"Prozac doesn't work" new study concludes

[andyandy]

.....for all but the most severely depressed that is....


Prozac, the bestselling antidepressant taken by 40 million people worldwide, does not work and nor do similar drugs in the same class, according to a major review released today.

The study examined all available data on the drugs, including results from clinical trials that the manufacturers chose not to publish at the time. The trials compared the effect on patients taking the drugs with those given a placebo or sugar pill.

When all the data was pulled together, it appeared that patients had improved - but those on placebo improved just as much as those on the drugs.

The only exception is in the most severely depressed patients, according to the authors - Prof Irving Kirsch from the department of psychology at Hull University and colleagues in the US and Canada. But that is probably because the placebo stopped working so well, they say, rather than the drugs having worked better.

"Given these results, there seems little reason to prescribe antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed," says Kirsch. "This study raises serious issues that need to be addressed surrounding drug licensing and how drug trial data is reported."

The paper, published today in the journal PLoS (Public Library of Science) Medicine, is likely to have a significant impact on the prescribing of the drugs. The National Institute for Health and Clinical Excellence (Nice) already recommends that counselling should be tried before doctors prescribe antidepressants. Kirsch, who was one of the consultants for the guidelines, says the new analysis "would suggest that the prescription of antidepressant medications might be restricted even more".

The review breaks new ground because Kirsch and his colleagues have obtained for the first time what they believe is a full set of trial data for four antidepressants.

They requested the full data under freedom of information rules from the Food and Drug Administration, which licenses medicines in the US and requires all data when it makes a decision.

The pattern they saw from the trial results of fluoxetine (Prozac), paroxetine (Seroxat), venlafaxine (Effexor) and nefazodone (Serzone) was consistent. "Using complete data sets (including unpublished data) and a substantially larger data set of this type than has been previously reported, we find the overall effect of new-generation antidepressant medication is below recommended criteria for clinical significance," they write.

Two more frequently prescribed antidepressants were omitted from the study because scientists were unable to obtain all the data.
[snip]

Eli Lilly was defiant last night. "Extensive scientific and medical experience has demonstrated that fluoxetine is an effective antidepressant," it said in a statement. "Since its discovery in 1972, fluoxetine has become one of the world's most-studied medicines. Lilly is proud of the difference fluoxetine has made to millions of people living with depression."

A spokesman for GlaxoSmithKline, which makes Seroxat, said the authors had failed to acknowledge the "very positive" benefits of the treatment and their conclusions were "at odds with what has been seen in actual clinical practice".

He added: "This analysis has only examined a small subset of the total data available while regulatory bodies around the world have conducted extensive reviews and evaluations of all the data available, and this one study should not be used to cause unnecessary alarm and concern for patients."http://www.guardian.co.uk/society/2008/feb/26/mentalhealth.medicalresearch

i think there might be a storm over this one :)

[JoeEllison]

I think there may be bunches of stupidity over this, thanks to media incompetence.

[tkingdoll]

Hmm, I'm surprised that this study was ethically approved, considering a previous study has shown that placebo groups (and exercise groups) do as well as prozac, but once the placebo group is informed that they were in fact the placebo group, they tend to spiral into depression worse than before the trial started.

Anyway, it's unsurprising. Exercise is also as effective, if not more effective, than drugs for mild to moderate depression.

[robinson]

i think there might be a storm over this one :)

Nah. Obviously the researcher is an antidrug nutcase.

[shep]

Interesting... time for some anecdotage!

I was on SSRIs for a while, and they appeared to help me a lot. One day I just never went to pick up my prescription. Still feeling fine.

However, that was Cipramil, in the same class as Prozac, but not exactly the same. I was first started on Prozac and after about 3 weeks my entire body was one huge, incredibly itchy rash. Agony. Apparently, the same thing had happened to my mum when she had tried it. I switched to Cipramil and didn't suffer the same effect, though it did appear to 'lift me out of' my depression.

So, placebo it may be, but there's definately some kind of active ingredient in Prozac that isn't in all other SSRIs, and I'm definately allergic to it!

To end the story on a humorous note, I went to pick up a prescription for some some malaria pills before heading off overseas to China (not really necessary but I was playin it safe), and once I got home and opened the box, there was my Cipramil from last August. Whoops. That'll learn me.

I will also note that placebo effect is nothing to be looked down on. If we shoot this stuff down too much in the media, we'll have to invent another miracle cure doctors can pretend they're giving us!

[Deetee]

But it does work - It's just as good as homeopathy!

[baron]

That's depressing news.

[Ivor the Engineer]

So does this indicate mild to moderate depression is a different condition physiologically to severe depression?

Or is the efficacy of treatment with SSRI's for severe depression also misleading?

[Big Les]

This is the article;

Kirsch, I., Deacon, B.J., Huedo-Medina, T.B., Scoboria, A., Moore, T.J., & Johnson, B.T. (2008) Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration. PLoS Medicine 5(2): e45. doi:10.1371/journal.pmed.0050045 (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.)

And one of the authors - http://psy.hull.ac.uk/Staff/i.kirsch/#L2

[Professor Yaffle]

This is very interesting, as I have had very mixed results with anti depressants. I started with tricyclics which seemed to work after a lot of tinkering with the dose, and me feeling better after about 5-6 months. However, that was before I knew that my depression was mostly seasonal, and I would have been getting better around about then. I later tried one or two SSRIs which didn't have much, if any, effect. Then I was put on venlafaxine (effexor) which seemed to help a bit then tail off, then help again when the dose was raised, etc until I got to the highest allowed dose and the doctor added mirtazepine and that seemed to have a really good effect. In hindsight, I think the way the mirtazepine worked was a little circuitous. When depressed I have really low motivation, and therefore do very little exercise etc. I also completely lose my appetite, so have no energy. Mirtazepine had definite side effects of increasing motivation and appetite. All of a sudden, I went from real apathy and lack of energy to rearranging all the furniture in my house and eating really well. Maybe it was the exercise and diet that resulted in me recovering from the depression, and the drug just facilitated me in getting that exercise.

[Acleron]

The results appear very solid. They might even have overestimated the drug/placebo results because some negative trials might have been excluded. I say 'might' because the discussion of what they included becomes a little vague.

Only quibble with it is the conclusion that the drugs only worked in the most severely affected patients because the placebo effect was lower. To only consider drugs to be working when showing an effect when a high placebo effect occurs is slightly ridiculous.

The GlaxoSmithKline response is slightly worrying.
at odds with what has been seen in actual clinical practice

Sort of response that comes from the homeopaths.

[Rolfe]

Well, both Prozac and Cipramil seemed to do something for me. It just wasn't good.

The first time, I went into my doctor's surgery with some physical symptoms, and burst into tears. He started off on a list of tests, but he also said "I think you need something to lift your mood right at the moment". To be fair this was in about 1995. He gave me Prozac. Within about 36 hours I was feeling so much worse that I threw the stuff in the bin. (After the test results came back I was sorted out quite easily, no antidepressants required.)

The second time was in 2000. An unrelated occurrence and I was more stressed and probably more anxious than depressed. This time, the prescription for the SSRI was probably more sensible. This time it was Cipramil. Same result. Because I felt worse than the first time I persevered for nearly a week. It was awful. About half an hour after taking a tablet I went crashing into a panic/anxiety attack. I eventually gave these tablets back to the doctor and told her I would not be taking any more like them. (Ironically, what really did help was lorazepam, but I was given such a tiny amount that it wasn't much practical good - all because of worries about dependence. I've never had the slightest trouble with benzodiazepine dependence and they do seem to work well for me.)

I think the fact that not only do these things not work for everyone, they are actually counterproductive to a subset of patients, needs to be better understood. You can find it in the small print, but most doctors seem to assume that at the very least, if it disnae dae ye ony guid, it'll no dae ye ony herm.

Rolfe.

[JoeEllison]

I think the fact that not only do these things not work for everyone, they are actually counterproductive to a subset of patients, needs to be better understood.

Well... that's "understood" to be normal, isn't it? My understanding is that the folks prescribing pretty much any drugs are supposed to look out for lack of effect/ negative side effects, and change drugs as needed. So, this "lack of effect" is completely expected, and doesn't necessarily point to a complete lack of effect.

Anecdote time: Prozac made me sick the one time I tried it... and Ambien, one of the most popular sleeping pills out there, doesn't work on me at all. In fact, the one time I took it I was up for 2 days. Does that mean that Ambien doesn't work, period, and it is all placebo?:confused:

[Dancing David]

The usual problem with these studies is the way that they rate the depression, the usually use the BDI( Beck Depression Inventory) which is a toool for assessing the precense of depression not the level of depression.

In this case the HRSD (Hamilton Rating Scale Depression) which I would categorise as a gross scale it has only very gross indicators of derpression and is not what i would term a fine scale for rating depression.

Take part 3 (suicide)

3
SUICIDE
0= Absent
1= Feels life is not worth living
2= Wishes he were dead or any thoughts of possible death to self
3= Suicidal ideas or gesture
4= Attempts at suicide (any serious attempt rates 4)

You could not use this gross a scale to determine risk of suicidal action. There is a very fine scaling when it comes to the difference betweent scores 2,3,4 and this is only a gross indication of suicidal patterns. Certainly not useful for assesing suicidai ideation, past and recent attemps, severity of plan, etc.

And it actually gets worse as the scale progresses, especialy on the sleep disturbance and somatization.

4
INSOMNIA EARLY
0= No difficulty falling asleep
1= Complains of occasional difficulty falling asleep—i.e., more than ½ hour
2= Complains of nightly difficulty falling asleep

5
INSOMNIA MIDDLE
0= No difficulty
1= patient complains of being restless and disturbed during the night
2= Waking during the night—any getting out of bed rates 2 (except for purposes of voiding)

6
INSOMNIA LATE
0= No difficulty
1= Waking in early hours of the morning but goes back to sleep
2= Unable to fall asleep again if he gets out of bed


This is not any more than a very groos assesment of sleep disturbance, i would have been fired if i had used something this vague in an assesment.


10
ANXIETY (PSYCHOLOGICAL)
0= No difficulty
1= subjective tension and irritability
2= worrying about minor matters
3= Apprehensive attitude apparent in face or speech
4= Fears expressed without questioning

11
ANXIETY SOMATIC: Physiological concomitants of anxiety, (i.e., effects of autonomic overactivity, “butterflies,” indigestion, stomach cramps, belching, diarrhea, palpitations, hyperventilation, paresthesia, sweating, flushing, tremor, headache, urinary frequency).
Avoid asking about possible medication side effects (i.e., dry mouth, constipation)
0= Absent
1= Mild
2= Moderate
3= Severe
4= Incapacitating

12
SOMATIC SYMPTOMS (GASTROINTESTINAL)
0= None
1= Loss of appetite but eating without encouragement from others. Food intake about
normal
2= Difficulty eating without urging from others. Marked reduction of appetite and food
intake

13
SOMATIC SYMPTOMS GENERAL
0= None
1= Heaviness in limbs, back or head. Backaches, headache, muscle aches. Loss of energy and fatigability
2= Any clear-cut symptom rates 2

14
GENITAL SYMPTOMS (Symptoms such as: loss of libido; impaired sexual performance; menstrual disturbances)
0= Absent
1= Mild
2= Severe

If I had been this vague and gross in assesment, the supervisors would have had a long talk with me and then i would have been fired.

This would be a great tool for determining if someone is depressed but a very poor tool for assesing the efficacy of treatment. This scale is not what i would call a good one for determining the level of depression.

[Ivor the Engineer]

<snip>

(Ironically, what really did help was lorazepam, but I was given such a tiny amount that it wasn't much practical good - all because of worries about dependence. I've never had the slightest trouble with benzodiazepine dependence and they do seem to work well for me.)

<snip>

Rolfe.

I thought the problem with use of benzodiazepines was tolerance, meaning higher doses are required to achieve the same therapeutic effect?

Don't low-dose benzodiazepines stop working after about two weeks of continuous use?

I've noticed the fast acting and short half-life benzodiazepines are becoming popular for conscious sedation during dental procedures in the UK. The other (desirable?) effect they have when used in this way is inducing anterograde amnesia.

[Dancing David]

I think the fact that not only do these things not work for everyone, they are actually counterproductive to a subset of patients, needs to be better understood. You can find it in the small print, but most doctors seem to assume that at the very least, if it disnae dae ye ony guid, it'll no dae ye ony herm.

Rolfe.

This is the crucial factor, the assesment and treatment of mental illness is a very art side of medicine. Diagnosis flows more from treatment than it does the other way. the categories in the DSM are useful but they require a substantial history and a very honest patient with great insight to be useful in the first interview.

In the ER, it is very hard to tell a person with depressed bipolar, psychotic depression and scizophrenia apart. In fact a person in the early stages of schizophrenia will show more agitation and psychomotor activity than the depressed bipolar person.

History is crucial and people, even family members are very poor historians. Add to that the use of substances, hiding of family history and outright denial and it is a real crap shoot. Clinicians are unfortunately often just left with the 'gut feeling' sort of differentiation in the first interview.

Administration of medications often defines the diagnosis, unfortunately.

I am glad they finaly found something that works for you, benzodiazepine dependance is usually a factor of two things the addiction profile of the medication (xanaxor ativan: very bad) and the dosing schedule, most benzos should never be perscribed PRN.

[Dancing David]

I thought the problem with use of benzodiazepines was tolerance, meaning higher doses are required to achieve the same therapeutic effect?

Don't low-dose benzodiazepines stop working after about two weeks of continuous use?

I've noticed the fast acting and short half-life benzodiazepines are becoming popular for conscious sedation during dental procedures in the UK. The other (desirable?) effect they have when used in this way is inducing anterograde amnesia.


Well thsi where the ruber meets the road and shows the difficulties inherent in mental health treatment.

To be effective a medication should also be accompanied by lifestyle changes and cognitive behavioral therapy.

So the sedation effects (which is very noticible in some medications) wears off and the consumer complains that their anxiety has returned. Does that mean it really has or that the sedation has been tolerated?

this gets into the other issues as well:
-is there another medical issue impacting the consumer
-lifestyle changes; is the consumer changing thier life around or just expecting the medication to perform miracles
-is the consumer using stimulants
-is the consumer engaging in drug seeking behavior (they are looking to be high not less anxious, often very indeliberate)
-how does the consumer define anxiety and what are the actual symptoms, frequence, settings and impacts

Now a GP or even a [sychiatrist is not going to have much time to go into this.

[aggle-rithm]

It all depends on what you mean by "works".

If you expect Prozac to be a "happy pill" (as the popular culture would lead you to believe), you might be disappointed.

It doesn't make normal people feel happier; it makes depressed people feel normal.

[Ivor the Engineer]

It all depends on what you mean by "works".

If you expect Prozac to be a "happy pill" (as the popular culture would lead you to believe), you might be disappointed.

It doesn't make normal people feel happier; it makes depressed people feel normal.

And therein lies the fundamental problem with providing mental health care to the masses: Defining what is "normal".

[Deetee]

Well, both Prozac and Cipramil seemed to do something for me. It just wasn't good.

....He gave me Prozac. Within about 36 hours I was feeling so much worse that I threw the stuff in the bin.

The second time was in 2000. This time it was Cipramil. Same result. Because I felt worse than the first time I persevered for nearly a week. It was awful. About half an hour after taking a tablet I went crashing into a panic/anxiety attack. Rolfe.

Rolfe - these were signs they were working - "Aggravations" as we medics like to call them.;)

[Ivor the Engineer]

Rolfe - these were signs they were working - "Aggravations" as we medics like to call them.;)

You may jest:

http://en.wikipedia.org/wiki/Citalopram

Occasionally, panic attacks, thoughts of suicide or self-injury may occur or increase in the first few weeks, before the antidepressant effect starts.[10]

[Professor Yaffle]

I thought this graph from the paper was a nice illustration:

http://medicine.plosjournals.org/perlserv/?request=slideshow&type=figure&doi=10.1371/journal.pmed.0050045&id=96823

I also just learned that NICE doesn't currently recommend antidepressants for mild depression, only for moderate to severe.

[Deetee]

Re the PLoS study (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045):
The first thing I noted was how the investigators grade efficacy:

Antidepressants are only viewed as being effective if they result in what is accepted as a "clinically significant" difference between drug and placebo. In the NICE (http://www.nice.org.uk/nicemedia/pdf/cg023fullguideline.pdf) scoring system, this is regarded as a 3 point difference on the HRSD scale (a 50% improvement in symptoms).

The investigators do show statistically significant differences between drug and placebo, however these fail to achieve the criterion for clinical significance except for severe depression.
Confirming earlier analyses [2 (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045#journal-pmed-0050045-b002)], but with a substantially larger number of clinical trials, weighted mean improvement was 9.60 points on the HRSD in the drug groups and 7.80 in the placebo groups, yielding a mean drug–placebo difference of 1.80 on HRSD improvement scores. Although the difference between these means easily attained statistical significance (Table 2 (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045#journal-pmed-0050045-t002), Model 3a), it does not meet the three-point drug–placebo criterion for clinical significance used by NICE. (my bold)


Now - for a side track rant:
Therein lies one of the primary differences regarding the between orthodox scientific enquiry and woo-woo quackery.
The homeopaths inundate us with reference to the handful of poor quality studies that show marginal statistical significance for selected outcomes that emerge from data-dredging exercises (oscillococcinum for flu, COPD studies etc), and then assume these demonstrate unequivocal benefit from homeopathy. However, the clinical significance of these differences is always negligible or irrelevant (eg the astounding reduction in flu symptoms by a whopping 0.28 days), yet the woos keep screaming their results from the rooftops as though they actually mean something.
ETA: Good heavens - I never knew the "rant" code produced something that looked like that.....

[Professor Yaffle]

And a nice redrawing of it in MS Paint here

http://endofphil.blogspot.com/2008/02/antidepression.html

:)

[Deetee]

And a nice redrawing of it in MS Paint here

http://endofphil.blogspot.com/2008/02/antidepression.html

:)Nice...
Also it provides a link to here (http://pyjamasinbananas.blogspot.com/2008/02/dugs-dont-work.html), where my point about clinical vs statistical significance is also expanded upon.

I find the authors' conclusions rather difficult to interpret:Thus, the increased benefit for extremely depressed patients seems attributable to a decrease in responsiveness to placebo, rather than an increase in responsiveness to medication.This seems a strange way to phrase things.

My own interpretation of the studies is that drug results in a clinically-significant improvement in depression scores for all types of depression. However, there is no clinically-significant benefit of drug as compared to placebo for grades of depression other than the most severe. This seems to be explained by the existence of a greater effect of placebo at lower grades of depression as compared to severe grades of depression, for which the placebo effect appears less relevant.

[Badly Shaved Monkey]

Re the PLoS study (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045):
The first thing I noted was how the investigators grade efficacy:

Antidepressants are only viewed as being effective if they result in what is accepted as a "clinically significant" difference between drug and placebo. In the NICE (http://www.nice.org.uk/nicemedia/pdf/cg023fullguideline.pdf) scoring system, this is regarded as a 3 point difference on the HRSD scale (a 50% improvement in symptoms).

The investigators do show statistically significant differences between drug and placebo, however these fail to achieve the criterion for clinical significance except for severe depression.


I did notice that in the Today programme coverage and was hoping to be able to see whether I had gained the correct impression. Clearly I had. The Big Pharma Stooge (=ABPI spokesman) missed the opportunity to point this out, because the headline version- "NO better than placebo" is rather different from "Not clinically significantly better than placebo for lower grades of depression using a specific definition of clinically significant". The latter hardly trips off the tongue but is more accurate.

Prof Kirsch seemed to give carefully nuanced answers but I don't think this point would have been clear to anyone who did not have some understanding of these technicalities.

[Deetee]

Once again, the importance of using placebo controls in drug efficacy trials is demonstrated.

[Terry]

well... another anecdote. I went to the doctor extremely reluctantly to get some help when I got to the point that exercising stopped making me feel better. Prozac worked very well for me.

ETA: this is somewhat in response to tkingdoll's "its not surprising, exercise works just as well as drugs", rather than to the study itself.

[Dancing David]

And therein lies the fundamental problem with providing mental health care to the masses: Defining what is "normal".

Well, if you have had multiple and longterm depression, it is sort of hard to remember.

But it is not 'normal' to wake at three am, have such a low mood that you can't function or obsess about death by fire.

[Dancing David]

well... another anecdote. I went to the doctor extremely reluctantly to get some help when I got to the point that exercising stopped making me feel better. Prozac worked very well for me.

ETA: this is somewhat in response to tkingdoll's "its not surprising, exercise works just as well as drugs", rather than to the study itself.


Well, some of us used to practice with the jo stick for two hours and stretch for an hour when waking at three am, and then was still depressed, I was in great shape however.

[Sefarst]

So Tom Cruise was right?

Psychiatry:mad:

[ponderingturtle]

So Tom Cruise was right?

Psychiatry:mad:

No. It is effective for seriously depressed people, it is even effective for less depressed people, but it might not be more effective than placebo for those people.

So Tom Cruise is still very very wrong.

[tkingdoll]

well... another anecdote. I went to the doctor extremely reluctantly to get some help when I got to the point that exercising stopped making me feel better. Prozac worked very well for me.

ETA: this is somewhat in response to tkingdoll's "its not surprising, exercise works just as well as drugs", rather than to the study itself.

Well, the studies I've seen show that exercise is as effective as drugs for mild/moderate depression, so could it be that you were wandering into the 'severe' category? Or maybe there's a cutoff point after which exercise ceases to work? After what sort of period of time did you find exercise no longer effective?

I must say, if I let my exercise levels drop, I get into a depressive state very quickly (part of that is simply because I put weight on, though). I wonder if exercise just 'tops you up' to normal, in which case it wouldn't help for severe depression.

[Arkan_Wolfshade]

It all depends on what you mean by "works".

If you expect Prozac to be a "happy pill" (as the popular culture would lead you to believe), you might be disappointed.

It doesn't make normal people feel happier; it makes depressed people feel normal.

Or, in the case of myself and Effexor, it allows me to interact w/ people w/o wanting to stab them in the face w/ a bazooka.

[Terry]

Well, some of us used to practice with the jo stick for two hours and stretch for an hour when waking at three am, and then was still depressed, I was in great shape however.

I used to ride my bike. Climbing a good stiff hill is remarkably effective at getting the heart pounding and the endorphins flowing. But there came a time when I hit the top of the hill and I still felt like everything was pointless and I might as well die. That's when I went to the doctor.

[ponderingturtle]

Well, the studies I've seen show that exercise is as effective as drugs for mild/moderate depression, so could it be that you were wandering into the 'severe' category? Or maybe there's a cutoff point after which exercise ceases to work? After what sort of period of time did you find exercise no longer effective?

Also just because they are effective in the same percentage of people, why would you assume that they are equally effective for an individual?

[Rolfe]

You may jest:

http://en.wikipedia.org/wiki/Citalopram


Indeed, exactly that was pointed out to me. That's why I gave the Cipramil a bit longer than the Prozac. However, before too long I decided that the game most certainly wasn't worth the candle.

There wasn't really a huge amount wrong with me, and if this is the point where I remark that hypnotherapy appeared to work wonders I suppose I'll get flamed. (But it did.) A bit more lorazepam short-term would have helped quite a bit I think, but the stuff does have a bad name.

Oh well, that was eight years ago anyway. I'm fine.

Rolfe.

[The Kilted Yaksman]

Or, in the case of myself and Effexor, it allows me to interact w/ people w/o wanting to stab them in the face w/ a bazooka.
Same here. I tried Prozac early in my treatment and it didn't make me feel any better, or any worse, but it did almost completely kill my appetite.

[JoeEllison]

Indeed, exactly that was pointed out to me. That's why I gave the Cipramil a bit longer than the Prozac. However, before too long I decided that the game most certainly wasn't worth the candle.

There wasn't really a huge amount wrong with me, and if this is the point where I remark that hypnotherapy appeared to work wonders I suppose I'll get flamed. (But it did.) A bit more lorazepam short-term would have helped quite a bit I think, but the stuff does have a bad name.

Oh well, that was eight years ago anyway. I'm fine.

Rolfe.
"Hypnotherapy"? Hey, it could have "worked", just not by the mechanism claimed by the more woo elements?

[annexw]

and Ambien, one of the most popular sleeping pills out there, doesn't work on me at all. In fact, the one time I took it I was up for 2 days. Does that mean that Ambien doesn't work, period, and it is all placebo?

Purely anecdotal, but codeine and other sleep aids make me completely wired. Have done since I was a child. Is it possible that our brains could just be reacting differently to whatever is in the pills?

that or we really really don't want to sleep. ;)

[Rolfe]

"Hypnotherapy"? Hey, it could have "worked", just not by the mechanism claimed by the more woo elements?


I don't know what the woos really claim, but it was like forcible relaxation, if there's such a thing. Not, "it is a good idea to lie down and breathe slowly and think happy thoughts", but "right now you will lie down and breathe slowly and think happy thoughts!" Remarkably effective in breaking an anxiety cycle.

Rolfe.

[JoeEllison]

Purely anecdotal, but codeine and other sleep aids make me completely wired. Have done since I was a child. Is it possible that our brains could just be reacting differently to whatever is in the pills?

that or we really really don't want to sleep. ;)
Trust me, I REALLY wanted to sleep! I was working 3rd shift at the time, 6 days a week, and the insomnia was combining with the normal inability to sleep during the day. It was UGLY. I took the Ambien at around noon... I'd already been up for like 20 hours. It kept me wide awake. I'm not ashamed to say that I was near tears by the end of the whole thing. :cool:

Now, we know that people are wired differently, so there's good reason to at least entertain the notion that Prozac simply doesn't work on some people at all, placebo effect or not.

[JoeEllison]

I don't know what the woos really claim, but it was like forcible relaxation, if there's such a thing. Not, "it is a good idea to lie down and breathe slowly and think happy thoughts", but "right now you will lie down and breathe slowly and think happy thoughts!" Remarkably effective in breaking an anxiety cycle.

Rolfe.

I've known people who have claimed that you can change someone's personality under hypnosis. *shrugs* I always figured it was guided relaxation with a side order of talk therapy.

[Rolfe]

That's what it appeared to be. Don't knock it in the right situation.

Rolfe.

[Miss Whiplash]

Well, the studies I've seen show that exercise is as effective as drugs for mild/moderate depression, so could it be that you were wandering into the 'severe' category? Or maybe there's a cutoff point after which exercise ceases to work? After what sort of period of time did you find exercise no longer effective?

I must say, if I let my exercise levels drop, I get into a depressive state very quickly (part of that is simply because I put weight on, though). I wonder if exercise just 'tops you up' to normal, in which case it wouldn't help for severe depression.

Teek, I must ask, is this depressive state just feeling bad about your body image so that you're more or less down in the dumps? If so, that's normal and not a depressive state. Everyone feels the blues sometimes. We aren't supposed to be happy all the time. Depression is when the unhappy feeling comes, sometimes for no reason at all, and makes a person feel helpless and hopeless until it interferes with a person's quality of life. What I'm getting at is where does normal unhappiness end and true depression begin? I've found the line between the two tends to be subjective.

I do agree exercise does make you feel better. It releases endomorphins. However, in a person who is heading into a downward spiral most likely doesn't feel like leaving the house, much less exercising.

My two cents on the whole thing:

After reading some of the responses, I would hazard a guess that many of you who took SSRIs and tossed the pills after a few days or weeks were not depressed to begin with. Unhappy and stressed? Sure. Depressed and on the way down the rabbit hole with no rope, I don't think so. That also makes me wonder about the mental state of the test subjects, but that's just my opinion and rambling.

As a person with unipolar chronic depression, I've found SSRIs were better for anxiety than the depression alone. Serzone was a nightmare of side effects. However, Wellbutrin XL freaking rocks! Two days after taking my first dose, I went on a two mile run and still felt like I could move a house. Two years later, I've not had one abnormal low.

[Professor Yaffle]

Ths seems like a good place for a book recommendation: Malignant Sadness by Lewis Wolpert. It is part a discussion of the research (this bit may be a little out of date by now) and part the story of his own encounters with depression and how it is different from normal sadness.


It was the worst experience of my life. More terrible even than watching my wife die of cancer. I am ashamed to admit that my depression felt worse than her death but it is true. I was in a state that bears no resemblance to anything I had experienced before. It was not just feeling very low, depressed in the commonly used sense of the word. I was seriously ill. I was totally self-involved, negative and thought about suicide most of the time. I could not think properly, let alone work, and wanted to remain curled up in bed all day. I could not ride my bicycle or go out on my own. I had panic attacks if left alone.

http://www.nytimes.com/books/first/w/wolpert-sadness.html

[KateHW]

Trust me, I REALLY wanted to sleep! I was working 3rd shift at the time, 6 days a week, and the insomnia was combining with the normal inability to sleep during the day. It was UGLY. I took the Ambien at around noon... I'd already been up for like 20 hours. It kept me wide awake. I'm not ashamed to say that I was near tears by the end of the whole thing. :cool:

Sleeping pills don't work for me, either. I know what it's like to be near tears. What's weird is that antihistamines knock me right out, but I have to keep upping the dose for them to keep working and they have that pesky side effect of hypertension when taken regularly.

So, yeah, so far I haven't discovered anything practical that works for insomnia.

As far as antidepressants go, they've always made me feel horrible - sort of a teeth-gritting manic, queasy feeling (and no, I'm not bi-polar). I've stayed on them for ages because doctors seem to think my body needs several months to adjust to them but when I feel just as bad (but in a different way) on meds as off meds, I'm hesitant to try them out again - and I've given them several chances. But I'm going to do it again because it's sort of a last resort right now.

But Prozac is one I can't touch for personal reasons. My first year off at boarding school my mother had a doctor friend prescribe it and Ritalin to me without seeing me so I spent nearly a year having to go to the school nurse every morning while she watched me take that medicine ("show me your tongue") that made me very genuinely sick feeling. My sense of reality was so distorted that I felt like I was in a video game. It's not Prozac's fault but I'm still entitled to my biases.

[Ivor the Engineer]

I wonder how many more people would be on antidepressants if homoeopathy didn't exist?

[Deetee]

Teek, I must ask, is this depressive state just feeling bad about your body image so that you're more or less down in the dumps? If Teek has body image problems, the rest of us are dooooomed I tell you!

[humber]

I thought the problem with use of benzodiazepines was tolerance, meaning higher doses are required to achieve the same therapeutic effect?


Another problem of definition, perhaps. Is alcoholism an addiction? Some say no, because to qualify as addictive, a drug must be connected with increasing level of consumption by the user. Alcoholics often stay at the same level of consumption for long periods, but alcoholism is commonly regarded as an addiction.

[Miss Whiplash]

If Teek has body image problems, the rest of us are dooooomed I tell you!

That is very true! :D

[Tsukasa Buddha]

Is this news? I already read this in a book that is at least five years old (forget which one).

I've never really felt the effects of my drugs. Not to say I haven't gotten better, but I don't think it had anything to do with medication. It was always "well it can take about two months to kick in, just wait a bit more" blah blah.

But then, it would be really hard to know, now wouldn't it :p ?

[LostAngeles]

Considering how badly I do with SSRIs and how eager some seem to be to give them out has put me off for far too long seeking help from Student Psych. Services. I need an outlet and a professional to let me know exactly how badly I'm doing and assist me in getting my **** together, not Charles Bonnet Syndrome.

[skeptigirl]

Interesting... time for some anecdotage!

I was on SSRIs for a while, and they appeared to help me a lot. One day I just never went to pick up my prescription. Still feeling fine.
..Well I'll see your anecdote and raise you one. There were 2 murder suicides and one suicide in my family on my father's side going back only 2 generations. My great uncle and great grandfather both killed themselves and their spouses and my grandfather killed himself.

An incident of severe stress triggered an onset of severe depression in me and after a trial of trazodone didn't help I began an SSRI, buproprion. I have been on it ever since. I miss a pill now and then, but if I miss a couple days worth, I know it. It is a very specific emotion, it isn't sadness at all. I experienced a similar emotion as a PMS symptom long before the stress event.

Essentially it feels like something's wrong but you can't put your finger on it. Worry is a key feature. And I have less tolerance for anything annoying.

This emotion is so specific, I know exactly what it is when I feel it. I spent months observing the pattern when I was younger to confirm it did involve menstrual hormones. And when it happens I know intellectually there really isn't something to worry about and it is neuro-chemical brain activity and nothing more. But that doesn't make the feeling of worry go away.

If I quit taking that SSRI, the feeling returns. When I have breakthrough feeling I have added Prozac since I'm maxed on the buproprion dose but that rarely happens. I'm not that impressed with Prozac but then I never took it in place of buproprion so I can't really say.

Brain serotonin levels in people with depression have been measured. It isn't like there isn't objective clinical evidence to support the use of the SSRIs. And the reason I mentioned my family history is a genetic factor in depression has also been evidenced.

What concerns me about this particular meta-analysis besides how the paper reports it, is how does one distinguish between actual causes of depression? We don't have the diagnosis down to know even how many different disorders we are talking about. I can't say my symptoms were really the kind of depression one thinks of as classic depression. Worry, anxiety, inability to sleep, and anger are just not classic symptoms. But those are my symptoms and they go away with my SSRI and come back without it.

[skeptigirl]

So does this indicate mild to moderate depression is a different condition physiologically to severe depression?

Or is the efficacy of treatment with SSRI's for severe depression also misleading?The former is true for sure. I doubt the latter is true. I haven't read the original research yet. I can't comment on it yet.

[skeptigirl]

The usual problem with these studies is the way that they rate the depression, the usually use the BDI( Beck Depression Inventory) which is a toool for assessing the precense of depression not the level of depression.

In this case the HRSD (Hamilton Rating Scale Depression) which I would categorise as a gross scale it has only very gross indicators of derpression and is not what i would term a fine scale for rating depression.

Take part 3 (suicide)

You could not use this gross a scale to determine risk of suicidal action. There is a very fine scaling when it comes to the difference betweent scores 2,3,4 and this is only a gross indication of suicidal patterns. Certainly not useful for assesing suicidai ideation, past and recent attemps, severity of plan, etc.

And it actually gets worse as the scale progresses, especialy on the sleep disturbance and somatization.


This is not any more than a very groos assesment of sleep disturbance, i would have been fired if i had used something this vague in an assesment.


If I had been this vague and gross in assesment, the supervisors would have had a long talk with me and then i would have been fired.

This would be a great tool for determining if someone is depressed but a very poor tool for assesing the efficacy of treatment. This scale is not what i would call a good one for determining the level of depression.I can't get to the article via the link but this sounds like a very good assessment of it and this correlates with my experience in that the symptoms I have that the SSRI is effective for aren't classic symptoms.

[skeptigirl]

Nice...
Also it provides a link to here (http://pyjamasinbananas.blogspot.com/2008/02/dugs-dont-work.html), where my point about clinical vs statistical significance is also expanded upon.

I find the authors' conclusions rather difficult to interpret:This seems a strange way to phrase things.

My own interpretation of the studies is that drug results in a clinically-significant improvement in depression scores for all types of depression. However, there is no clinically-significant benefit of drug as compared to placebo for grades of depression other than the most severe. This seems to be explained by the existence of a greater effect of placebo at lower grades of depression as compared to severe grades of depression, for which the placebo effect appears less relevant.Excellent discussion of the study there. And for those who don't find the article from previous link, here's another try. (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045)

[skeptigirl]

This is the article;

Kirsch, I., Deacon, B.J., Huedo-Medina, T.B., Scoboria, A., Moore, T.J., & Johnson, B.T. (2008) Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration. PLoS Medicine 5(2): e45. doi:10.1371/journal.pmed.0050045 (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.)

And one of the authors - http://psy.hull.ac.uk/Staff/i.kirsch/#L2I don't know why your link doesn't work for me. It is to the entire paper?

This link (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045) at least gets to the summary.Conclusions

Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.



Wait, I see the problem, you appear to have extra stuff in the title that is maybe interfering with the url.

Let's see what happens here: Kirsch, I., Deacon, B.J., (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.)

Nope, didn't help.

[skeptigirl]

This will be one for the CTers to claim the drug companies are all frauds. Too bad the news media rarely uses anyone who knows what they are actually reading when they report on scientific research.

[Big Les]

Gawd knows how I arsed up that link, but you sorted it at least. Ben Goldacre's blog post is now up;

http://www.badscience.net/?p=619

He focusses on the damning implications for the drug companies, but for me the snippet at the end was most interesting;

1. It was not a study of SSRI antidepressant drugs: neither nefazodone nor venlafaxine are SSRI drugs.

2. It did not look at all the trials ever done on these drugs: it looked only at the trials done before they were licensed, and specifically excluded all the trials done after they were licensed. It is common for quacks and journalists to think that the moment of licensing is some kind of definitive “it works” stamp of approval. It’s not, it’s just the beginning of the story of a drugs’ evidence, usually.

3. It did not show that these drugs have no benefit over placebo: it showed that they do have a statistically significant (”measurable”) benefit over placebo, but for mild and moderate depression that benefit was not big enough for most people to consider it clinically significant, ie there was an improvement, but not enough points improvement on a depression rating scale for anyone to get too excited over it.

[pipelineaudio]

THis comes right on the heels of being asked to try one of these things again (lexapro)

Last time it was paxil, to combat the efeects of severe tooth and gum infections the doctors had diagnosed as anxiety. I went from 125 pounds to 250 pounds and ended my bike riding career.

This time my tongue is numb, my ears are ringing and numb, my eyes hurt like someone is shoving hot coals into them and I get up to pee 5 time a night instead of sleeping.

Im trying the lexapro but it costs about a quarter of my monthly pay so if it doesnt work, I'd rather try something else

I realize this study is flawed, but its making me nuerotic anyhow

[shep]

An incident of severe stress triggered an onset of severe depression in me and after a trial of trazodone didn't help I began an SSRI, buproprion. I have been on it ever since. I miss a pill now and then, but if I miss a couple days worth, I know it.

I didn't mean for my story to be supporting the argument that SSRIs were no better than placebos, necessarily, just saying what happened to me. I left bits out, too, which might not have helped :blush:

I would definately not consider the depression I was suffering to have been 'severe'.

Like you, however, I noticed when I skipped pills for a few days... I would get quite low, get back on them, and within another 2-3 days, feel OK again.

It wasn't until I made a hard decision (without consulting my GP, I must confess) about 8 - 10 months later that I stopped them totally.

I should also note that when I started taking the pills, I had also decided to make some other pretty big changes in my life, including where I lived, what I ate, how many hours I worked, and tried a bit of CBT as well.

[Kiosk]

I began an SSRI, buproprion.

Buproprion isn't an SSRI.

Brain serotonin levels in people with depression have been measured.

No they haven't: there is no reliable test for brain serotonin levels in a live human.

Just saying, like. Despite being what certain people would call an "SSRI victim", I'm not about to go Tom Cruise on you or anything.

[Kiosk]

It was the worst experience of my life. More terrible even than watching my wife die of cancer. I am ashamed to admit that my depression felt worse than her death but it is true. I was in a state that bears no resemblance to anything I had experienced before. It was not just feeling very low, depressed in the commonly used sense of the word. I was seriously ill. I was totally self-involved, negative and thought about suicide most of the time. I could not think properly, let alone work, and wanted to remain curled up in bed all day. I could not ride my bicycle or go out on my own. I had panic attacks if left alone.

That was not quite how I felt before I took sertraline, so I should probably never have taken it. If you replace "wife" with "father", it's a sickeningly accurate description of how I felt for the first year after coming off sertraline, and to a significantly lesser extent now, at well over 2 years off - but you'd have to add a very long list of pretty extreme physical symptoms to that list.

Severe withdrawal and post-withdrawal effects are the elephant in the room when it comes to SSRIs. Since the phenomenon is almost impossible to study, it gets almost no attention, and if you've not experienced it yourself it's horribly tempting to write the whole thing off as the ravings of folk who should just get back on their meds (until the same thing shows up in people who were prescribed off-label for insomnia or IBS, which it has).

Rather than how well the drugs perform against placebo - and long before this meta-analysis, it was widely known that they didn't set the world alight in trials - I feel the real issue here is potential danger to mental and physical health in the long term, whether by ultimately worsening the course of an existing condition, or creating a condition in those who didn't need the meds in the first place. Despite my personal experience, I'm not an anti-SSRI zealot, and I'm well aware of the positives (besides, if it were possible to take them forever without the damn things pooping out, you wouldn't hear me complaining), but it worries me that there's a certain complacency on this issue. As a sceptic, I accept that there's no hard evidence of damage from long-term SSRI use; as an antidepressant veteran, I rather suspect there's just no hard evidence yet.

[Dancing David]

Sleeping pills don't work for me, either. I know what it's like to be near tears. What's weird is that antihistamines knock me right out, but I have to keep upping the dose for them to keep working and they have that pesky side effect of hypertension when taken regularly.

So, yeah, so far I haven't discovered anything practical that works for insomnia.

As far as antidepressants go, they've always made me feel horrible - sort of a teeth-gritting manic, queasy feeling (and no, I'm not bi-polar). I've stayed on them for ages because doctors seem to think my body needs several months to adjust to them but when I feel just as bad (but in a different way) on meds as off meds, I'm hesitant to try them out again - and I've given them several chances. But I'm going to do it again because it's sort of a last resort right now.

Ugh, you had bad doctoring there.

There is a syndrome of hypomania and even mania induced by ADs especialy tricyclics, but SSRIs to a lesser extenet. Your doctor should have been listening to you.
There is also paradoxical anxiety in the administration of SSRIs and it should resolve within six weeks (receptor rollover) not months.

I don't know your history but you need a better doctor and one versed in treatment refractory depression.

Perhaps the diagnosis also needs to be reconsidered and treatment alternatives explored.

Mood stabalizers (if you have good insurance) are often effective in treatment refractory depression, a good medical work up is always advised and perhaps consultation with other specialists (yeah like that is not a six month wait).

This is just my opinion, that and 98 cents will buy you a cup of coffee.

But Prozac is one I can't touch for personal reasons. My first year off at boarding school my mother had a doctor friend prescribe it and Ritalin to me without seeing me so I spent nearly a year having to go to the school nurse every morning while she watched me take that medicine ("show me your tongue") that made me very genuinely sick feeling. My sense of reality was so distorted that I felt like I was in a video game. It's not Prozac's fault but I'm still entitled to my biases.


That is not a bias, that is a report of a personal subjective experience and those are ALL there are to go on in medication side effects unless there is something like akesthesia or other visible motor activity.

Perhaps some exploration on your own of reputable medical articles on ADHD, depression, Bipolar II and other disorders will help you to speak with the doctors more effectively.

Do you feel that you have anything like ADHD? That is a stimulant you were given there, if it made you hyper you don't have ADHD, depersonalization is not a good experience and it sure sounds like you had a serotonin overload.

[Dancing David]

Well I'll see your anecdote and raise you one. There were 2 murder suicides and one suicide in my family on my father's side going back only 2 generations. My great uncle and great grandfather both killed themselves and their spouses and my grandfather killed himself.

An incident of severe stress triggered an onset of severe depression in me and after a trial of trazodone didn't help I began an SSRI, buproprion.

isn't that wellbutrin?

I have been on it ever since. I miss a pill now and then, but if I miss a couple days worth, I know it. It is a very specific emotion, it isn't sadness at all. I experienced a similar emotion as a PMS symptom long before the stress event.

Essentially it feels like something's wrong but you can't put your finger on it. Worry is a key feature. And I have less tolerance for anything annoying.

Yup, I know that one too, irritability. Ugh.


This emotion is so specific, I know exactly what it is when I feel it. I spent months observing the pattern when I was younger to confirm it did involve menstrual hormones. And when it happens I know intellectually there really isn't something to worry about and it is neuro-chemical brain activity and nothing more. But that doesn't make the feeling of worry go away.
Nope, you have my sympathy.



If I quit taking that SSRI, the feeling returns. When I have breakthrough feeling I have added Prozac since I'm maxed on the buproprion dose but that rarely happens. I'm not that impressed with Prozac but then I never took it in place of buproprion so I can't really say.

Brain serotonin levels in people with depression have been measured. It isn't like there isn't objective clinical evidence to support the use of the SSRIs. And the reason I mentioned my family history is a genetic factor in depression has also been evidenced.

thank you, I could slap Thomas Szasz.


What concerns me about this particular meta-analysis besides how the paper reports it, is how does one distinguish between actual causes of depression? We don't have the diagnosis down to know even how many different disorders we are talking about. I can't say my symptoms were really the kind of depression one thinks of as classic depression. Worry, anxiety, inability to sleep, and anger are just not classic symptoms. But those are my symptoms and they go away with my SSRI and come back without it.


I as a former mental health worker would say that i sure looked for those in an assesment.

But then ihave an anxious OCD and depressive thing going on.

[Dancing David]

Buproprion isn't an SSRI.



No they haven't: there is no reliable test for brain serotonin levels in a live human.

Just saying, like. Despite being what certain people would call an "SSRI victim", I'm not about to go Tom Cruise on you or anything.


Sorry to read that.

All ADs should be monitored weekly during the start of treatment (as if that will happen) and SSRIs and SNRIs are not for every one.

Side effects are real and often terrible.
I had some great side effects but the relief was significant so I persevered.

[Dancing David]

That was not quite how I felt before I took sertraline, so I should probably never have taken it. If you replace "wife" with "father", it's a sickeningly accurate description of how I felt for the first year after coming off sertraline, and to a significantly lesser extent now, at well over 2 years off - but you'd have to add a very long list of pretty extreme physical symptoms to that list.

Severe withdrawal and post-withdrawal effects are the elephant in the room when it comes to SSRIs. Since the phenomenon is almost impossible to study, it gets almost no attention, and if you've not experienced it yourself it's horribly tempting to write the whole thing off as the ravings of folk who should just get back on their meds (until the same thing shows up in people who were prescribed off-label for insomnia or IBS, which it has).

Rather than how well the drugs perform against placebo - and long before this meta-analysis, it was widely known that they didn't set the world alight in trials - I feel the real issue here is potential danger to mental and physical health in the long term, whether by ultimately worsening the course of an existing condition, or creating a condition in those who didn't need the meds in the first place. Despite my personal experience, I'm not an anti-SSRI zealot, and I'm well aware of the positives (besides, if it were possible to take them forever without the damn things pooping out, you wouldn't hear me complaining), but it worries me that there's a certain complacency on this issue. As a sceptic, I accept that there's no hard evidence of damage from long-term SSRI use; as an antidepressant veteran, I rather suspect there's just no hard evidence yet.


ADs are not for everyone, but as a former crisis worker (and a survivor of collateral suicide trauma), the toll of depression is rather staggering. It is very gruesome especially when the blood isn't cleaned up. Strangely however the one that freaked me out the most was watching the suffering of someone my daughters age who had ODed and was really, really, really sick.

[Soapy Sam]

The observation that "real" depression is totally different from "feeling depressed" is one that often comes up in discussion like this.

I would like to know how anybody knows this to be the case.

I've seen a man with two fingers torn off his hand actually continue to hold the object that caused the damage, as if he let it go it would possibly kill someone. I've also seen someone in tears because he tore his new suit.
These are both human responses to damage and presumably "normal".
How do we know that what seems like a kindofa bummer to Jim may not feel like the catastrophic end of the world to John?

Is there any objective test for emotion?

[Michael C]

Ben Goldacre has some made some sensible comments on this: http://www.badscience.net/?p=619. He points out that it was already known that antidepressants are of little value for mild and moderate depression. The main point he makes is that pharmaceutical companies are good at burying the results of negative studies.

[Mr. Scott]

Time for my own Prozac anecdote:

I was warned it would take a couple of weeks to take effect, but noticed within 24 hours I was feeling generally numb. It even numbed my sex drive, which depressed me more. I hypothesized that Prozac worked by numbing all feelings. After complaining about the lost sex drive, I was prescribed something to take an hour before sex that purportedly would be a temporary antidote to the Prozac (it may have been Viagra -- it was too long ago to remember). After about 6 months on Prozac I got tired of feeling numb and stopped taking it for good.

There was a scandal a few years ago when patients on Prozac appeared to have an increased chance of killing themselves. The hypothesis was that some patients, too depressed to carry out their suicide fantasies, become well enough carry it out but not so well that they changed their mind about doing it. Don't know the long term outcome of that.

My personal opinion from my own experience is Prozac's a stupid drug.

[tkingdoll]

Teek, I must ask, is this depressive state just feeling bad about your body image so that you're more or less down in the dumps?

No. I've suffered from chronic depression since I was twelve, attempted suicide twice, and had post-traumatic stress disorder twice. The second time I didn't leave the bedroom for three months. I was in therapy for over fifteen years.

That was some time ago. I am an extremely high-functioning depressive now but little things can trigger a bad patch (my birthday, putting on weight, etc). I am fortunate enough to have a very strong support network around me though.

I don't, however, do Prozac. I tried it once, I didn't enjoy feeling 'medicated'. I suspect that's a similar mentality to the one that leads to homeopathy and other woo.

[Ivor the Engineer]

So is depression defined by its duration combined with a disproportionate feeling of sadness/despair relative to the absolute situation?

[Big Les]

Ben Goldacre has some made some sensible comments on this: http://www.badscience.net/?p=619. He points out that it was already known that antidepressants are of little value for mild and moderate depression. The main point he makes is that pharmaceutical companies are good at burying the results of negative studies.

What am I, chopped liver (http://forums.randi.org/showpost.php?p=3474611&postcount=60)? ;) Seriously, as soon as I saw the news reports, I was waiting for Ben's take on it. He should be government science advisor or something.

[Arkan_Wolfshade]

So is depression defined by its duration combined with a disproportionate feeling of sadness/despair relative to the absolute situation?


Symptoms
Symptoms of depression include the following:

depressed mood (such as feelings of sadness or emptiness)
reduced interest in activities that used to be enjoyed, sleep disturbances (either not being able to sleep well or sleeping to much)
loss of energy or a significant reduction in energy level
difficulty concentrating, holding a conversation, paying attention, or making decisions that used to be made fairly easily
suicidal thoughts or intentions. per: http://allpsych.com/disorders/mood/majordepression.html

[Professor Yaffle]

From DSMIV


Major Depressive Episode
A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

Note: Do note include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.

(1) depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood.

(2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)

(3) significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.

(4) insomnia or hypersomnia nearly every day

(5) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)

(6) fatigue or loss of energy nearly every day

(7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)

(8) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)

(9) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B. The symptoms do not meet criteria for a Mixed Episode.

C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).

E. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

[Ivor the Engineer]

I've had all those, except for 3 and 5. I still don't think I've been "inexplicably" depressed. I.e., I can always think of an event which has precipitated the symptoms, and more importantly, have learned to recognize the early signs and how I can "head it off at the pass", so to speak.

[Dancing David]

So is depression defined by its duration combined with a disproportionate feeling of sadness/despair relative to the absolute situation?

The short definition, a sad persistent mood lasting more than one month.

[Dancing David]

Ben Goldacre has some made some sensible comments on this: http://www.badscience.net/?p=619. He points out that it was already known that antidepressants are of little value for mild and moderate depression. The main point he makes is that pharmaceutical companies are good at burying the results of negative studies.


Sorry Michael but I have to say that is a rather glossy and vague web site post that does little to actualy discuss the issues of treating depression and seems to be sort of just a rant.

Is there a specific issue you would like to address from the article?

[Dancing David]

Time for my own Prozac anecdote:

I was warned it would take a couple of weeks to take effect, but noticed within 24 hours I was feeling generally numb. It even numbed my sex drive, which depressed me more. I hypothesized that Prozac worked by numbing all feelings. After complaining about the lost sex drive, I was prescribed something to take an hour before sex that purportedly would be a temporary antidote to the Prozac (it may have been Viagra -- it was too long ago to remember). After about 6 months on Prozac I got tired of feeling numb and stopped taking it for good.

Sounds like bad doctoring.

They should have monitored and listened to your c/o side effects.

There was a scandal a few years ago when patients on Prozac appeared to have an increased chance of killing themselves. The hypothesis was that some patients, too depressed to carry out their suicide fantasies, become well enough carry it out but not so well that they changed their mind about doing it. Don't know the long term outcome of that.

Um it is a fact of treatment, what would you like to know?

the last year for which there is data shows there is an increase in teen suicide since the infamous black box warnings about ADs.

So while there is a very small percentage of cases that involve suicide caused by ADs, most suicide might be caused by something else.



My personal opinion from my own experience is Prozac's a stupid drug.

probably not the drug for you and bad doctoring.

[Dancing David]

I've had all those, except for 3 and 5. I still don't think I've been "inexplicably" depressed. I.e., I can always think of an event which has precipitated the symptoms, and more importantly, have learned to recognize the early signs and how I can "head it off at the pass", so to speak.


So you had a least five?

that is part of the key, the other key is how it effects your functioning.

if it does not impact your functioning then there is not an issue.

I personally never assesed major depression unless there had been a functional impairment thatw as fairly noticible and the symptoms were reported to have lasted a month.

For depression to be moderate to severe I used a criterion of physical symptoms, IE insomnia, panic attacks or strong appetite changes.

i think that the real issue for people who haven't done an assesment is the use of the phrase

"represent a change from previous functioning","markedly", "significant distress or impairment " because it isn't really spelled out for people who aren't mental health clinicians.

[Professor Yaffle]

Oh and the ICD classification which includes the mild/moderate/severe distinction can be found here:

http://www.mentalhealth.com/icd/p22-md01.html#Head_2

From reading that, I have had one (possibly 2) severe episodes, and several moderate ones. I don't tend to sek treatment when I meet the criteria for mild depression, just look on it as a warning sign that I may be spiralling into a "proper" depression and try to avert it myself.

[aggle-rithm]

I've had all those, except for 3 and 5. I still don't think I've been "inexplicably" depressed. I.e., I can always think of an event which has precipitated the symptoms, and more importantly, have learned to recognize the early signs and how I can "head it off at the pass", so to speak.

Depressed people often come up with ad hoc explanations for their depression, and so often don't seek treatment. It's part of human nature, I think: For every effect, we search for a simple and direct cause in order to make sense of it.

[aggle-rithm]

Time for my own Prozac anecdote:

I was warned it would take a couple of weeks to take effect, but noticed within 24 hours I was feeling generally numb. It even numbed my sex drive, which depressed me more.


SSRI's can take a while to have a positive effect, but some of the side effects are immediate.


I hypothesized that Prozac worked by numbing all feelings.

A lot of people think that. The error is in assuming that depression is about feelings. According to cognitive psychology (and probably others), negative feelings are just a side effect of depression. Depression is about your brain not working properly, and it affects not just emotion but cognition as well.

Cognitive psychology theorizes that this defect in cognition actually causes the emotional side effects. At any rate, SSRI's seem to address both problems, although the exact mechanism is not known. I don't think merely numbing a person's feelings would be sufficient to accomplish this.

[LostAngeles]

isn't that wellbutrin?
...

Ahh, of all the anti-depressants I was ever given, wellbutrin was the best. Tremors and succeeding in being in two places simultaneously. It was like dreaming and being awake at the same time and seeing both of them in the same space.

Since that one, I refused all meds except the TCA I was given for migraines which made me weird and insomniac.

Bupropion is a norepinephrine reuptake inhibitor according to wiki.

[Deetee]

Some interesting fall-out regarding this study.

There are a number of interesting responses on the PLoS medicine (http://medicine.plosjournals.org/perlserv/?request=read-response&doi=10.1371/journal.pmed.0050045#r2145)publication site.

One blogger (http://pyjamasinbananas.blogspot.com/2008/02/antidepressants-redux-2.html) has performed a reanalysis of the data, which actually shows a clinically-significant effect is easily achieved for both paroxetine and venlafaxine. (the other blog posts from him are also interesting)

[bethanythemartian]

Interesting anecdote: when I was a teenager I was seeing a student in the psych department at the local college. We talked about many of my issues, but we never brought up my depression. A week or two after I brought it up (having been prodded about it by my mother) I was told to go to a licensed psychiatrist- she could talk to me, but couldn't prescribe drugs. I spoke to him for about fifteen minutes, and he gave me a prescription for an anti-depressant. (After we spoke about Sleep-Paralysis related to my insomnia, which he recommended over the counter sleep medication for.)

I took the prescription for about.. oh, a month. Maybe a month in a half. Terribly sorry, I really can't remember what was prescribed. This has been... 6 years or so. All I remember is this medicine gave me the WORST migraines I've ever had, on a daily basis. I was miserable. I'm a very pain tolerant person, but I was pushed to vomit from pain more than once during this period of time.

Let me tell you, if I thought I was depressed BEFORE daily migraines that made me want to vomit...

But this is pretty interesting. Is it possible that depression is over-diagnosed (like ADD in kids) and the most severe cases were people who were ACTUALLY depressed? Interesting...

[Miss Whiplash]

Interesting anecdote: when I was a teenager I was seeing a student in the psych department at the local college. We talked about many of my issues, but we never brought up my depression. A week or two after I brought it up (having been prodded about it by my mother) I was told to go to a licensed psychiatrist- she could talk to me, but couldn't prescribe drugs. I spoke to him for about fifteen minutes, and he gave me a prescription for an anti-depressant. (After we spoke about Sleep-Paralysis related to my insomnia, which he recommended over the counter sleep medication for.)

I took the prescription for about.. oh, a month. Maybe a month in a half. Terribly sorry, I really can't remember what was prescribed. This has been... 6 years or so. All I remember is this medicine gave me the WORST migraines I've ever had, on a daily basis. I was miserable. I'm a very pain tolerant person, but I was pushed to vomit from pain more than once during this period of time.

Let me tell you, if I thought I was depressed BEFORE daily migraines that made me want to vomit...

But this is pretty interesting. Is it possible that depression is over-diagnosed (like ADD in kids) and the most severe cases were people who were ACTUALLY depressed? Interesting...

What anti-depressant were you given? SSRIs are not recommended for teenagers.

Is depression over diagnosed? Very probable (http://www.guardian.co.uk/medicine/story/0,,2151096,00.html).

It's interesting reading, some of these anecdotes. Also, I wonder if the doctor bothered to discuss adverse reactions to the medication. All the stories I've read here note common reactions to various antidepressants that are listed on the Prescription Information sheets that should accompanying every Rx. Anyone taking any type of new medication should be aware of adverse side effects, be prepared for them after taking the medication, and reporting the side effects to a doctor when they happen.

[bethanythemartian]

What anti-depressant were you given? SSRIs are not recommended for teenagers.

I am aware of that, very much so. But, if memory serves, that study came out AFTER I got off of that particular medication. And, so sorry, it has been well over five years and I can't clearly remember the name of the medication. I didn't take it very long.


It's interesting reading, some of these anecdotes. Also, I wonder if the doctor bothered to discuss adverse reactions to the medication. All the stories I've read here note common reactions to various antidepressants that are listed on the Prescription Information sheets that should accompanying every Rx. Anyone taking any type of new medication should be aware of adverse side effects, be prepared for them after taking the medication, and reporting the side effects to a doctor when they happen.

A little more background, since you mentioned it: the psychiatrist who prescribed my medication had never seen me before, and I never saw him again.

When I realized that the headaches were a result of the medication I went to my family doctor, a very nice man who said he'd prescribe me some sleep med if I *really* thought I needed some, but gave me some good tips on going to sleep and told me to drop the anti-depressant. (The reason I bring up the sleep med is my psychiatrist told me my insomnia and depression were related.)

Now I read those sheets that come with scrips VERY carefully, and keep an eye out for common side-effects.

[Jeff Corey]

I am aware of that, very much so. But, if memory serves, that study came out AFTER I got off of that particular medication. And, so sorry, it has been well over five years and I can't clearly remember the name of the medication. I didn't take it very long.



A little more background, since you mentioned it: the psychiatrist who prescribed my medication had never seen me before, and I never saw him again.

When I realized that the headaches were a result of the medication I went to my family doctor, a very nice man who said he'd prescribe me some sleep med if I *really* thought I needed some, but gave me some good tips on going to sleep and told me to drop the anti-depressant. (The reason I bring up the sleep med is my psychiatrist told me my insomnia and depression were related.)

Now I read those sheets that come with scrips VERY carefully, and keep an eye out for common side-effects.

One problem is that combinations of different drugs prescribed by different doctors may have synergistic or other interactive effects and the sheets don't always list them all. How can they? Think of all the possible combinations and permutations of all the effects of all the legal drugs out there. Not to mention
I believe Linda posted a similar spiel on another thread. Using one pharmacist with good records can save your life.
Also, not lying to you doctor about your recreational use of ibocaine.

[Tsukasa Buddha]

What anti-depressant were you given? SSRIs are not recommended for teenagers.

Really? I recall the commercial for my med now said you had to be over eighteen (Which I just turned).

[Miss Whiplash]

Really? I recall the commercial for my med now said you had to be over eighteen (Which I just turned).

I forget when the FDA issued the warning, but SSRIs can increase suicidal behavior in teenagers and children, so the FDA black boxed the pills for teens.

I agree with Jeff, one must disclose all medications to a physicians and it's best to have one pharmacist who can keep track of the medicines. Never assume what a doctor prescribes is safe and harmless and will not interact with what you are taking, or not have adverse side effects. Even aspirin can be deadly if taken with the wrong medication.

I always read the package inserts throughly. I also do a Google on any medication to see a complete list of side effects, indications and contraindications. Also, when I take a new medication, I let someone know what I've taken, and what side effects to look for. Reactions happen and informed people mean the difference between life and death.

There was a time when prescriptions were dispensed and even the name of the drug was not disclosed to the patient. We live in much more informed times. Not only to patients have information sheets on the drugs, side effect can be found on the internet. Really, there is no excuse for not knowing the basic side effects of any medication. It pays to be informed. One only gets one life.

[Dancing David]

I forget when the FDA issued the warning, but SSRIs can increase suicidal behavior in teenagers and children, so the FDA black boxed the pills for teens.

.

am not arguing with you. I would suggest however that data are incomplete at best and that the attribution of suicidal impulses and ideation may not be solely to the introduction of the AD. There are many confounding factors involved ( please note I am not saying that it does not happen, because it does).

-Incomplete histories and lack of valid historical data on individuals. Self report and family report can be , um, rather lacking at times. A family saying that there teen never had suicidal or homicidal ideation and acts does not mean that they didn't. This is one source of possible error.
-Misdiagnosis and misattribution of the symptoms. Families with resources and even those without are capable or doctor/therapist/diagnosis shopping. The most likely culprits of misdiagnosis due to shopping and denial : domestic violence/sexual/emotional abuse by a parent, conduct disorder, substance abuse and seeking a preferential diagnosis.
-Outright denial and confirmation bias
-The very valid risk of onset of treatment increasing suicidal risk.
-The interactive dance of individual, staff and medication seeking.
-Lack of consistent monitoring by staff and parents.

So while it is demonstrated that there are people who when exposed to ADs develop thoughts and actions that they had not shown before, in many ways that is also blamed by some for many other confounding factors.

And the disturbing thing is that the suicide rate rose for the one year we have data for after the black box warning. I will have to look and see if they have released 2006 yet.

Please note, I am not saying that there are not cases where treatment causes very adverse, dangerous and lethal situations but in the rush to condemn ADs many confounding factors seem to have been ignored.

I only say this because as a mental health , domestic violence and crisis worker I became aware of a number of things:
-families would deny any sort of violent history at the intake but then three years later tell you that so and so had tried to choke mom with the phone cord prior to treatment
-children and adolescents under trauma are often the 'identified client' when really they are the victim of abuse
-even in the ER you will ask family a very pertinent question about violence, asked carefully and you still get really strange answers in response



And I am very aware of the bizzre family interactions about kid in treatment, who gets treatment and who doesn't and the terrible things a medication can do.