Selective Serotonin Reuptake Inhibitors (SSRI) Information Sheet

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What is an SSRI?

SSRI is an acronym for Selective serotonin reuptake inhibitor.

SSRI Description:

Selective serotonin reuptake inhibitors are a class of antidepressants used for the treatment of depression. The drugs are designed to allow the neurotransmitter serotonin to be utilized more effectively. Low-level serotonin is currently seen as one of numerous neurochemical symptoms of depression. These low levels of serotonin can be caused by an anxiety disorder, because serotonin is necessary to metabolize stress hormones.

SSRI effects take place at the serotonin transporter (a monoamine transporter protein that includes neurons, platelets, and other cells to accumulate serotonin). They increase the extracellular level of serotonin by inhibiting its reuptake into the presynaptic cell. They have no (or at best weak) effects on other monoamine transporters, and as such have little direct influence over the level of other neurotransmitters. This differentiates them from older tricyclic antidepressants (TCAs), which is why they are called selective. SSRIs are considered much safer than TCAs, since the toxic dose threshold is much higher and they are believed to have fewer and weaker side effects and drug interactions.

SSRI Treatment and usage:

SSRIs are mainly indicated for treating clinical depression, but they are often prescribed for anxiety disorders, panic disorders, obsessive compulsive disorder (OCD) and eating disorders. The manufacturers do not specifically indicate them for treatment of irritable bowel syndrome, but they are sometimes employed for this purpose. As well, SSRIs have been found to be an effective treatment for premature ejaculation in up to 60% of men.

SSRI Method of action:

A depressive disorder is believed to be caused by a chemical imbalance in the brain. Messages are passed between two neurons (nerve cells) via a synapse, or small gap between the cells. The neuron sending the information releases neurotransmitters (including serotonin) into that gap. These neurotransmitters are recognized by receptors on the surface of the recipient cell, which relays the signal. Approximately 10% of the neurotransmitters are lost in this process, with the other 90% released from the receptors and taken up again by monoamine transporters (the reuptake process).

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

Normally, several weeks of continuous SSRI use are necessary for the antidepressant effects to fully manifest themselves. This delay is due to a side-effect of the initially high levels of serotonin within the synaptic gap. The body must first adapt to high levels of serotonin by down-regulating the sensitivity of the receptors, which can take up to 3 weeks. To expedite the desired effect, bi-functional SSRIs are currently being developed, which will help the effects manifest more quickly.

Warnings or dangers associated with SSRIs:

There has been controversy surrounding SSRIs. Some people feel that the drugs are prescribed by over-zealous psychiatrists or doctors when there use is only marginally indicated. According to this argument, societal pressures have created the pursuit of “normal” mental or emotional functioning by chemical means rather than holistic approaches (altering diet, exercise, sleep habits, stress reduction, etc).

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As well, in late 2004 a media firestorm ensued after it was announced that SSRIs may be linked to teen suicide. Because of this, the FDA now warrants a cautionary statement to parents and children who may be prescribed SSRIs by their doctor. The FDA has ordered a “black box warning” be placed on the package inserts of the drugs. A pooled analysis of placebo-controlled trials of 9 antidepressants (including several SSRIs) resulted in a risk of suicidality (suicidal thought and behavior) twice has high as with placebo. Other studies have shown no increase in suicidality but a small increase of non-fatal self-harm, and even of a reduction in incidence of suicide.

There have been some studies that suggest SSRIs may be neurotoxic. Neurotoxicity has been observed in cell lines, and there have been anecdotal reports of “mental fog” arising from SSRI use. Still other studies have suggested SSRIs may promote the growth of new neural pathways, and may protect against neurotoxicity caused by other compounds as well as by depression itself.

SSRI medications should not be taken by patients also taking monoamine oxidase inhibitors (MAOIs). This can lead to increased serotonin levels and cause serotonin syndrome (a rare, but serious and potentially life-threatening condition unfortunately often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition). People taking SSRIs should avoid taking pimozide (an antipsychotic drug, sold as Orap®). As well, individuals on SSRI therapy should not take tramadol hydrochloride (Ultram, Ultracet) due to the rare, but possible, risk of seizures when taken in conjunction with an SSRI or tricyclic antidepressant.

SSRI Side effects:

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The most common side effects when taking SSRIs include headache, nausea, somnolence (drowsiness), weight/appetite fluctuations, changes in sexual behavior and increased feelings of anxiety or depression. These side effects are mostly present during the initial 1-4 weeks while the body adapts to the drug.

It is well documented that SSRIs can cause various sexual dysfunctions such as anorgasmia (inability to reach orgasm), diminished libido (sex drive) and erectile dysfunction or difficult/premature ejaculation in men. Such side effects have been found present in between 41% and 83% of patients responding to physician inquiry. These side effects occasionally disappear spontaneously without discontinuing use of the drug, and in most cases resolve themselves after stopping taking the SSRI.

SSRI Overdose and withdrawal:

SSRIs are not found to be addictive in the convention sense, but suddenly discontinuing them is not recommended, as it can produce both somatic (physical) and psychological withdrawal symptoms, a phenomenon known as “SSRI discontinuation syndrome.” Compared to the withdrawal symptoms of opiates, alcohol, or cocaine, these reactions are markedly different and frequently less significant, though some people may experience (as noted on the prescribing labels) “intolerable” discontinuation reactions and some patients may never fully withdraw from them. In Europe, SSRI manufacturers cannot promote the drugs as “non-habit forming”.

SSRI overdose rarely produces a fatal outcome, and overdosage does not necessarily lead to the development of serotonin syndrome. Patients with an overdosage who remain asymptomatic for several hours afterward are unlikely to need any further medical treatment.

As with any type of antidepressant, sudden discontinuation of use is not advised. Your physician will likely recommend a gradual tapering off your dosage to avoid the risk of side effects.

Precautions with SSRIs in children and the elderly:

A recent Canadian study found that elderly patients prescribed SSRI antidepressants such as Paxil, Prozac and Zoloft, were nearly five times more likely to commit suicide in the initial month of treatment than seniors taking other classes of medications to treat depression.

Studies have shown that children and adolescents taking SSRIs, as well as other antidepressants, may be more likely to experience suicidal thoughts or behavior. If children or teenagers have been prescribed antidepressants, their behavior should be carefully monitored and any changes noted promptly, especially during the beginning of treatment or any time the dose is changed.

Young patients may develop serious symptoms suddenly, and it is important to pay attention to his or her behavior every day. The physician should be contacted immediately if your child experiences any of the following: panic attacks, agitation, extreme worry or anxiety, new or worsening depression, suicidal thoughts or behavior, sleep difficulties, aggressive or irrational behavior, extreme restlessness, frenzied, abnormal excitement, or any other abrupt unusual changes in behavior.

Types of SSRIs:

Common SSRIs include Lexapro (escitalopram oxalate), Celexa (citalopram), Luvox (fluvoxamine), Paxil (paroxetine), Zoloft (sertraline) and Prozac (fluoxetine).

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