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Redirect: A few thoughts on mirtazapine (Remeron)

Posted by SLS on March 12, 2014, at 15:40:41

> Thanks, Scott. I have an appointment with a new provider on Friday. I think
I'm done with antipsychotics for now. Abilify didn't really help me, and I was
on Lamictal at the time. I'll keep Wellbutrin in mind.
>
> What is your opinion of mirtazapine?


For some people, it is a miracle.

NE = norepinephrine
5-HT = serotonin
DA = dopamine

Mirtazapine (Remeron) is very different from SSRIs, SNRIs, MAOIs, and TCAs. It is different enough that it might be worth trying. It is the only antidepressant in the USA to act as an antagonist (blocker) at the NE alpha-2 presynaptic autoreceptor (Mianserin is still available in Europe). Normally, these receptors are inhibitory when stimulated by 5-HT. When blocked, the neuron is told to manufacture and release more NE. NE is usually considered to be a excitatory neurotransmitter. It can be activating. Remeron also blocks 5-HT2a, 5-HT2c, and 5-HT3 receptors. Blocking the 5-HT2a/c receptors increases NE activity. 5-HT2a blockade also increases DA activity.

The problem with the way many doctors use mirtazapine for depression is that they don't prescribe a dosage high enough to block sufficiently the inhibitory NE autorceptors. Lower dosages are soporific and sedating because mirtazapine is a potent antihistamine. People sleep and eat too much on low dosages of mirtazapine (15-30 mg/day) because of this. For many, mirtazapine at low dosages makes for a good sleeping-pill, but not an effective antidepressant. At higher dosages (45-90 mg/day), antidepressant effects emerge and the sleepiness and increased appetite often mitigate.

Mirtazapine can be a great adjunct to SRIs (SSRIs and SNRIs) because of its ability to block the 5-HT2a/c receptors. Without this blockade, 5-HT can flood these receptors and suppress NE and DA activity downstream in areas thought to be involved in motivation and interest (prefrontal cortex, nucleus accumbens, and hippocampus). This probably explains the amotivation and apathy that can occur with SRI drugs. Does mirtazapine reverse these unwanted behavioral effects? I don't know. It may not if the apathy is an effect of 5-HT2b activation. Unfortunately, this receptor must remain unblocked for antidepressants to work.

In a very few people, mirtazapine exacerbates their depression. It does mine. I attribute this to its antagonism of NE alpha-2 autoreceptors. Latuda and Saphris are both antipsychotics that block these receptors. I did not react well to these drugs at all. I had a difficult time rejecting suicidal ideations while taking Latuda.

It is reasonable to try mirtazapine if you have not responded well to other classes of medication. If you are already taking a SRI, you could even add mirtazapine rather than switch. I would just make sure that your doctor is willing to go up to at least 60 mg/day before beginning treatment.


- Scott


Some see things as they are and ask why.
I dream of things that never were and ask why not.

- George Bernard Shaw

 

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