Paroxetine (Paxil®) and sertraline (Zoloft®) are examples of selective serotonin reuptake inhibitor (SSRI) antidepressant drugs available by prescription that appear to have neuroprotective benefit in some mouse models. Both are used widely for treating depression, and if mouse results translate to people, may provide neuroprotective benefit.

Mechanisms of Action: SSRIs increase the brain concentration of serotonin, a neurotransmitter that is decreased in depression and in Huntington's. SSRIs also increase brain levels of brain-derived neurotrophic factor (BDNF), which promotes nerve cell health [Duan W 2004].

Rationale for Use in Huntington's: Sertraline and paroxetine reduce brain injury, improve motor dysfunction, and increase survival in Huntington's model mice when given either before or after the development of symptoms [Duan W 2004, Duan 2005]. And they are known to stimulate the growth of new neurons as well [Grote HE 2005].

Dosage of sertraline (Zoloft®) for the treatment of depression varies with each individual ranging from 50 to 150 mg per day. Paroxetine (Paxil®) dose range is 20 to 60 mg per day. Based on the mouse model study, it appears that dosages at the high end will be needed to treat Huntington's by increasing BDNF levels.

Side Effects include nausea, headache, sleepiness or insomnia, dry mouth, and sexual difficulty. Higher dosages should not be used with tricyclic drugs (like amitriptyline (Elavil®) or trazadone).

Sources: Both of these drugs are available by prescription.

References

Duan W, Guo Z, Jiang H, Ladenheim B, Xu X, Cadet JL, Mattson MP. Paroxetine retards disease onset and progression in Huntingtin mutant mice. Ann Neurol. 2004 Apr;55(4):590-4. PubMed abstract

Duan W, Peng Q, Zhao M, Ladenheim B, Masuda N, Cadet JL, Ross CA (2005) Sertraline Retards Progression and Improves Survival in a Mouse Model of Huntington's Disease. Society for Neuroscience 2005 (Abstract)

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. PubMed abstract