These medications can soften the pain of depression, calm the jagged edge of anxiety, lessen the nightmare of post traumatic stress disorder, and reduce the symptoms of premenstrual stress—SSRIs can do all this, but at a risk of unwanted, sometimes dangerous, adverse events.
SSRIs Defined
Selective Serotonin Reuptake Inhibitors (SSRIs) increase the concentration of serotonin in parts of the brain. They do this not by making more serotonin, but, as the name suggests, they inhibit the removal (reuptake) of already-made serotonin. This makes the natural serotonin effect last longer and perhaps be more potent.
Serotonin’s Function
Serotonin (5HT, 5HIAA) is one of the brain’s major neurotransmitters. Neurotransmitters are chemicals that bridge the gap between nerve cells and allow them to “talk” to each other. Serotonin is associated with brain regions that affect or create mood. Serotonin tends to produce calmness.
Relatively low brain serotonin has been suggested as the cause of depression and some other conditions. Increasing brain serotonin to treat these conditions then makes sense. However, low serotonin has never been proven to cause depression. Increasing brain serotonin by other means has not been effective. SSRIs might produce benefit by some other mechanism.
Benefits of SSRIs
The first major SSRI was Prozac (fluoxetine), introduced in 1987 as a major breakthrough to treat depression. (Other SSRIs had preceded Prozac, but were either withdrawn due to adverse effects or not marketed intensely.) Prior to fluoxetine, tricyclic antidepressants (TCAs) were the major oral (pill) treatment for depression. TCAs all inhibit the removal of norepinephrine, and some also inhibit serotonin removal. While effective, TCAs are felt to have a higher risk of adverse effects than SSRIs.
Target Conditions for SSRIs Approved by the FDA
At least one SSRI is approved for each of the following:
- Depression. While some critics have suggested SSRIs do little to improve depression, which responds well to placebos, and tends to improve on its own anyway, studies have generally shown benefit. Dutch investigator P. Cuijpers and colleagues did a meta-analysis of 30 randomized trials and found that SSRIs “were significantly more effective than psychological treatments” for depression. (Journal of Clinical Psychiatry, e-published 2008/10/24; print publication 2009/01/17)
- Obsessive Compulsive Disorder. Studies have shown about 70% of subjects improved at a dose of 40 mg each day.
- Panic Disorder
- Social anxiety disorder (SAD)
- Premenstrual dysphoric disorder (PMDD) and
- Post-traumatic stress disorder (PTSD).
Risks from SSRIs
The major risks are rare. Most people who take SSRIs have no serious adverse effects. Nevertheless, it’s important to be aware of the possibilities so that if a condition occurs, the possibility that an SSRI contributed to it would be considered.
All SSRIs must point out in a “Black Box Warning” that this class of drugs has been associated with suicides. The risk appears greater in children and adolescents, but the risk may be present at all ages.
SSRIs may increase the risk of gastrointestinal bleeding. In one compilation of studies, bleeding was twice as common among people taking SSRIs. If they were also taking NSAIDS (ibuprofen, others), the risk was six times greater.
Low blood sodium can be caused by SSRIs, which can lead to weakness, and if low enough, can be fatal.
SSRIs may interact with other medications to increase or lower the blood level of the other drug, e.g., warfarin, digitoxin.
Other Risks
Undesirable Mood Changes—anxiety, hostility, aggressiveness
Body function changes—headache, diarrhea, tremor
Effects on Sexuality, including decreased libido, delayed ejaculation
Other adverse effects have also been reported.
Sources
Adverse effect information: product information provided by drug distributors and approved by the US Food and Drug Administration.
Lacasse JR, Leo J (2005) Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med 2(12): e392 doi:10.1371/journal.pmed.0020392
