Improving Health-Related Quality of Life in Patients With Bipolar Depression

Wendy Marsh, MD
University of Massachusetts Memorial Medical Center, Worcester, Massachusetts

Key Takeaways

  • Until recently, clinical trials did not adequately assess quality of life when evaluating treatments for bipolar depression.
  • Individuals with bipolar depression generally present with symptoms that are more severe, more frequent, and of longer duration than the symptoms experienced by individuals with unipolar depression.
  • Although numerous classes of drug therapies are effective for the treatment of unipolar depression, most of these are ineffective for bipolar depression.
  • Three new antipsychotic drug therapies have been approved specifically for the treatment of bipolar depression.

Frequent episodes of depression in individuals with bipolar disorder are linked to negative effects on quality of life. Research suggests that episodes of depression have a greater negative impact on general functioning than does mania.1

Wendy Marsh, MD, MS, associate professor in the Department of Psychiatry and director of the Bipolar Disorders and Depression Specialty Clinics at the University of Massachusetts Chan Medical School/UMass Memorial Medical Center in Worcester, Massachusetts, discusses how treatment can better address quality-of-life issues for individuals with bipolar depression.

Clinical trials evaluating treatment efficacy in bipolar depression have mostly focused on symptom remission using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) or clinician-reported outcome assessments such as the Montgomery-Asberg Depression Rating Scale (MADRS) score to indicate disease control. Do you believe that issues related to health-related quality of life have been adequately addressed by the current endpoints?

Current endpoints that focus on symptom remission are key in addressing quality of life. Health-related quality of life is divided into mental health and physical health. Assessing symptoms of mood and mental health thus addresses a key aspect of quality of life. However, focusing on mood symptoms alone fails to encompass the greater picture of quality of life in these individuals. Alternative mood rating instruments — such as the Hamilton depression scale (HAM-D) — may include more physical symptoms related to quality of life, such as more questions related to sleep and physical symptoms, whereas the MADRS focuses more on mood and cognitive symptoms. An even better option would be to include a rating scale that is focused solely on health-related quality of life.

What are the effects on quality of life, and how do we measure them? Can you comment on the clinical implications?

The US Centers for Disease Control and Prevention (CDC) defines health-related quality of life as an individual’s or a group’s perceived physical and mental health over time. It is associated with one’s sense of well-being. The CDC reports, “Well-being is a positive outcome that is meaningful for people and for many sectors of society, because it tells us that people perceive that their lives are going well.”2 As defined by the CDC, well-being includes “what people think and feel about their lives, such as the quality of their relationships, their positive emotions and resilience, the realization of their potential, or their overall satisfaction with life” and “feelings ranging from depression to joy.”2

The CDC uses a quick measure for health-related quality of life.3 The tool asks questions about mental health, physical health (severity and duration of symptoms), and need for support. The validation, reproducibility, and responsiveness to changes of this tool are cited on the CDC website.3

Another often-used measure of quality of life is the 36-item Short Form Health Survey (SF-36), which is a patient-reported survey of health that measures health status. A 6-dimensional abbreviated version (SF-6D) is also available.

How do you suggest clinicians approach treating the depressive episode?

The best evidence of benefit to mood in individuals with bipolar disorder is for medication. The US Food and Drug Administration (FDA) has approved several medications for the treatment of bipolar depression. I encourage clinicians to take a look at whether a medication that is called a “mood stabilizer” is really effective in the treatment of acute bipolar depression. For example, divalproex has a long history of use as a mood stabilizer, but it doesn’t have the strongest evidence for treating acute depressive episodes. In contrast, we have medications that have undergone testing with strong study design and have an FDA indication for reduction of symptoms in acute depression; these include lurasidone, cariprazine, and lumateperone, which are 3 new atypical antipsychotic agents that have become available in the last few years. Lamotrigine, an antiseizure medication, is also worth mentioning, given it has a unique indication for the prevention of bipolar depression.

Anticonvulsants, antipsychotics, atypical antipsychotics, mood stabilizers, and antipsychotic/antidepressant combination therapy are currently approved by the FDA for treatment of bipolar depression.

What treatment approaches for bipolar depression have been demonstrated to have an impact on quality-of-life measures, and do you recommend pharmacologic treatments for comorbid conditions such as sleep disorders in addition to antidepressant, antipsychotic, and mood-stabilizing therapies?

Bipolar mood episodes can have a profound impact on quality of life. An ideal treatment would be one that resolves acute mood symptoms and prevents further mood episodes but does not worsen quality of life with other concerns, like adverse effects. Because symptoms of mood episodes include changes in sleep, concentration, and energy — and can even include psychosis — I strongly recommend treating the mood episode first before adding multiple medications for each symptom. Resolution of the mood episode means resolution of its symptoms. That being said, some of our first-line treatments do not fully treat symptoms, or there may be an alternative reason (ie, poor sleep due to obstructive sleep apnea or energy alteration due to thyroid dysregulation) that needs treatment in itself.

An ideal treatment would be one that resolves acute mood symptoms and prevents further mood episodes but does not worsen quality of life with other concerns, like adverse effects.

What role does lifestyle modification — including diet, exercise, sleep hygiene, smoking, and alcohol cessation — play in improving health-related quality of life in people with bipolar depression? How can clinicians support their patients in implementing positive lifestyle changes?

I strongly encourage a healthy lifestyle in the pursuit of well-being. In the context of bipolar disorder, there is a long history of evidence regarding light/dark and sleep/wake cycles and their impact on mood stability or disruption. Some of the more modern aspects of this come into play with the use of full-spectrum bright light therapy in the morning to decrease symptoms of bipolar depression, and one of the key components in interpersonal and social rhythm therapy (IPSRT) is waking up at the same time (or within 30 to 60 minutes of that time) every morning.4 I also recommend avoidance of screens in the evening because the blue light emitted suppresses melatonin, making sleep onset more difficult or delayed.

Individuals with bipolar disorder are at higher risk for substance misuse than the general population. For better quality of life, I absolutely recommend cessation of use of substances. If the person is attempting to treat real symptoms (such as marijuana use for insomnia), then evidence-based treatments are recommended.

Diet and exercise are critical for a healthy quality of life. However, evidence of their benefit in persons with bipolar disorder is less well documented. Exercise helps to reduce anxiety (and about one-half of individuals with bipolar disorder also experience comorbid anxiety5) and depression, although evidence in bipolar depression is limited. Diets including high amounts of omega-3 fatty acids (eg, up to 1 g/d) may reduce depressive symptoms,6 and inclusion of probiotics may reduce psychiatric hospitalization in those with bipolar disorder.7 However, the strength of the evidence for these approaches varies and currently, medications are the mainstay for treatment of bipolar disorder.

A positive link has been identified between active peer-led mutual-help organizations and improvements in functioning and well-being in individuals with mood disorders.8 What are the barriers to implementing peer-led mutual-help organizations in the United States to address further unmet needs?

We are social beings, and the ability to relate and connect with others benefits quality of life for all of us. Unfortunately, bipolar disorder still carries a stigma in the United States, and this often creates a hurdle to acknowledging the diagnosis to others, much less joining a group with individuals sharing a similar diagnosis. Another barrier has been precautions put in place as a result of the COVID-19 pandemic. Groups have largely gone virtual; although these are perhaps easier to attend, much may be lost in the bond and connections that come about through live interaction.

What are the gaps now, and where should research be going to improve quality of life in individuals with bipolar depression?

It is important to keep the bigger picture in mind. We are really good at assessing symptom severity, but how does this connect to overall well-being, including self-perception of health and meaningful life? What about healthy behaviors, sense of purpose, and social connectedness? When depressed, the first thing people often let go is connecting with their loved ones. We’re more apt to make note if one misses or loses a job because of depression, but we are less likely to assess how meaningful a maintained job may be. Or we rate in detail symptoms that may be an adverse effect in a medication trial, but we are less vigilant about how physical experiences may change depending on mood. In our goal of treating patients, we need to keep in sight not just symptom remission but the patient’s overall well-being.

This Q&A was edited for clarity and length.


Dr Marsh reports serving as a consultant for Guidepoint and GLG.


1. Miller S, Dell’Osso B, Ketter TA. The prevalence and burden of bipolar depression. J Affect Dis. 2014;169(Suppl 1):S3-S11.

2. Health-related quality of life (HRQOL). Centers for Disease Control and Prevention website. Updated June 16, 2021. Accessed August 22, 2022.

3. Health-related quality of life (HRQOL). Methods and measures. Centers for Disease Control and Prevention website. Updated October 31, 2018. Accessed August 22, 2022.

4. Frank E, Swartz HA, Boland E. Interpersonal and social rhythm therapy: an intervention addressing rhythm dysregulation in bipolar disorder. Dialogues Clin Neurosci. 2007;9(3):325-232.

5. Spoorthy MS, Chakrabarti S, Grover S. Comorbidity of bipolar and anxiety disorders: an overview of trends in research. World J Psychiatry. 2019;9(1):7-29. doi:10.5498/wjp.v9.i1.7

6. Liao Y, Zhang H, He Q, et al. Efficacy of omega-2 PUFAs in depression: a meta-analysis. Transl Psychiatry. 2019;9:190. doi:10.1038/s41398-019-0515-5

7. Dickerson F, Adamos M, Katsafanas E, et al. Adjunctive probiotic microorganisms to prevent rehospitalization in patients with acute mania: a randomized controlled trial. Bipolar Disord. 2018;20(7):614-621. doi:10.1111/bdi.12652

8. Kelly JF, Hoffman L, Vilsaint C, Weiss R, Nierenberg A, Hoeppner B. Peer support for mood disorder: characteristics and benefits from attending the Depression and Bipolar Support Alliance mutual-help organization. J Affect Dis. 2019;255:127-135. doi:0.1016/j.jad.2019.05.039

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Reviewed August 2022