SSRI+Antidepressants+as+a+Possible+Agonist+of+Suicide

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**Highlighting an Issue- Background and Statistics on Depression, Suicide, and Antidepressant Use**
Major Depressive Disorder, known more colloquially as “depression”, is a serious psychological disease normally characterized by a chronic, persistent gloomy feeling and loss of interest in normal activities. Serious cases of depression can lead more serious neurological conditions such as schizophrenia, bipolar disorder, and variou s types of dementia. Most commonly, though, depression is precursor to suicide. While it is true that most people will suffer a bout of depression at some point in their lives, statistics show that depression occurrences over the last 30 years have increased. From this, it is likely that rates of its associated diseases have increased alongside. Among these is suicide.
 * Understanding Depression and Suicide**

Per the World Health Organization, 16 out of every 100,000 people worldwide commit suicide every year, and at least 1 and 12 have suicidal thoughts or actions. This number, despite the resources available to people with depression, is very high. And, according to research, it isn’t changing. A study performed by Nock et al. found that suicide rates amongst most age demographics have actually stayed fairly constant in the last 25 years (the graph to the right is directly from the study).

While depression and suicide have occurred amongst individuals over thousands of years, treatment and preventative measures have changed wildly in the last several decades. This stems mostly from the advent of prescription antidepressant medications. Several classes of antidepressants are used today, but the original and most widely prescribed of these are Selective Serotonin Re uptake Inhibitors (SSRIs). These operate by inhibiting a neuron’s ability to reabsorb serotonin, a neurotransmitter in the brain. This serotonin that is not reabsorbed pools in the synapse. The increased serotonin levels in the brain is believed (but not yet proven) to improve social behavior and mental disposition, thus treating symptoms of depression.
 * Depression Treatment and SSRI prescriptions**

Since entering the pharmaceutical market in the late 1970s, SSRI use has becoming increasingly widespread and common. From just 2005 to 2008, SSRI prescriptions increased by almost 400%. This statistic highlights their popularity and ease of acquiring. Because of this, people are often scheduling an appointment with a psychiatrist for medication before a visit to a psychologist for therapy. If they are so popular, they must be effective, right? Research hints otherwise.

If SSRI antidepressants are a viable treatment for depression, then why have depression rates increased and suicide rates stayed the same while their prescription rates have quadrupled? From a purely quantitative outlook, SSRI consumption is increasing without a decrease in the condition they are designed to treat. This arises 3 concerning questions. Are SSRIs effective in treating depression? And if not, what dangers do they pose? Is it possible that antidepressants, SSRIs in particular, could increase the risk of suicide? The answers to these questions branch off of one another. Data suggests that SSRIs aren’t as effectively as portrayed. Their possible inefficacy stirs questions about their safety and the legitimacy of the risks they are associated with. Collectively, their efficacy and risks are high enough to illustrate the need to search for relationships between SSRI use and suicidal behavior.
 * The Math Does Not Add Up**

**Are SSRIs as Operative as Believed to Be?**
Since SSRIs began being distributed, several studies have been conducted to find potential long-term effects of prolonged SSRI use; most of these, frustratingly, have inconsistent or negligible results. Though results from several experiments suggest that SSRI use is effective in treating depression, many have small, if not negligible rates of success. Experiments testing against placebo groups and studies observing treatment relapse rates are the main source of insignificant results.

A study by Kirsch et al. analyzed information gathered by the FDA to compare how Prozac, Zoloft, and Paxil (all SSRIs) worked in treating depression when compared to a placebo control group. Results of the test found that the treatment success rate of the three drugs only differed significantly from the placebo control on the most advanced cases of depression. According to the group, “Drug-Placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients.” Thus, only small deviations occurred in the worst depression cases, and average cases viewed very little difference from the placebo control.
 * Placebo Tests**

Another study viewed the difference in response between patients receiving Welbutrin (SSRI) and a “new experimental antidepressant” placebo that mimics the effect opiate narcotics. Astonishingly, the group receiving the placebo reported stronger relief of symptoms than did e Welbutrin. Furthermore, at week 5 of the 10 week experiment the two group’s medications were knowingly switched. After the switch, 43% of the new group receiving the placebo control reported an improved condition, while just 11% of the group now receiving Welbutrin reported feeling any change at all.

A poll conducted by Medscape, an online resource for physicians, found that 89% of psychiatrists see deteriorating depressive episodes happen shortly after a positive response to SSRI treatment, even while the SSRI was still being taken. Additionally, close to one-quarter of the patients reported some type of relapse within the first six months of treatment. Per the same study, the most common response to these episodes included either increasing the dose of the current medication or switching to a different antidepressant. Therefore, the same medical professionals believe that the most suitable response to the ineffective medication is to either increase dose taken or switch to a different drug of the same class.
 * Relapse Rates**

Off the Label- Risks Associated with SSRI Use
If it is true that SSRIs aren’t as medically operative as widely believed, the question “Can they be harmful?” has to be asked. A study done by Fava et al. tested the effect that antidepressants would have over 29 months on subjects with no history of depression. The results found that 27% of these people developed some type of cyclothymic condition (random, uncontrollable mood changes). This condition persisted for an average of 12 months after discontinuation of the antidepressant. A different study tested the dimorphic effects of Citalopram (SSRI) on healthy women with no prior antidepressant use. Results of this experiment saw almost 25% of the women develop an eye twitch, and 38% reported feelings of drowsiness, unease, and anxiety. Though these two experiments only show mild side effects associated with prolonged SSRI exposure, life-threatening conditions have been reported.
 * Mild to Severe Side Effects**

A 2008 case report by Bilal et al. detailed the deteriorated condition of a man who developed severe chronic post-traumatic pain that was accompanied with depression. His doctor prescribed him a series of two antidepressants, to which he reported few side effects. This was reduced to one different antidepressant, Duloxetine (SSRI), taken at a high dose. In the first week following the transition he reported feeling restlessness, insomnia, and difficulty concentrating. In the next two weeks his symptoms worsened drastically until he slit his radial and popliteal arteries. Only four weeks separated the switch to Duloxetine and his attempted suicide.

Severe forms of treatment-resistant depression can develop following long-term use of potent serotonin reuptake antagonists. Among the most aggressive of these is a condition called tardive dysphoria (TDp). TDp is characterized by chronic, advanced symptoms of depression that have become largely resistant to antidepressant treatment. A study on tardive dyskinesia, a similar but less severe condition that afflicts its victims with uncontrollable muscle movements, found that as high as 30% of patients taking older SSRIs (Prozac, Paxil, Lexapro) show symptoms that media type="youtube" key="KMoZcmm-9Ew" width="237" height="177" align="right" are characteristic with the onset of dangerous depressive conditions (TDp included). Furthermore, these symptoms are either perpetuated or worsened by continuous antidepressant use, and may not necessarily end following discontinuation of medication.
 * Chronic Conditions- Tardive Dysphoria**

Though scientists do not yet know how antidepressants cause TDp, its occurrences happen only in patients taking antidepressants; thus, antidepressants, in some way, are responsible for its onset. One explanation defended by researchers is that removal of SSRI medication is followed by trouble to naturally produce serotonin. So, if it is correct that serotonin is responsible for relieving symptoms of depression, the abs ence of it can lead to far exacerbated cases of depression. TDp, regardless of its mechanism, is just one of many conditions showing a link between SSRIs and worsening degenerative neurological conditions.

Linking the Bridge Between SSRI Use and Suicide- The Need for More Research
As evidence from placebo tests and relapse occurrences show, there are reasonable means to doubt that SSRIs are truly effective in treating symptoms of depression. The conclusions of the two experiments from placebo groups reveal that there are insignificant differences between placebo control groups and groups given actual antidepressants, and subjects can actually be tricked by the placebo effect in some instances. Additionally, almost one-quarter of depressed people treated with SSRIs will have a relapse episode within the first six months of treatment beginning. Results like these show SSRIs are an imperfect depression treatment, and argue that their effectiveness may come as a result of their ability to masks symptoms of depression, as opposed to treating them.
 * Analyzing SSRI Effectiveness and Risks**

Though their medical capabilities are contestable, their known ability to increase the risk of developing severe, possibly life-threatening conditions are not. Reports show that near one-third of people exposed to antidepressants will develop some degree of long-lasting negative side effects. Cases have also been reported indicating that antidepressants can lead to suicidal episodes. Furthermore, antidepressant use is shown to occasionally cause treatment-resistant forms of depression. All of these lead to an argument suggesting that antidepressants, SSRIs included, may actually increase the risk of suicide.

It is difficult to directly relate SSRI use to increased suicidal behavior. While ample evidence from multiple perspectives show that SSRI antidepressants have arguable efficacies and have the ability to cause dangerous psychological side effects, directly relating suicide to SSRIs is inferential and implicit at best.
 * Can a Scientifically-Backed Link be Made?**

There are two explanations for this. The first, and most prominent,is that there is no known cause or root of depression. With no known cause, it is impossible to form a hypothesis or design to prove any relationship that has a legitimate scientific backing. Secondly, little if any research exists showing a brain scan of someone right before committing suicide. Thus, it is uncertain which areas of the brain are most active right at the moment of suicide.

Fudamentally speaking, the limits of understanding the relationship between SSRI use and suicide come from a current limited understanding of the brain itself. With this being said, only future innovation and the work following it will allow the scientific community to extend the branches connecting the two factors. This research simply lays down the basis for argument once that day comes.