Troy Centazzo and Chris Kressler

In Part 1 of this Series, I discussed the massive increase of the use of prescription drugs to treat depression (indeed, they have become the most subscribed drug in the US), as well as recent medical research that questions their effectiveness. I also reviewed James S. Gordon's new book, "Unstuck," which offers a depression treatment program using natural techniques, such as stress management, physical exercise and eating nutritiously, among other techniques, and discusses the various issues with taking antidepressants.

In Part 2, I focus on the common - and significant - side effects of antidepressants, and have been granted permission by Chris Kressler, a health researcher and educator, who runs the popular health and wellness blog, "The Healthy Skeptic," to publish an excerpt from his article, "The Dark Side of Antidepressants". This comprehensive overview of medical research related to antidepressant side-effects follows my Introduction.

Part A - Introduction

Positive anecdotal stories of antidepressant users who have suffered from the debilitating symptoms of untreated depression and anxiety often involve feelings after taking prescription drugs of feeling better, clearer and just plain happier. One of the most popular antidepressants, which I will not name, has a website with persuasive - often heart wrenching - patient testimonials that begin with pre-treatment stories of lives in turmoil that are almost unbearable and include post-treatment discussions of a good attitude, an awakening, a new vigor, and a family that finally enjoys spend time with the patient because she is no longer irritable, a negative personality shift originally caused by stress on the job.

These personal stories are of course compelling. Some readers of this column, no doubt, feel the same way. Antidepressants have in fact helped many people "lift the dark veil," as the saying goes. Drug companies certainly want you to believe antidepressants are the safe, quick solution to your blues. According to a recent report in the New England Journal of Medicine, pharmaceutical companies spend over 1 billion dollars each year on marketing and promoting antidepressants to consumers and the doctors who prescribe them, including direct-to-consumer advertising on television and significant investments in "detailing" doctors' offices, or having sales representatives visit the doctor and leave drug samples, drug information and freebies like pens and pads. The report also suggests that "the F&DA's capacity to enforce advertising regulations has been weakened in recent years."(1)

The marketing certainly has worked. As mentioned in Part 1 of this Series, I discussed how antidepressants have become the most commonly prescribed drugs in the United States, prescribed more often than drugs for high cholesterol, high blood pressure, asthma, or headaches.(2) The U.S. Centers for Disease Control and Prevention (CDC) reviewed 2.4 billion drugs prescribed in visits to doctors and hospitals in 2005. 118 million were for antidepressants (high blood pressure drugs were the second most common, with 113 million prescriptions). Almost 232 million prescriptions for antidepressants were written last year, a large increase. (3) Approximately 30 million patients in the US spent $12 billion on antidepressants in 2007. (4) The average time a general practitioner (MD) will spend with each patient to determine the best approach to treat a patient for the condition at issue during a visit? About 15 minutes. (5) The use of antidepressants and other related drugs have ballooned over the last decade and that trend is projected to continue.

One of the most interesting statements I came across during researching this article was - to paraphrase - the popularity of antidepressants may be a triumph of marketing over science. Why is that? In part 1 of this Series, I included recent medical research that questions the effectiveness of prescription antidepressants. Now we are increasingly realizing that these drugs also may come with serious side effects.

A Wake Up Call For this Author ? Is the Situation More Serious Than Just Whether the Drugs Work or Not?

I am not a medical researcher. I attempt to write lay focused articles that include a significant amount of research and objective investigation. I imagine that virtually everyone who engages in this process, whether a hobbyist like me or a professional journalist, conducts a "Google search" during the beginning stage of the article writing process. Saying that I "Googled" a subject is like my asking someone to "FedEx" a package when I really just want it sent overnight. Google searches not only provide useful sources of information, but I would contend that they also offer a barometer of what is both available on the Web and what topics are of significant interest because Google actually tells you. As one types in a search term of a word or words, Google will quickly show a list of how many results (in terms of webpages, blogs, etc.) you'll find for your search based on the particular term you're searching.

When I began researching this article, I "Googled" various terms related to depression, its treatment, antidepressants and their side effects, among others, and then spent time seeing what was on the Web. To be frank, the results were fairly shocking. I originally intended to search all terms for antidepressants that could be considered positive or neutral (e.g., "antidepressant benefits") and then all terms that could be considered negative ("antidepressant side effects"), but quickly realized there are simply too many possible key words to come up with. One thing became clear pretty quickly after searching a few hundred terms - there are tens of millions of search results related to the problems of antidepressants. Intrigued, I continued to dig.

As I followed up on several of those search results, I realized that there is a massive Web-based movement - on websites, blogs, postings in forums, chat rooms, etc. - to discuss and warn of the dangers and side effects of antidepressants, selective serotonin reuptake inhibitors (SSRIs, the newer generation of drugs), in particular. The blogs and sites are filled with horror stories about using the drugs, about suicidal thoughts, about that fact that people can't believe more isn't being done to change the way depression in being treated. I couldn't venture a guess at home many people are currently participating in this online grassroots movement. I suggest that everyone interested in the subject surf around the way I did.

My discussion largely has been based on the anecdotal discussions of individuals and families I came across while researching this article. But what has medical research discovered about the likelihood, types, and severity of antidepressant side effects? For that discussion, Chris Kressler, a medical researcher and educator, has loaned an excerpt from his comprehensive research-based article on the physiological, psychological and social consequences of antidepressant use.

Part B ? ?The Dark Side of Antidepressants? Excerpt by Chris Kressler

Side Effects of Antidepressant Use - A Review of the Medical Research

Although these [antidepressant] drugs are generally considered to be safe by the media and amongst medical professionals and patients, a close look at the evidence suggests otherwise. Antidepressants have serious and potentially fatal adverse effects, cause potentially permanent brain damage, increase the risk of suicide and violent behavior in both children and adults, and increase the frequency and chronicity of depression. Chronic use of antidepressants also promotes dependency on drugs rather than empowering people to make positive life changes, and places a tremendous burden on healthcare systems in the U.S. and abroad.

Physiological side effects

The adverse effects of antidepressants include movement disorders, agitation, sexual dysfunction, improper bone development, improper brain development, gastrointestinal bleeding, and a variety of other lesser known problems. These are not rare events, but the most significant harm comes only after months or years of use, which leads to the false impression that antidepressants seem quite safe.

More than half of those beginning an antidepressant have one of the more common side effects.(6)

While some side effects may not carry serious health risks, others do. Gastrointestinal bleeding can become a life-threatening condition, and improper bone development in children is a serious problem that can lead to increased skeletal problems and frequent bone fractures as they age. It has been shown that serotonin exposure in young mice impairs their brain's cerebral development, and many researchers believe that the use of SSRI medications in pregnant mothers and young children may predispose children to emotional disorders later in life. (7)(8)

Another problem with the side effects caused by antidepressants that is often not discussed is the likelihood that additional medications will be prescribed to control them. It is well-known that Prozac produces anxiety and agitation, so physicians often prescribe a sedative (typically a benzodiazapene) along with it. Since recent studies have shown that antidepressants cause gastrointestinal bleeding, doctors are starting to prescribe acid-inhibiting drugs such as Nexium to prevent this side effect. These drugs also inevitably cause side effects, which may lead to the prescription of even more drugs. (This is not uncommon.)

Psychological Side Effects

Perhaps the best known psychological side effect of SSRIs is "amotivational syndrome", a condition with symptoms that are clinically similar to those that develop when the frontal lobes of the brain are damaged. The syndrome is characterized by apathy, disinhibited behavior, demotivation and a personality change similar to the effects of lobotomy. All psychoactive drugs, including antidepressants, are known to blunt our emotional responses to some extent.

Clinical studies of SSRIs report that agitation is a common side effect. When Yale University's Department of Psychiatry analyzed the admissions to their hospital's psychiatric unit, they found that 8.1% of the patients were "found to have been admitted owing to antidepressant mania or psychosis." (10) Agitation is such a common side effect with SSRIs that the drug companies have consistently sought to hide it during clinical trials by prescribing a tranquilizer or sedative along with the antidepressant. Studies by Eli Lilly employees found that between 21% and 28% of patients taking Prozac experienced insomnia, agitation, anxiety, nervousness and restlessness, with the highest rates among people taking the highest doses. (11)

From their inception, antidepressants have been recognized as having a worrisome capacity to incite changes between episodes of depression (characterized by dysphoria, insomnia, low energy, poor concentration, reduced appetite and diminished libido) and episodes of mania (characterized by euphoria, increased activity, rapid speech, racing thoughts, diminished need for sleep, hypersexuality and diminished impulse control).

Several reports suggest that SSRIs are associated with movement disorders such as akathisia, Parkinson's disease, dystonia (acute rigidity), dyskinesia (abnormal involuntary choreic movements) and tardive dyskiniesia. (12)

These movement disorders are serious enough on their own. However, what is even more alarming is the potential for akathisia to induce aggression and suicide. Akathisia, a condition of inner restlessness or severe agitation, is the most commonly occurring movement disorder associated with psychoactive drug use. Akathisia-related violence receives specific attention in the Diagnostic and Statistical Manual of Mental Disorders (DSM). Akathisia has been shown to increase violent behavior and suicide, and antidepressants are known to cause akathisia.

Suicide

After years of foot-dragging and thousands of excess suicides, the FDA finally admitted that "two to three children out of every hundred" could be expected to develop suicidal thoughts or actions as a result of antidepressant therapy. (13) The risk of suicide events for children receiving SSRIs has been three times higher than placebo. (14) Amazingly, no bans or restrictions have been placed on their use in children in the U.S.

While the increased risk of suicide in children has become better known, most people are unaware that a similar risk exists for adults. When adult antidepressant trials were re-analyzed to compensate for erroneous methodologies, SSRIs have consistently revealed a risk of suicide (completed or attempted) that is two to four times higher than placebo. (15)

Turning short-term suffering into long-term misery

A growing body of research supports the hypothesis that antidepressants worsen the chronicity, if not severity, of depressive features in many subjects. Antidepressant therapy is often associated with the poorest outcomes. In a large, retrospective study in the Netherlands of more than 12,000 patients, antidepressant exposure was associated with the worst long term results. 72-79% of the patients who relapsed received antidepressants during their initial episode of depression. In contrast, only one of the patients who did not relapse received no antidepressants during or following the initial episode. (16)

Longitudinal (long-term) follow-up stuides show very poor outcomes for people treated for depression in both hospital and outpatient settings, and the overall prevalence of depression is rising despite increased use of antidepressants. (17)

Epidemiological observations have long held that most episodes of depression end after three to six months. However, almost half of all Americans treated with antidepressants have remained on medication for more than a year. (18)

Antidepressants have been shown to produce long-term, and in some cases, irreversible chemical and structural changes to the body and brain.

The administration of Prozac and Paxil raises cortisol levels in human subjects. (19) Given the fact that elevated cortisol levels are associated with depression, weight gain, immune dysfunction, and memory problems, the possibility that antidepressants may contribute to prolonged elevations in cortisol is alarming to say the least.

In a study designed to investigate the anatomic effects of serotonergenic compounds, researchers at Thomas Jefferson University found that high-dose, short-term exposure to SSRIs in rats was sufficient to produce swelling and kinking in the serotonin nerve fibers (20) Conclusion.