Lamictal, Physostigmine, Norepinephrine
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Q:  Lamictal, Physostigmine, Norepinephrine

I'm a rapid cycler. My cycles seem to be from 3 weeks to a month in length with the good times lasting for 2 to 3 weeks & the bad times lasting for a week to 10 days. My doctor is trying me on lamictal. So far no luck. I thought I was cured until this week when I quite unexpectedly dropped into the abyss again. Three questions:

1. I'm currently on 200mg of lamictal. Is it possible that a higher dose would do the trick? I'm 6'3" & 250lb. if that makes any difference.

2. I read something about physostigmine which according to my interpretation of the article, given by injection would bring a patient out of the depressive phase. Do you know whether this might be true or not?

3. Does norepinephrine level play a role in manic depression? Do norepinephrine reuptake inhibitors help to relieve the cycling?

Dear John --
Doctors who have used lamotrigine (Lamictal) up to the limit that the neurologists usually use as a maximum, namely 400 mg per day, were reporting verbally in a recent conference I attended that they saw additional benefit at the higher doses and would not hesitate to go higher if getting less than a full response. To my knowledge we have no data on this strategy, however. (Hint: the 200 mg pill costs about the same as a 100 mg pill; so definitely use bigger pills and chop to keep costs down, but make sure you go up slowly according to your doctor's directions, too).

Taking #3 next: Norepinephrine reuptake inhibitors, like serotonin reuptake inhibitors (or Effexor, which is both in one pill) are antidepressants and pose a risk of inducing cycling. We have very few data suggesting that any antidepressant is any less likely than the others to induce manic-side symptoms and cycling; some people think Wellbutrin (buproprion) might be better that way but one study by Gary Sachs did not show this difference (may have been too small for that purpose), and many people think MAOI's might also be better in this way.

Physostigmine: don't know about such a connection. A lit' search produced a couple of interesting things, including physostigmine making depression mildly worse in borderline "personality disorder"Steinberg; and use of donepizil (Aricept), a medication for Alzheimer's dementia, showing that it -- like physostigmine -- shortens the time to REM sleep. Basically it looks like there is some research looking into the acetlycholine as a neurotransmitter and its relationship to mood disorders, but there is nothing conclusive there yet and no mention I saw about physostigmine as a treatment.

Don't forget lithium has antidepressant as well as anticycling properties, if you're hunting for something to add...

Dr. Phelps

Published December, 2003


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