"I don't feel that combo is doing its job": What are the expectations of treatment? What symptoms are suppose to be addressed by treatment?
I think any combination of antidepressants (and/or other medications) is fine so long as it achieves the intended purpose, the benefits outweigh the risks of treatment, and the side effects are tolerable and don't impair functioning.
Medications which increase serotonin (such as Celexa, Prozac, Effexor) can also reduce dopamine. If the reduction in dopamine is too low, it may manifest as impaired memory, increased weight, agitationed/restlessness, lethargy, anxiety, sexual dysfunction, among other side effects. Serotonin, itself, can directly impair sexual function in excessively high doses for the person.
Wellbutrin works by increasing norepinephrine. If the dose is too high, increased norepinephrine can increase a person's stress level. The appropriate dose depends on the person. The range of doses I use is between 37.5 mg to 500 mg a day. The risk of seizure at 600 mg a day is about 1 in 20. Wellbutrin can significantly inhibit cytochrome P450 2D6 - an enzyme in the liver which metabolizes many medications, and is needed to convert thyroid hormone
T4 to the active version T3.
In general (which needs to be interpreted for every individual patient) Effexor works primarily by increasing serotonin at doses from 1 to 150 mg a day. Above 150 mg a day, it also increases norepinephrine significantly. Around 300 mg a day, it also increases dopamine significantly. Thus its pharmacological effect will depend on the dose. My own maximum dose is 575 mg a day - rarely needed, or tolerated (due to side effects).
When a patient does well on an antidepressant or combination of medications then the medication or combination seems to stop working, it is the patient's illness or condition that has changed, not the medication. The medications always work the same way - their mechanisms of action do not change. But other factors in the patient's condition or health may change the patient's response to treatment. These factors may include other neurotransmitter-hormone changes and health related changes (hypothyroidism, further decreases in
testosterone, obesity, diabetes, stress and othe psychological factors, etc.) as well as the addition of other medications with interactions.
Some practitioners believe in "SSRI Poop-out" - where it is thought that "tolerance" develops to an SSRI (serotonin reuptake inhibitor - such as Prozac), which is why it will stop working. I do not believe this generally happens. I think the patient's illness either changes in characteristics or the diagnosis needs to be reassessed (e.g. bipolar disorder rather than major depressive disorder may be present) or other complicating health factors contribute to worsening of their symptoms.
The patient will have to continue working with his/her doctor to determine what factors have changed.