Treatment-resistant bipolar disorder (TRBD) refers to bipolar disorder symptoms that have not significantly improved after trying standard treatments for the condition.
However, it is important to note that this does not mean no treatment will ever work. There are many medications and therapies for bipolar disorder, and sometimes, it takes time to find the right combination.
Read on to learn more about the definition of TRBD, how common it is, what causes it, and what helps.
TRBD describes cases of bipolar disorder that do not significantly improve after a person tries standard treatments.
“Standard treatments” refers to the first-line medications doctors typically prescribe for bipolar disorder, such as:
Doctors may also refer to TRBD as non-remission or non-response.
The point at which doctors consider bipolar disorder to be treatment-resistant can vary, as there is no official clinical definition.
A 2019 paper defines it as a lack of “sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses”.
This means a person with TRBD has usually tried at least two medications, or one medication and a combination of medications, without seeing a consistent improvement in their symptoms.
Remission in bipolar disorder
In bipolar disorder, “remission” means a person has had no symptoms of depression or mania for a certain period of time.
If a drug is not effective for bipolar disorder, a person will continue having some or all of their original symptoms. Depending on the type of bipolar disorder, they may experience mania, depression, or both.
Mania may cause:
- a feeling of elation
- irritability or agitation
- racing thoughts
- flight of ideas, which involves talking fast about many different things
- feeling unusually confident, powerful, or energetic
- difficulty sleeping
- increased appetite
- increased desire to engage in risky activities without thinking about the consequences
Depression may cause:
- feelings of sadness, hopelessness, or emptiness
- loss of interest in pleasurable activities
- sleeping too much or too little
- talking slowly
- difficulty remembering or concentrating
- suicidal thoughts
For some, the symptoms may remain exactly the same. For others, there may be a small or partial improvement, but not enough to reach remission.
For example, a person may experience fewer manic episodes but still experience depression, or find their symptoms go away for a while but come back again.
According to a 2021 review, past research has estimated that TRBD affects around 25% of people with bipolar disorder.
However, because there is no exact definition of the term, different studies have had differing results. This means scientists are not sure of TRBD’s prevalence.
Doctors are not always sure why TRBD occurs. Factors that may play a role in some people include:
Coexisting conditions
Coexisting mental or physical health conditions are common in people with bipolar disorder, particularly:
Doctors should assess people with TRBD for other conditions, as having more than one can affect treatment, including the effectiveness of certain medications.
Symptom presentation
The type and severity of a person’s bipolar disorder can influence the response to treatment.
For example, a 2019 review mentions previous research in which adding gabapentin or pregabalin to treatment plans helped with treatment-resistant mania, but among those with rapid cycling, the same drugs were less effective.
Differences in neurobiology
A 2021 review notes that differences in neurobiology could explain TRBD. This includes brain chemistry, brain activity, and genetics.
For example, in a
More research on this is necessary, but it may offer a way for doctors to tailor treatments.
Disruption in treatment
Although medication is usually effective for bipolar disorder, many people with the condition do not take their medications consistently. This can happen for a variety of reasons.
In a study in Finland of over 33,000 people, 59.1% of participants had at least one prescription for a mood stabilizer or antipsychotic that they had not collected.
If there are interruptions in treatment, it may appear as though the medication is not working.
Misdiagnosis
The symptoms of bipolar disorder can be similar to those of other conditions, such as:
- depression, which can occur in episodes similarly to bipolar II
- attention deficit hyperactivity disorder, which can cause excessive energy and emotional dysregulation
- post-traumatic stress disorder, which can cause mood changes, difficulty sleeping, and agitation or hypervigilance
As a result, people with bipolar disorder
A 2021 paper notes that there is evidence that bipolar disorder is overdiagnosed among vulnerable people with a history of traumatic experiences or from a low-income background.
People in these communities may have less access to trauma-informed healthcare, leading to incorrect diagnoses.
However, it is important to note that non-responsiveness to bipolar disorder medications does not necessarily mean a person has the wrong diagnosis. People with concerns about their diagnosis should speak with a mental health professional.
There are several treatment options people can consider when first-line drugs for bipolar disorder do not help. They include:
Nonstandard medications
Nonstandard medications are newer drugs that have less scientific evidence supporting their use for bipolar disorder than standard options, such as lithium.
A 2019 review states there is evidence that some may help with TRBD, on their own or in combination with other drugs.
Another emerging potential treatment for bipolar disorder is ketamine. However, there is currently stronger evidence supporting ketamine as a treatment for depression, rather than bipolar disorder. More research is necessary.
Psychotherapy
While people with bipolar disorder often need medications, adding psychotherapy, or talk therapy, can also be beneficial.
A 2019 review notes that cognitive behavioral therapy (CBT) may be useful during depressive episodes or for people with insomnia.
However, previous research also suggests that in people with treatment resistance, psychotherapy may become more effective over time. Overall, there is less research on psychotherapy for TRBD than for medications.
Nondrug treatments and procedures
Other therapies doctors may suggest for TRBD include:
People should discuss any treatment for bipolar disorder, including non-drug treatments, with a doctor before trying them.
TRBD is one of the obstacles that can come up during bipolar disorder treatment. Others include:
- Recurrence: Recurrence in bipolar disorder means that the symptoms entered remission for a significant amount of time, but then came back later on. This is common and not necessarily a sign of treatment resistance, though it may mean a person requires changes to their treatment plan.
- Side effects: The drugs for bipolar disorder can cause side effects. Sometimes, the side effects may resemble a person’s existing symptoms, or may be too severe to keep taking it. A doctor may suggest switching to another, but this is also distinct from treatment resistance.
- Multi-therapy resistant bipolar disorder (MTRBD): TRBD refers to people who have not responded to bipolar disorder medications, but MTRBD means a person has also tried other therapies, such as psychotherapy or ECT, without improvement.
If a person has concerns that their bipolar disorder medication is not working, or they feel their symptoms are getting worse, they should contact their doctor or psychiatrist as soon as possible.
The sooner a person can get support, the better for their well-being. A mental health professional may be able to provide reassurance on how long the medications may take to work and can discuss the next steps.
Do not stop or alter the dose of medications prescribed for bipolar disorder without speaking with a doctor first.
Help is out there
If you or someone you know is in crisis and considering suicide or self-harm, please seek support:
- Call or text the 988 Lifeline at 988 or chat at 988lifeline.org. Caring counselors are available to listen and provide free and confidential support 24/7.
- Text HOME to the Crisis Text Line at 741741 to connect with a volunteer crisis counselor for free and confidential support 24/7.
- Not in the United States? Find a helpline in your country with Befrienders Worldwide.
- Call 911 or your local emergency services number if you feel safe to do so.
If you’re calling on behalf of someone else, stay with them until help arrives. You may remove weapons or substances that can cause harm if you can do so safely.
If you’re not in the same household, stay on the phone with them until help arrives.
Treatment-resistant bipolar disorder (TRBD) occurs when two or more first-line drugs for the condition do not significantly help a person’s symptoms, even when they take the drugs for a sufficient time and at a sufficient dosage.
Most people with bipolar disorder do not appear to experience TRBD, but it can happen. If it does, there are other treatment options people can try, including nonstandard drugs, psychotherapy, and other interventions.
TRBD does not mean treatment will stop working entirely. People who are worried their treatment is not working, notice early signs of an episode, or feel hopeless about the future should speak with their doctor.
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