Au Revoir

The survey final results will be my last post for a while. The time has come to polish my research paper and compile my powerpoint presentation. I will give a final summary of my project later in May. I hope to see some of you at my presentation! Thank you for your readership. As of now, I'm not sure who reads this, if anyone does, but I hope I provided an informative overview of the antidepressant controversy.

-Savannah

Survey Finale

 

The third question: In a typical doctor-patient relationship, would it be ethical for a doctor to prescribe a patient a pill that is a placebo but represent that pill as an actual medicine?

Now, the most important ethical point has been reached. Can a doctor give a patient a placebo and call it medicine? Can they lie in an attempt to produce a benefit? Is a placebo a reasonable treatment plan?

This time 67.9% of responders said it was unethical while 24.5% said it was ethical. 7.5% of people were unsure.

The final question: If you answered no to the previous question, please mark the answers below that best explain why.

58.3% of people said it was unethical because doctors should not lie to their patients.

83.3% of people said it was unethical because patients have a right to know what they are being prescribed.

69.4% of people said it was unethical because it is not medically safe for a patient to be in the dark about the prescription(s) he is on.

13.9% of people said they did not think inducing placebo effect is an effective medical treatment.

The last option was to write a unique reason that the responder thought it was unethical. I received five.

1. "The only case a placebo may be effective is if the patient is a hypochondriac, but even then its a very subjective thing to describe. Also, if the patient is actually experiencing symptoms that prompt the doctor to prescribe something, I'd prefer the doctor to actually prescribe a REAL drug then just test his own theories on me (giving me placebo instead of a real drug for his own reasons). I would feel like a lab rat."

This response takes into consideration the risk of doctors "experimenting" on their patients by giving them non-drugs without being clear about the treatment plan. However, valid as that observation is, it is not correct to claim that only hypochondriacs would be positively affected by a placebo. Perhaps, it is unlikely anyone but a hypochondriac would be completely cured by a placebo, but even that is not certain.

2. "I think that the patient should be informed that it COULD be a placebo, but maybe it's not."

This is a good idea. It gives the patient much more control over their treatment. If they objected to the possibility of receiving a placebo, they would be able to express that to their doctor.

3. "Patients has a right to know the medication prescribed by a doctor-name of medication, purpose, side effects, etc. A placebo is to be used only in a study to benefit the medical community, not support drug company study or misguide a patient."

This objection seems to focus primarily on the patient's right and need to have all the information about their prescriptions. The mention of supporting drug company study is interesting. One could argue that the use of placebos in clinical trials helps protect against drug company manipulation of success rates by providing a standard of efficacy.

4. "At that stage of the of the doctor-patient relationship, the doctor is a well-schooled and trained expert in his/her field. He/she is well-aware of all the treatments that would undoubtedly cure the patient permanently or temporarily of their problem. Thus, if any medical doctor who is trained to administer medicine or perform typical doctoral procedure even considers giving his/he patient a placebo to see if it builds patient confidence, then THAT doctor is merely treating a genuine, hurting patient as an essential "lab-rat" to see if the placebo actually works. The patient is paying a lot of money to be treated properly with proper medicine that will properly and safely cure his/her illness. A placebo would be unethical and unfair to the patient in this sense."

This responder brings up the factor of paying for treatment and not receiving genuine medicine as a problem. He or she also brings up the issue of unauthorized doctor-patient experimentation as being unethical.

5. "In a double-blind study, patients know that there is a chance that they are receiving a placebo, but this understanding is not part of the doctor-patient relationship."

This response also addresses the concept that the placebo administration would be more acceptable if the patient was aware of the possibility.

This review of placebo ethics is relevant to the efficacy of antidepressants because it is important to consider whether or not taking the  side effect risks of the current medications is superior to administering placebo in order to cure what many people view as a problem "in the patient's head."

However, it is clear that placebo treatment is ethically questionable in many cases as well as less effective than antidepressants. There are biological symptoms to be treated in the case of depression and it is unlikely that a placebo would be enough to seriously treat the condition.

A link to the survey is provided in the sidebar.

Survey Says

After my last posts about placebos, I was interested in what the general opinion of placebo ethics might be. It seemed that my opinions and those of majority of doctors did not match up based on the following image.

For this reason, I created and distributed a survey to gauge the opinions of my peers. Fifty-three people responded to the survey. I will examine the results of the survey in my final two posts before my conclusion post due to their relevance to the superiority of antidepressants over other treatments namely placebos.

The first question: Placebos are used to determine the effectiveness of medicine in many studies. A double blind study involves a group of patients with a condition who will be administered either a placebo or the actual medicine. Neither the doctors nor the patients know who is being given medicine and who is being given placebo until the end of the trial. The placebo effect successful responses and the actual medicine successful responses are compared to determine the clinical worth of the actual medicine. Do you consider this an ethical use of the placebo effect?

The majority of people (83%) considered this ethical, including me. The rest of the people either considered it unethical (7.5%) or did not have an opinion (9.4%). I thought these results were unsurprising and I asked the question mainly to present how placebos are usually used.

The second question: Now consider a basic doctor-patient relationship completely separate from clinical trials. Would it be ethical for a doctor to promote a treatment primarily to increase the patient's confidence in that treatment and thus the likelihood that the patient will experience a helpful placebo effect?

This is a more interesting question. A doctor's positive presentation of a procedure or treatment can seriously affect a patient's confidence, and thus possibly the placebo effect the patient experiences. What can that hurt? The answer is less clear. This is especially relevant in the case of depression, in which many patients are consistently hopeless and demoralized. Should the doctor be getting the patient's hopes up or is it worth the benefit to over-represent the possibility for success? I would even argue that in prescribing any treatment the doctor must advocate it to a certain extent so where do you draw the line?

This was still voted ethical though by a smaller margin (only 62.3%). 34% of survey takers considered this unethical and 3.8% were unsure.

A link to the survey is provided in the sidebar. More information will be provided in my next post.

Placebo Effect, Part 2

Not so fast, just how severe is the depression?

Maybe the placebo effect is not enough but can antidepressants actually beat it? Generally, in basic studies of adults, antidepressants are more effective than placebos. However, those who do not trust antidepressants are quick to say that the margin of effectiveness between the two is not enough to outweigh the side effect risks of the actual medicine. Some go so far as to say that a significant portion of antidepressants effectiveness outside of clinical trials can be attributed to placebo effect. This claim is supported by the risk of relapse after initial signs of remission during antidepressant treatment. The argument is essentially that patients feel better due to a placebo effect when first given antidepressants but that this improvement cannot last long term and therefore, the antidepressants are not better than a placebo. Personally, I do not think my research has supported that claim however. In a previous post,  I discussed a study that indicated that patients whose monoamines were more abundant (the main biological effect that antidepressants induce) were less likely to have recurring symptoms of depression after initial remission. Also, I have found a new study that indicates that the more severe the depression, the more the antidepressants outshine placebos. This study does mention that the difference in success between antidepressants and placebos can be almost nonexistent in more mild or moderate cases of depression.

While I have detailed a variety of alternative treatments for depression, the two options that are considered genuinely substantial are psychotherapy and antidepressants. This fact combined with the prevalence of depression as a condition means that psychiatry and psychology are fighting against a formidable foe with limited resources. Severe depression especially can result in death. Furthermore, these deaths tend to be suicides which can have a profound effect on the loved ones of the deceased, resulting in the propagation of depression in even more people. Depression has a certain stigma to it because it is easier to blame on personal weakness than more straightforward biological malfunctions, however, the condition must be seriously addressed. If severe depression really is treated more successfully by antidepressant medications than mild to moderate depression, the treatment of depression can only be improved by that fact and having an effective way to help the severely depressed is indispensable.

You have to have confidence in your placebo or it's unlikely to succeed.

Another thing that is relevant about the placebo effect in depression treatment: while the concept that a placebo effect in the treatment of depression can lead to later recurrence due to inadequate treatment may be a valid complaint, it is my opinion that patients should not let fear of placebo effects reduce their confidence in their medicine. It is unfortunate if a placebo effect that cannot be sustained long term causes the helpful effects of a medication to cease, however, the fact remains that the placebo effect is not likely to be harmful. In the event that one medication no longer works, it can either be determined that the patient might find more long term success with a different antidepressant or perhaps it can even be considered that the severity of that patient's depression is not high enough for the medication to have more than a possibly temporary placebo effect. So long as there are no intolerable side effects, even a placebo-effect induced improvement is better than no improvement at all. In addition, there is another way to improve the long term success of a drug depression treatment and that is by adding psychotherapy to the treatment plan.

Moran, Mark. "Does Placebo Effect Mask True Efficacy of Antidepressants?" Psychiatric News. 2 July 2010. Web. 25 Apr. 2012. <http://pnhw.psychiatryonline.org/content/45/13/17.2.full>.

Sipkoff, Martin. "Antidepressants Work Best For the Severely Depressed." Managed Care Magazine Online. Web. 25 Apr. 2012. <http://www.managedcaremag.com/archives/1003/1003.medmgmt_antidep.html>.

Nauert, Rick. "Placebo Effect Among Antidepressants | Psych Central News." Psych Central.com. Web. 25 Apr. 2012. <http://psychcentral.com/news/2007/08/15/placebo-effect-among-antidepressants/1131.html>.

Placebo Effect, Part 1

In double blind clinical trials, patients are split up into two groups. In the case of an antidepressant trial, some of the patients are given the antidepressant and some are given a sugar pill (called a placebo) but no one, including the doctors, knows who got which treatment. As mentioned in previous posts, this is how the effectiveness of antidepressants is usually measured: the effects on the patients taking the real antidepressants are compared to the effects experienced by those taking the sugar pill. The placebo effect (the amount to which the sugar pill is described as effective) in antidepressant trials has been known to range between 15 percent and 70 percent response rates. It also seems that over the time, as antidepressant trials have been performed, the placebo effects documented in the more recent trials are higher.





The placebo effect is a powerful though not well understood phenomena of medicine and of life. To what extent can the power of positive thinking and expectation produce medical results? The basis of the placebo effect seems to be that if a patient expects to be affected by a medicine or treatment in a specific way, they are more likely to perceive that effects. In a way, this is similar to the concept of confirmation bias in psychology: if a person has an opinion, they will be more likely to notice evidence that supports that opinion. However, the placebo effect in a condition like depression that is significantly subjective in some aspects cannot be underestimated. The extent to which psychology can affect illness, especially mental illness, is still mysterious due to the limited knowledge of the causes of depression and other mental illnesses. Why have the placebo effect statistics in antidepressant trials increased over time? It is possible that as the drugs became less new and more commonly prescribed, public opinion of their usefulness increased thus increasing the placebo effect.

In this way, the placebo effect seems like a very good thing. If belief in a medicine alone is enough to produce improvement in depression symptoms, why bother with risky complex medications at all? The reason why sugar pills are not just prescribed in everyday life rather than antidepressants is as follows. The placebo effect is reliant on the patient's belief that they are taking an effective medicine, so obviously if a doctor were to prescribe sugar pills to a patient to attempt to induce a helpful placebo effect, the ethical and practical issues may be tricky. It seems inherent that a doctor should not simply lie to a patient. As the person taking the pill, the patient needs to know what the pill he is taking contains for medical safety reasons and because it is his right. In a clinical trial, the situation is more controlled and the participants know that they might be receiving a placebo so the concealment is acceptable. In fact, as the main goal of the doctors has shifted from treating one patient's depression successfully to measuring how successful a certain drug is typically, the difference in objective makes the concealment more than just acceptable but also necessary. In the end, the placebo effect is used in clinical trials to determine the worth of the other medicine tested. To treat serious conditions like major depression, it is ideal to produce more improvement than the placebos can provide on their own even in the best case scenario. In studies, medicines are compared to placebos and the extent to which the success of the medicine exceeds the success of the placebo is measured. This measurement is extremely important. If the effect of an antidepressant is indistinguishable from a placebo pill then the medicine is no more helpful than a sugar pill while the antidepressant is more dangerous than a placebo due to the side effects of the former.

Or maybe my grasp on what is considered ethical in medicine nowadays isn't so on point?

Are antidepressants actually more successful than placebos? Survey says, hear more about the implications of the placebo effect on the efficacy of antidepressants in my next blog post.

"MedicineNet.com." Medterms. 14 Mar. 2004. Web. 24 Apr. 2012. <http://www.medterms.com/script/main/art.asp?articlekey=31481>.

 Kirsch, Irving. "Challenging Received Wisdom: Antidepressants and the Placebo Effect." McGill Journal of Medicine. Web. 24 Apr. 2012. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582668/>.

"Confirmation Bias." ScienceDaily. ScienceDaily. Web. 24 Apr. 2012. <http://www.sciencedaily.com/articles/c/confirmation_bias.htm>.

Lakoff, Andrew. "The Right Patients for the Drug: Managing the Placebo Effect in Antidepressant Trials." BioSocieties. Web. 25 Apr. 2012. <http://www.palgrave-journals.com/biosoc/journal/v2/n1/full/biosoc20075a.html>.

Hope After All?

Antidepressants can cause dangerous suicidal thoughts in people of all ages. The FDA requires labels and brochures distributed with the drugs to warn about all of the possible side effects. The question is: is warning the public enough or should more drastic measures be taken?

In the case of adults, I think that personal choice should be allowed. An adult with a prescription from a doctor should not be kept from taking antidepressants, despite the risks. However, I do not think the same is true for children. In children, the prescription of certain antidepressants should be discouraged, if not outlawed. The difference is that in children the odds of positive effects from tricyclic antidepressants are slim to none, making the risk of administering these drugs to children a foolish one to take. In doing more research, I found that while tricyclic antidepressants do not usually help children, fluoxetine (the SSRI usually known as Prozac) has been showed to be effective, especially when combined with cognitive behavioral therapy. This indicates that since the original FDA study claiming the effects of SSRIs was "clinically insignificant" in children the matter has been further researched in a way that may have encouraged doctors to prescribe the pills to children.

It is fortunate that the SSRIs were studied further as the need for an effective treatment in severely depressed children is great. It seems that the atypical antidepressant bupropion (often marketed as Wellbutrin) has also shown positive effects in children. It is interesting to consider why there is such a difference in effectiveness in children and adults. Most likely, the mechanism of depression on the brain is different in children than in adults due to the process of brain development.

In the end, I think that the question of personal choice versus social responsibility comes down to effectiveness. If there is a chance that the doctor-prescribed medication may help the patient, the patient should have the right to take that chance.

"Open Trial of Bupropion SR in Adolescent Major Depression." 25 Aug. 2004. Web. 20 Apr. 2012. <http://onlinelibrary.wiley.com/doi/10.1111/j.1744-6171.2003.00123.x/abstract>.

 "The Treatment for Adolescents With Depression Study (TADS): Long-term Effectiveness and Safety Outcomes." Archives of General Psychiatry, Oct. 2007. Web. 19 Apr. 2012. <focus.psychiatryonline.org/data/Journals/FOCUS/1833/foc00108000063.pdf>.

Think About the Children

 You are worried about seeing him spend his early years in doing nothing.  What!  Is it nothing to be happy?  Nothing to skip, play, and run around all day long?  Never in his life will he be so busy again.  ~Jean-Jacques Rousseau, Emile, 1762

They don't work? Why do we prescribe them?

One special subgroup of the depressed population consists of depressed children. As mentioned in my previous post, children (which we can consider anyone up to the age of 18) are depressed in large numbers. However, on the other hand, according to Peter Breggin's book Medication Madness: A Psychiatrist Exposes the Dangers of Mood-Altering Medication, antidepressants are currently considered by the FDA as no more effective than placebos in depressed children. In fact, Breggin claims that due to the risks of side effects, including increased suicidal tendencies, antidepressants are not helpful to children but are actually consistently harmful to them if there is any effect. So how do the depressed children get help? Some families have opted out of medicating their kids with antidepressants, favoring instead child psychologists. However, despite what Breggin seems to consider a decisive verdict of ineffectiveness for antidepressants in children, they are still commonly prescribed. I have mentioned highly sought after child psychiatrists who charge between hundreds and thousands of dollars for an initial assessment. The rest of this blog post will be an attempt to understand why this medicine continues to be prescribed to a vulnerable social group if it is known to be useless or harmful.

In 2004, the FDA applied a black box warning to antidepressants that states that they can increase "the risk of suicidal thinking and behavior in pediatric patients." By doing this, the FDA drew attention to a serious side effect and directly mentioned the group they considered the most at risk. It is definite that harmful antidepressant side effects have been documented in children. However, these risks also exist to a lesser extent in adults but, unless lethal or intolerable side effects are certain or overwhelmingly likely, I do not think the prescription of antidepressants should stop due to those side effect risks. There's still a chance that an adult individual will find an antidepressant that can help them with manageable or negligible side effects. Does this possibility for improvement not exist for children?

After examining the FDA-sponsored study, it seems that Dr. Irving Kirsch concluded that, in children, as compared to placebo, the effects of tricyclic antidepressants were statistically insignificant and that while SSRIs were statistically significant, they were not "clinically significant." The FDA has spoken. Who disagrees? I am not sure. I can find a variety of studies concluding that tricyclics are worthless for children and while most studies say more information needs to be ascertained about SSRIs for children, they admit that SSRIs are minimally effective, if at all. Even the drug company GlaxoSmithKline sent out warnings about prescribing paroxetine to children due to the suicide risks in 2003, before the FDA put out the black box warning.

Overall, it seems that science does not support the effectiveness of antidepressants in children. The fact remains that there are children, even small children, taking these drugs. SSRIs are considered by many in the medical profession as the safest antidepressant to prescribe to children despite the apparent lack of therapeutic reward that accompanies the drugs serious side effects. Why are children taking these medications? Perhaps, there is evidence of effectiveness that I have not been able to find. Perhaps, their lack of effectiveness is not widely known or agreed upon among the doctors actually making prescriptions. Perhaps, science cannot yet give us a full evaluation of the positive effects these drugs can potentially have, effects that could be observed in practice. Perhaps, doctors suppose that some cases of depression in children are severe enough to risk side effects to attempt to achieve even a slight improvement. I fear I do not have the resources to decisively explain why children are still prescribed antidepressants. In the end, the FDA did not create a ban, it simply issued a warning. If doctors continue to prescribe these pills to children, they do so at their own risk. Unfortunately, they also do it at the risk of the patient and his loved ones, who often rely primarily on the advice of their doctor. Should we allow parents and their children to collaborate with their doctors and make up their own minds or should the prescription of antidepressants to children be limited by law? This important juncture between social responsibility and personal choice in psychiatry will be discussed further in my next blog post.  

"Efficacy and Safety of Antidepressants for Children and Adolescents." BMJ Group. Web. 18 Apr. 2012. <http://www.bmj.com/content/328/7444/879.full>.

"Dr. Irving Kirsch and Dr. David Antonuccio on the Efficacy of Antidepressants with Children." Web. 18 Apr. 2012. <http://www.ahrp.org/risks/SSRI0204/KirschAntonuccio.php>.

Papanikolaou, K., C. Richardson, A. Pehlivanidis, and Z. Daifoti-Papadopoulou. "Efficacy of Antidepressants in Child and Adolescent Depression: A Meta-analytic Study." National Center for Biotechnology Information. U.S. National Library of Medicine, 3 Aug. 2005. Web. 18 Apr. 2012. <http://www.ncbi.nlm.nih.gov/pubmed/16075184>.

Tsapakis, EM, F. Soldani, L. Tondo, and RJ Baldessarini. "Efficacy of Antidepressants in Juvenile Depression: Meta-analysis." National Center for Biotechnology Information. U.S. National Library of Medicine, July 2008. Web. 18 Apr. 2012. <http://www.ncbi.nlm.nih.gov/pubmed/18700212>.

Hazell, P., D. O'Connell, D. Heathcote, J. Robertson, and D. Henry. "Efficacy of Tricyclic Drugs in Treating Child and Adolescent Depression: A Meta-analysis." BMJ Group, 8 Apr. 1995. Web. 18 Apr. 2012. <http://www.bmj.com/content/310/6984/897.short>.

"A Black-Box Warning for Antidepressants in Children?" The New England Journal of Medicine. 14 Oct. 2004. Web. 18 Apr. 2012. <http://www.nejm.org/doi/full/10.1056/nejmp048279>.