Should Antidepressants Be Used to Treat Bipolar Disorder?

January 6, 2011 Natasha Tracy

While many people with bipolar disorder have and continue to be treated with antidepressants along with many other medications, there is a controversy in the medical community as to whether this is an appropriate approach. In bipolar disorder there is some risk of antidepressants inducing mania or perhaps worsening rapid-cycling.

But is this true? What evidence is there that antidepressants work in bipolar disorder? What evidence is there that they will make bipolar disorder worse? What do you do if you can’t take an antidepressant?

Antidepressants Cause a Switch to Mania in Bipolar Disorder

This concern came to light in the 1960’s when Tricyclic antidepressants (TCAs) were used to treat depression in bipolar disorder (bipolar I). This concern continues today and now includes concerns with bipolar II. Therefore, some doctors are very reluctant to prescribe antidepressants in cases of bipolar.


However, it is extremely difficult to ascertain (in a statistical sense) whether a switch into mania or hypomania is related to an antidepressant or simply a natural factor of the disease. It should be noted that it is thought in cases of true antidepressant-induced polarity switches, symptoms may continue even if the antidepressant is stopped.

Switching into mania or hypomania, or increasing rapid cycling is a dangerous effect that can result in worsening, or more, depressions. Recent literature suggests that about 10% - 25% of the reemergence of mania or hypomania symptoms can be attributed to antidepressant use. (Note: which antidepressant is used effects the likelihood dramatically.)

Antidepressants Don’t Work for Bipolar Depression

People fall on both sides of this argument but one thing we know for sure is that enough studies haven’t been done to draw an absolute conclusion either way. Not enough studies have been done comparing antidepressant use in bipolar vs. unipolar depression. Moreover, when you take into account bipolar II, things become even murkier.

Antidepressants with positive study data for bipolar depression include paroxetine, bupropion, and imipramine. Data on efficacy of an antidepressant combined with a mood stabilizer includes venlafaxine, sertraline, and bupropion. This evidence is not perfect though as it doesn’t account for confounding factors in a heterogeneous population. (The studies don't take into account all variables.)

Antidepressant and Bipolar Disorder Takeaways

Understanding there is controversy and limited data, here is what we know right now:

  • Bipolar I has relatively high rates of switching when they are treated with a TCA or monoamine oxidase inhibitor (MAOI) alone
  • In bipolar II, superior outcomes have been found when treated with venalfaxine over lithium alone, with no additional mood destabilization
  • Antidepressants with positive study data and low risk of destabilization include: bupropion, sertraline, fluoxetine, tranylcypromine or venlafaxine in bipolar II depression
  • If mania or hypomania appears, discontinuing the antidepressant is preferable over adding additional mood-stabilization agents

In general, antidepressants are more appropriate for:

  • Bipolar II
  • Depressed (non-mixed) states
  • Absence of rapid-cycling
  • Absence of recent mania or hypomania episodes
  • Absence of substance abuse issues
  • Previous favorable antidepressant response, without mood destabilization

If You Don’t Respond to Antidepressants or Switch Polarity


There is some evidence to suggest that the following are worth considering:

  • Pramipexole
  • Modafinil
  • Riluzole
  • n-acetyl cysteine
  • adjunctive thyroid hormone
  • Light therapy (if a seasonal component is evident)
  • electroconvulsive therapy

The Lesson

The lesson, I think, is this: if you’re bipolar and only being treated with antidepressants you might not be doing yourself any favors. (This problem is often seen in cases where the bipolar isn't detected.) On the other hand, if you’re bipolar and depressed and you haven't tried an antidepressant, your doctor might be overestimating the danger.

(And keep in mind, just because your treatment isn’t listed here, that doesn’t mean anything is wrong; your doctor is just using his/her best clinical judgment and everyone is differentyou are not a statistic. In all honesty, this information is just a starting point. Also remember that older drugs have more data just because, well, they’re older. Oh, and in case you forgot, I’m not a doctor; go see one if you have questions.)


The information in this article mostly comes from the journal Current Psychiatry online, article: Antidepressants in bipolar disorder: 7 myths and realities; Vol. 9, No. 5 / May 2010; but unfortunately you can’t get to the article without a subscription. You can see though for lots of information on this topic.

Drug Brand Names

Bupropion • Wellbutrin
Fluoxetine • Prozac
Imipramine • Tofranil
Lithium • Lithobid, Eskalith
Modafinil • Provigil
Paroxetine • Paxil
Pramipexole • Mirapex
Riluzole • Rilutek
Sertraline • Zoloft
Tranylcypromine • Parnate
Venlafaxine • Effexor

You can find Natasha Tracy on Facebook or @Natasha_Tracy on Twitter.

APA Reference
Tracy, N. (2011, January 6). Should Antidepressants Be Used to Treat Bipolar Disorder?, HealthyPlace. Retrieved on 2024, April 17 from

Author: Natasha Tracy

Natasha Tracy is a renowned speaker, award-winning advocate, and author of Lost Marbles: Insights into My Life with Depression & Bipolar. She's also the host of the podcast Snap Out of It! The Mental Illness in the Workplace Podcast.

Find Natasha Tracy on her blog, Bipolar BurbleTwitter, InstagramFacebook, and YouTube.

August, 6 2014 at 2:07 am

SSRI's made me suicidal. I have bipolar 1.

July, 18 2012 at 2:12 am

My brother 65 year old brother had open heart surgery about 10 years ago. Before his surgery he had crippling anxiety and depression and his Dr. put him on Celexa. His behaviour became very bizarre and he had to be cared for 24/7 for months until after his surgery. Eventually the Celexa was withdrawn and he returned to normal.
We saw him in January of this year and he seemed fine. February we started getting phone calls. He was frequently in ER with extreme anxiety, gut pain and depression. He was having trouble sleeping and had significant weight loss. He was put on Remeron. Almost immediately his behaviour changed.
He only needs a few hours sleep. He talks incessantly, telling the same stories over and over usually acting out parts of them in what appears to be a compulsive manner. He becomes agitated if anyone interrupts him. His driving has become aggressive and erratic. He sends bizarre emails out to people in the middle of the night. He finds his own thinking on the drug "brilliant". We went out to visit him because we were so concerned and couldn't stay with him. It was just too hard to be around him.
I have faxed his Dr. with my concern but have heard nothing back. I'm afraid my brother likes feeling this was and will not get off the drug.
He has never been diagnosed with Bipolar Disorder.
Any comments would be appreciated.

Natasha Tracy
April, 13 2011 at 4:49 pm

I'm not really sure the order of events as you've described them. I can't tell what your symptoms were, what was prescribed and when.
If you were on muscle relaxants, then they should have checked drug interactions before any new meds were added. Did a GP give you a prescription? The same doctor that gave you your muscle relaxants? You'd have to ask a doctor about interactions, but that should be an easy answer as they can plug it into a computer.
If you're taking lamictal now and it's working for you then it sounds like you may have a bipolar disorder of some type, but I certainly couldn't say for sure.
It's pretty much impossible to know whether a person will have a manic episode from an antidepressant. The best guess, of course, is assessing them for a bipolar disorder. GPs don't always know how to properly do this, however.
I'm sorry the ride has been so rough but hopefully you are feeling some peace now.
- Natasha

April, 13 2011 at 4:10 pm

I had a manic reaction the second day I took a half dose of Citalopram. After that I was diagnosed Bipolar 2. I couldn't get any of the docs to look at the two muscle relaxants that I had been prescribed just before "my epiphany" happened. I looked into both of them and they both had mood disorders as side effects. One was a known Seratonin mutiplier. I was trying to pull the medical term out but I'm not a doctor and I'm too lazy to look it up right now. The one muscle relaxant also affected another brain chemical. Why wouldn't any of the docs and specialist read the material I provided for them and look at that? To me it was very clear. The episode I had happened immediately after taking those two drugs for a couple of weeks.
Anyway the next day, after my delusional and panic attack episode that landed me in the ER my wife took me in to see my "new doc" I had never seen this guy before in my life and I was in a very distraught mood. He immediately decided I was depressed and prescribed Citalopram. Within two days I went into a pretty severe manic state. Now I take Lamictal. I was on Depakote too but my Psychiatric Nurse took me off of that. The whole incident cost me my marriage. My wife supported me through the ER visits but I guess our marriage wasn't strong enough to handle it. We had other problems and it gave her a great excuse to run. Anyway just wondering what you'd think of this whole situation. Thanks in advance. Scott

Dr Musli Ferati
January, 16 2011 at 6:12 am

Prescription of antidepressant in bipolar disorder presents a challenge psychiatric treatment of this morbid entity. The fundamental rule is that antidepressants aren't the first line medication in bipolar disorder, because in whichever form of the same deviation of mood there are manic episodes that are sensitive on antidepressant therapy. According to my opinion the psychostabilizators are the primary medication in bipolar mood digression. Whereas the antidepressant therapy is reserved for specific case, in which ones depressive features dominate this psychiatric disorder. Clinical experiences are contradictory and the best guide to recommend the antidepressant is the patient compliance and adherence to the same medication.

January, 15 2011 at 5:12 am

Antidepressants actually made me psychotic for about a month, so I'm a believer that they shouldn't be combined with bi-polar. I took Wellbutrin for my ADHD, stopped it, not abruptly, and added Paxil. I was already on Ascendin. Way too many, huh. Anyway, I didn't even know I was hypo-manic until that point, when I experienced mania for the first time. I had always had more depressive symptoms. Now I'm on lithium for about 3 years now, and the depression is pretty much gone.
Thanks. Caroline

Natasha Tracy
January, 13 2011 at 10:29 am

Hi Leah,
Yes, I absolutely know it can be done. I've done it many times. Obviously, some of the worry is about people with bipolar who are not also on a mood stabilizer and some antidepressants are more likely to cause a switch than others. Like anything, it's about clinical judgment.
(FYI Dr. Jim Phelps, the doctor who wrote makes the argument that antidepressants worsen bipolar in general and not necessarily just because of switching polarity. But that is just one Dr's opinion.)
- Natasha

Leah Thronson MD
January, 13 2011 at 6:08 am

I have used anti-depressants in conjunction with mood stabilizers for my bipolar patients for over 25 years and have never tipped a patient into mania. i have several colleagues who do the same. Of course, it is done slowly and carefully and my patients are carefully monitored and instructed.

Natasha Tracy
January, 6 2011 at 3:29 pm

Hi Linda,
Great, I'm glad you found it useful.
I actually find this online journal _very_ useful as it's intended for treating physicians, so I can read about the most up-to-date ideas in treatment. But, it is a bit complicated for the average reader so a summary here I thought would be helpful.
And really, I find this point something to keep in mind for treatment in general. We bipolars are a picky bunch. There's lots to watch for. Hopefully you're right and it's a springboard for some conversations with doctors.
- Natasha

January, 6 2011 at 2:21 pm

This is an incredibly useful article -- thank you!
I'm BP II and recently had a depressive episode that didn't respond to anything except a last ditch attempt to throw an SSRI at it (Lexapro). I was still on my normal Lithium/Lamictal regime.
Adding the Lexapro did work, but there was a narrow window to get me back off of it again. Just as I had gotten over the depression I slid directly into hypomania. Tricky, tricky. It all ended well, but wasn't as easy as just adding a pill, as you point out.
I wish I had had this article to mull over at the time, and it would have been a helpful tool--discussion springboard--to take to my P-doc.

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