Treatment resistant bipolar disorder

///Treatment resistant bipolar disorder

What is treatment resistant bipolar disorder?

There is no single, official or clinical definition for this term.

Basically it means refractory, intractable, difficult or unmanageable in the sense that the patient is not responsive to the standard, and usually
successful, treatments.

Some studies have shown increasing treatment resistance with number of episodes.

This is consistent with the kindling theory of bipolar disorder whereby episodes become more serious and more frequent without effective treatment.1

A typical threshold will be the failure to respond to 2, 3 or 4 of the most recognized and proven bipolar medications (mood stabilizers).

Treatment resistant bipolar disorder is an urgent problem. Why?

Three seems to be emerging as the most common measure but there is a lot of variance.

For example, someone who tries lithium, Depakote, Lamictal and Zyprexa with no relief could be fairly classified as treatment resistant.

The best overview I have found is from Molecular Psychiatry on Treatment Resistance in Bipolar Disorder.

There are many factors that make the issue more complicated.

The three main sources of confusion are:

1. What stage of the illness the patient is at. It is now well established that some medications work best for treating mania but different medications are better for treating bipolar depression, and still others are best suited for ongoing maintenance.


It is NOT unusual to try a few meds before finding your best bipolar treatment.

2. The difference between treatment resistance and treatment intolerance. What does mean? The issue is, is it fair to categorize someone as treatment resistant if they abandon their medication not because of ineffectiveness but because of disliking the side effects?

3. What role does misdiagnosis pay? If I don’t respond to my bipolar medication, perhaps it is because I am sick with something else. Instead of asking “Why doesn’t this work?”, ask “Am I bipolar?”

Different treatments for mania, depression and maintenance


What looks like treatment resistant bipolar disorder can arise when we try to treat the wrong phase of the illness.

For example, for severe bipolar depression, lithium or Lamictal plus an antidepressant should be considered. Alternatives are quetiapine (Seroquel) or a olanzapine/fluoxetine combination (i.e Symbyax).

However, in acute mania when traditional mood stabilizers are inadequate, an atypical antipsychotic with strong anti-manic properties such as risperidone (Risperdal), aripiprazole (Abilify), or ziprasidone (Geodon).

For maintenance where lithium or Depakote are ineffective, olanzapine (brand name Zyprexa) can be tried.

Alternatives in treatment resistant bipolar

What do psychiatrists usually try in the face of treatment resistant bipolar disorder? The main “fall-back” positions are:2

1. Combining traditional mood stabilizers such as lithium and Depakote with the newer atypical anti-psychotics.


2. Trialling alternative drugs such as clozapine – the first of the atypical anti-psychotics developed in 1971 to treat schizophrenia and widely regarded as a medication of “last resort”.

3. Electroconvulsive therapy (ECT).

4. Calcium channel blockers.

5. High-dose thyroid augmentation.

It is also worth reading about emerging treatment alternatives, such as Mexiletine in treatment-resistant bipolar disorder.

(Mexiletine is used to treat certain types of abnormal heart rhythms. It works by blocking certain electrical signals in the heart to stabilize the heart rhythm and by blocking sodium channels.)

Improve compliance to improve results

There are many reasons why people are not medication compliant, even when the medications are actually very effective and it would be an excellent idea to take them.

However, it is not unusual for people with poor medication compliance to claim that “nothing works” and present themselves as having treatment resistant bipolar disorder.

It is very important not to confuse non-compliance with treatment resistance in bipolar disorder.


Research findings differ, but a UCLA study found that from a patient’s perspective, they did not take their bipolar medications because:

1. They disliked the idea of medication controlling their moods.

2. They missed their highs.

3. They felt depressed.

4. They disliked the idea of having a chronic illness, symbolized by the necessity for drug therapy.

In Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression, 2nd Edition, Doctors Goodwin and Jamison suggest the following to improve bipolar medication adherence:

1. Minimize dosage to the lowest possible effective dose.


2. Aggressively treat side effects.

3. Track compliance.

4. Examine concerns about long-term medication.

5. Educate patient and families about the role of medication and the dangers of “kindling”.

6. Encourage psychotherapy as well as medication.

Misdiagnosis – Am I bipolar?

Seemingly treatment resistant bipolar disorder may in fact be misdiagnosed “some other disorder”.

Researchers at Rhode Island discovered that many patients diagnosed as bipolar actually had borderline personality disorder instead. In fact, it appears to be becoming one of the most common misdiagnosis traps.

How to tell? Bipolar disorder is episodic, whereas borderline personality is a more pervasive and constant state.

Often “treatment resistant” really means “misdiagnosed”!

After beginning treatment, Am I Bipolar? will answer itself in that if mood stabilizers make you “better”, (remove bipolar symptoms) then it is probably the underlying condition.

However, consider that if the traditional bipolar disorder treatment of mood stabilizers does not help, that there may be an alternative underlying condition.



2019-04-06T19:26:51+00:00November 15th, 2015|Categories: Treatments|7 Comments


  1. Alan May 23, 2017 at 9:21 pm - Reply

    What is this article talking about. It’s all about from a Doctors perspetive, not the patients. One’s not treatment resistant because they hate the meds. They all sucked for me. Made me worse. Every mood stabilizer made me sicker than my illness, These drugs are horrible for me and so many patients. It doesn’t matter what doctors say, it’s the patients that matter and how they feel. Hum. a study from UCLA. Again, from a doctors point of view. not the patients. How about if the doctors took the medications?. Lets see how they like all the awful side effects of feeling , sedated all day or wired that can’t sleep, crazy hunger, zombie like, fat, no sex drive, forgetful, dizzy all day long. This article says, Usually succesfull treatments! That’s a flat out lie. The facts are only about a third of patients respond to meds. People come off their meds or change them all the time. Why is that? It’s because they suck. . The article says this: However, it is not unusual for people with poor medication compliance to claim that “nothing works” and present themselves as having treatment resistant bipolar disorder. Duh, they can’t comply because the drugs are HORRIBLE, which means , it Doesn’t work. Who the hell can put up with the way they make one feel. What good is a drug if one can’t stay on it because they feel terrible. Have they come out with any new meds in the last decade besides Latuda? NO, nothing new. It’s the same drugs for the past 20 years. Same mood stabilizers. Nothing has progressed with newer more tolerable medications. Psychiatry is not a science. Dr’s have no idea which med will work and which ones don’t , everyone is different and they have no idea why. Dr’s all say TRY IT. Like its a piece of candy. Its messing with one’s brain. If one has an infection they take an antibiotic. With Bipolar you can go to 4 different doctors for an initial visit and each one will put you one something different from the other. I have seen over 20 different psychiatrists over the past 36 years. Each one has their favorite drug. Its trial and error. Expect when your suffering , who has the time for this you want to get better fast. They say stay on the meds for at least 6-8 weeks to see if it works. Your odds of a medication working are slim. Now you’ve wasted and suffered all that time to try another again for 6-8 weeks. It’s pathetic. We need meds that work faster and are more tolerable. I speak from 36 years of trying medications. I have a sibling who it took 12 years until she found Seroquel that worked. She was on every mood stibalizer and stayed on them for weeks on end suffering and waiting for them to work. It’s pathetic. This is the truth.

    • Beth August 7, 2017 at 8:32 am - Reply

      You are absolutely right. I was blown away by all the guessing. It is like physical illness 50 years ago. This is the best the psychiatric community has to offer? We need much more research and development to provide better treatment. If cancer was treated like this everyone would be outraged.

  2. Sabrina Giglio August 26, 2017 at 3:41 am - Reply

    Nothing is helping me. After eight different medications I am sick of it. I felt better without taking medication. I. 100%✓ Sicilian this is probably a genetic disposition. I can’t sleep it’s 3 am right now I’m.habing bad bad headaches from geodon. I’m done with this. If I lived 42 years of my life without meds maybe I can live out the rest of my days at least being alert. Screw this

  3. Colt October 5, 2017 at 11:11 pm - Reply

    Alan is absolutely right!!! If i still had all the different bottles of all the crummy meds they told me to take i could open my own pharmacy! And he is so very right about the whole “take it for 6-8 weeks for full effect” bit. You suffer that whole time only to find out it’s not working and you have to start from square one. This is absolutely written from the physician’s point of view and no consideration has been given to the patient. Absolutely disgusted with this article as a whole.

  4. Tony November 2, 2017 at 3:38 pm - Reply

    ALAN! i hear you 100%. I have been on the medication roller coaster for years and have not found a mood stabilizer that hasn’t made me wish i had never even tried them.

  5. Marianne Wilson-Redman November 11, 2017 at 8:22 am - Reply

    I hear you. Medication is not a magic bullet cure because their isn’t one. I take Seroquel and an antidepressant and it keeps my head above water preventing me from committing suicide, thats it. Im bipolar, have severe, relentless anxiety and boderline personality disorder. I have chronic fits of anger, agitation and resentment several times a day. I think the BPD is more responsible for that than the BP issue. But yes, I agree with you that doctors have not taken the meds that we have amd therefore, dont know what the side effects are like. Many cannot take medication becaus the side effects are so ungodly intolerable. No argument there. Medication doesn’t work that well in general. I give the overall effectiveness of my medication a C- to a D. When people say medication say meds don’t work, I wonder if they have been misdiagnosed and have BPD instead…

  6. Marissa Katrin Maldonado November 11, 2017 at 7:59 pm - Reply

    This article hits on some really good points and also outlines some really good alternatives to medications. I wanted to add another potential option for anyone who has found that their medications are not working out very well for their depression. Transcranial Magnetic Stimulation also known as TMS Depression Therapy has become available since 2008 to help those with medication resistant depression. TMS is an outpatient treatment and works by sending magnetic pulses to the part of the brain where the chemicals are sluggish and causing depression. TMS activates these chemicals and helps alleviate the depressive symptoms. It is an option worth checking out and also much less invasive than ETC. Source:

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