I've taken Tramadol and SSRI's together many times without issues. But I wouldn't risk it in the future. If you have to, try and potentiate the Tramadol with something so that you can use a lower dose. I used to use oxycodone to potentiate Tramadol on zoloft (yes, Tramadol was a measurably more euphoric drug for me compared to oxycodone). I would also strongly recommend keeping some cyproheptadine on hand, it's the drug used in hospitals to reverse serotonin syndrome. Have some diazepam on hand also in case the worst happens.
I haven't seen any research assessing the risk or incidence of serotonin syndrome with Tramadol-SSRI combinations at reasonable doses. So we don't really know how risky it is. For what it's worth one of my closest friends is a pharmacologist. I asked him about this interaction and he told me that the incidence is so rare that it's not worth worrying that much about.
It is also likely that most individuals that have suffered from serotonin syndrome as a result of this interaction, are part of the minority of poor metabolisers. Tramadol is metabolised via the CYP2D6 enzyme. Individuals lacking this enzyme will have more Tramadol in their bloodstream because it's not being metabolised properly. Tramadol itself has appreciable serotonin activity but it's metabolites have little to none. It's chief metabolite O-Desmethyltramadol is responsible for the entirety of Tramadol's opioid activity. Poor metabolisers will have excess serotonergic activity as a result, and a deficit of opioid activity. Around 10% of the western population are poor metabolisers.
A rather crude way of assessing whether you're a poor metaboliser is by describing the nature of the 'high' that you get from Tramadol. For me it feels like a strong opiate, with more opioid-esque euphoria than oxycodone. That's how I know I'm getting a lot of Tramadol's metabolite, O-Desmethyl, since Tramadol itself doesn't really have any opioid activity. The likelihood is therefore that I'm a very good metaboliser. So my risk of serotonin syndrome is much lower than the average user. Be aware that there's another metabolic pathway with Tramadol that involves a different enzyme. So how well this pathway is working will also influence the levels of Tramadol in the bloodstream. The metabolite of this pathway doesn't have much appreciable psychoactivity.
The other complication is that certain antidepressants inhibit the CYP2D6 enzyme and can therefore reduce metabolisation to O-Desmethyltramadol. So you might find yourself needing to raise the dose to get the same opioid activity. This is obviously a problem as the levels of Tramadol in your blood stream will rise. If the antidepressant is effectively inhibiting CYP2D6 you'll have more trarnadol in your bloodstream with the same dose compared to when you weren't on SSRI's. Raising the dose on top of that is asking for trouble. Sertraline/zoloft inhibits CYP2D6 the least of the SSRIs. Anecdotally the intensity of the Tramadol high was unchanged for me off v on sertraline.
If you really want to do this, my advice would be to get cyproheptadine and diazepam. Find a non serotonergic potentiator for the Tramadol. Ideally you should also change antidepressants. I would recommend combination depression therapy with ketamine, tianeptine and agomelatine. 3 different accepted and authorised anti depressants. All at least as effective as the anti depressant you're currently taking, and without the risk of negative interactions with Tramadol or other drugs like mdma. All have a vastly reduced side effect and dependence-liability profile compared to mainstream anti depressants. Neither of those 3 anti depressants will cause physical dependence unlike the one that you're taking, and they've all been found to be at least as effective (with ketamine found to be significantly more effective) according to the available published research. I'm personally using tianeptine and ketamine, and it's worked much better than SSRI's ever did with 0 side effects to boot. I'm considering adding agomelatine because I haven't had complete remission. I have however, gone from severely depressed and housebound to mild-moderately depressed and functional with these medications. Best part is I can use as much Tramadol and MDMA is I like whilst keeping depression at bay
. Although to be honest, past MDMA abuse and twice weekly use of Tramadol is probably contributing to my depression. I'm trying to reduce my opioid use though. I've now got it down to 3 times one week, 0 times the next in a cycle. I've discontinued MDMA for about 6 months to heal my serotonergic system from past MDMA abuse :/
But yeah don't use Tramadol as a regular antidepressant as prolonged mu-opioid receptor agonism (of which Tramadol, or rather its metabolite, is an agonist) is associated with the development of depression. Ideally you should only use it when you have a special occasion that you want to enjoy without the awful weight of depression.
