Posted on 02/10/2010 5:15:40 PM PST by neverdem
The efficacy of antidepressant treatment over placebo for major depressive disorder varies considerably, depending upon symptom severity, according to a meta-analysis.
Only patients whose depression is classified as very severe appear to have a greater benefit from antidepressants than from placebo pills, according to the study by Jay C. Fournier of the University of Pennsylvania, Philadelphia, and his colleagues (JAMA 2010;303:4753).
Most placebo-controlled studies of antidepressants specifically exclude individuals who score below 23 on the Hamilton Depression Rating Scale (HDRS). HDRS scores of 813 indicate mild depression, scores of 1418 indicate moderate depression, scores of 1922 indicate severe depression, and scores of 23 or above indicate very severe depression.
In addition, many antidepressant studies include a placebo washout period in which all patients receive placebo pills for several days to 2 weeks before randomization. Often, patients who improve by 20% or more in the HDRS are excluded from the trial. Removing known placebo responders at the outset is thought to enhance the statistical power of the antidepressant-placebo comparison. This design feature severely limits the ability to generate accurate estimates of the placebo response rate, wrote Mr. Fournier and his colleagues, noting that the true rate of placebo response may be underestimated in trials that use this feature.
To determine the true placebo response rate across the entire range of depression severity, the investigators combed the literature for randomized, controlled studies of minor depressive disorder that did not include a placebo washout period.
Of the 2,146 randomized controlled trials of depressants published in English from January 1980 to March 2009, only 23 studies met those criteria. But only six of those studies could provide patient-level data to the investigators. It was those six studies, comprising 434 patients in antidepressant groups and 284 patients in placebo groups, that were the subject of the meta-analysis.
Actually, most meta-analyses include only group-level data. A study such as this one that includes patient-level data is called a mega-analysis. This approach allows investigators to conduct a more fine-grained multivariate analysis.
Three of the six studies used imipramine, a tricyclic antidepressant, and the other three used paroxetine, a selective serotonin reuptake inhibitor. The mean baseline HDRS score in the studies ranged from 14 to 24.
As expected, the higher the patient's baseline HDRS score, the more improvement was seen with both the active drug and the placebo. A difference of 3 points or more on the HDRS is considered clinically significant. It was only at HDRS baseline levels of 25 and above that active drug was both statistically and clinically better than placebo. This finding was the same for imipramine and paroxetine.
The investigators wrote that in marketing antidepressants, pharmaceutical manufacturers rarely mention that most efficacy studies specifically exclude patients who derive little benefit from their medications.
Commenting on the meta-analysis, Dr. Eric G. Tangalos emphasized that conclusions based on studies published as early as 1980 might not be relevant to current medical practice. Papers published in the 1980s took their data from clinical practice in the 1970s, and papers in the 1990s took their information from the 1980s. SSRIs, which are the current mainstay of therapy, did not emerge until the 1990s. Prior to the advent of SSRIs, physicians were reluctant to even identify depression because the available treatments (MAO inhibitors and, later, tricyclics) carried so many serious side effects, said Dr. Tangalos, professor of medicine at the Mayo Clinic in Rochester, Minn. He reported no relevant conflicts of interest.
The National Institute of Mental Health funded the study. Mr. Fournier stated that he had no relevant financial conflicts. Several of the other investigators did report financial relationships with several pharmaceutical companies.
Antidepressant Drug Effects and Depression Severity
Well, we sure do agree on that. I've been noting the link between anti-depressants and these senseless psycho killers for years now.
Might be easier if she switches to a different benzodiazepine first.
Maybe the killers would have been in looney bins without the medications. How can you tell?
You'll have to spar with someone else tonight over this. I don't have the time or the inclination.
You've got to do some digging on the subject if you really want to see how big this is.
Like many other things that we in this camp see clearly, the linkage between psych drugs and psycho killers is something that the SRM will not touch. The evidence is right under their noses, but they just will not report it.
Big Pharma influence? I don't know, but as many have said, "follow the money".
Could be. But we have all pretty much given up on trying to persuade her to do anything. When a responsible MD suggested that the Xanax was doing her no good, and recommended different medication, she got belligerent and refused to see him again. 2 docs later she found one that gives her the stuff.
She’s a lost cause. I just wish she was located much further away from us than she is now. Sounds cold, but after 30+ years of her, I have no more sympathy.
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For some of us, the meds are life-saving. I think the best plan is to have a psychiatrist who only tweaks the meds, and a therapist for talk therapy. If you have depression or bipolar disorder that is partly biological, you probably have to take meds the rest of your life. Given what happens when I am not on them, I have accepted the “life sentence”.
In saying/doing that you have overcome a tremendous hurdle. An accomplishment to be sure.
However I agree with your point that animals are not very subject to the placebo effect, and I would agree with the potential validity of observations of changes in behavior as a result of an antidepressant.
This kitty had no physical problems with *normal* urination after starting on amitryptiline. The anticholinergic effect may have helped a bit, but I seriously doubt it was the main mechanism that got the job done. While the hoped-for no-more-inappropriate-peeing result was unusually quick — quicker than one would expect the antidepressant/antianxiety effect to kick in (at least in humans, may be different for cats), this was probably due the effect that this (and many) antidepressants have when they’re first started, of causing excessive sleeping and drowsiness. While he was out cold or walking around groggily, kitty was not on his usual high alert for opportunities to get attention by peeing on stuff. By the time that effect wore off, the antidepressant/antianxiety effect had presumably kicked in. He settled down in other ways too, allowing me to clip his claws, which had previously been a major battle, and not getting into spats with my other cats. He also became very compliant about pill-taking — previously, giving him a pill had been a two-person job with kitty often winning the battle.
Amitryptyline has both antidepressant and antianxiety effects in humans. In cats, I think it’s really mostly antianxiety (though perhaps this is just because few owners would seek drug treatment for a “depressed” cat, as they wouldn’t likely be causing any trouble for their humans). It’s also effective in both dogs and cats for separation anxiety (usually it’s dogs who have problematic behavior due to this) and obsessive grooming (I once had a friend whose cat had licked itself completely hairless except for the top of its head and back of its neck, which it couldn’t reach, and had continued licking to produce bleeding and scabbing sores all over its skin).
http://www.marvistavet.com/html/body_amitriptyline.html
Prozac is also very effective in dealing with cats’ inappropriate peeing problems, as well as other psychological problems like aggression towards a new baby in the family. It’s also used in dogs and birds (for compulsive feather-picking) http://en.allexperts.com/q/Cats-1606/Cat-Spraying-Prozac.htm http://www.veterinarypartner.com/Content.plx?P=A&A=2742&S=2
Yes, and in that case you may try to get them into chewing gum:
Relieved Anxiety: When chewing gum, participants reported lower levels of anxiety.
Gum chewers showed a reduction in anxiety as compared to non-gum chewers by nearly 17 percent during mild stress and nearly 10 percent in moderate stress.
Increased Alertness: Participants experienced greater levels of alertness when they chewed gum.
Gum chewers showed improvement in alertness over non-gum chewers by nearly 19 percent during mild stress and 8 percent in moderate stress.
Reduced Stress: Stress levels were lower in participants who chewed gum.
Levels of salivary cortisol (a physiological stress marker) in gum chewers were lower than those of non-gum chewers by 16 percent during mild stress and nearly 12 percent in moderate stress.
Improved Performance: Chewing gum resulted in a significant improvement in overall performance on multi-tasking activities. Both gum-chewers and non-chewers showed improvement from their baseline scores; however, chewing gum improved mean performance scores over non-gum chewers by 67 percent during moderate stress and 109 percent in mild stress.
http://www.eurekalert.org/pub_releases/2008-08/epr-nrf082908.php
High levels of cortisol for a long time is probably a very common cause of depression. However, the etiology is very complex.
I was convinced I was depressed, took one version after another and only got a range of side effects that make great party talk. It wasn’t until a year after the real cause of my depression divorced me that I got better. Imagine that.
High levels of cortisol can be bumped down by exogenous DHEA (and vice versa). Which would explain why DHEA has been found effective for mild midlife depression (and may well be found effective for others types of depression, in future studies).
IMHO anti depressants should not be allowed to be prescribed by GP’s but only by Doctors who specilize in mental health. Perhaps everyone should be given a placebo as a first step to observe the reaction of the patient?
They don't have enough shrinks. IIRC, only a few states, if that many, permit psychologists to prescribe psychiatric meds. As it is very few docs can recognize adverse effects from psych meds such as serotonin syndrome. You're going to be hard pressed finding psychiatrists beyond cities, IMHO.
Thanks for the info. There are 90 studies with DHEA http://www.clinicaltrials.gov/ct2/results?term=DHEA
For sure DHEA is very interesting.
There is sufficient evidence supporting the use of DHEA in the treatment of adrenal insufficiency, depression, induction of labor, and systemic lupus erythematosus.
No studies on the long-term effects of DHEA have been conducted. DHEA can cause higher than normal levels of androgens and estrogens in the body, and theoretically may increase the risk of prostate, breast, ovarian, and other hormone-sensitive cancers. Therefore, it is not recommended for regular use without supervision by a licensed health professional.
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