side effects

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depressed personThis week’s article in my continuing series on depression and antidepressants will examine the physiological, psychological and social consequences of antidepressant use.

Although these 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 – but I will discuss those issues in next week’s article.

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 (Brambilla et al. 2005).

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 (Esaki et al. 2005), 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 (Ansorge et al. 2004).

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, as I pointed out in last week’s article.)

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 (Marangell et al. 2001, p.1059). 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” (Preda et al. 2001). 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 (Beasley et al. 2001).

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 (Gerber & Lynd 1998).

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 (Harris 2004). The risk of suicide events for children receiving SSRIs has been three times higher than placebo. (Healy 2005). 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 (Healy 2005).

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. (Weel-Baumgarten 2000)

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 (Moncrieff & Kirsch 2006).

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 (Antonuccio et al. 2004).

Long-term effects of antidepressants

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 (Jackson 2005, p.90). 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 (Kalia 2000). Research performed by a different team of investigators demonstrated a reduction in dendritic length and dendritic spine density, and in contrast to the previous study, these changes did not reverse even after a prolonged recovery period. The results were interpreted to suggest that chronic exposure to SSRIs may arrest the normal development of neurons.

I want to emphasize that what I’ve covered here is only the beginning of the story when it comes to the adverse effects of antidepressants. There are volumes of published research and many books which present this information with much more detail. I recommend Peter Breggin’s landmark “Brain Disabling Treatments in Psychiatry” and Grace Jackson’s “Rethinking Psychiatric Drugs” as resources if you are interested in pursuing this further.

pile of pills I just came across a recently published study which revealed that SSRIs (the most popular class of antidepressants) can cause gastrointestinal bleeding. The first thing I always do when reading a study is check to see who the authors are, where they receive funding from and who the sponsor is.

So you can imagine my surprise when I learned that this study, which casts antidepressants in an unfavorable light, was sponsored by a large pharmaceutical company (AstraZeneca).

Could drug companies be experiencing a change of heart? A pang of conscience? Could this mark a new era of integrity and honesty in the reporting of results from drug trials?

Not so much.

Being the skeptic that I am, I thought for a moment about why a drug company would sponsor and then publish a study investigating the side effects of antidepressant when the results are so clearly negative? We know from my previous article on conflicts of interest in the medical field that drug companies are under no obligation to publish study results – and often they do not when the results are unfavorable.

One reason came immediately to my mind: what if that company happened to manufacture a drug that could be used to counter the side effects antidepressants? And what if their study not only demonstrated the side effect antidepressants, but also the effectiveness of their drug in mitigating or treating that side effect?

Turns out that’s exactly what’s happening here. AstraZeneca is the manufacturer of Nexium, one of the most popularly prescribed medications for heartburn. Nexium works by inhibiting the production of acid in the stomach.

Now, check out how the study was designed. There were three groups. The first group was people taking SSRIs only. The second group was people taking SSRIs and NSAIDs (ibuprofen, aspirin, etc.) and other anti-inflammatory drugs known to be harmful to the stomach lining. The third group took SSRIs along with acid-suppressing agents (agents like Nexium, for example).

People taking the SSRIs were more likely to have G.I. bleeding than people on placebo, and those taking both SSRIs and anti-inflammatory drugs were even more likely to bleed than people on SSRIs alone.

But guess what? Acid suppressing agents (like, um, let’s say… Nexium) were associated with a reduced risk of upper GI bleeding in those taking SSRIs.

We can see where this is leading, right? The solution to the G.I. bleeding caused by SSRIs is not to stop taking the SSRIs. The solution is to take another drug! In this case, a drug that is manufactured by the company who sponsored the study.

Unfortunately, this vicious cycle of medication use is very common. A common scenario might be someone takes an SSRI for depression, but it causes anxiety. So the doctor prescribes something for anxiety. Unfortunately, many medications for anxiety also cause constipation. But there’s a pill for that too, which the doctor also prescribes. Then the patient finds they’re getting some acid reflux (a side effect of some of the medicines for constipation), so the doctor prescribes an acid-suppressing agent.

You might be laughing (or crying) as you read this, but I am not exaggerating. This is very often how it works, especially in the elderly who now take an average of 6-8 medications every day.

And this is bound to continue to happen as long as research is primarily sponsored by pharmaceutical companies. The author of the study, Dr. García-Rodríguez, has received “unrestricted research grants from Pfizer Inc., AstraZeneca and Novartis Pharmaceuticals Group”.

There’s no way to prove that Dr. Garcia-Rodriguez’s work is being unduly influenced by his close connection with drug companies. But common sense, as well as many published scientific studies, indicates that this is very likely. For example, several studies have shown that researchers who produce data that is contrary to the interests of the pharmaceutical industry risk legal, professional, or even personal attack – directly or indirectly financed by the industry. (Bosley, 2002; Healy, 2002; Monbiot, 2002).

Fortunately, many influential leaders are calling for changes to be made to the way medical research is performed and distributed. But they are facing the opposition of a $500 billion dollar industry with more lobbyists than there are members of Congress. It’s not going to be easy.

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