I'm reopening this thread, since it looks like it deals with some issues I have with anhedonia and lack of motivation.
From my experience I've found that I need a combination of dopamine AND norepinephrine, and for me, I need it for more than a 24 hour period to work. I've tried all kinds of dopaminergic supplements that did nothing. I tried wellbutrin which did nothing except give me side effects so I couldn't go up to 450 mgs. I tried ritalin, which surprisingly did nothing. I've found a low dose of prozac, 5 mg every other day(it has a long half life), increases motivation and some interest but still not much emotional depth. Prozac blocks 5 HT2C receptor which is probably why this is effective in small doses but not in higher doses. But blocking this receptor increase norepinephrine and dopamine in the Prefrontal Cortex (PFC) and increase norepinephrine in this area more than dopamine. I think that norepinephrine is key to concentrating and motivation along with dopamine.
There are rat studies that show that norepinephrine depleted mice do not show a place preference to cocaine and morphine over food unlike regular mice. This indicates that that norepinephrine is some how tied to enjoying, motivation and perhaps anhedonia.
Recently I've experienced this myself. I have been taking mirtazapine for awhile with no benefit. At first there was some motivation but it kind of pooped out in less than two weeks. Going up 15mg didn't help. Then my pdoc added abilify. After getting to 2.5 mg I started feeling more interested in things, similar to how low dose prozac effects me. We thought the abilify was helping but not the mirtazapine, so we started to decrease mirtazapine. After awhile I noticed I had no interest in doing things anymore.
So two things could have happened. Everything pooped out or the increase in dopamine in the PFC needs the increase in norepinephrine from mirtazapine as well.
Unfortunately these two drugs and prozac only increase dopamine and norepinephrine in the PFC. They don't get into the mesolimbic areas or the striatum. Well higher doses of abilify do block dopamine in the nucleus accumbens.
Here are some studies showing I'm not shoveling you bullsh*t
Aripiprazole increases dopamine but not noradrenaline and serotonin levels in the mouse prefrontal cortex
Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of α2-adrenergic and serotonin2C receptors: a comparison with citalopram
There are plenty of studies showing that NE depleted mice don't show a preference to drugs like cocaine or amphetamine. Just google conditioned place preference, norepinephrine followed by cocaine, morphine, or amphetamine.
Just something to consider for the folks who have had limited success with DA selective drugs or shorter acting stimulants. TCAs and 5 HT2C antagonistist might help. Pristiq even added some emotional depth until it began to feel like an normal SSRI.
Edited by conundrum, 30 August 2010 - 10:37 AM.