The Frontal Cortex

Prozac

Wed, 03 Feb 2010 15:54:54 -0500

Sharon Begley has an excellent Newsweek cover story on the rise and fall of anti-depressant medications, or how a class of drugs that were once hailed as medical miracles are now seen as barely better than placebos:

In just over half of the published and unpublished studies, Kirsch and colleagues reported in 2002, the drug alleviated depression no better than a placebo. "And the extra benefit of antidepressants was even less than we saw when we analyzed only published studies," Kirsch recalls. About 82 percent of the response to antidepressants--not the 75 percent he had calculated from examining only published studies--had also been achieved by a dummy pill.
The extra effect of real drugs wasn't much to celebrate, either. It amounted to 1.8 points on the 54-point scale doctors use to gauge the severity of depression, through questions about mood, sleep habits, and the like. Sleeping better counts as six points. Being less fidgety during the assessment is worth two points. In other words, the clinical significance of the 1.8 extra points from real drugs was underwhelming. Now Kirsch was certain. "The belief that antidepressants can cure depression chemically is simply wrong," he told me in January on the eve of the publication of his book The Emperor's New Drugs: Exploding the Anti-depressant Myth.

The 2002 study ignited a furious debate, but more and more scientists were becoming convinced that Kirsch--who had won respect for research on the placebo response and who had published scores of scientific papers--was on to something. One team of researchers wondered if antidepressants were "a triumph of marketing over science." Even defenders of antidepressants agreed that the drugs have "relatively small" effects. "Many have long been unimpressed by the magnitude of the differences observed between treatments and controls," psychology researcher Steven Hollon of Vanderbilt University and colleagues wrote--"what some of our colleagues refer to as 'the dirty little secret.' " In Britain, the agency that assesses which treatments are effective enough for the government to pay for stopped recommending antidepressants as a first-line treatment, especially for mild or moderate depression.

I'm currently working on a longer article on a related subject, so I won't go into detail here, but I think it's worth pointing out that anti-depressants might still prove to be a very useful class of drugs, just not for depression. To understand why, it's important to realize that antidepressants don't work the way the way the big pharm companies tell you they work, at least on their websites.

Their neat little story goes like this: antidepressants increase the brain's supply of serotonin, thus correcting our chemical imbalance. This implies that sadness is simply a lack of chemical happiness. The little blue pills cheer us up because they give the brain what it has been missing.

There's only one problem with this theory of depression: it's almost certainly wrong, or at the very least woefully incomplete. Experiments have since shown that lowering people's serotonin levels does not make them depressed, nor does it worsen their symptoms if they are already depressed. And then there's the "Prozac lag": although antidepressants increase the amount of serotonin in the brain within hours, their beneficial effects are not usually felt for weeks.

But just because antidepressants don't work via some silly and obsolete chemical model of depression doesn't mean the drugs don't trigger important changes in the brain. In recent years, scientists have found that the little blue pills modulate the neural pathways of plasticity, up-regulating trophic factors and neurogenesis. Because they make our mind more malleable - and help counter the the toxic effects of stress - the drugs have potential implications far beyond the treatment of depression.

Consider this 2008 study by Italian researchers, published in the journal Science. The scientists were interested in seeing if fluoxetine, the active ingredient of Prozac, could increase the potential of brain cells in the adult rat. They studied animals with severe cases of "lazy eye," a condition characterized by poor vision in one eye due to underdevelopment of the visual cortex. The scientists showed that fluoxetine gave brain cells the ability to take on new roles and form new connections, which erased the symptoms of the disorder.

Jose Vettencourt, a lead author on this paper, told me that "The drug appears to make brain cells quite young". The scientists are currently repeating the experiment with humans, raising the possibility that fluoxetine might one day be used to treat lazy eye and related conditions.

And then there's this brand new paper:

Widely used antidepressants may help patients recover cognitive functions, such as memory skills, that are damaged following a stroke, according to research released Monday.
Escitalopram, a type of selective serotonin reuptake inhibitor, or SSRI, was linked to improved cognitive functioning in a group of stroke patients who did not have symptoms of depression, scientists found.

Participants were treated within three months of the stroke in one of three ways: a low dose -- 5 to 10 milligrams -- of escitalopram, a placebo pill or problem-solving therapy but no medication. (The standard dose of escitalopram, also known by the brand name Lexapro, for treating depression is 20 milligrams.)

After one year, the group on escitalopram had higher scores on tests assessing thinking, learning and memory functions as well as ones testing verbal and visual memory. The group treated with medication also had greater improvements in activities related to daily living.

The point is that we might still be taking Prozac, et. al. years from now, just not for depression. The pills do something - they just aren't great at cheering us up.

The Frontal Cortex

Prozac

The Blue Brain

Sex Ed

Musical Predictions, Redux

Self-Control and Peer Groups

Cable News

Power

Musical Predictions

Chess Intuition

Charity is Social

Haiti

Falsification

How We Decide (Paperback Remix)

Intelligence and the Idle Mind

Funding Innovation