In serious bipolar disorder polypharmacy is more the rule than the exception, so do not fear it when it gets someone better, but do not jump to it, and check the diagnosis first. Before adding a drug, ask what would change if it worked, and question standing medications no one has revisited.
When it is warranted
It is rare to find a serious bipolar disorder that needs only one or two medications. Polypharmacy is more the rule than the exception; do not jump to it, but do not be afraid of it in the service of getting somebody better.
“It's rare for me to find a serious bipolar disorder that needs only one or two medications. Polypharmacy seems to be more the rule than the exception. This doesn't mean you should jump to polypharmacy, okay? But you shouldn't necessarily be afraid of it in the service of getting somebody better”
8:38Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 Combinations can make each drug easier to take: many people can get away with a lower daily dose of lithium when they are on 200 of lamotrigine, which is much more tolerable than lithium alone.
“A lot of people can get away with having a lower daily dose of lithium if they're on their 200 of lamotrigine. And then it'll be much more tolerable than trying to do just the lithium, for example”
51:46Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026
Before adding another drug
Make sure the diagnosis is correct. Calling polypharmacy the rule risks giving permission to over-medicate personality disorders, or to stack lithium, Depakote and Lamictal when the diagnosis really needs reassessing.
“I call it throwing spaghetti at the wall. You're just throwing something at the problem to see what sticks, right? And so when you're not principled about diagnosis, you run into that type of problem quite frequently”
34:34Diagnostic Hierarchy Explained: Why Patients Get 5 DiagnosesNov 2026Guest episode Also said in 1 more episode
“make sure you have the diagnosis correct because I do fear by saying polypharmacy is the rule, not the exception, that we're giving permission to over-medicate personality disorders or have someone on lithium and Depakote and Lamictal when someone really needs to reassess the diagnosis”
9:10Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 Ask what would be different if the medication worked and the patient felt better. If they cannot answer that well, there is little utility in futile prescribing.
“you've asked them, what would you do if you felt better? What if this medication worked and everything changed and you felt differently? What would be different about your life? What would you do differently? And if someone can't answer that very well, I don't see the utility in futile prescribing”
41:26Affective Neuroscience: Understanding Patients Beyond DSM DiagnosesAug 2026Guest episode
Pruning
Question standing medications nobody has revisited. A patient on clozapine, where EPS is not expected, was on benztropine with no overt EPS; after coming off it he never noticed a difference, and it likely spared him cognitive problems later.
“With clozapine, you wouldn't expect EPS, so it didn't make a lot of sense for me why he would be on cogettin if he didn't overtly have some weird EPS. He never noticed any difference, and I think I saved him some cognitive problems in the future”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025
Pitfalls and myths
Long diagnosis lists drive it. Many patients now arrive with four, five or six psychiatric diagnoses, which before DSM-III was exceptionally rare, and that usually results in excessive polypharmacy and symptom-based descriptions; inappropriate polypharmacy is rampant in borderline personality disorder.
“so many patients that I see for psychotherapy come to me and they have been diagnosed with four or five or six different psychiatric conditions. Historically, by the way, that was never done. Before DSM-3, That was an exceptionally rare situation”
18:48Diagnostic Hierarchy Explained: Why Patients Get 5 DiagnosesNov 2026Guest episode Also said in 1 more episode
“It usually results in excessive polypharmacy. It results in symptom-based descriptions. And a lot of the patients that I see these days have a personality disorder, especially borderline personality disorder, rampant Inappropriate polypharmacy in that group of patients”
20:17Diagnostic Hierarchy Explained: Why Patients Get 5 DiagnosesNov 2026Guest episode
From these episodes
- Diagnostic Hierarchy Explained: Why Patients Get 5 DiagnosesNov 2026 · 3 points
- Affective Neuroscience: Understanding Patients Beyond DSM DiagnosesAug 2026 · 1 point
- Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 · 3 points
- Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 · 1 point
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.