I'm probably not the best person to ask about that. I have never been married and have had problems with both depression and autoimmune disorders for nearly 30 years (since my mid-20s.)

Autoimmune disorders often have a "waxing and waning" pattern, as does depression (unless you're really unlucky). When I was younger, I would end up in a pattern of trying to date/start a new relationship when my health was somewhat better, and then when my health got worse again, the relationship would almost always end.

My limited experience with the sexual side effects of Effexor and Cymbalta are that both drugs can cause decreased libido. Both also caused delayed orgasm for me. These effects seemed to decrease with time and also seemed to be less severe if I had a regular sex partner. I'm not sure of the reason for that. It was almost like my brain was "rewiring" itself to get rid of the sexual side effects.

I never tried taking Wellbutrin for sexual side effects, because the one time I did take it in the late 1990s, I had severe jitteriness and anxiety and stomach problems. I think I was taking 225 mg non-sustained-release form then. That's a pretty high dose, so I probably just got put off the drug because of that experience.

I think Effexor was more energizing for me and helped my motivation more, but it also caused insomnia. I should say that I was taking a dose of 375 mg/day because I also have fibromyalgia, and that's the dose you need to get significant pain relieving effect from Effexor, so my conclusion that it was more energizing may just be because of the dose I took.

This article contains a table that lists the "estimated selectivity ratios" of 5-HT (serotonin) to NE (norepinephrine) for the four SNRI antidepressant drugs (Effexor, Cymbalta, Fetzima, & Pristiq.) It's 1:30 for Effexor and 1:9 for Cymbalta.

Now that I've told you this, I've forgotten what 5-HT is associated with and what NE is associated with, aside from that NE is associated with fibromyalgia pain relief, and I doubt that that's useful info to you.

With Cymbalta, the same dose works for pain relief as is used most commonly for depression (60 mg.) For the first 3 years or so that I took it, Cymbalta was sedating for me and I took it at bedtime for that reason.

I think people more often find it to be not sedating and take it in the morning. I have no idea why people experience that difference with it.

Moogie's suggestion of an SNRI + Remeron is what I'm taking now. If you do a search for drugs recommended for treatment-resistant depression, that's one of the combos that will come up.

My doctor only prescribed 7.5-15 mg Remeron for me, because he said that it works better for insomnia at lower doses. I think that 30-45 mg is a more typical dose for treatment of depression.

Remeron/mirtazapine is an interesting medication. It affects serotonin and norepinephrine, but not in the same manner as other drugs. Read this for details if that kind of stuff makes sense to you.

The Remeron has also helped my motivation, or maybe it's helping the Cymbalta to work again. (I've been taking Cymbalta for around five years now. I took Effexor for six. I've ended up on those drugs for so long because of needing them to treat fibromyalgia. There's not much available that helps fibromyalgia pain for me as much as the SNRI antidepressants.)

If you end up taking Remeron/mirtazapine, I'd recommend starting off at 7.5 mg for 3 days or so. In my experience, doctors tend to start patients off at 15 or even 30 mg and it will knock you on your ***. Literally, in some cases.

Some other posters mentioned tricyclic drugs. I took nortriptyline a very long time ago and found it to be effective but didn't like the side effects. Ditto for Parnate, an MAO inhibitor.

I think you have to find a very knowledgeable prescriber (or a very old one) before they usually want to try tricyclics or MAOIs. Anyway, there are still plenty of drugs that you haven't tried. (Yay!)