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Selective serotonin reuptake inhibitor

Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants. They act within the brain to increase the amount of the neurotransmitter, serotonin (5-hydroxytryptamine or 5-HT), in the synaptic gap by inhibiting its reuptake. One notable characteristic of SSRIs is that, unlike other classes of antidepressants, SSRIs were rationally designed drugs. Instead of being discovered by accident, SSRIs were specifically designed while considering the biological causes of depression. SSRIs are frequently prescribed for anxiety disorders, obsessive-compulsive disorder, and eating disorders. Though not specifically indicated by the manufacturers, they are also sometimes prescribed to treat Irritable Bowel Syndrome.

SSRIs are not addictive in the strict sense of the word (i.e. animals given free access to the drug do not actively seek it out and do not seek to increase the dose), but suddenly discontinuing their use is known to produce both somatic and psychological withdrawal symptoms, a phenomenon known as "SSRI discontinuation syndrome" (Tamam & Ozpoyraz, 2002). Compared to the withdrawal symptoms of such drugs as opiates, alcohol or cocaine, these are slight.

Their effectiveness does not appear to be higher than tricyclic antidepressants, which were the most commonly used class of antidepressants before the development of SSRIs. However, SSRIs have the important advantage that their toxic dose is high, and, therefore, they are much more difficult to use as a means to commit suicide. Further, they have fewer or milder side effects.


List of SSRIs

Many drugs in this class are familiar through advertising, including

How they work

In the brain, information is passed between two neurons (nerve cells) via a synapse, a small gap between the cells. The neuron that sends the information releases neurotransmitters (with serotonin among them) into that gap. The neurotransmitters are then recognized by receptors on the surface of the recipient cell, which upon this stimulation, in turn, relays the signal. About 10% of the neurotransmitters are lost in this process, the other 90% are released from the receptors and taken up again by monoamine transporters in the sending cell (thus reuptake).

Depression has been linked to a lack of stimulation of the recipient neuron at a synapse. To stimulate the recipient cell, SSRIs inhibit the reuptake of serotonin. As a result, the serotonin stays in the synaptic gap longer than it normally would, and has the chance to be recognized again (and again) by the receptors of the recipient cell, which can finally be stimulated that way.

Why not give serotonin directly? First, serotonin ingested orally will not cross the blood-brain barrier, and therefore won't have an effect on brain functions. Second, pure serotonin would turn on every synapse it reaches, whereas SSRIs only enhance a signal that is already present, but too weak to come through.

SSRIs are described as 'selective' because they affect only the reuptake pumps responsible for serotonin, as opposed to earlier antidepressants, which affect other monoamine neurotransmitters as well. Because of this, SSRIs lack some of the side effects of the more general drugs.

Serotonin is made from tryptophan, an amino acid. If depression is caused by lack of serotonin, rather than insensitivity to it, SSRIs alone will not work well, whereas supplementing with tryptophan will. In 1989, the FDA made tryptophan available by prescription only, in response to an outbreak of eosinophilia-myalgia syndrome caused by impure L-tryptophan supplements sold over-the-counter. As the production error responsible for the contamination would have been easily correctable, some critics have suggested that this appears to have been done to make money for the manufacturers of SSRIs. Pharmaceutical grade L-tryptophan is currently available over the counter in the U.S.

Criticism of SSRIs

SSRIs have been the focus of much controversy. Some feel that SSRIs are prescribed by overzealous doctors or psychiatrists in cases where their use is only marginally indicated. According to this argument, societal pressures have created a precedent for the pursuit of "normal" mental or emotional functioning by chemical means versus a more holistic approach (diet, exercise, sleep, stress reduction, etc). Furthermore, in late 2004 was much media attention given to a proposed link between SSRI use and juvenile suicide. For this reason, the use of SSRIs in pediatric cases of depression is now recognized by the FDA as warranting a cautionary statement to the parents of children who may be prescribed SSRIs by a family doctor. [1]

Effect not well understood

Some say that the supposed biological causes of depression, which SSRIs were designed for, have never in fact been proven scientifically. They claim that there is no scientific evidence for the existence of the disorders that SSRIs are designed to treat, or that they are based on a chemical imbalance of the brain, or that SSRIs effectively handle this chemical imbalance.

Allen J. Frances, professor of psychiatry at Duke University Medical Center writes: "psychiatry’s claim that mental illnesses are brain diseases... is not true. There are no objective diagnostic tests to confirm or disconfirm the diagnosis of depression... There is no blood or other biological test to ascertain the presence or absence of a mental illness, as there is for most bodily diseases. If such a test were developed... then the condition would cease to be a mental illness and would be classified, instead, as a symptom of a bodily disease."

The mode of action of these antidepressant drugs on their direct target, the serotonin transport protein, and possible regulatory mechanisms with respect to long-term alleviation of depression, although having been investigated both neurobiologically and clinically over the last years, are not yet understood.

Newer medications

The majority of medications most recently approved to treat depression work on multiple neurotransmitters. Venlafaxine and duloxetine are both members of the SNRI class of antidepressant medication. SNRIs (serotonin-norepinephrine reuptake inhibitors) work on the norepinephrine and serotonin neurotransmitters. Mirtazapine also increases levels of norepinephrine and serotonin, but it is a tetracyclic antidepressant, not a SSRI or SNRI. The arrival of these new drugs suggest that future antidepressants will not work on serotonin exclusively. Since the expiration of Eli Lilly's Prozac patent, Lilly has been promoting their new SNRI, duloxetine.

5-HTP supplements instead of SSRIs

In mid 2004, a Congressional hearing on prescription drugs noted that 1 in 6 children in the United States are being prescribed an anti-depressant product. At the end of 2004, some "block buster" anti-inflammatory drugs were in the news for being dangerous, bringing new focus to the safety and moral issues regarding targeted end-user marketing of prescription drugs. Some think that anti-depressants are vulnerable to similar allegations.

Natural healing professionals often recommend 5-HTP supplements instead of standard SSRI/MAOI prescriptions as 5-HTP allegedly accomplishes the same goal without resorting to disturbing the brain's natural metabolic procedures. Instead of interrupting the recycling of serotonin as in the case of SSRIs, and instead of preventing the end consumption of serotonin as in the case of MAOIs, 5-HTP supplements are claimed to provide more raw material to be used in the body's natural serotonin production process. This raw material that is processed by the body to produce needed serotonin is called tryptophan and its only source is through ingestion of certain foods, turkey being the most cited example. Tryptophan was also sold as a suppliement in health food stores until a contaminated shipment, which resulted in 1500 cases of eosinophilia-myalgia syndrome and over 30 deaths, prompted the United States Food and Drug Administration to ban it as an over-the-counter nutrient. As a response to this ban, health supplement producers decided to market 5-HTP in its place. Recently however, as noted above, pharmaceutical grade L-tryptophan has become available "over the counter" in the U.S.

5-HTP supplements are claimed to be more effective than tryptophan in raising serotonin levels, due to the liver being less interested in metabolizing 5-HTP before it can enter than brain, compared to tryptophan. However, they do not receive as much marketing attention as the patentable drugs.

External links


  • Tamam, L. and Ozpoyraz, N. (2002). Selective serotonin reuptake inhibitor discontinuation syndrome: a review. Advances in Therapy 19(1): 17-26. ..

Last updated: 08-31-2005 15:04:25