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How to Handle Treatment-Resistant Bipolar Disorder

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A womanAs I discussed last time, treatment-resistant bipolar disorder is often the exception and not the rule. But once standard treatments have been tried, what is left for those who have been designated treatment-resistant?

Standard Treatment of Bipolar Mania

The most used standard first step in treating bipolar mania or a mixed episode is to discontinue antidepressants, if present. This is critical and some doctors feel antidepressants should not be used in the treatment of bipolar disorder at all.

Once that is done, evidence shows that several treatments (lithium, anticonvulsants, and antipsychotics) are useful in treating mania while antipsychotics have been shown useful in treating acute mixed episodes.

(Information on treating mixed moods here.)

Treating Treatment-Resistant Bipolar Mania

If those standard treatments fail, the most common nonstandard treatments recommended for treatment-resistant mania include clozapine and electroconvulsive therapy (ECT). A combination of both is also possible. Other possible nonstandard treatments include:

  • higher doses of an atypical antipsychotic like ziprasidone or aripiprazole
  • lithium combined with divalproex
  • a combination of anticonvulsants like carbamazepine and divalproex
  • other combinations

Some treatments involve the addition of another drug to standard treatment. These drugs, used for treatment augmentation, include:

  • Donepezil (a centrally acting reversible acetylcholinesterase inhibitor, typically used in Alzheimer’s treatment)
  • Gabapentin
  • Topiramate
  • Mexiletine (an anti-arrhythmic agent, typically used to treat heart arrhythmias)
  • Intravenous magnesium sulphate
  • Tamoxifen

Standard Treatment of Bipolar Depression

There are fewer standard treatments when treating bipolar depression. Only two treatments have been approved by the U.S. Food and Drug Administration (FDA) for bipolar depression treatment and they are:

  • Quetiapine (an antipsychotic)
  • A combination of olanzapine and fluoxetine (sold under the trade name Symbax)

Lamotrigine and lithium are also suggested as frontline treatments and vagus nerve stimulation (VNS, augmentation) may also help. Various psychotherapies, like cognitive-behavioral therapy, have also been shown to help in cases of bipolar depression.

Treating Treatment-Resistant Bipolar Depression

Antidepressants are commonly used to treat bipolar depression in combination with antimanic treatments (like lithium) but this is controversial as research has not shown efficacy and antidepressants may cause switching from depression into a manic, hypomanic, or mixed state, which may be very difficult to treat. Some antidepressants, like tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors, may induce switching more than standard selective serotonin reuptake inhibitors (SSRIs).

Common nonstandard treatments include any combination of lamotrigine, lithium, and quetiapine.

Other nonstandard treatments include using the augmentation agents:

  • Pramipexole (a dopamine agonist)
  • Modafinil (a wakefulness promoting agent)
  • Donepezil
  • Bupropion
  • Riluzole
  • Gabapentin
  • Levetiracetam
  • Aripiprazole

Magnetic seizure therapy and repetitive transcranial magnetic stimulation may also be effective.

Treating Treatment-Resistant Bipolar Maintenance

Most often the maintenance phase of bipolar disorder simply continues the acute treatments forward but this many not always be the best approach. Complex treatments can often be simplified during this time and it should be noted that the patient should be protected against whatever mood state is more likely to reoccur. For example, lamotrigine protects more against depression while lithium protects more against mania. Lithium is the only drug that has been shown to have anti-suicidal effects. Psychotherapies have also been shown to improve bipolar maintenance.

Again, use of antidepressants is controversial during maintenance, but their withdrawal can be tricky as it can lead to depression relapse in some patients.

It’s also critical during maintenance that any comorbidities such as addiction issues or eating disorders also be addressed in order to maintain treatment effectiveness.

Nonstandard treatments for those who experience treatment-resistant bipolar maintenance include:

  • Clozapine
  • Levetiracetam
  • Maintenance ECT
  • Augmentation with hypermetabolic thyroid supplementation, diltiazem, aripiprazole, topiramate, gabapentin, mexiletine, levetiracetam, chromium, or VNS
  • Topiramate and clozapine combination

Things to Remember About Nonstandard Treatments

As I said last time, treatment-resistant is not the same thing as treatment-impossible, so it’s important that patients not give up hope as there are so many options available. It is important to remember that many of these options come from very limited trial data and clinical experience, so their success rate may be low when compared with standard treatments.

Also, it’s important to treat any mood episode until no symptoms persist as that is the best way to protect against future episodes, so simply accepting partial recovery is often not good enough. Patients should demand better because it’s what they deserve and it’s what is best for their health.

For more information on these treatments as well as evidence base, please see Treatment-Resistant Bipolar Disorder in Psychiatric Times.

Feeling creative? Share your experience with bipolar disorder by participating in Healthline’s Creative Side of Bipolar Competition. Deadline for entries is Jan. 15. 

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About the Author

Natasha Tracy is an award-winning writer who specializes in writing about bipolar disorder.

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