Tag Archives: Psychology

Antidepressant Drugs: Accountability and Open Data

Antidepressant drug effects (red line) are flat across the severity of patient depression (x-axis). In contrast, placebo effect (blue line) decreases as the severity of depression increases.
Figure 1. Antidepressant drug effects (red line) are flat across the severity of patient depression (x-axis). In contrast, placebo effect (blue line) decreases as the severity of depression increases. From Figure 3 in “Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food and drug administration” (published February 2008 in PLoS Medicine). The article is being displayed in iPad using JournaLink version 1.5.

Current controversy surrounding the research, marketing, and the United States Food and Drug Administration (FDA) approval of prescription drugs points towards some of the benefits of open data (see note below for some general references). One piece of the controversy revolves around the question of whether or not the FDA approval process is working. That is, does the FDA approval process protect the consumer from ineffective or potentially harmful products?

Note: The principle investigator of the research paper discussed here published a book during 2010 titled “The Emperor’s New Drugs: Exploding the Antidepressant Myth.” During the same year a psychiatrist published “Unhinged: The Trouble with Psychiatry – A Doctor’s Revelations about a Profession in Crisis” and an investigative reporter published “Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America.”

A paper published a few years ago presented the reanalysis of data submitted to the FDA that led to FDA approval of four major antidepressant drugs for market. The authors of “Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food and drug administration” (published February 2008 in PLoS Medicine) had to use the Freedom of Information Act to get “all publicly releasable information about the clinical trials” for fluoxetine (Prozac), venlafaxine (Effexor), nefazodone (Serzone), paroxetine (Paxil), sertraline (Zoloft), and citalopram (Celexa). These are all selective serotonin reuptake inhibitors (SSRIs) that are thought to work by making more serotonin available to postsynaptic neurons.

Interestingly, the data disclosed by the FDA was not sufficient to analyze the effects of sertraline (Zoloft), and citalopram (Celexa) and the authors were unable to fill the gap with data from pharmaceutical companies or the published literature. Results of the meta-analysis on the four other drugs fluoxetine (Prozac), venlafaxine (Effexor), nefazodone (Serzone), and paroxetine (Paxil) was presented.

The authors ran across other problems with the data. Sometimes discrepancies appeared between published versions of the data and those data provided by the FDA. In addition, they found that a pharmaceutical company would occasionally publish a trial more than once “with slight discrepancies in the data between publications.” When these discrepancies appeared the authors used the data submitted to the FDA.

The results of the meta-analysis found that the overall effect of these antidepressant medications was below recommended criteria for clinical significance. They also found that the clinically significant effect found for extremely depressed patients was due to a decrease in the response to placebo rather than an increase in the response to medication (see Figure 1 above).

Clearly data should be readily available so that third parties may reanalyze data relevant to the health and well being of millions of people. More eyes and brains working on and reviewing data will help everyone to understand those data better. Our understanding of how many of the body’s processes work is incomplete at best and often provisional. This is especially the case with our understanding of the brain. Let’s speed our understanding by making clinical trial data publicly available. Everyone will benefit, including pharmaceutical companies.

Infant and Adult Susceptibility to Others’ Beliefs

Research has shown that thoughts of events can have similar effects on brain processes as events themselves (for an example see my blog post “Imagine Eating 30 M&M Candies and Eat Less“). Could other peoples’ beliefs have similar effects on our brain processes as do our own beliefs? The new paper “The Social Sense: Susceptibility to Others’ Beliefs in Human Infants and Adults” (published December 24, 2010 in Science) examines this question in 7 month old infants and adults.

The authors reason that if our abilities to infer what others believe are an innate social sense then these inferences should be spontaneous and automatic and the beliefs of others should be “computed online and effortlessly, just as we compute representations of what we perceive in the environment.” If this is indeed the case then the “representations about others’ beliefs” should affect our behavior.

The research team used an object detection task to investigate the following two questions:

  • Are belief computations automatically triggered by the mere presence of an agent [with its own beliefs] in adults and in infants as young as 7 months, even when the [agent’s] beliefs are entirely irrelevant to the task participants have to perform?
  • Are beliefs about others’ beliefs stored in a format sufficiently similar to our own representations about the environment that both types of representations can affect our behavior?

The results of their experiments suggest that both 7 month old infants and adults automatically compute and store the beliefs of others. Also, the beliefs of others appear to be similarly accessible to our own beliefs. Once a belief is computed, it seems to remain active even in the absence of the person who was thought to hold the belief. It’d be interesting to image brain function using functional Magnetic Resonance Imaging (fMRI) during the same tasks carried out by human subjects in this investigation.

Other related blog posts:

Imagine Eating 30 M&M Candies and Eat Less

Imagine Eating 30 M&M Candies and Eat Less

Eating a food item, pasta for instance, typically leads to the person eating less of that food less for a while. This well studied phenomenon is known as habituation. However, intuitively we believe that imagining a food item increases its desirability and our subsequent consumption. Research has been showing that perception and mental imagery engage similar brain systems and have similar outcomes. This would suggest that imagining a food item would result in habituating to that food item. A team from Carnegie Mellon University set out to experimentally test what would happen.

Reported in the paper “Thought for Food: Imagined Consumption Reduces Actual Consumption” published December 10, 2010 in Science.

The research team carried out a set of five experiments using M&M candies to see if repeated mental simulation of eating the M&Ms alone can result in habituation. Indeed, the results repeatedly showed that when individuals imagined eating 30 M&M candies they ate significantly fewer actual M&Ms than those who imagined eating just 3 candies. Their seems to be little difference between imagined food and real food to to the brain systems involved in habituation.