Erin - I am currently taking 225mg of Effexor XR (venlafaxine) and 300mg of Wellbutrin SR (bupropion) daily (the Effexor XR in the morning and 150mg of Wellutrin SR twice daily). It took about six months to find this combination. I was taking 450mg of Effexor XR daily, but I was in such a fog and was so fatigued and tired that I was pretty much nonfunctional.

After a month of 450mg Effexor XR daily, my doc and I decided to lower the dose to 300mg daily, but the fog was still there. I was taking 10mg of Dexedrine Spansules (dextroamphetamine, slow release) in the morning and at noon (and sometimes another 10mg at 1:00pm) and that help with the fatigue and tiredness. I was able to work, but wasn't as alert as I should have been.

My doc said to try to add Wellbutrin SR since it had worked for me in the past (although I tried it for two months before switching to Effexor XR). I was able to drop the Effexor dose to 225mg daily. Well that did the trick; the fog is gone (more often than not) and this combination is still working for me (as far as I can tell) I find it hard to objectively gauge my own progress, so I rely on my wife and my doc to tell me if am euthymic or more depressed than usual.

I still take 10mg of Dexedrine Spansules in the morning, but I really think that this is more of a security blanket than an actual necessity. My doc doesn't want me to stop this drug until after the lawsuit is settled.

As for the new formulations, they are more gimmicky than providing better therapeutic relief. The only reason to take a once daily Wellbutrin is if you are constantly forgetting the afternoon dose. Other than that I don't see a once daily Wellbutrin as having any clinically significant advantages over the twice daily version.

That being said, drugs with very short half-lives (eg. less than 12 hours of efficacy per tablet) are an inconvenience. It is not that they work better or give better blood levels of the drug, but, as stated above, it is an issue of convenience. Both regular Effexor and Wellbutrin must be taken three times daily because of their extremely short half-lives. A missed dose of Wellbutrin is not so much a problem as a missed dose of Effexor.

When you miss a dose of Effexor you risk experiencing serotonergic withdrawl effects, as is seen with Paxil (paroxetine), Luvox (fluvoxamine), and Zoloft (sertraline). These withdrawl effects (eg. headache, lightheadedness, flu-like symptoms, etc.) can occur within 8 hours of a missed dose of the regular Effexor.

Personally, I do not like regular Effexor because I have seen withdrawl effects from it far too often. I was involved in a case where a 90 year man with Alzheimer's disease was given 37.5mg of Effexor in the morning (depression is quite common in those with Alzheimer's). The pdoc that wrote the prescription assumed that the pharmacist would give Effexor XR, as the dose was once daily. Because the prescription only read Effexor, the pharmacist gave the regular Effexor (I make no excuses for those in my profession; I just shake my head and sigh a lot). The elderly gentleman was feeling awful every night at bedtime; he'd get a headache, runny nose, and feel nauseous. This went on for 4 or 5 months. His psychiatric nurse consulted with me on this case and I started to go through the drug file to see if I could find anything. I should add that this was in the days (mid-1990's) when the drug companies were still denying the existence of serotonergic withdrawl effects. I had the file for a couple of days, but found nothing exciting in the way of drug interactions, or dosages at were too high for the patient's age.

Then one night, just as I was falling to sleep, a thought just sprung into my mind to check which type of Effexor the gentleman was taking. His drug file at the Mental Health Clinic said Effexor XR. I called the pharmacy at the nursing home where this man was living and asked the pharmacist to fax me the man's drug file.

Bingo! The pharmacist was giving the regular Effexor, not the XR (extended-release version). The minimal effective blood concentration of Effexor was not maintained over 24 hours. In other words, this gentleman was going through mini-withdrawls every night! It was this case that convinced me of the existence (and potential severity) of serotonergic withdrawl.

Enough of my preaching; the only advise that I can give to you is to start the Effexor XR at a low dose (37.5mg/day) and then increase it slowly. How slowly you raise it depends upon how you feel; if the start-up side effects (eg. headache, nausea, etc.) are still bad at one dose, either ask the doc to lower the dose for awhile before increasing it. I usually say to increase the dose in increments of 37.5mg once or twice a week, depending upon how you feel. This does mean that it will take a lot longer than normal to reach a target dose (150mg to 300mg), but you do reach it with a minimum of discomfort. Also, using this method is more expensive than the normal initial dosing regimen. Ask your doc if this method is right for you.

I hope that this is of some help. - Cam
P.S. More on the case of the elderly gentleman; I called the pharmacist back and told him about the mini-withdrawls and he hadn't heard about it, but changed the gentleman over to Effexor XR. The pharmacist called me back within a week and thanked me; he also revealed that he had a few other patients taking the same drug and had the same complaints. He just thought that it was an unfortunate side effect of Effexor in the elderly.