Drug Summary: Paroxetine (also known as Paxil) is part of the class of drugs known as selective serotonin reuptake inhibitors (SSRIs). Paroxetine is a commonly prescribed drug for depression and severe anxiety in people with and without HD. While it has traditionally been used to treat psychiatric disorders, new research suggests that it may also be helpful in treating the symptoms and slowing the progression of HD.
Research on Paroxetine
Duan, et al. (2004) noted that SSRIs are very helpful in treating psychiatric symptoms in people with HD, yet no one had tested how they might affect neurodegeneration and the progression of the disease. These researchers created four different experimental groups of mice: transgenic (mouse models of HD) and nontransgenic mice that were injected with paroxetine, and transgenic and nontransgenic mice that were injected with a placebo. The progression of the disease was observed in the mice each day, and they were weighed each week. Their motor performance was tested by placing them on a rotating rod and recording the amount of time that they were able to stay on. Levels of different brain chemicals were measured, including serotonin and the related molecule 5-HIAA.
The mice received treatment (or placebo) starting at eight weeks of age. At 14 weeks it was found that HD mice had lower levels of serotonin and 5-HIAA in the striatum compared to the nontransgenic mice. Serotonin was increased in both transgenic and nontransgenic mice that received paroxetine. Furthermore, administration of serotonin did not affect the levels of any other important brain chemicals tested, such as dopamine.
Paroxetine also delayed the beginning of behavioral symptoms by an average of 2 weeks in the HD mice, and even helped them survive for an average of 15 days longer than the previous maximum life span (this is a significant amount of time in the life of a mouse). While weight loss is a problem both for HD mice and people with HD, paroxetine slowed the loss of weight in HD mice compared to untreated HD mice. At 16 weeks the HD mice treated with paroxetine performed significantly better than the untreated HD mice on the motor tests.
In order to assess the drug’s effect on the neurodegenerative process, the researchers examined the brains of HD mice and compared them to nontransgenic mice. While untreated HD mice showed deterioration of the brain with larger lateral ventricles and a thinner cerebral cortex, HD mice treated with paroxetine had less enlarged ventricles. Having less enlarged ventricles means that the HD mice treated with paroxetine lost fewer nerve cells in their brains. (For more information on HD and the brain, click here.)
This study suggests that paroxetine not only improves serotonin signaling in HD mice, but it also slows neurodegeneration and improves overall survival. This slowing of the neurodegenerative process may also help to slow the typical weight loss caused by HD. By using an SSRI such as paroxetine to increase serotonin in the brain, serotonin-induced signaling is increased, as is the expression of the important brain-derived neurotrophic factor (BDNF) . (For more information on BDNF, click here.) Additionally, this research found that paroxetine was helpful when given both before and after the onset of motor symptoms. This finding is important because it may indicate that paroxetine might still have beneficial effects even if it is given later in the course of the disease. SSRIs appear to be safe for long-term use in humans, so starting paroxetine early should not rule out its later use as well.
While these results are hopeful, it is important to remember that the study was conducted on mice made to look like they have HD, not on humans or people with HD themselves. Even if paroxetine is relatively safe for use in human use, it nevertheless may not help neurodegeneration in humans the same way that it is indicated in the mouse study. Overall, the use of paroxetine to treat both the symptoms and progression of HD is a promising idea that needs more investigation.