DXM is by far not a weak SSRI, it is not as
potent as e.g. paroxetine but since you're also dosing much higher, it becomes equally strong. I get remarkable SSRI activity from just 1-2x 22mg DXM HBr per day and with <100mg the NRI effect sets in strongly.
But you're right on the point to question why a combination of two SSRIs should be worse than a high dose of just one. And I think this actually is not true (the max effect achievable is complete blockade of the SERT, independent of how many agents you take if they are selective, and then you still have the monoamine oxidase recycling the serotonin). One can get serotonin syndrome by just eating an acute overdose of any SSRI if he/she's predisposed to. I actually think some of the overdose incidents aren't really serotonin syndromes but result from excess serotonin activating the 5-HT2a & 5-HT2b receptors (those responsible for the psychedelic effects from e.g. LSD and psilocybin as well as crucial for MDMA).. this mechanism, if activated too quick and too strong, can lead to things like Temporal Lobe Seizures in some individuals --> Psychosis. Also it causes a cascade of downstream dopamine release etc.
I would
speculate that using DXM for cough should be safe on moderate doses of SSRIs, if one's not taking it in the very first 1-2 weeks of introducing a new antidepressant. But the dosage needs to be kept low, from the full therapeutic dose (<120mg HBr per day?) you
will notice serotonergic effects, e.g. hypomania, possibly anxiety if you're sensitive to that.
SS risk fades probably over time when one is on a SSRI as the 5-HT receptors down regulate, making one less sensitive to serotonin.
The true real danger is when anything MAO inhibiting enters the game, or a serotonin releasing agent like MDAI, MDMA, alpha-methyltryptamine etc (that having additional MAOI effects on high doses!)
(As a side note, I have speculated before that DXM
could actually have some minor serotonin releasing effects by possibly acting as an inverse agonist at SERT because it is so strong on serotonin. This would make it
much more dangerous. But it probably is not true.)
I've done low-moderate doses of DXM (<150mg/d I think, but could have been <250mg on some occasions) whilst on 150mg venlafaxine SR over the course of several months. This has been completely reckless and I did not know much at all about the matter back then, but it was 'just' hypomanic and strongly anti depressive, when I was a non-responder to the SSRIs usually. I did not get serious adverse effects, DXM+methylphenidate, as low as 18mg/d, has been much more serious physically and eventually led to angina pectoris from the excess norepinephrine.
But do not do this, it could have gone wrong.
Edit: Maybe this should be moved into NSPD to get better responses?
