SSRI's with Tricyclics?

[icebird200]

Could this end up fatal?

Are there any bad reactions from mixing these meds? I know somebody who takes

Zoloft and Sinequan, but he wants to eliminate the Sinequan for some reason.

Is it a good or bad idea to be on these two classes at one time?

Just an Idea I want to bring up with my pdoc. My anxiety is hella treatment resistant.

for instance, Lexapro plus 10 mg Sinequan?

[null0trooper]

Could this end up fatal?

Yes, no, or maybe. It depends on *which* tricyclic antidepressant, because they are not all alike in function or metabolism. It also depends on *which* SSRI, because while they work similarly their metabolism differs.

Sinequan, or doxepin hydrochloride, is a good case in point. It is a very strong antihistamine, and inhibits noradrenaline reuptake, but it's not a very strong serotonin reuptake inhibitor. In that respect it may not be a problem.

However, brain chemicals and the possibility of serotonin syndrome aren't the whole story. Doxepin is metabolized by the liver using the Cytochrome P450 enzyme, mostly via the 2D6 isoenzyme. It also inhibits that isoenzyme, which can prevent other medications from being metabolized. Among the medications metabolized by 2D6 are Paxil, Prozac, and Fluvox. Paxil and Prozac are also strong 2D6 inhibitors. So taking Sinequan in combination with *certain* SSRIs the blood concentrations of both medications can be much higher than they would be when taken individually. This is why the PI sheet (example at RxList) cautions against combining the medications.

An SSRI that is not metabolized extensively by 2D6 and which doesn't strongly inhibit it (e.g., Lexapro) might be OK with Sinequan. Zoloft/sertraline could elevate Sinequan levels by inhibiting that 2D6 isoenzyme, but not as badly as some other meds can.