Psychopharmacology Made Simple: What’s it like when Wellbutrin works?

Wellbutrin (bupropion) works quite differently from SSRIs such as Lexapro (escitalopram), the subject of a previous blog post.

How does it work? Per UpToDate[1], “like other antidepressants the mechanism of bupropion’s activity is not fully understood”. [2]


Clinically, it’s useful to think of it as a selective norepinephrine reuptake inhibitor, or SNRI. It helps depressed mood, low energy level, hypersomnia (sleeping too much), and anhedonia. [3] It’s quite different from the SSRIs, which help anxiety, rumination, and irritability.

Here is one patient’s experience with it. He reported chronic depression for many years that worsened in the last 12 months since he became clean and sober, and got even worse when he quit his lifelong smoking habit, which  increased his irritability. “I want to sleep all day. I have no passion to do anything I used to love doing. I’m not interested or excited by anything.” He had been attending AA meetings daily, then decreased for the last couple of months to 1 or 2 meetings/week. He had no sponsor. He hadn’t progressed beyond the third step because “I feel worn out when I think about picking up a book”.

He started Wellbutrin XL 150 mg/day for one week, and then increased to 300 mg/day, but after 3 days on the higher dosage, he called me to report he was “waking up at 4 AM, ready to go, with a lot of energy. I started to get racy, I felt like I couldn’t breathe, I had  little shocks, “air hiccups”, like I was out of breath. Last night I felt a lot of anxiety, panicky, my heart was heart racing.”


Dosing of Wellbutrin has to be individualized. Some people need 300 mg, some can’t tolerate it and do better on 150 mg. I told him to stop it for a day or two until his symptoms resolved, and then to restart on 150 mg/day.


I saw him one month after he reported the side effects.  “The Wellbutrin is doing good; I feel pretty normal, not elated. Before, I couldn’t get out of bed, I had very low energy, I wanted to sleep 18 hours/day, be horizontal, I felt worn out all the time”. Now, he reported he was going to more meetings, 2-3/day, and working his program.


For depression, one of the  most common conditions seen in outpatient practice, either the SSRIs or the SNRI bupropion are probably the most common first medications tried. [4]



[1] UpToDate is an evidence based, peer reviewed medical information resource.

[2] Wikipedia notes that it is characterized as a weak norepinephrine-dopamine reuptake inhibitor (NDRI). Bupropion is converted into several active metabolites that “are present in much higher concentrations in the body compared to bupropion itself. The most important example is the major metabolite of bupropion, hydroxybupropion, a selective norepinephrine reuptake inhibitor (and likely releasing agent) and nicotinic acetylcholine receptor (nAChR) antagonist … which, with oral bupropion treatment, can reach area under the curve (AUC) plasma concentrations that are as much as 16–20 times greater than those of bupropion itself.”

[3] Anhedonia, or the inability to experience pleasure, is one of the cardinal symptoms of depression. I ask, “Is there stuff you enjoyed doing before (exercising, being with friends, reading, watching movies) that you don’t do now?”

[4] Somewhat analogous to e4 and d4, probably the two most common  first moves in chess, and, like chess, there are infinite variations after these simple beginnings.

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