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SSRI Antidepressants

As a general rule, all of the selective seritonin uptake inhibitors (SSRI) drugs give similar antidepressant and antianxiety benefits. They differ mostly by side effects.

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 2004].

Fluoxetine (Prozac®) Dosing starts at 10 to 20 mg per day, effective antidepressant dose is usually between 20 and 40 mg with maximum dosage at 80 mg/day. This drug is used for anxiety and obsessive compulsive symptoms. Dry mouth, decreased libido, nausea, insomnia, headache, and anxiety can be side effects.

Sertraline (Zoloft®) Dosing starts at 25 to 50 mg with maximum dosage up to 200 mg/day. Side effects include more nausea and diarrhea than other SSRIs, insomnia, and sexual dysfunction. This drug has been shown to be neuroprotective in genetic mouse models of Huntington's at dosage equivalent of about 150 mg/day [Duan 2005].

Paroxetine (Paxil®) tends to be more sedating than Prozac and Zoloft. Dosing starts at 10 to 20 mg/day with maximum dosage at 80 mg/day. It tends to cause constipation, and sexual dysfunction may be slightly higher with this drug than other SSRIs. This drug is associated with more birth defects, so should not be used in pregnancy. If discontinued, this drug should be tapered over several weeks, not stopped abruptly. In such cases a withdrawal syndrome can occur. This drug has been shown to be neuroprotective in genetic mouse models of Huntington's at dosage equivalent of 60-80 mg/day [Duan 2004].

Citalopram (Celexa®) performs better than Zoloft for anxiety, and is claimed to cause less sexual dysfunction that other SSRIs. Starting dose is 10- 20 mg per day, but average therapeutic dose is 40 mg/day, with maximum dose of 60 mg/day. This drug is more sedating than Zoloft.

Escitalopram (Lexapro®) is a drug chemically similar to citalopram that has both antidepressant and antianxiety activity. The starting dose is usually 5-10 mg per day increasing to maximum dosage of 30-40 mg/day. Side effects include nausea, headache, diarrhea, agitation or sleepiness.

Fluvoxamine (Luvox®) is FDA approved for obsessive compulsive disorders, but is also used for depression and anxiety. Starting dosage is 50 mg, but therapeutic dose is usually much higher in the 150 to 250 mg range. Side effects of nausea and vomiting are more common than with other SSRIs. This drug is more expensive and is not available in generic form.

NSRI Antidepressants

There are two norepinephrine and serotonin reuptake inhibitor (NSRI)antidepressant drugs. Similar to the SSRI drugs, they are used to treat depression and anxiety. They tend to cause less sleepiness than many of the SSRI drugs.

Venlafaxime (Effexor®) increases both serotonin and norepinephrine levels. It comes in short acting tablets that must be taken two or three times per day, and in a once daily (ER) form. Dosages range from 25 to 225 mg/day total dosage. Side effects are headache, insomnia, nervousness. Because this drug can increase blood pressure, this should always be checked by your doctor after starting it. This is a good antidepressant to use with tetrabenazine, which is known to decrease both serotonin and norepinephrine levels. This drug should not be stopped quickly beauses withdrawal symptoms of dizziness, muscle aches and anxiety often occur. Always taper it off over several weeks.

Duloxetine (Cymbalta®) is a drug that is similar to Effexor. It increases both serotonin and norepinephrine levels. It comes in 20, 40, and 60 mg capsules which should not be split. The larger dose is usually needed for depression. It is also helpful in treating chronic pain. Side effects include muscle aches, insomnia, headaches, and nervousness.

Atypical Antidepressants

These drugs are called "atypical" only because they don't fit into other categories. These drugs can be used alone, but are often used in combination with other drugs.

Buspirone (Buspar®) though used primarily for anxiety, is useful for depression particularly when combined with other antidepressants. It can decrease irritability and aggressive behavior. This drug is often used to counteract the sexual dysfunction caused by SSRIs. Dosing starts at 7.5 mg twice daily, with maximum total dose of 60 mg/day. Side effects are drowsiness, nervousness, headache, and lightheadedness.

Bupropion (Wellbutrin®) is thought to work primarily through dopamine regulation. It is often used in Huntington clinics, however because increased dopamine (at least theoretically) may be harmful in Huntington's, I personally limit the use of this drug.

Mirtazepine (Remeron®) increases serotonin and norepinephrine levels by a different mechanism than SSRI and other drugs. It is often helpful in severe depression, and is often used in addition to other antidepressants. It is very helpful for anxiety and is used to treat obsessive-compulsive and panic disorders. Dosages start at 7.5 mg. This dose usually caused sleepiness and should be taken at night. Often with larger doses there is less sedation. Side effects include increased appetite, weight gain, high blood pressure and vivid dreams.

Tricyclic Antidepressants

These are older drugs that are not used frequently. They include amitriptyline (Elavil®), nortryptiline (Pamalor®), and imipramine (Tofranil®). Because larger doses are required to effectively treat depression, side effects often limit the use of these drugs. They can be used as helpful "add ons" when other antidepressants aren't effective alone. They can be useful for insomnia.

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)

 
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