Serotonin Reuptake Inhibitors Essay, Research Paper

The medications most frequently prescribed for uncomplicated depressive illness are the selective serotonin reuptake inhibitors, or SSRI s. These medications increase levels of serotonin in synapses in the brain by reducing the ability of the presynaptic nerve cell to reabsorb the neurotransmitter after it is released. As far as the postsynaptic nerve cell can tell, the presynaptic cell is releasing more serotonin.

Research into serotonin has taken center stage in the 1990 s due to the therapeutic success of Prozac and related antidepressants that manipulate serotonin level. Serotonin levels at the synaptic cleft of depressed patients are low. In addition, levels of a surface molecule unique to serotonin-releasing cells in the brain are lower in depressed patients than in healthy subjects. Studies have also shown that the density of at least one form of serotonin receptor is greater in postmortem brain tissue of depressed patients. This greater up-regulation is a suggestion of a compensatory response to too little serotonin in the synaptic cleft. SSRI s work by blocking the reuptake of serotonin, therefore allowing a higher serotonin concentration at the synaptic cleft.

SSRI s are increasingly prescribed because they are effective and have fewer side effects than the older tricyclic antidepressants. In addition to being prescribed as an antidepressant, SSRI s are helpful in treating panic disorder, obsessive-compulsive disorder (OCD), eating disorders, social phobia, and possibly post-traumatic stress disorder (PTSD). A good response to SSRI s is seen in 70% or so of uncomplicated major depression, as compared with a 30% placebo rate. A similar success rate is seen in treating panic attacks, but they are less effective than the minor tranquilizers in reducing generalized anxiety. In OCD, it is common to see a 50% reduction in symptoms. Given the various symptoms SSRI s can treat, clinicians view them as a broad-spectrum psychiatric medication.

SSRI s usually do not work immediately, but require two to four weeks for the full therapeutic effect to develop. This can be frustrating for the patient, because the side effects are generally the worst during the first week or two of treatment. Some symptoms, such as crying spells, may improve faster than others may, such as insomnia and low energy. Identification of target symptoms of major depression that are easy to monitor, such as crying spells, suicidal ideation, or early morning awakenings, help to follow medication response. Ideally, complete improvement in all of the original depressive symptoms is seen. However, it is possible to have a partial response to the medication, which can often be improved by adjustment of dosage or, if necessary, augmentation with a second medication.

Many patients experience significant side effects from SSRI s. These medications often have a stimulating effect. Insomnia, feeling wired , and an increase in anxiety and restlessness often mark this stimulating effect. Other common side effects are headache, nausea, and an increase in vivid dreams. These effects are usually more annoying to the patient than serious. Sexual dysfunction is one of the most common and problematic side effects seen with SSRI s. This problem most commonly involves a decrease in sexual interest or drive, and may occur in over 50% of individuals on these medications. These effects are reversible with discontinuation of medication, and can sometimes be managed with the addition of other medications, and occasionally by switching to a different SSRI.

Like all other antidepressants, the SSRI s can cause mood to become less stable. Some patients may respond well, perhaps too well, to SSRI s, and then develop either excessively elevated mood or increased instability of mood. Individuals with bipolar types of mood disorders are most vulnerable to this effect. A good psychiatric evaluation by a qualified professional, combined with responsible follow up which includes ongoing mood monitoring, is the best protection against this potentially serious complication.

The SSRI s are not the only medications, which increase levels of serotonin. Other drugs which can have this effect include tricyclic antidepressants, the monoamine oxidase inhibitor antidepressants, lithium, stimulants, some herbal remedies (St. John s Wart), and some street drugs such as speed, cocaine, and ecstasy. These substances are collectively called serotonergic agents.

If serotonin levels in the brain become too high, a number of mental and physical side effects can result. Collectively, these symptoms are called the serotonin syndrome. This syndrome can be mild, but occasionally becomes severe, and has resulted in fatalities. It is most likely to occur when two or more serotonergic agents are taken simultaneously. Symptoms commonly include restlessness, tremor, diarrhea, nausea, confusion, agitation, anxiety, muscle jerks or rigidity, fever, dilated pupils, shortness of breath, sweating, rapid heart rate, and altered blood pressure. Although serious forms of this syndrome are rare, particularly as a single therapeutic agent, symptoms of this nature should be monitored by a physician.

For a number of years, psychiatrists happily explained to patients that there were no problems with discontinuing the SSRI antidepressants abruptly. However, as more patients have complained that this is not the case, it has become recognized that abrupt discontinuation of SSRI s can cause several annoying, although not serious, side effects. These may include light-headedness or dizziness, nausea, diarrhea, jitteriness, muscle jerks, and tremors. This syndrome is usually mild, begins 2-4 days after stopping a SSRI, and resolves in about a week. It can be avoided by gradually tapering the medication rather than stopping it abruptly.

SSRI s, being mildly sedating, require extra caution to be exercised when driving, operating equipment, etc., especially if combined with other drugs such as antihistamines or tranquilizers which can also cause sedation. SSRI s can inhibit normal enzymes in the liver, which break down and help remove other drugs from the system. This can effect the elimination of other drugs that use these enzymes. These interactions are complex and it is always advisable to check drug interactions with a physician before starting a new medication when taking an SSRI. A few drugs must be avoided altogether because increases of their blood concentrations can become dangerous.

Some individuals report that they become more easily intoxicated from drinking alcohol when taking an SSRI. Drinking alcohol when taking an SSRI is not a good idea for several reasons. Alcohol is a central nervous system depressant, and since the SSRI s can cause sedation, the combination can be dangerous. One drink may feel like two to four. In addition, alcohol can depress mood. SSRI s are an antidepressant. It makes little sense to be taking both a depressant and an antidepressant, particularly if the SSRI has been prescribed to combat depression. Alcohol is not absolutely contraindicated when taking an SSRI, but cautious and responsible social use of alcohol is recommended.

Prozac, which was released in this county in 1987, was the first medication of this type released in the U.S. We now have several drugs available which appear to work in this manner. Although all these agents have the same efficacy, risks, and side effects in clinical studies, individuals often react very differently to different medications in this class. The reason for this is unknown, but probably involves genetic variation in receptors and brain physiology.

Reference:

Kalat, J.W. 1999. Mood Disorder In: Introduction to Psychology 5th Edition. Wadsworth Publishing Co. Belmont, CA, pp 614 635.

Harris, R.W. 1998. The Neurobiology of Depression. Scientific American. June 1998:Featured Article.

Norden, M.J. 1995. Beyond Prozac. Harper Collins Publishing, NY. 258 pp.