Arches. Photo by Daniel Chia
Jun
30
2010

Fluoxetine

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Drug Summary: Fluoxetine (also known as Prozac) is part of the class of drugs known as selective serotonin reuptake inhibitors (SSRIs) . It is usually prescribed to treat depression and obsessive-compulsive disorder (OCD) in people with and without HD. While fluoxetine has traditionally been used to treat behavioral symptoms, recent observations indicate that it may also be helpful in treating other aspects of HD.

Research on Fluoxetine

Como et al. (1997) performed a randomized, double-blind study of 30 nondepressed patients with HD. 17 subjects received fluoxetine for 4 months, while 13 received placebo. The study did not find that fluoxetine was helpful; patients receiving fluoxetine did not demonstrate improvements in motor or cognitive symptoms, and did not improve in measures of functional capacity (the ability to perform day-to-day tasks. While this study suggests that fluoxetine is not helpful for nondepressed people with HD, the researchers had previously reported that treating 8 depressed HD patients with fluoxetine helped those patients deal with symptoms much better – so fluoxetine may be useful to treat depression in HD.

DeMarchi, et al. (2001) observed two people with HD who were given fluoxetine for psychiatric issues. They tested the two patients each month using the HD motor rating scale (HDMRS) to measure movement abilities, and the mini mental state examination (MMSE) for cognitive (or thinking) abilities. These tests were also accompanied by psychiatric and neurological examinations.

The first case study was on a 60-year-old woman who had symptoms of HD beginning in her mid-forties and symptoms of OCD beginning at age 25. She had not been successfully treated for her chorea, declining cognitive functioning, or aggressive behavior. Before treatment, her symptoms were so bad that her speech could not be understood and her cognitive functioning so impaired that she could not even take the MMSE. She was given the HDMRS, and her motor functioning scored 20 on a scale of 25 (with 0 as the least impaired, and 25 as the most impaired). She began treatment with fluoxetine, and after a month she was clearly less agitated and had a better mood. Her motor performance progressively improved during treatment, scoring 12 on the HDMRS after 4-6 months. The improvement in her motor functioning allowed her to begin walking again and speak coherently. Perhaps most surprising was her improvement in cognitive functioning. Cognitive improvement began after about 4-6 months of treatment, and after about a year she could take the MMSE and scored 12 out of 25. She continues to improve 6 years after beginning treatment with fluoxetine. Additionally, her movement became worse during the two periods in which she stopped taking the medication.

The second case study was on a 55-year-old woman who had symptoms of HD for the past 8 years. Her main symptom was the involuntary movements characteristic of HD, and she mostly retained her cognitive functioning. When tested before treatment began she received a score of 13 on the HDMRS and 19 on MMSE. She began treatment with fluoxetine and another drug to treat her insomnia (since fluoxetine was making the insomnia worse). She began to improve in her motor performance after about 2 months of treatment and reached the height of her improvement after 6 months, with a score of 8 on the HDMRS. She maintained this level of motor functioning for the next year and was able to return to her job. The patient did not change significantly in cognitive functioning, maintaining a score of 20 on the MMSE for as long as she was observed. She went off of the medication for a period of 3 months after a year of treatment and her motor performance deteriorated during this time. When she started taking fluoxetine again, she regained her previous level of motor functioning.

These two case studies show that fluoxetine may be beneficial to people with HD who have not responded well to other treatments for both behavioral and movement symptoms. The motor functioning probably improved as a result of increased serotonin signaling in the brain. It is unclear how the patient in Case One had such impressive cognitive improvement; this has never been seen before and may only be partially due to the beneficial effects of serotonin. It is possible that the reason why fluoxetine was so helpful in these two cases has to do with them both having a history of OCD in their families. In other words, a possible reason for success in these cases had to do with improvements in their OCD rather than, or in addition to, HD. It is important to note that this study only represents two cases of people with HD. More research needs to be done before making assessments about fluoxetine’s effect on people with HD. However, judging by these cases, fluoxetine may at least be helpful to people with HD who also have a family history of OCD.

Grote et al. (2005) studied fluoxetine in a mouse model of HD, and found that fluoxetine might help fight some of the effects of the disease. R6/1 mice were either treated with fluoxetine or a placebo. Scientists found that there was no improvement in motor symptoms, but HD mice treated with fluoxetine had improvements in cognitive symptoms; untreated HD mice tend to repeatedly explore the same paths in a maze, and the treated HD mice behaved more like normal mice by exploring the maze more thoroughly. Treated HD mice also showed fewer symptoms of depression than untreated HD mice.

The results were more than just behavioral; when the researchers looked at the brains of these mice, they found that fluoxetine reversed many of the problems HD causes in the brain. Treated HD mice had much larger dentate gyruses than untreated HD mice, and had an increase in neurogenesis.

Altogether, research results on fluoxetine are mixed; an animal study reports some improvement, while a small clinical trial does not.

For further reading

  1. Como PG, Rubin AJ, O’Brien CF, Lawler K, Hickey C, Rubin AE, Henderson R, McDermott MP, McDermott M, Steinberg K, Shoulson I. A controlled trial of fluoxetine in nondepressed patients with Huntington’s disease. Mov Disord. 1997 May;12(3):397-401. This medium-difficulty study describes the clinical trial of fluoxetine
  2. DeMarchi, et al. Fluoxetine in the treatment of Huntington’s disease. 2001. Psychopharmacology 153: 264-266. This is a scientific article of medium difficulty that describes two case studies of people with HD that were treated successfully with fluoxetine.
  3. Grote HE, Bull ND, Howard ML, van Dellen A, Blakemore C, Bartlett PF, Hannan AJ. Cognitive disorders and neurogenesis deficits in Huntington’s disease mice are rescued by fluoxetine. Eur J Neurosci. 2005 Oct;22(8):2081-8. This technical article discusses how fluoxetine improved some symptoms in a mouse model of HD

-K. Taub, 1-29-06, updated by M. Hedlin 8.9.11