A classification of antidepressant medications that work by delaying the reuptake, or reabsorption, of serotonin, a brain neurotransmit-ter essential to mood. These drugs are considered “selective” because they block only the reabsorption of serotonin, extending its presence and activity without directly altering the functions of other brain neurotransmitters. Because of this, SSRIs typically are the drugs of first choice prescribed to relieve depression in people with Parkinson’s as other antidepressants such as tricyclics (amitripty-line, imipramine) and monoamine oxidase inhibitors (MAOIs) affect the actions of other brain neurotransmitters including dopamine.
Depression is common in people with Parkinson’s, affecting as many as four in 10 who have the disease (many clinicians believe the number to be much higher, as many as seven in 10). The reasons for this are not entirely clear. Depression has multiple biochemical, emotional, and psychosocial components and is a common companion of many degenerative, progressive, and incurable diseases. Some researchers believe depression is an early sign of Parkinson’s, which develops in response to the fluctuating brain dopamine levels that occur in the earliest stages of Parkinson’s and in some people even before other symptoms are apparent. In the substantia nigra and other structures of the basal ganglia, dopamine conducts nerve signals related to voluntary muscle control and movement. In the cerebrum and parts of the brain other than those involved in movement, dopamine facilitates neuron communication related to mood, emotion, and pleasure (and is believed a key player in addiction). Researchers suspect the diminishing dopamine levels characteristic of Parkinson’s affect function and activity throughout the brain, though the primary consequences are focused in the substantia nigra and the basal ganglia. As well, the declining dopamine levels affect the overall balance of neurotransmitters in the brain, thus altering the way each of them functions.
SSRIs became available in the 1980s; the first to debut was fluoxetine, better known by its trade name Prozac. For most people SSRIs cause fewer side effects than other antidepressants such as tricyclics and MAOIs and they are usually the antidepressants of choice for people with Parkinson’s as they have fewer interactions with anti-parkinson’s medications. Commonly prescribed SSRIs include:
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Fluvoxamine (Luvox)
• Sertraline (Zoloft)
• Citalopram (Celexa)
Although the SSRIs generally are considered therapeutically equivalent to one another, each medication has a different chemical formulation and method of action within the body and brain. For this reason, people respond differently to the SSRIs. If one SSRI does not relieve depression, another may. Side effects of SSRIs, which are generally mild, include nausea, constipation, weight loss, anxiety, and SEXUAL dysfunction. Often these side effects end after the medication is taken for six to eight weeks; if they do not, another SSRI may be equally effective and not produce the side effects. As many people who have Parkinson’s have these symptoms as a function of the disease process, determining their causes can be difficult.
Because SSRIs have relatively long half-lives, they remain at high enough levels in the blood to exert a serotonin reuptake inhibitory effect for as long as several days after a dose. A rare but serious complication of SSRIs is serotonin syndrome, in which an excess of serotonin accumulates in the brain. This occurs most often in people who are taking other antidepressants (including over the counter products such as St.-John’s-wort) that also extend the activity of serotonin. Symptoms of serotonin syndrome include confusion, disorientation, myoclonus (involuntary muscle contractions), tremors, rigidity, rapid heartbeat, excessive sweating (diaphoresis), and high fever. These symptoms require immediate medical evaluation.
It is important to stop taking any other antide-pressant at least 14 days before starting an SSRI. It also is important to tape the dose gradually (over two weeks) when stopping an SSRI at the high end of its therapeutic range, to give the brain’s biochemistry opportunity to adjust to the drug’s withdrawal. Although SSRIs are the least likely of the antidepressants to interact with anti-Parkinson’s medications, they can intensify the effects of levodopa, the cornerstone of pharmacotherapy for Parkinson’s disease, causing symptoms such as dystonia (extreme rigidity) and choreioform dyskinesia (involuntary, dancelike movements). The SSRI that seems most likely to do this is flu-oxetine. Because these side effects can appear even after the SSRI has been taken for some time, associating their occurrence with the SSRI sometimes is difficult.