Fluoxetine and paroxetine are two medications that are used to treat depression, as well as other mood and anxiety disorders. They are both part of the family of drugs known as selective serotonin reuptake inhibitors (SSRIs.) Both drugs have a similar action in the brain, and exert similar effects. There are important differences between them, however, that lead to differences in how and when they are prescribed.
Some patients with depression show differences in their responses to fluoxetine versus paroxetine. This is due to individual differences in an enzyme in the brain called the polyglycoprotein (Pgp) transporter. Certain people have copies of this protein that cause it to be extremely active, and remove paroxetine from the brain before it can affect an individual. Fluoxetine is not affected by the Pgp transporter, so it can treat depression in individuals with the more active version of this enzyme.
Both fluoxetine and paroxetine prevent the neurotransmitter serotonin from breaking down in the brain. This allows serotonin to exert greater effects on the brain as a result. Slight differences in their actions mean that these drugs can be used to treat slightly different disorders. For example, fluoxetine is typically used to treat bipolar disorder and cataplexy, whereas paroxetine is most often used to treat generalized anxiety disorder and erectile dysfunction. Both drugs are used in the treatment of major depression, bipolar disorder, panic disorder, and obsessive compulsive disorder, however.
The length of time these drugs remain in the body before being broken down represent a key difference between fluoxetine and paroxetine. Paroxetine is broken down after about a day in most people, whereas fluoxetine remains for about one to three days. This difference has functional significance, because when doctors are weaning patients off of an SSRI, they prefer to use one with a longer half-life to minimize withdrawal effects. A person taking paroxetine may be switched to fluoxetine by a doctor as they taper their dose down in order to avoid withdrawal.
Side effects that occur from taking fluoxetine and paroxetine are quite similar. There are some small differences in the incidence rates of individual side effects, however. Patients taking fluoxetine tend to report slightly more incidents of insomnia and loss of appetite, but those taking paroxetine show higher rates of nausea and somnolence, or drowsiness. Studies that have investigated the efficacy and side effect rates show that both of these drugs are well-tolerated by most people, however, and that the side effects do not impact their usefulness.