 40%. Prozac 14%. These are the increased apparent effectiveness of the drug treatments because of the omission of negative reports. You could read this as X% less effective when the positive bias is removed.

Effexor: "Baddest of the bad."

Just ran across this article that claims that the British Medical Journal in 2007 found that people on Effexor were three times as likely to attempt suicide compared to those on other antidepressants.

Effexor, baddest of the bad? I believe it.  Part of the reason is likely the very short halflife of Effexor.  On the order of 18-20 hours.  Prozac in comparison is on the order of 3-7 days.  This makes discontinuation syndrome excruciating for most, if they choose to get off the drug.

Antidepressants: The baddest of the bad is revealed

08 February 2007

Antidepressants are a family of drugs that are bad and dangerous to know – and now researchers have named Effexor (venlafaxine) as the baddest of the bad. Patients are much more likely to attempt suicide while taking Effexor than any of the other antidepressants, a new study has found.

The news comes as no surprise to those who’ve already been exposed to the drug. It’s considered to be one of the most powerful antidepressants, and one of the hardest to tolerate. In fact, around 19 per cent of patients stop taking the drug early because they can’t stand the side effects, which include anxiety, sexual dysfunction, weight gain, high blood pressure and thyroid depression. One patient even reported a sudden change of hair colour.
They are the lucky ones. Once over the initial hurdles of life-destroying side effects, withdrawal symptoms are so severe that it’s almost impossible to stop taking the drug.

Thousands of patients who signed a petition to the drug’s manufacturer, Wyeth-Ayerst, claim the drug company knew about the side effects and the withdrawal problems, but failed to properly disclose the facts.
Most of the problems were slowly drip-fed into the public arena over a period of eight years after the drug was first licensed, they say.

Now the last piece of the jigsaw has been revealed. Researchers from RTI Health Solutions at Manchester Science Park analysed the safety records of 219,088 patients from the UK who were taking an antidepressant between 1995 and 2005. Patients taking Effexor were nearly three times as likely to attempt suicide compared with a patient taking another antidepressant, including Prozac (fluoxetine).

(Source: British Medical Journal, 2007; 334: 242-5).

Quick Links

Mish links to a Bloomberg article stating that half of Americans take at least one prescription pill a month. I agree with Mish's statement that: "Throughout grade and high school, I do not recall any kids with attention problems. How is it that attention-deficit disorder is now so widespread? Are kids today different? Why?"  Very good questions, Mish. 

I personally think kids are kids, and they should allowed to be kids. And if they have problems, it is likely something in their environment (*cough* parenting, or lack thereof) that is causing it.

Almost half of Americans took at least one prescription drug per month in 2008, an increase of 10 percent over the past decade, a U.S. study found.

One of every five children ages 11 or younger took at least one medication each month in 2008, led by asthma and allergy treatments, according to the survey released today by the U.S. Centers for Disease Control and Prevention. Among those ages 60 or older, 37 percent used five or more prescriptions per month.

The most common medications for adolescents were treatments for attention-deficit disorder, a condition in which people have trouble paying attention and engage in impulsive behavior.

For adults ages 20 to 59, antidepressants, including Eli Lilly & Co.’s Cymbalta and Pfizer Inc.’s Zoloft, were the most-used drugs. Cholesterol-lowering medications, including Pfizer Inc.’s Lipitor and AstraZeneca Plc’s Crestor, were the most common drugs taken by people ages 60 and over, with 45 percent of those in that age group on such therapies.

Also, this article from the NYT "Child’s Ordeal Shows Risks of Psychosis Drugs for Young" shows how some parents have gone full retard to deal with their kids.

“

Kyle at the time was very aggressive and easily agitated, so you try to find medication that can make him more easily controlled, because you can’t reason with an 18-month-old,” Dr. deGravelle said in a telephone interview. But Kyle was not autistic — according to several later evaluations, including one that Dr. deGravelle arranged with a neurologist. Kyle did not have the autistic child’s core deficit of social interaction, Dr. Gleason said. Instead, he craved more positive attention from his mother.

“He had trouble communicating,” Dr. Gleason said. “He didn’t have people to listen to him.”

After the neurologist review, the diagnosis changed to “oppositional defiant disorder” and the Risperdal continued.

Just 18 months old. Unreal.

"Anatomy of an Epidemic" Part 2: The Origins of Psychopharmacology

The modern day view of science conjures up almost godlike images of mastery over the physical world. Particularly in the area of medicine, we like to think that for any given ailment, we have a drug that will cure it. The reason we think this is that it is actually true, in some but not all cases. Antibiotics can cure bacterial infections; the polio vaccine has damn near eradicated polio from the planet; pain relievers can do a very good job at helping people manage pain even though they don't cure it. So there are good medicines out there that are clearly beneficial.

Modern day psychiatry is saying they can do the same thing. Feeling a little down? Cure it with this SSRI. Having problems focusing? No problem, how about some ritalin. The problem is that while psychiatry and the pharmaceutical companies want you to believe that these are "magic bullets," and that they understand exactly their long term impact on the brain, they really don't. They basically know that there are three chemicals that affect the functioning of the brain: serotonin, dopamine, and norepinephrine. But how these all interact to produce memory, emotion, ethics, behavior, instinct -- in short, YOU -- they really have no idea. They claim that because 28% of depressed people had low serotonin levels in a study that boosting serotonin levels will cure depression. Nevermind that 25% of the normal control group also had similarly low serotonin levels. But I'm getting ahead of myself. That is for part three which will be about the theory of chemical imbalances in the brain.

The point is, these drugs are not cures. They exhibit certain effects whose ultimate impact are not entirely understood. They also burden the user with uncomfortable side effects, and then later agonizing withdrawal should the user decide to stop. The users of antidepressants are quite literally addicts, and Effexor is one of the worst, if not THE worst to come off of because of it's relatively short half life of around 20 hours (vs Prozac which has a half life of 1-7 days, depending).

Psychopharmacology would like you to think that these drugs were all carefully tailored and engineered specifically for the intended purpose. This isn't really true.

Thorozine, the drug that started it all, was originally discovered when searching for a cure for malaria. When that didn't work, they found it had antihistamine and possibly anesthetic properties. They began testing it in surgery and Henri Laborit noticed it could be used in psychiatry.

This new drug, chlorpromazine [marketed as Thorozine in the U.S.], apparently disconnected brain regions that controlled both motor movement and the mounting of emotional responses, and yet did so without causing the rats to lose consciousness.

...

Although today we think of lobotomy as a mutilating surgery, at that time it was regarded as a useful operation. Only two years earlier, the Nobel Prize in Medicine had been awarded to the Portuguese neurologist, Egas Moniz, who had invented it. The press, in its most breathless moments, had even touted lobotomy as an operation that plucked madness neatly from the mind. But what the surgery most reliably did, and this was well understood by those who performed the operation, was change people in a profound way. It made them lethargic, disinterested, and childlike. That was seen by the promoters of lobotomy as an improvement over what the patients had been before -- anxious, agitated, and filled with psychotic thoughts -- and now, if Laborit was to be believed, a pill had been discovered that could transform patients in a similar way.

Anatomy of an Epidemic, page 49

Physicians in the United States similarly understood that this new drug was not fixing any known pathology. "We have to remember that we are not treating diseases with this drug," said psychiatrist E. H. Parsons, at a 1955 meeting in Philadelphia on chlorpromazine. "We are using a neuropharmacologic agent to produce a specific effect."

Anatomy of an Epidemic, page 50-51

Next was Miltown, a minor tranquilizer that was discovered while trying to discover a compound that would kill gram-negative bacteria, and started development by researching the commercial disinfectant called Phenoxetol. This was eventually synthesized into meprobamate and sold for human consumption.

An article published in the Science News Letter ... put the animal experiments into a human frame of reference. If you took a minor tranquilizer, he explained, "this would mean that you might still feel scared when you see a car speeding towards you, but the fear would not make you run."

Anatomy of an Epidemic, page 52-53

By the spring of 1957, the first antidepressant, iproniazid, was brought to market as Marsilid. It's source? A Nazi Germany substitute for rocket fuel called hydrazine. It was originally used to treat TB (Tuberculosis) patients, but seemed to also act as a "psychic energizer."

Iproniazid was seen as having the greater potential, but initial tests did not find it to be particularly effective in lifting spirits, and there were reports that it could provoke mania. Tuberculosis patients treated with iproniazid were also developing so many nasty side effects -- dizziness, constipation, difficulty urinating, neuritis, perverse skin sensations, confusion, and psychosis -- that its use had to be curtailed in sanitariums.

Anatomy of an Epidemic, page 53

So there you have it. The drugs that launched the Psychopharmacology revolution were originally intended to treat malaria, gram negative bacterial infections, and TB, but were then used to induce certain psychological effects in humans. It seems clear that the developers did not fully understand the full long term implications of the drugs they were issuing and that trend seems to persist today.

I guess the bottom line is, if you knew your antidepressant was derived from rocket fuel... would you take it?