I empathize with your situation as I am in a similar situation.

One thing I want to know from you is that over the past 20 years trying various meds - how long did you stay on a med before moving to another? I ask this because many times a patient will have side effects at the beginning of treatment and either they or their doc will immediately take them off of it instead of lowering the dosage significantly to see if that remedies the side effects.

A good trial on a med is at least 6-12 weeks if not longer. 1-4 weeks is not long enough to determine if the med will work for you or not.

With Treatment-Resistant cases of depression, some people respond quickly to new meds/med changes only to have the rug pulled out from under them within a couple weeks. No one knows why this happens unfortunately. Also, there are some meds and med cocktails that seem to work better for those with Treatment-Resistant cases like:

SSRI + Simulant combo (Dexedrine, Adderall, Ritalin or Vyvanse)

SNRI (Effexor) + Stimulant

SSRI/SNRI+ Remeron (+Stimulant)

Effexor in dosages above 450mg + Lithium

MAOIs + small amounts of a stimulant (even though this is contraindicated many psych docs and psychopharmacologists use it with close monitoring)

SSRI/SNRI + tricyclic

Tricyclic + Stimulant

SSRI/SNRI + Lamictal

SSRi/SNRI + Atypical Antipsychotic (Abilify, Seroquel, Geodon, Risperdal)

It's also a VERY good idea to have your doctor do a complete blood work-up testing your thyroid, hormone levels, iron levels, vitamin deficiencies, etc.

Low thyroid (hypothyroidism) can cause depression
Low Testosterone in men can cause depression
Sleep Apnea can cause depression
Low iron/vitamin levels can cause fatigue, insomnia, low motivation and depression

Usually those who have treatment-resistant cases of depression have a more melancholic depression - trouble with motivation, fatigue, lost of interest, hypersomnia, etc that's why a combo + stimulant is frequently used.

Personally, after 20 years of med trial not unlike yourself (including ECT, therapy, and the Vegal Nerve Stimulator) I've found the best combination to be Effexor + Adderall + Abilify. However, what works for me may not work for you.

After switching doctors, my new doc ordered blood tests and found my thyroid was low, my testosterone was low and that I had sleep apnea - all of which I am currently on replacement therapy for. The thyroid controls metabolism and if yours is out of whack you will not be metabolizing medications "correctly." So I urge you to ask your doctor about some blood tests to rule out anything biological.

Hoep this helps
Jerry

P.S. Wellbutrin can cause a state called hypomania which is not full-blown mania. Actually Wellbutrin is sometimes prescribed to bipolar patients. Many of the SSRIs and SNRIs can cause hypomania as well however it is important to note that this does not mean you are bipolar.