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How to improve treatment effectiveness in your patients with bipolar disorder

Updated: Nov 7, 2020

Finding effective and consistently reliable treatment options for bipolar disorder is one of the biggest challenges that the field of clinical psychiatry is facing today. [1] In recent years, the practice of using traditional antidepressants to treat bipolar disorder has even been called into question because of concern that they may induce manic switches or rapid cycling. Putting this hotly-debated topic aside, the fact remains that bipolar disorder is an area of psychiatry that is in need of additional treatment options. Unaddressed or incompletely addressed bipolar disorder can be extremely debilitating, which is one of the reasons why there is such great need for novel stand-alone and adjunctive treatment options. In this article, I’ll share two adjunctive interventions that may help improve the outcomes of your patients’ bipolar disorder treatment.

Bipolar disorder: a review of the facts concerning this condition

Before we discuss ways to improve treatment outcomes, let’s review the facts surrounding bipolar disorder. Bipolar disorder (formerly referred to as manic-depressive illness or manic depression) is a psychiatric condition that is characterized by extreme shifts in mood. In addition to affecting mood, bipolar disorder can also affect energy and activity levels, a person’s ability to focus, and their ability to complete their activities of daily living.

There are three main types of bipolar disorder—bipolar disorder type 1, bipolar disorder type 2, and cyclothymic disorder (also known as cyclothymia). Bipolar disorder tends to be characterized by manic or hypomanic states and depressed states. Both bipolar disorder 1 and bipolar 2 are characterized by depressive episodes, but bipolar 1 is characterized by mania, while bipolar 2 is characterized by hypomania. Cyclothymic disorder is characterized by depressive and hypomanic symptoms that do not meet the criteria for hypomania or depression. Symptoms of bipolar disorder that do not meet the diagnostic criteria for any of the three main types of bipolar disorder may be classified as “other specified and unspecified bipolar and related disorders.”

Risk factors for bipolar disorder include family history of the condition and some research suggests that brain structure and function may play an important role in bipolar disorder risk.

How to improve treatment efficacy in bipolar disorder

While research is actively being conducted on novel treatment options that may be extremely beneficial in the treatment of bipolar disorder, we have to use the therapies and resources that we currently have available to us. At the present, research regarding psychotherapy and levothyroxine as adjunctive therapies in the treatment of bipolar disorder appears to be promising.

Adjunctive psychotherapy in the treatment of bipolar disorder

A review of 18 trials involving various forms of psychotherapy (individual psychoeducation, group psychoeducation, family psychoeducation, multifamily psychoeducation groups, and cognitive behavioral therapy, etc.) and patients with bipolar disorder demonstrated that adjunctive psychotherapy is associated with improved treatment outcomes in cases of bipolar disorder. [2] The study revealed that the forms of psychotherapy that focused on early recognition of mood symptoms and medication adherence had greater beneficial effects on manic symptoms, whereas psychotherapy that focused on interpersonal and cognitive coping strategies was more beneficial in reducing symptoms of depression.

Another more recent review concluded that because of these beneficial effects, outpatients with bipolar disorder who are being treated with pharmacotherapy should also be offered therapies that emphasize the learning of coping strategies, and especially those delivered in family or group formats. [3]

Adjunctive levothyroxine in the treatment of bipolar disorder

In a small, double-blind, placebo-controlled trial involving 32 treatment-resistant, rapid cycling bipolar disorder patients who had failed a trial of lithium, study participants were divided into three groups. One group was given levothyroxine, another was given triiodothyronine, and the third was given a placebo pill. Patients were followed for 4 months or more, and they received weekly endocrine and clinical assessments. By the end of the study, patients treated adjunctively with levothyroxine experienced improvements in previously treatment-resistant depression, spent less time in mixed states, and spent more time in euthymic states compared to bipolar patients who were treated with triiodothyronine and those who were treated with placebo. [4]


To summarize, the challenge of how to reliably and effectively treat bipolar disorder is an enigma that the field of psychiatry is seeking to solve today. At the present, research suggests that we may be able to enhance treatment response to available medications by using psychotherapy or levothyroxine as adjunctive therapies.

If your patients’ bipolar depression does not respond to conventional therapies, even after adding in these adjunctive therapies, consider ketamine. As a therapy, ketamine infusions have shown promise in quickly reducing symptoms in patients with treatment resistant unipolar and bipolar depression. [5]


1. Young L. T. (2008). What is the best treatment for bipolar depression?. Journal of psychiatry & neuroscience : JPN, 33(6), 487–488.

2. Miklowitz D. J. (2008). Adjunctive psychotherapy for bipolar disorder: state of the evidence. The American journal of psychiatry, 165(11), 1408–1419.

3. Miklowitz, D. J., Efthimiou, O., Furukawa, T. A., Scott, J., McLaren, R., Geddes, J. R., & Cipriani, A. (2020). Adjunctive Psychotherapy for Bipolar Disorder: A Systematic Review and Component Network Meta-analysis. JAMA psychiatry, e202993. Advance online publication.

4. Walshaw, P. D., Gyulai, L., Bauer, M., Bauer, M. S., Calimlim, B., Sugar, C. A., & Whybrow, P. C. (2018). Adjunctive thyroid hormone treatment in rapid cycling bipolar disorder: A double-blind placebo-controlled trial of levothyroxine (L-T4 ) and triiodothyronine (T3 ). Bipolar disorders, 20(7), 594–603.

5. Grady, S. E., Marsh, T. A., Tenhouse, A., & Klein, K. (2018). Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature. The mental health clinician, 7(1), 16–23.


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