Bupropion is A tier for us as an add-on for depression that has not responded to one drug, and for low energy and SSRI sexual side effects, but we rarely start with it. It is great for depression with anxious features and risky when anxiety is the main problem, and its easy side-effect profile should never keep a patient from the treatment they actually need.
When we reach for it
We rank it A tier and add it for almost everyone who does not respond to just one medication. It can put a pep in your step.
“Love to throw this on on almost everyone who doesn't respond to just one medication. A-class, certainly A-class as well. Great medication, can give you a pep in your step”
50:03Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 It is one of our early antidepressants, but we push sertraline or escitalopram first and think of bupropion more as an augmenting agent. It is fine to start with for a patient who does not want the SSRI side effects of a little weight gain or sexual problems.
“I typically consider there to be four first line in how I practice. I have pretty much four first line antidepressants that I use. As you said, it's Zoloft and Lexapro. If I'm choosing an SSRI, how I choose between those depends on how I'm feeling that day”
10:17Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 Also said in 2 more episodes
“To me, they're early meds to the Bupro and the mirtazapine. In my mind, I consider them to be augmenting agents”
10:45Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 “for a patient who doesn't want the SSRI side effects of a little bit of weight gain or sexual side effects, then I am fine with bupropion. And then mirtazapine for a patient where sleep is a big issue and patients either underweight or not concerned with their weight. I would say underweight”
11:59Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 We do not use it first line because enough people get jitteriness, insomnia or an appetite drop they do not want. For patients who are not too anxious, sleep fine and eat too much, it becomes a very nice choice.
“But why don't I do it first line? Well... It's just enough people who respond with too much jitteriness, insomnia, or appetite decrease that they don't want. But if you have people who are not too anxious, sleeping fine, and eating too much, you know, then Wellbutrin becomes a very nice choice”
11:29Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 It is a great augmenting choice for low energy and for anorgasmia from SSRIs, and it seems to help anorgasmia even without a mood disorder.
“great augmenting choice for people with energy issues and anorgasmia from the SRIs. You can actually give bupropion for anorgasmia in the absence of a mood disorder. It seems to help”
11:13Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 For SSRI sexual side effects, buspirone and bupropion are the most helpful additions. Otherwise your choices are switching the medication or lowering the dose.
“For sexual side effects, main ones, buspar and bupropion. Those are going to be most helpful. and otherwise switching of the medication or lowering the dose are pretty much your choices”
57:09Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 When there is possible depression, no bipolar disorder, some ADHD features and the patient agrees, we do a trial of bupropion.
“If I think that there is possible depressive and there's no bipolar and there is some ADHD stuff and they agree, I'll do a trial of Wellbutrin”
54:02How to Decide When ADHD Is Actually ADHDNov 2025
Anxiety
It helps anxiety that is part of the depression and is great for depression with anxious features. When anxiety is the predominant problem we tend to avoid it: in our opinion it does not help anxiety on its own and worsens generalized anxiety disorder long term.
“Bupropion, in my opinion, worsens generalized anxiety disorder long term. It helps anxiety if the anxiety is This is a part of the depression. Depression. It doesn't help anxiety on its own, in my opinion”
34:04Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026 Also said in 1 more episode
“I do try to tend to avoid it if anxiety is the predominant problem. If it's depression with anxious features, I think it's great”
38:58Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025 We have seen it many times: patients with OCD, PTSD or anxiety on bupropion get better when you pull it off.
“I've just seen so many times patients with OCD, PTSD, anxiety on bupropion. You pull it off and they get better”
35:46Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026 It helps anxiety for some patients but worsens it for a lot of others. For some depressed patients, sertraline will be a much more effective medication.
“There are patients with depression that I'm telling you that Zoloft will be a much more effective medication for you. As you mentioned, with anxiety. Yes, it does help anxiety for some patients, but it does worsen anxiety for a lot of other patients”
51:50Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 The data do show it works in anxiety disorders if patients get over the hump: at the start it is more activating and anxiety-provoking for anxious people, but if they tolerate it and stay on it, it is effective.
“Wellbutrin is actually effective in anxiety disorders, but you have to get over the hump of the initial part. It's more activating and anxiety-provoking for anxious people at the beginning, but if they can tolerate it and stay on it, the data does show that it's effective in anxiety disorders, and in my experience, it is”
36:48Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025 If an anxious patient is going to trial it, have them take the first dose on a weekend or when they have nothing to do.
“if we are going to trial it, I recommend they try it for the first time on a weekend or something or when they have nothing to do”
53:28Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026
In bipolar disorder
Antidepressants in bipolar disorder are not never-use, but they come after you have tried multiple other things. For the specific subset of patients where there may be a role, bupropion would be the choice.
“it's not a never use them. It's a use them after you've tried multiple other things. And there's a specific subset of patients for whom I think there is a potential role. And when I finally come around to that, it would be bupropion”
48:30Dr. Jim Phelps’ Bipolar Treatment Tier List: Lessons from 30+ Years in PsychiatryJul 2026Guest episode Its reputation in the community as the safer antidepressant in bipolar disorder is kind of a myth; we do not think there are data to demonstrate it.
“What are the antidepressants that I find a little safer? Not Wellbutrin, not Bupropion. That's what kind of is out there in the community. Kind of myth, if you ask me. I don't think we have any data to demonstrate that”
50:12The Best Bipolar Medication Review From The Best Bipolar ExpertJan 2025
Pearls
It is a 2D6 inhibitor, so it can be used to raise the effective dose of aripiprazole, including the long-acting injectable forms.
“2D6 inhibitor, and thus can be used to increase effective dose of your Abilifying antenna and Aristata, which maxes out at a 15 to 20 milligram daily dose”
53:43Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026
Pitfalls and myths
Because it has few side effects, clinicians can keep patients on it and never offer what the correct treatment is.
“sometimes I worry that medications without side effects like lamotrigine and bupropion, people will keep patients on and then not offer what the correct treatment is”
51:09Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026
It also comes up on
- AugmentationFor someone on an adequately dosed SSRI or SNRI, add-on options include bupropion, mirtazapine and buspirone, and then the second-generation antipsychotics, which are very popular in the US but high risk.
- AugmentationAt the bottom of the evidence ladder for difficult depression sit bupropion, mirtazapine and buspirone as add-ons. Taking two antidepressants rarely works better than one, yet it is what we most often do.
- Bipolar disorderAvoid SSRIs, SNRIs and bupropion like the plague unless you cannot get away without them. If someone is already rock-solid stable on an antidepressant, that is fine.
- Treatment-resistant depressionAt the bottom of the evidence ladder sit bupropion, mirtazapine and buspirone augmentation. Taking two antidepressants rarely works better than one, yet that is what we most often do.
- BuspironeFor an adequately dosed SSRI or SNRI that needs an add-on, buspirone sits alongside bupropion and mirtazapine. Second-generation antipsychotics are the popular but high-risk alternative.
From these episodes
- Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 · 1 point
- Dr. Jim Phelps’ Bipolar Treatment Tier List: Lessons from 30+ Years in PsychiatryJul 2026 · 1 point
- Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026 · 2 points
- Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 · 4 points
- How to Decide When ADHD Is Actually ADHDNov 2025 · 1 point
- Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025 · 2 points
- The Best Bipolar Medication Review From The Best Bipolar ExpertJan 2025 · 1 point
- Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 · 6 points
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.