combining SSRI's with 5ht2a antagonists: is my med regimen safe?

[Arsenic_X]

I've been only recently searching for an answer to a question I've had for a while now, and i can't seem to find anything on google or in any research paper ive come across, so I'll pose this question to you guys.

I take 3 different serotonin affecting antidepressants (sertraline 200 mg in the morning 50 mg at night, mirtazapine 30 mg, often split into 2 15 mg doses for day and night, and trazadone 300 mg(although taken for sleep, I'm on a dose which is a prescribed dose for depression)). I also get a monthly shot of invega sustenna 234 mg. of course sertraline is a SSRI and i understand how they work, but every day I combine it with mirtazapine, which is a NaSSA which acts as an antagonist at 5ht2a and 5ht2c, and trazadone, another 5ht2a antagonist, and also my invega is always in my system, which has the effect of 5ht2a antagonism. I don't understand all that well how all these serotonergic drugs work in tandem together, but I do know that since I've added mirtazapine to my daily regimen first for sleep, then using half my dose in the morning, I've noticed improved symptom relief and overall an overall increase in mental stability and overall mental health well-being. I also noticed the same effects at night after first having my trazadone raised to 300 mg, then adding 50 mg sertraline, then finally adding at first 30 mg (now 15) mirtazapine at night. Am i over doing my antidepressant regimen and at risk of some serious health issuses, or have i found a perfect balance for me and im not doing harm to my brain? And just how so these meds work together? in very intrigued and look forward to your knowledgeable answers.

In case it matters, I'll list my other medications:

bupropion 450 mg/day
gabapentin 600 mg 3x daily
divalproex sodium ER 1500 mg/night
triazolam 0.5 mg/night

 

[Hodor]

Combining SSRI's with 5HT2A antagonists is, in principle, perfectly safe.

What is honestly concerning is that you're on so many different antidepressants - do you get these prescribed from a single doc?

300 mg of Trazodone is in the upper dose range for this compound; 450 mg is normally considered the maximum dose for Wellbutrin; 250 mg's of sertraline is above the normal maximum dose. While "only" trazodone and sertraline have a significant effect on serotonin levels, they still have to compete with the other meds for the same enzymes. Bupropion, in particular, is a pretty notorious offender, as it can significantly decrease the seizure threshold *and* strongly potentiate anything metabolized via the CYP2D6 enzyme. Basically, you're skirting dangerously cause to seizure territory with this cocktail.

Anyway, regarding the mirtazapine: That one's a pretty interesting drug as far as its pharmacology goes - instead of inhibiting the re-uptake of serotonin and noradrenaline (like a tricyclic or SNRI), the tetracyclics/NaSSA's bind to a number of serotonin and adrenaline receptors that normally suppress the release of monoamine neurotransmitters; by antagonizing these receptors, the NaSSA's thus allow for more neurotransmitters to be released, producing a rapid antidepressant effect without a significant risk of serotonin syndrome (they may still be indirectly involved in SS through the potentiation of other antidepressants via the inhibition of CYP enzymes, though).