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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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« Sand Won't Save You This Time | Main | ApoE4: Test or Not? »

February 27, 2008

Antidepressants: Depressing News or Not?

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Posted by Derek

There’s an interesting analysis in the latest PLoS Medicine on the clinical effectiveness of four modern antidepressant drugs: Prozac (fluoxetine), Effexor (venlafaxine), the partially discontinued Serzone (nefazodone), and Paxil (paroxetine). The authors compared all the published placebo-controlled studies on these drugs, and further included all the regulatory filing data. (Update: not so! See below). The result made headlines all over the place yesterday, because one of the things they found was that these drugs hardly seem, compared to placebo, to do anything at all.

Here’s the odd part: that shouldn’t have been such a big surprise. It wasn’t surprising to the authors of the paper – in fact, they started with the belief that this would be the case, because that analysis has been done before. Their interest was in seeing if there was some difference between different populations of depressed patients – is there some group for which the drugs really show efficacy or not?

As it turns out, there is, but perhaps not for the reasons you’d think. The most severely depressed cohort do seem to show a statistically meaningful response, but that seems largely because the placebo group’s response goes down. That’s been the difficulty with antidepressant clinical trials forever: there is a huge placebo response. This isn’t news; people have been studying this effect and trying to figure out what it means (or figure out a way around it) for years.

So, what does this do to the whole popular culture around the SSRI drugs – you know, “Listening to Prozac”, “Prozac Nation”, all that sort of thing? In this case, popular culture probably has it wrong. These drugs are not magical happy pills, but “Placebo Nation” just doesn’t have the same ring to it. The whole subject is too tangled to make for a catchy title.

It makes sense, though, that this is the area of drug discovery where the biggest placebo effect would turn up – you’d have to think that for depressed patients, a big step would have to be the thought that something can actually affect their condition. It’s bound to help for them to believe (correctly) that their moods aren’t necessarily part of the drab fabric of the universe, but depend instead on the (changeable) chemical weather inside their brains. Knowing those things, and the act of taking a medication that is supposed to work, is enough to help between a quarter and a half of depressed patients right there.

The actual mechanism of the placebo effect is a field of great interest and potentially great importance. (See here, here, here, and here). News like this makes a person wonder, though: if large parts of the public become convinced that antidepressant drugs don’t work, will they? And the question remains: do the SSRI drugs do anything at all through their supposed chemical mechanisms? (It's not like we know). One way to find out would be to run a placebo versus placebo trial. You could blind things at the start, even though everyone was getting the same sugar pills, and you’d presumably see the same response in each group. Then you unblind and cross everyone over, telling people that they’d been in one group and were now headed to the other. Careful work would give you four study arms: (1) people who responded to placebo, and who were then told they’d been taking sugar but were now getting the real drug, (2) people who responded and were told that they were taking a real drug but were now being switched off of it, (3) people who didn’t respond, but were told that this was because they’d been taking sugar, but help was now on the way, and (4) people who didn’t respond, and were told that they’d been getting (apparently ineffective) drug, but were now coming off even that. Fascinating stuff, but we’re going to have to wait for the North Koreans to set it up for us, because no other regulatory agency would let it through.

But from this latest analysis, we can conclude something interesting. The fact that the placebo effect diminishes in the most severely depressed patients, but that the drugs continue to show the same level of efficacy, suggests that they do have some effects of their own. To me, that’s the real news from this study. It reminds me of G. K. Chesterton’s line about journalism being the business of saying “Lord Jones Is Dead” to people who never knew he was alive. In this case, the headlines have been “Antidepressants Don’t Work”, but that should have been the headline years ago. This one should have come in as “Antidepressants Might Actually Do Something”.

Update: A closer look, as suggested in the comments section, shows that the trials included in the meta-analysis were mostly quite short (six weeks or less), when a good deal of evidence would suggest that these drugs take longer to become truly worthwhile. And there is only one study on moderate depressed patients, making it hard to draw conclusions about that group. See the comments page on the article here for more criticisms. So, do antidepressants work or not? You can find an answer that fits, no matter what you need it to be. . .

Comments (32) + TrackBacks (0) | Category: Clinical Trials | The Central Nervous System


COMMENTS

1. LNT on February 27, 2008 9:57 AM writes...

One thing I have not seen pointed out yet is that IT MAKES SENSE that the most depressed patients have the lowest placebo response. Severely depressed people are unlikely to believe that anything will help them -- and that becomes a self-fulfilling prophesy.

A lot of people are up-in-arms over the fact that the drugs have little effect over placebo. However, those same people would cry foul if their doctor gave them a sugar pill and told them that it was an effective treatment for depression. It seems to me that placebo only works under the guise of deception. If patients were honestly told that they were receiving a sugar pill, then the placebo effect would likely no longer exist.

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2. Still Scared of Dinosaurs on February 27, 2008 10:55 AM writes...

I think that "the placebo effect" is as confounded a phrase as "the cure for cancer". There are many different "placebo effects" that need to be considered when interpreting trial data. One is that the presence of a placebo arm in a trial often changes the population of patients willing to enroll, especially when comparing trials conducted prior to the first approval for a new class such as SSRI's versus subsequent trials.
Another is that "placebo" really means "everything in the trial except the agent of interest" which in the context of a trial for an antidepressant could include talking to a nurse and/or doctor on a weekly basis. Also, since trials often include people who don't have adequate health coverage those talks may be the first in a substantial period of time. This can lead to a bolus of newly diagnosed conditions at the start of the participation that are nonetheless classified as treatment emergent events.

There are many more possibilities but in every case context is hugely important in interpreting what the relevant factors might be. The effects of patients' beliefs are only a part of what might be going on.

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4. MTK on February 27, 2008 11:00 AM writes...

First, a disclaimer, I haven't read the study only the commentaries and reports about it. Also the SRRI's treat more than depression. Anxiety, OCD, etc. and I don't know if the same conclusions hold for those indications.

One of the more interesting aspects of all this is reading people's responses to the popular press reports whose tone was generally that antidepressants don’t work. The responses essentially fell into 3 general categories. 1) "Bull. They've done wonders for me. I can tell you firsthand that they work.", 2) "Just another example of the pharma companies ripping us off.", and 3) "you don't need to take what pharma is feeding you, use Vitamin X instead." The irony of each of these is astounding given that the whole point is that the placebo effect is huge.

#2 is my favorite, because if anything the "joke" is on pharma for spending all the money to develop these things. The alternative to getting ripped off by pharma would be to get ripped off even more by a placebo maker who would have to charge pharma-like prices to make the placebo convincing.

BTW, anyone know how bad the side effects are in the placebo groups in these studies?

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5. Placebo Side Effects? on February 27, 2008 11:36 AM writes...

If these drugs dont have a measurable effect, a "Placebo only" homeopathic treatment would be more cost effective including ZERO side effects. For the patient, the effect counts, even if it is a Placebo one.
But big pharma seems to be interested in making big money, even with (Placebo?) side effects...

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6. DrSnowboard on February 27, 2008 11:57 AM writes...

Similar disclaimers as above but the placebo effect is also surprisingly high in pain trials. Not only for subjective scoring in antimigraine trials but also for other situations. I seem to recall there was a small but stoic placebo group for some of the COX-2 trials given post-double wisdom tooth extraction...

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7. Sigivald on February 27, 2008 1:06 PM writes...

#5: Placebos have side effects too. The same mechanism that makes them "work" sometimes also makes them cause side effects.

I've seen enough "placebo vs. medicine" side-effect charts to see that simply giving someone a pill will cause some side effects in a number of people.

Plus you neglect the real-world issue of giving people a placebo outside of a trial - the ethical issues are huge, as are the ones of not letting them ever find out it's a placebo. Because, you see, if they know the pill itself is doing nothing, the effect flies out the window.

(And yes, scary old "big pharma" wants to make money. Because if they don't, their shareholders sue them, and if that doesn't happen, they simply go out of business, and nobody gets anything, ever from them.

Side effects are inevitable with any drug that does anything, short of a radical and far-off improvement in our understanding of the entire human body's most subtle processes and interactions. (Assuming we bracket off placebo-induced side effects.)

Considering that we have only a gross and rough understanding of any but the most major and obvious processes, you can call back in a century, minimum. Maybe two.)

Permalink to Comment

8. Anon on February 27, 2008 2:27 PM writes...


Hi Derek,

I'm a bit surprised by your take on this study - I would take a closer look at the methods section of the paper/some of the comments the discussion page (for example this one and this one).

Basically, the meta-analysis is potentially flawed because quite a bit of the data came from very short trials. It's pretty well known that SSRIs don't 'kick in' right away (usually two-four weeks) and patients often need to try a few different SSRIs before they find one that 'works' for them - so I think people need to approach this particular meta-analysis with a bit more skepticism. (I'd actually approach all meta-analyses with quite a bit of skepticism...)

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9. confused on February 27, 2008 2:35 PM writes...

I'm confused... why can't the trial be run in the following way. Give everyone a placebo and after a given time x swap a proportion over to the actual drug. That way the people who would have had the 'placebo effect' could be accounted for in the study and of those who showed improvement on placebo any additional effect of the trial drug would reveal itself?? I don't think the ethics here are any worse than a double-blind study, but could be on the wrong track here and it seems more simple than the plan proposed in the post.

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10. MTK on February 27, 2008 3:19 PM writes...

Confused,

It's unethical to give patients who could receive treatment, no treatment. In fact it is forbidden by the Helsinki human rights protocols of 1964. That's why Dinosaur's reminder of what is meant by placebo is important and that's why Derek mentioned a non-signatory country.

In the case of depression, however, the placebo treatment is psychotherapy alone, so one might be able to do it. I'm not an ethicist, so don't take my word. In other indications, the double-blind is compared to a standard of care. One of the challenges in formulations and clinical development is devising ways to make the pills and protocols so you don't provide a tell.

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11. Mac on February 27, 2008 5:19 PM writes...

Sometimes ethics just goes against the best means of scientifically achieving useful results. One of those annoying realities of life.

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12. sroy on February 27, 2008 7:07 PM writes...

Just my 2 cents,

As some one above has pointed out meta-analysis of clinical trials by a group known to have a bias against SSRIs need to be taken with some skepticism.

Having said that it is important to understand why this particular result is possible.

SSRIs not only take a few weeks to work, but they also do not treat depression as such. They reduce the anxiety, intense emotions, repetitive behavior and thought patterns caused by depression. The best evidence for a therapeutic effects of SSRIs are in treating anxiety and OCD. SSRIs dampen all emotional response by raising serotonin (and have sexual side effects + delay ejaculation).

The brain had particularly good feedback loops to reinforce behavior and emotions. SSRIs essentially trick the brain into working as if it were not depressed. If you remove the negative emotion feedback loop, things cannot get worser than they were and the depression will eventually improve.

However if your cause of depression was too bad, your brain will recover pretty quickly on it's own. Most SSRI prescriptions are for mild reactive depression (life events), rather than a strong medical history of severe depression.

Noradrenaline and Dopamine reuptake inhibitors (Bupropion and Methylphenidate) on the other hand improve mood and motivation and dampen the negative emotion feedback loop by 'raising the bar' required for a negative emotion to have any effect. That is why they do not have sexual side effects (do not dampen emotion). Infact they seem to help with desire issues in non-depressed people. They also work much faster - often within 3 days for methylphenidate (ritalin).

I have always believed that NA and Dopamine reuptake inhibitors are the way to go for treating most cases of depression (especially the mild ones).

Non-selective MAO inhibitors are even more effective, but have issues with safety due to interactions with dietary tryptophan. Given that the first MAO inhibitor was discovered because of unexpected happiness in TB patients treated with an analogue of isoniazid (iproniazid), I do not doubt that it works. Non-selective MAO inhibitors such as phenelzine and tranylcypromine are still the last hope for severely depressed patients before ECT.

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13. Skeptic on February 27, 2008 7:42 PM writes...

"Considering that we have only a gross and rough understanding of any but the most major and obvious [biological]processes, you can call back in a century, minimum. Maybe two."

Probably never in North America. With all of academia kissing corporate butt in a last ditch attempt to keep overinflated stock prices of pharma from collapsing I wonder who is going to have the foresight to attack the protein interacterome with a novel viewpoint(meaning no more nodes and links, computationalism, holism)

Surely the medicinal chemists are in way over their heads?

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14. Polymer Bound on February 27, 2008 8:17 PM writes...

Skeptic, we're waiting for you to descend on our industry and show us the light. I'm a fan of Nature Reviews Drug Discovery... how about an opinion piece?

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15. MTK on February 27, 2008 8:48 PM writes...

sroy,

A very reasoned response. Only one thing. It doesn't address the large placebo effect.

So while your analysis of SSRI's vs NA vs. dopamine, etc all sounds great, it won't mean much in treating less than severe cases of depression if the placebo effect requires clinical trials of any drug in the 100,000's to see significance.

Maybe a clinical protocol needs to be written where the doctor providing the drug or placebo has to whisper to the clinical trial patient "I think this drug is a load of crap, but hey, you never know."

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16. OrgChemPostdoc on February 27, 2008 9:30 PM writes...

Drug development is based on lottery (screening). Then voodoo (biology) is coming in. Finally, the holy council (FDA) decides whether Lottery x Voodoo = Drug.
Within Pharma, this process is called "scientific". And the integrity of the system is out of question, since it is all ethical...

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17. Skeptic on February 28, 2008 12:28 AM writes...

Polymer Bound,

I will take your advice and do so.

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18. milkshake on February 28, 2008 1:26 AM writes...

roy: dietary tyramine, not tryptophane.

With some MAOs you cannot consume large quantity of aged cheese, fava beans and Chianti, Clarice.

Deprenyl (selegiline) being somewhat MAO-subtype selective has fewer complications than other MAOs, it can be used in elderly patients for exmple.

The problem with SSRIs is that they are known to be "safe" in sense that it is hard to overdose on them. So we end up with every goddamned psychologist hired by HMO instead of a real doctor "treating" patients by behavioural therapy. And of course he has a nurse who can write prescriptions for SSRI to augment the therapy. Then we get a bipolar patients misdiagnosed as being depressed. You put them on short-acting SSRI like Citalopram and you turn them into fast cycling between frank mania and depression.

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19. sroy on February 28, 2008 1:26 AM writes...

Hi MTK,

The strong placebo response for pain, anxiety, depression meds is the result of the your brain's neuron net filters readjusting the effect of
feedback loops. It will happen by itself in most people unless the condition is severe. The human brain is an incredibly flexible,versatile and self-equilibrating emergent system

Antidepressants merely help the process. However if I wanted an antidepressant I would go for bupropion or methylphenidate. Methylphenidate is somewhat harder to obtain though. If some company
made a longer lasting analog of methylphenidate and pushed it properly they would score big . Think about it - works in less than 3 days, no
significant anxiety (bupropion), no sexual dysfunction (SSRIs), no real tolerance or abuse potential (amphetamines). It is very effective in mild to moderate atypical depression, which accounts for the vast majority of depression.

Methylphenidate is overused in kids and vastly underused in adults. And it is quite safe in overdoses (treat with haloperidol and phenytoin).

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20. emjeff on February 28, 2008 8:18 AM writes...

The fact that all of the trials used in this study were of only 6 weeks duration is reason enough to discount it. I wonder when the journals are going to stop publishing this meta-analysis nonsense from groups with a political axe to grind?

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21. MTK on February 28, 2008 9:50 AM writes...

emjeff,

I would agree with you. In fact, my first thought was that the reason why these studies weren't published in journals was not some sinister selective publication by pharma, but that the investigators reasoned they weren't publication-worthy due to their short duration. The follow-up to that is why plan and run them in the first place? Or were these studies that were halted for one reason or another, which would also make them non-publishable.

Maybe someone out there who has been involved in the clinical part of anti-depression program can help answer that for us.

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22. Don B. on February 28, 2008 10:38 AM writes...

Derek:

My wife of many decades had a father who had a heart attack when she was twelve.

As far as I can tell she has been worrying abaout a heart attack since she passed 40.

We used to visit the ER about twice a year with her complaining of "chest pains" or "chest pressure". After giving her a baby aspirin, the MDs would run through the usual tests showing no problem.

A few years ago her internist prescribed 10mg of Zoloft(TM), one pill every morning. We have not been back to the ER since.

The major side effect that I have seen is that it turned off the connection between her brain and mouth.
She will say things to people that she did not used to say. I have explained this to our sons and relatives so they would not be offended by accurate but possibly insulting comments.

I realize this is an N of one. It has convinced me "that in a couple only one can be on an SSRI".

Regards,

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23. getonthetreadmill on February 28, 2008 10:39 AM writes...

What about all the studies showing that regular exercise was more effective than any of these drugs!
What's wrong with being a little depressed anyway, it's a tough world out there, most happy go lucky people are just plain stupid and don't see what's going on around them. Human beings are designed to handle stress, it's been bred in from millions of years of evolution. Pharmaceutical companies are trying to make everyone believe that you can have a happy life through antidepressants. There are people out there who really do need help, but they are in the minority of this over prescribed snake oil.

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24. Morten on February 28, 2008 6:05 PM writes...

@#23

Mammals are designed to withstand stress, true, but not continuous stress. Some people/animals are resistant to continuous stress though and it seems to somewhat random who is and who isn't.
The problem with regular exercise is that a person affected by continuous stress will feel that they have no time to spare on "frivolous" activities and will cut it from their daily routine. Stress will paralyze you and invoke a vicious cycle of: things you have to do -> stress -> paralysis -> even more things you have to do.
I believe that exercise reduces the chances of being afflicted by depression but as a scientist I can't say for sure that the cessation of physical activity isn't caused by a pre-depression state.

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25. Still Scared of Dinosaurs on February 29, 2008 1:59 PM writes...

Don’t buy into the notion that there is a conflict between scientific validity and ethics. It’s easy to see that if a study is not scientifically valid it cannot be ethical. It’s harder for me to close the logical loop on saying that unethical research is inherently unscientific but that’s largely because I’m just willing to accept the assertion as is.
Which sort of leads me to the issue that one of the studies of placebo effects and brain activity linked in the original post (Scott, et. al.) seems to me to be about as sloppy as research gets. First of all they claim to be looking into the placebo effect but they didn’t give their participants anything BUT placebo. And they appear to have lied about it (saying half would get pain meds) which in my world is a Class A no-no.
But more to the point of my earlier post, there is no testable placebo effect here because there is no comparison – they’ve just inverted the situation where all benefit observed in a trial is credited to a drug because there was nothing to compare it to. To really get at a placebo effect in this trial it would have been necessary to do something like have 3 groups one of which got real meds, another which got placebo, and the third which got nothing but the pain. The presence of the first group is necessary to create the expectation of benefit in the second, and the third group is necessary to estimate what the effects would have been in the second without that belief.
Also, while I know this may seem like a silly point, the “inactive” agent used as a sham treatment in this trial is the same (more or less? both are labeled “salt solution” but the concentrations aren’t given) as the one used to induce the pain they were testing. Can anybody declare that one injection of saltwater will have no desensitizing effect on some patients to a second injection of the same substance in the same experiment? (Please disregard the fact that if this does occur it would be a confounding factor in my proposed study design.)

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26. tgibbs on February 29, 2008 10:44 PM writes...

sroy,

Methylphenidate (and amphetamine) used to be used more widely for treatment of depression. They are very effective in improving mood, but fell into disfavor for two reasons: some people abuse them, and there is often a strong rebound depression if treatment is terminated--in fact, you can get this even in people who weren't depressed to begin with.

Permalink to Comment

27. sroy on March 1, 2008 2:36 PM writes...

Hi tgibbs,

I am aware of that- however too many people confuse methylphenidate (blocks Dopamine and NA reuptake only) with amphetamine (also releases dopamine in addition to dopamine and NA reuptake). It is the dopamine releasing effect that accounts for abuse and rebound depression (think cocaine and amphetamine).

In that respect methylphenidate is much more like bupropion than amphetamine. It is however less likely to cause anxiety than bupropion.


If you test people who have experienced both amphetamine and bupropion, people given a either these drugs and methylphenidate are more likely to mistake methylphenidate for bupropion (over 80%) than amphetamine (20%).

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28. steve hayes on March 1, 2008 10:52 PM writes...

As a fellow Arkansan and the director of Novus Medical Detox, I appreciate Derek's logical approach but don't find it persuasive. I often see patients who are on alcohol or opioids, central nervous system depressants, also taking antidepressants. When they detox they find they don't need the antidepressants.

This is good news because a Swedish study showed that 52% of the 2006 suicides by women on antidepressants. Since antidepressants work no better than placebos and are less effective than exercise in dealing with depression.

There is a prescription drug epidemic and these are leaders in the list of terribe abuses.

Steve Hayes
http://novusdetox.com

Permalink to Comment

29. Brooks Moses on March 4, 2008 8:45 PM writes...

It should be noted, in response to statistics like the ones that Steve quoted, that there is indeed known to be a small increased suicide risk for depressed people first going on antidepressants -- not because they're harmful, but ironically because they are helping. Severe depression tends to combine a feeling of wanting to have an out, with a feeling of being too overwhelmed to actually do anything about it. Antidepressants tend to fix the latter effect first -- with the result that people who were suicidal but too depressed to follow through on it get to a point where they are able to follow through, before they get to a point where they don't want to.

The moral of this is obviously not that antidepressants should be avoided, but that care should be taken to provide appropriate support when they're first prescribed.

Permalink to Comment

30. Dan on July 23, 2008 11:23 PM writes...

Misunderstandings and Popularity: SSRI Anti-Depressants


Presently, for the treatment of depression and other what some claim are other types of mental disorders, as some claim certain mental disorders are somewhat questionable, selective serotonin reuptake inhibitors (SSRIs) are the drugs of choice by most prescribers today. Such meds, meds that affect the mind are called psychotropic medications. SSRIs also include a few meds in this class with the addition of a norepinephrine uptake inhibitor added to the SSRI, and these are referred to SNRI medications, which combined with SSRIs, are the number 1 top therapeutic class of prescriptions presently. While there are several available SSRIs presently, two SNRIs available are Cymbalta and Effexor. Some consider these classes of meds a next generation mood enhancer after the benzodiazepine hype decades ago, as there are similarities regarding their intake by others, yet the mechanisms of action are clearly different, but not their continued use by others. Furthermore, regarding SNRIs, adding the additional agent of norepinepherine is presumed to increase the effectiveness of SSRIs by some.
Some Definitions:
Serotonin is a neurotransmitter thought to be associated with mood. The hypothesis was first suggested in the mid 1960s that this neurotransmitter may play a role in moods and emotions in humans. Yet to this day, the serotonin correlation with such behavioral and mental conditions is only theoretical. In fact, the psychiatrist’s bible, which is known as the DSM, states that the definite etiology of depression remains a mystery and remains unknown with complete certainty. So a chemical imbalance in the brain is not proven to be the cause of mood disorders, it is only suspected as a result of limited scientific evidence. In fact, diagnosing mental diseases such as depression is based on subjective assessment only, as interpreted by the prescriber, so one could question the accuracy of such diagnoses.
Norepinepherine is a stress hormone, which many believe help those who have such mood disorders as depression. Basically, with the theory that by adding this hormone, the SSRI will be more efficacious for a patient prescribed such a med, as suggested earlier.
And depression is only one of those mood disorders that may exist in certain patients, yet possibly the most devastating one. An accurate diagnosis of these mood conditions lack complete accuracy, as they can only be defined conceptually, so the diagnosis or impression concluded by the patient’s doctor is dependent on subjective criteria, such as questionnaires and patient observation. A social patient history is uncertain and tricky as well, some have said. There is no objective diagnostic testing for depression. Yet the diagnosis of depression in patients has increased quite a bit over the past few decades. Also, few would argue that depression does not exist in other people to the degree that the affected patient believes their mental condition is presently. Yet, one may contemplate, actually how many people are really depressed? What is believed is that if one is disabled or impaired from a mental paradigm, treatment is necessary and appropriate with medication.
In Time magazine’s June 16th 2008 cover story, it was reported that the military personnel in the Iraq war are pounding down SSRIs often. Every time there is a new war, there is a new drug, it seems.
Several decades ago, less than 1 percent of the U.S. population were diagnosed with depression, some have said. Today, it is believed that about 10 percent of the total population in the United States have or have experienced depression at some time in their lives that may vary in severity and longevity. Why this great increase in the growth of this condition remains unknown and is subject to speculation.
What is known is that the psychiatry specialty is the one specialty most paid to by certain pharmaceutical companies for ultimately and eventual support of their psychotropic meds that they currently promote to these doctors, as this aspect of the pharmaceutical industry clearly desires market growth of these products.
Regardless, SSRIs and SRNIs are the preferred treatment methods if depression or other mood disorders are suspected by a health care provider. Yet these meds discussed clearly are not the only treatments, medicinally or otherwise, for depression and other related and suspected disease states.
Over 30 million scripts of these types of meds are written annually, and the franchise is around 20 billion dollars a year now, along with some of the meds costing over 3 dollars per tablet. There are about ten different SSRI/SRNI meds available, many of which are now generic, yet essentially, they appear to be similar in regards to their efficacy and adverse events. The newest one, a SNRI called Pristiq, was approved in 2008, and is believed to be launched as a treatment for menopause. The first one of these SSRI meds was Prozac, which was available in 1988, and the drug was greatly praised for its ability to transform the lives of those who consumed this medication in the years that followed. Some termed Prozac, ‘the happy pill’. In addition, as the years went by and more drugs in this class became available, Prozac was the one of preference for many doctors for children. A favorable book was published specifically regarding this medication soon after it became so popular with others.
Furthermore, these meds have received upon request of their manufacturers additional indications besides depression for some really questionable conditions, such as social phobia and premenstrual syndrome. With the latter, I find it hard to believe that a natural female experience can be considered a treatable disease. Social phobia is a personality trait, in my opinion, which has been called shyness or perhaps a term coined by Dr. Carl Jung, which is introversion, so this probably should not be labeled a treatable disease as well. There are other indications for certain behavioral manifestations as well with the different SSRIs or SRNIs. So the market continues to grow with these meds. Yet, it is believed that these meds are effective in only about half of those who take them, so they are not going to be beneficial for those suspected of having certain medical illnesses treated by such meds. The makers of such meds seemed to have created such conditions besides depression for additional utilization of these types of medications, which is a process known as disease mongering. Drug companies that make these medications are active and have been active in forming mutual relationships with related disease- specific support groups, such as providing financial support for screenings for the indicated conditions of their meds- which includes the screening of children and adolescents in particular, I understand. As a layperson, I consider such activities dangerous and inappropriate for several reasons.
Danger and concerns by others with these psychotropics primarily involves the adverse effects associated with these types of meds, which include suicidal thoughts and actions, violence, including acts of homicide, and aggression, among others, and the makers of such drugs are suspected to have known about these effects and did not share them with the public in a timely and critical manner. While most SSRIs and SNRIs are approved for use in adults only, prescribing these meds to children and adolescents has drawn the most attention and debate with others, such as those in the medical profession as well as citizen watchdog groups. The reasons for this attention are due to the potential off-label use of these meds in this population, yet what may be most shocking is the fact that some of the makers of these meds did not release clinical study information about the risks of suicide as well as the other adverse events related to such populations, including the decreased efficacy of SSRIs in general, which is believed to be less than 10 percent more effective than a placebo. Paxil caught the attention of the government regarding this issue of data suppression some time ago, this hiding such important information- Elliot Spitzer specifically was the catalyst for this awareness, as I recall. Furthermore, that drug is in the spotlight once again years later. Some believe the drug maker knew about possible risk to the youth as early as 1991.
And there are very serious questions about the use of SSRIs in children and adolescents regarding the possible damaging effects of these meds on them. For example, do the SSRIs correct or create brain states considered not within normal limits, which in effect could cause harm rather than benefit? Are adolescents really depressed, or just experiencing what was once considered normal teenage angst? Do SSRIs have an effect on the brain development and their identity of such young people? Do adolescents in particular become dangerous or bizarre due to SSRIs interfering with the myelination occurring within their still developing brains? No one seems to know the correct answer to such questions, yet the danger associated with the use of SSRIs does in fact exist. It is observed in some who take such meds, but not all who take these meds. Yet health care providers possibly should be much more aware of these possibilities, possibly, along with the black box warning now on SSRI prescribing information for the youth that has existed since 1994.
Finally, if SSRIs or SNRIs are discontinued by a patient without medical supervision, withdrawals are believed to be quite brutal, and may be a catalyst for suicide in itself, as not only are these meds habit forming, but discontinuing these meds abruptly, I understand, leaves the brain in a state of neurochemical instability, as the neurons are recalibrating upon discontinuation of the SSRI or SNRI that altered the brain of the consumer of this type of med. This occurs to some degree with any psychotropic med, yet the withdrawals can reach a state of danger for the victim in some classes of meds such as SSRIs and SNRIs, it is believed.
SSRIs and SRNIs have been claimed by doctors and patients to be extremely beneficial for the patient’s well -being regarding the patient’s mental issues where these types of meds are used, yet the risk factors associated with this class of medications may outweigh any perceived benefit for the patient taking such a drug. Before these medications mentioned were developed, doctors praised trycyclics, another class of anti-depressants, in a similar manner some time ago. Considering the lack of efficacy that has been demonstrated objectively with the newer psychotropics, along with the deadly adverse events with these SSRI and SSNI meds only recently brought to the attention of others, other treatment options should probably be considered, but that is up to the discretion of the prescriber.
It is my hope that such a prescriber rules out possible other etiologies for their patients’ mental conditions before they conclude that such a patient is suffering from true mental illness requiring the medications mentioned earlier, such as asking their patients about life stressors and other medications these patients have taken in the past, for example. Because at times, a doctor can in fact do harm without intent.
“I use to care, but now I take a pill for that.” --- Author unknown
Dan Abshear
Author’s note: What has been written is based upon information and belief

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31. Anonymous on February 20, 2011 6:11 AM writes...

chemical treatments, whether synthesized or extracted from plant/"natural" sources, aren't the only real treatments for depression.

of course, there's nothing wrong with chemical treatment, either as a starter course or for the long term for some patients, but it's not the only thing out there.

Psychotherapy is also clearly effective, exercise is effective, there's increasing evidence that Seasonal Affective Disorder-based light therapy is effective for many general cases of depression, meditation has decent initial support in studies along with mind-body arts like yoga and Tai Chi, and while it makes "skeptics" everywhere shake their fists at the sky and wail and lament to their signed and numbered copies of The Zetetic, religious and spiritual experiences have plenty of documented effects in a fair number of people, although good luck getting those to occur on demand in a double-blind RCT anytime soon.

depression is not infrequently also a symptom or cause of larger psychological problems, like coincident mental illness or substance dependency problems (figuring out what started what can be hard there), and working on or medicating those can not uncommonly lift the depression.

this is all without resorting to the chemist's favorite punching bag, homeopathy (although things like the dilution nonsense mean my sympathy for them is limited).

will everything work for everyone? probably not, there's a good chance depression is to some degree syndrome-like.

if you're dealing with depression from the perspective of a patient and not that of a researcher, throw everything at it that's probably useful and not harmful.

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32. Johm on January 26, 2014 6:52 AM writes...

One way around the ethical problem with placebos is to research one medication a lot till it's effectiveness is known completely and use that as the alternate treatment and then factor out it's effects for the study so you could even tell the people that you are getting one of either boring safe well know drug a with some level of positive effect or exiting new drug B that may be even better or not.

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