Can exercise treat drepession?

by Ava Sadeghi

Run! by Steve Garner

Every morning, you wake up, brush your teeth, go for a run, and then head to work. If you are stressed out, unhappy, or concerned, daily exercise can lift your moods and make you happier. Exercising and getting into a routine that you enjoy can relieve depression, anxiety and ultimately increase your happiness.

In recent studies, it has been shown that exercise works well for depression patients. Psychologists have been using exercise as a form of medication and treatment for many of their anxiety and depression patients (UT Southwestern Medical Center, 2011).

A clinical psychologist, James Blumenthal, at Duke University set up an experimental study to see the connection between mood and exercise. In this study, patients with a major depressive disorder were put into four groups: supervised exercise, home-based exercise, antidepressant therapy, and a placebo pill. After several months of treatment the study showed that exercise effects were similar to antidepressant medications.

A year later, Blumenthal, followed up with the patients and found that the patients who kept exercising did not go into remission. They still had low depression scores. With this study, psychologists have now started to couple antidepressant treatment with exercise, to increase mood and lessen depression.

Not only can exercise improve moods, but it can relieve anxiety as well. Jasper Smits of Southern Methodist University in Dallas performed an experiment involving 60 subjects with anxiety disorders.  These subjects were asked to take a carbon-dioxide challenge test. This test triggers symptoms of panic attacks. According to this study, Smits concluded that people with high anxiety were less likely to panic if they had high activity levels. This finding supports the idea that exercise can help lessen panic attacks (Weir, 2011).

The next step is figuring out why exercise brightens your mood. There are not many studies on this, but many psychologists believe that it has to do with increasing antibodies, endorphins, and other neurotransmitters.

Love, obsession, and chemistry

by Dan Schwarzman

May 22nd (Don't Say That You Love Me) by Phoney Nickle

What is love, and why does it exist? Chemical similarities have been found linking love to OCD and depression. Anthropologist Helen Fisher PhD of Rutgers University has been doing research on love, which she has divided into three chemically separate states. Fisher says that lust is driven by androgens and estrogen, while romantic love, characterized by intensely emotional mood swings and obsessive craving, is driven by high dopamine and norepinephrine levels, along with low serotonin. The third state, of stable attachment, is driven by the hormones oxytocin and vasopressin.

An evolutionary anthropologist, Fisher explains the evolutionary value of these three states. According to evolutionary theory, adaptations show up in species if they lead to increased survival and reproduction. Fisher says that lust evolved as a mechanism for people to be interested on a basic level in reproduction with others, while romantic love developed to focus one’s mating energy on just one individual. Stable attachment works to tolerate this individual long enough to raise children as a team. The obsessive energy output of being in love might seem illogical in the context of evolutionary theory, especially since love is often not reciprocated, but this ability to forgo short term efficiency in favor of greater long term reproductive success makes sense as an important adaptation for the continuation of the human race.

When exercise beats meds

by Jonathan Brummer

Photo by Darren Waters

As a college athlete in an extremely physically demanding sport, a great deal of my life centers around exercise.  I have always known that exercise is an activity which promotes physical health and for that reason alone, was enough motivation to partake in it.  Who in their right mind does not want to ward of diseases like diabetes or maintain strong and healthy heart functions?  With a formerly weak immune system and terrible asthma, exercise has improved the quality of my life in ways that I could not have imagined.

This lack of imagination has once again gotten the better of me.   It turns out there are surprising psychological benefits of exercise.   A  study performed at Duke University which studied the levels of depression among subjects divided into three specific treatment groups.  These included a group being treated with SSRI’s (Serotonin Specific Reuptake Inhibitors), one with an exercise regime and the final one with a combination of both SSRI’s and exercise.  Not surprisingly, all formerly depressed patients showed a significant decrease in depression levels at the end of the study, with two thirds of the group having eradicated it all together.  What is surprising however, is the fact that six months after the conclusion of the study, participants in the exercise only group were in better shape, psychologically, than members of either of the other groups.  Specifically, the were more likely to have experienced full or partial recovery, even when compared to the exercise plus medication groups.

As a rower, I am intimately familiar with one of the brain’s responses under prolonged physical exertion.  The release of endorphin neurotransmitters under such conditions lessen pain and boost mood in what is often called a “runner’s high.”  This “high” has very short term effects however, ending shortly after or even during the workout (Myers, 2007).   While the sense of accomplishment from achieving a physical goal may also stimulate endorphin release, even this fades within a relatively short time span.  This begs the question of how exercise actually affects us in the long run.  Does habitual exercise physiologically remap our brains in some way that we naturally maintain higher levels of serotonin or have neurons that are more receptive to these pleasurable neurotransmitters?  Or maybe positive changes in one’s self-image through weight loss or an increase in one’s perceived health eventually leads to a physiological change in the brain.  If this is the case, then just how necessary are SSRI’s like Prozac and Zoloft, especially given a slew of negative and potentially dangerous side effects that can arise from frequent use?

References:
American Psychological Association (May 28, 2004).  Exercise Helps Keep Your Psyche Fit.  Retrieved October 10, 2008 from http://www.psychologymatters.org/exercise.html.

Mayo Clinic Staff (2006). Selective serotonin reuptake inhibitors (SSRIs).  Retrieved November 6, 208 from http://www.mayoclinic.com/health/ssris/MH00066

Myers, David G. (2007).  Psychology (8th ed.  in Modules).  New York: Worth.

Talking: My Anti-Drug

by Julie Carlsen

In recent years, society has seen an incredible leap in science and medicine. We’ve evolved from treating wounds with plants and locking up the mentally unstable to curing everything with a pill. While in many cases, these medical advances are incredibly beneficial, sometimes pills seem to be too readily chosen as the answer for every problem; a recent study published in the New York Times discusses alternative therapies for depressed adolescents other than simply drugging the patient up and leaving him be.
Researchers in the article Talk Therapy for Depressed Youth tested 654 clinically depressed twelve – seventeen year olds for a year and examined how different anti-depression mechanisms worked. Patients were either given Prozac, placebo pills, cognitive behavioral therapy (“talk therapy”), or a combination of Prozac and talk therapy. Those taking Prozac or the combination of Prozac and talk therapy were deemed better within twelve weeks, while talk therapy alone was just as ineffective as placebo pills. After nine months, most of the group had shaken off their depression, but those who hadn’t received talk therapy with their Prozac reported sudden suicidal feelings. The mixture of the healing drug with the healing conversations proved to better the person best overall.

Suicidal thoughts, SSRIs, and genes

by Kelly Long

In a world where illnesses once thought debilitating have become more treatable than ever, the question of whether or not a treatment is available for an affliction like depression has become almost obsolete. The difficulty has shifted to the issue of which drug is best for which patient, and how a balance may be found between treatment and side effects.
Recent government-funded studies, reported in the New York Times, have shown that Celexa, an anti-depressant drug belonging to the class of selective serotonin reuptake inhibitors (SSRIs) may cause patients to experience suicidal thoughts. Interestingly, those same suicidal thoughts tended to be found in patients who did not actually attempt suicide, while it has been noted that the one patient in the study that did actually attempt suicide vehemently denied any thoughts of suicide.

Unsurprisingly, the physiology of the connection may be traced to the brain. Throughout the course of the study, two out of the sixty-eight genetic markers studied were noteworthy, as 36 percent of the subjects in possession of the markers experienced suicidal thoughts after taking Celexa. The markers coded for an amino acid called glutamate, which, aside from working as a natural antidepressant by activating neurons, is involved with learning and memory in the brain. Although the results of the tests were inconclusive, they raise the serious question of how treatment can be achieved without a flurry of undesirable (and sometimes dangerous) side effects. It is also remarkable to think that, with time and more research, a genetic test may be developed that is capable of pinpointing exactly which depression treatment is best for each patient.

[Editor's note: Interested readers may also want to look at this post about why the added caution around SSRIs also causes problems.]

Source:

Carey, Benedict. (2007 September 28). Genes Tied to Bad Reactions to Antidepressant Drug. New York Times. Retrieved September 30, 2007, from http://www.nytimes.com.

ADHD, smoking, and bupropion

What constitutes the main effect of a drug, and what constitutes the side effect?  Aspirin relieves headaches, but also thins your blood as a side effect.  Unless you are taking aspirin to prevent a heart attack, and then it is the other way around.  With psychoactive drugs, that target one or more neurotransmitters, it can be even harder to sort out.  It takes complicated research to figure out the complicated effects of many psychoactive medications.

Here is a story about a complicated study that looks at one effect of one well-known drug, bupropion, which is marketed as both Zyban and as Wellbutrin. The patients studied were all ADHD patients, boys and girls, ranging from 9 to 18 years old. Half were given a daily dose of bupropion, and half were given a placebo, and then they were followed for about a year.

Wellbutrin is marketed as an antidepressant. Why give people with ADHD an antidepressant? At first glance, this seems odd at best. Most modern antidepressants, like Prozac, Paxil, and Zoloft are SSRIs (selective serotonin reuptake inhibitors). They primarily target the neurotransmitter serotonin, which helps to regulate mood, among many other functions. Wellbutrin, by contrast, targets dopamine primarily, as well as norepinephrine and serotonin. All three play a role in mood regulation, so Wellbutrin provides an alternative when SSRIs are not very effective. Norepinephrine and serotonin may be at least as important in depression, but it is the dopamine that we focus on here.

Dopamine is another neurotransmitter, one that is associated with motivation, pleasure, rewards, and addiction. Ritalin, the best-known drug which is used to treat ADHD, boosts dopamine levels. According to Nora Volkow, of Brookhaven Laboratories,

“We now know that by increasing the levels of extracellular dopamine, you can activate these motivational circuits and make the tasks that children are performing seem much more exciting. By raising that level of interest, you can significantly increase the ability of the child to focus on the task.”

In other words, a controlled rise in dopamine levels improves motivation and focus in kids who have trouble with both.

Compared to cocaine or amphetamines, which also boost dopamine, ritalin’s action is much slower (when taken in pill form). That probably explains why cocaine and amphetamines are highly addictive, but Ritalin is not. A slow boost in dopamine may also explain why bupropian/Wellbutrin is effective as an ADHD treatment. It is working in a similar fashion to Ritalin, though by a different chemical mechanism.

So one drug, bupropion, is useful in treating both depression and ADHD. But what does this have to do with smoking?

Zyban, which is exactly the same drug as Wellbutrin, is marketed as a helper in stopping smoking. As far as I know, there is no definitive research to show how it works. But I will speculate that since nicotine in cigarette smoke provides a dopamine boost, nicotine withdrawal involves the body expecting that dopamine boost and not getting it. Zyban may relieve that craving by raising dopamine levels, although more slowly and not as much as nicotine does.

Now, back to the complicated study. If bupropion (as Zyban) helps people quit smoking, should it also help adolescents avoid smoking in the first place? Dr. Michael C. Monuteaux and his colleagues (reported in the Journal of Clinical Psychiatry, July 2007) tested this by experimentally manipulating whether patients got bupropion or a placebo. They could not, of course, manipulate whether the patients had ADHD. They all did. Nor did they control whether they were taking Ritalin or another stimulant-based drug, but they carefully tracked this. They had patients of different ages, but the results cited in the news story do not point to any age-related differences. They checked on the outcome variable, whether or not the patients smoked, by looking for a nicotine by-product in their urine.

The result must have been disappointing: The patients in the bupropion group were actually more likely to start smoking than the patients in the placebo group.  The drug that works well for stopping smoking was no good at all in preventing these patients from starting to smoke.  I don’t know why that was any more than Dr. Monuteaux.  I can speculate that maybe starting and stopping reflect different underlying neural mechanisms.

There was another result.  Unexpectedly, the patients who were taking stimulant-based drugs, like Ritalin or a generic equivalent, were less likely to smoke.  So now Ritalin may turn out to have an unexpected, but beneficial side-effect.  As usual, we need more research.

One question lingers with me most of all: Why are kids with an ADHD diagnosis more likely to take up smoking in the first place. Some researchers have suggested that this is an attempt to self-medicate. That raises the interesting possibility that understanding more about nicotine addiction may help us to understand more about ADHD as well. But I promise it will still  be complicated.

When caution kills: Antidepressants and suicide risk

Imagine that your best friend is really, truly depressed. And imagine that they are given a bottle of pills with the following label: “Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders.” Pretty scary, huh? You and your friend might think that the risk (suicide) outweighs the potential benefit (some relief from that depression). At the very least, you might think about an alternative treatment plan that does not involve such scary drugs. Evidently, a lot of doctors have been thinking the same thing, because the prescription rates for antidepressants have been falling ever since the FDA started requiring those labels.

It is easy to understand why. No one, whether they are a doctor, a parent, or a best friend, wants to contribute to a suicide. Everyone wants to be cautious when they are dealing with someone who is already at risk, for fear they will make things worse. The FDA labels speak exactly to that fear.

Where does this fear come from?  There have been plenty of anecdotes about people, including teens, committing suicide shortly after starting an antidepressant.  These anecdotes led to studies looking closely at teens in the first months following a new prescription to SSRI (selective serotonin  reuptake inhibitor) antidepressants.  In requiring new labels, the FDA was responding to studies showing a link between SSRI’s and increased suicidal thoughts.

You may be wondering why these studies track suicidal thoughts, and other indexes of “suicidality” and not suicides themselves.  There is a very good reason, actually.  Suicides are, thank goodness, very rare events, measured in the single digits per 100,000 patients.  So for a study to find a statistically significant increase in actual suicides, even among depressed patients being prescribed antidepressants, it would need millions of subjects.  Can’t be done.  So even though suicidal thoughts are not the same as suicides, they do provide some measure of danger signs.  Which is better than no data at all.

But was the FDA response to these studies just a healthy dose of caution?  Maybe not. In fact, as prescription rates for antidepressants declined, suicide rates increased.

In hindsight, this might look pretty obvious.  Being depressed is obviously a risk factor for suicide, after all.  In fact, some researchers have been arguing since before the FDA required the warnings that they were a bad idea.  Their data showed a very different side of SSRIs – a decrease in suicides in counties in the US where SSRIs were prescribed more heavily.  Although these data were correlational, they suggested a net benefit to these newer antidepressants.  And although a correlation can’t tell us much about cause and effect, it is really hard to argue that SSRIs cause more suicides if higher rates of use are correlated with lower rates of suicides.

Why did the FDA focus on the studies that showed a risk to SSRIs, and not on the studies that showed a benefit.  One possibility is that they fell victim to a very common bias in the way people reason about risks and benefits.  We have an aversion to risks, which is disproportional to our attraction to gains.  When told that  a new drug might kill one patient out of a thousand, we focus on that one.  This is a more powerful force in our thinking than the idea that in the other 999 patients, there might be more than one that the drug saves.

So what about that friend looking at a “black label” warning on a bottle of SSRIs?  Should they avoid the SSRIs altogether? In this case, a little caution may do  a lot more harm than good.  On the other hand, the data showing an increased risk when first taking the drug should not be ignored.  I would speculate that for some depressed teens, the SSRI may provide just enough relief to allow them to carry out a suicide they were too apathetic to manage before.  The critical period of risk seems to be the first weeks and maybe months of a prescription.  So that is when your friend needs your support the most.

The placebo effect: Friend or foe?

Sometimes when a patient is given a treatment, like an antidepressant, the symptoms go away for awhile, and then come back. This is called a relapse. One reason for a relapse would be that the drug stops working. Another possibility, raised by this study, is that the drug was really working by means of a placebo effect. The placebo effect is something we have all heard of, but we tend to dismiss it as a problem in experiments, rather than an issue in the real world of treatments. The placebo effect is important in both settings.

In an experiment, the placebo effect is well-known potential problem, and good experiments are designed to avoid it.  Here is how it works:  If you give someone a new drug, or a new kind of therapy,  or really any treatment at all, they usually expect it will work.  After all, the person giving the treatment, be it doctor, therapist or scientist, is presumed to be some kind of expert.  That expectation, that the treatment will do some good, can be a powerful force all on its own.  In a depressed patient, the hopefulness that accompanies the expectation of a treatment working may be enough to improve a patient’s mood.  That in turn will improve their interactions with other people.  Better interactions will also help to improve their mood.  So the expectation of getting better really does make the patient better.  You can see why this is sometimes called one kind of expectancy effect.

The problem in an experiment is that we want to isolate one variable, the treatment effect, from any other variables, including expectancy effects.  It is actually pretty simple to do.  In an experiment looking at the effectiveness of an anti-depressant we need to have two groups getting pills, and one group not getting pills.  One of the pill groups gets the antidepressant.  The other one gets sugar pills, which are the placebos.  The third group gets nothing.  It is important that these three groups are otherwise as similar as possible.  It is also important that those patients getting pills not know whether they are getting the real antidepressant or a placebo.  We want the expectations to be the same for both groups.

Now let us imagine that the 66% of treatment group, the one that got the antidepressants. gets a lot better.  That sounds good, but it is not really a measure of the effectiveness of the drug.  It is really a measure of the drug effects, plus that expectancy effect.   If 66% of the placebo group also got a lot better, then it looks like the drug was not effective after all, except by creating an expectation of improvement.  If only 10% of the placebo group got a lot better, then it looks like the drug had a lot of benefit beyond just creating the expectation of improvement.  We can use a similar logic to estimate the extent of the placebo effect, itself, by comparing the placebo group to the no-treatment group.

Now let’s switch from the world of experiments to the world of treatments.  If someone who is depressed seeks treatment from a doctor, and that doctor prescribes some kind of pills, they had better not be sugar pills!  The patient has a right to expect the doctor will prescribe something that has proven to be more effective than a placebo.  But what does that mean about expectations?  Most patients probably expect that whatever the doctor gives them will help them get better, and just like in an experiment, that expectation can be a powerful force in and of itself.

On the face of it, that should be a good thing.  The patient’s expectations should combine with the drugs effects to give them a double-whammy.  On the other hand, no drug, especially not an antidepressant, is going to work for everybody.  And that expectation, or placebo effect, is probably not going to last forever.  So what may happen is that some patients, who seemed to be doing well on whatever drug was prescribed, have a relapse some months down the line.

Here’s the question I have, and I really don’t know which answer I prefer.  Should a doctor, in prescribing a new antidepressant,  be as positive as possible about the potential benefit?  In other words, should they try to maximize the placebo effect?  Or should they strike a cautious tone, emphasizing that not every drug works for every patient?

Reference:

Zimmerman, M and Thongy, T. (2007). How Often Do SSRIs and Other New-Generation Antidepressants Lose Their Effect During Continuation Treatment? Evidence Suggesting the Rate of True Tachyphylaxis During Continuation Treatment Is Low. Journal of Clinical Psychiatry (68) 8, 1271-1276.