Presently, for the treatment of depression and other what some claim are mental disorders, as they are questionable, selective serotonin reuptake inhibitors are the drugs of choice by most prescribers. 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. Examples of SNRIs are Cymbalta and Effexor. Some consider these classes of meds a next generation after benzodiazepines, as there are similarities regarding their intake by others, yet the mechanisms of action are clearly different, but not their continued use and popularity by others.

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 the DSM, states that the definite etiology of depression remains a mystery and is unknown. So a chemical imbalance in the brain is not proven to be the cause of mood disorders, it is only suspected with limited scientific evidence. In fact, diagnosing diseases such as depression is based on subjective assessment only, as interpreted by the prescriber, so one could question the accuracy of such diagnoses.

Norepinephrine 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.

And depression is only one of those mood disorders that may exist, 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 is dependent on subjective criteria, such as questionnaires. There is no objective diagnostic testing for depression. Yet the diagnosis of depression in patients has increased quite a bit over the decades. Also, few would argue that depression does not exist in other people. Yet, one may contemplate, actually how many other people are really depressed?

Several decades ago, less than 1 percent of the U.S. populations were thought to have depression. Today, it is believed that about 10 percent of the populations have depression at some time in their lives. 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, as this 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 disease states.

Over 30 million scripts of these types of meds are written annually, and the franchise is around 20 billion dollars a year, 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 being promoted for 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 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, and are active and have been active in forming symbiotic relationships with related disease- specific support groups, such as providing financial support for screenings for the indicated conditions of their meds- screening of children and adolescents in particular, I understand, and as a layperson, I consider such activities dangerous and inappropriate for several reasons.

Danger and concerns by others 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, as I recall.

And there are very serious questions about the use of SSRIs in children and adolescents regarding the 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 in 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.

Finally, if SSRIs are discontinued, immediately in particular instead of a gradual discontinuation, 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, I understand, leaves the brain in a state of neurochemical instability, as the neurons are recalibrating upon discontinuation of the SSRI 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, 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. Considering the lack of efficacy that has been demonstrated objectively, along with the deadly adverse events with these 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.

“I use to care, but now I take a pill for that.” — Author unknown

Dan Abshear

http://www.badscience.net/?page_id=420

If you’re depressed it means your brain mal-adapted over a LONG PERIOD OF TIME to unhealthy situations in your life…weather it be personal, job or relationship or even developmental related. It takes a long time and some hard work on YOUR part to see to the truth and fix your emotional system. You…and your brain needs to be self-aware and in a healthy emotional environment and in time your brain will re-adjust, grow the new synapses, connections, produce the chemicals, etc so that you won’t be ‘depressed’ without drugs.

Taking a prozac pill each day is no different than going out and getting drunk or smoking a joint. The difference is with those they wear off and you have a hangover waking you up to the reality that is going on in your life. On an antidepressant you HAVE NO HANGOVER and basically are “numbed” and learn to live in the unhappy situation you’re in. You only get the “hangover” months or years later if you ever get off the drug. Fix the actual problems in your life and long-term you will be happy…an drug free…not to mention have more money in your pocket and not the drug companies. Which of course is what they want.

Wake up and see the truth of what you’re doing to yourself. Don’t use drugs as a crutch long-term. It’s exactly what you’re doing.

http://news.bbc.co.uk/2/hi/health/7280798.stm

With them, I am just fine, really. It’s that dramatic.

The journos can go on pontificating about whether or not they feel like taking a pill, but if I want to live a normal life, I have to take the medication.

I would certainly hope that people with a serious illness who need treatment are not told to go away and get on a 6-month waiting list for CBT.

The ideal place for an initial consultation with a psychiatrist is not your local hospital’s A&E department.

But, as you say, they didn’t do that, even though they had the data to do it, and instead looked at the difference between SMDs between the groups – I don’t even want to attempt to try and interpret what that measure is supposed to mean, and I’m certainly not sure it should be interpreted as being the same as Cohen’s d.

Ah, crap, looking at the paper they report:

“We conducted two types of data analysis, one in which each group’s change was represented as a standardized mean difference (d), which divides change by the standard deviation of the change score (SDc) [10]”

But that, as you point out, isn’t a proper SMD (it isn’t even a Z-score). But, the paper referenced is about the Hedges g! I’m confused. If we look at their Table 1 we can see that calculating the standard deviation from the 95% confidence intervals of the ‘d’ gives us values of the same order as ‘d’ itself (e.g. study ‘ELC 19′, ‘d’=1.44, SD=1.47), dividing the raw change score by ‘d’ gives us 8.7.

‘d’ is supposed to be the raw change divided by its SD (SDr). We can calculate the SD of ‘d’ from the 95% confidence interval (SDd). So in theory if we multiply ‘d’ and SDd by the SDr we should get the raw change and its standard deviation (SDr). So the SDd must be 1, which it isn’t.

So ‘d’ can’t be the raw change divided by SDr, but is something else. I’m guessing it really is d or some variant.

(a) Cohen’s d is the difference in means/pooled SD (or SD of the control group). So d=0.5 indicates that the mean of one group is 0.5SD higher than the other. Some might call this “interesting”.

(b) If d is calculated from change score/SD of change score, then d=0.5 doesn’t mean the same thing, mainly because the SD of the change score depends on the correlation between baseline and outcome scores.

As you point out, this study calculates (b) for the treatment group and the control group for each study, then subtracts them. As far as I can tell, this gives a d equivalent to (a) only if the SDs of the two groups are equal AND the correlation between baseline and outcome scores is r=0.5 for both groups.

So this seems a very silly way to go about it: you can’t really compare these ds within one study, let alone across several. And I think the NICE guidelines refer to (a) not (b), but I can’t be sure.

But the effect size in this study seems to actually be the difference between the standardised mean difference between baseline and outcome for each group i.e. one SMD minus the other SMD, rather than the mean HRSD change minus the other mean HRSD change.

But my point was that the effect size used in this study wasn’t Cohen’s d. The SD of the difference score is not the same as the pooled SD, or the SD of one of the groups.

Cohen originally suggested using the control/baseline group SD, but the pooled SD tends to be used if it seems likely that the groups have equal or near equal variance of if there isn’t an obvious control/baseline. Arguably, for comparison of differences once should use the original control group SD – not that of the differences – to keep all the effects (drug, placebo, and drug-placebo) on a similar scale.

* There are studies showing that choice of measures of precision and effect can change how its interpreted.

ralaven: The CBT comparison would be interesting. NICE recommend it for mild and moderate depression – if I recall correctly – where it appears the drug treatments may be less effective.

Thom – If I understand you correctly, you are suggesting that the sole use of the funnel plot is to indicate ‘missed’ studies. Certainly in the paper I referred to, that was their application. But the exact same methodology, as I understand it, is also an indication of study quality, and a useful means to present data on the spread of conclusions based upon study sizes. Given software tools can easily produce these plots, I can see little reason to exclude them.

ii) The absence of a funnel plot isn’t a problem. A funnel plot is a useful screening tool for publication bias – but a far from infallible one. In this study they had a complete set of all pre-licensing studies. Therefore, a priori, there can be no publication bias. (Though of course it is crucial to remember – as Ben notes – that this study replicates the state of evidence prior to licensing not the current state of the literature).