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Symptom Management Suggested Before Bright Light Therapy for Patients with Bipolar Depression

April 29, 2021

Dorothy Sit, MD, will present a session on the current clinical indications of bright light therapy and discuss novel visual and neural biomarkers in patients with bipolar depression at the virtual 2021 American Psychiatric Association (APA) Annual Meeting. The session will also explore relevant studies to examine the approaches in managing antidepressant treatment in perinatal women and reflect on Dr. Sit’s career in research, education, and advocacy of women’s health.

In this Q&A, presenter Dr. Sit discusses some of the topics she will address in the session "Bright Light Therapy for Treatment of Bipolar Disorder" to be held at 2 p.m. on May 1.

Read the transcript:

Hi, my name is Dr. Dorothy Sit. I am an associate professor in the Department of Psychiatry and Behavioral Sciences at Northwestern University's Feinberg School of Medicine. I am here today to present a talk for the Alexandra Simmons Award.

Q: What are the main points or messages from your upcoming session, “Bright Light Therapy for Treatment of Bipolar Disorder”? (00:29)

The main points, or objectives, or messages from this session would include the following.

The first objective is to discuss the known and novel clinical indications of bright light therapy, particularly for the treatment of seasonal affective disorder, nonseasonal major depression, bipolar depression, and perinatal depression.

Objective 2 is to examine the outcome measures of light therapy response that are relevant to patients who have bipolar disorder, examining their remission rates, depression scores, changes in functioning, other measures that could help gauge response, including their sleep quality, chronotype, the level of seasonality in their mood symptoms, and also the risk for mood polarity switch.

Objective 3 is to explore and discuss some of the putative novel visual and neural biomarkers that we can examine in understanding the response to bright light therapy in patients who have bipolar depression.

The fourth objective is to segue into some of the work that encompasses the phenomenology, pathophysiology, and pharmacological responses in women across the life cycle and to examine and discuss the approaches in the management of antidepressant therapy in perinatal women, given our study findings.

Objective five is a reflection on a career path in psychiatry that encompasses research, clinical care, teaching and education, and advocacy of women's mental health.

Q: Please briefly describe the methods and key findings from the study you will be discussing in your session. (2:24)

In this program, I will discuss the methods and key findings from our primary study, which has to do with examining bright light therapy as an adjunctive treatment for bipolar depression.

To give it a little bit of context, conventionally, bright light therapy that is used for the treatment of seasonal affective disorder and other types of depression are administered in the morning time. Usually, treatment is implemented for 30 minutes shortly after awakening.

Used daily, it can improve seasonal affective symptoms within 2 to 4 weeks. The onset is very quick and usually within 3 to 4 days.

In our earlier case series report, we implemented the morning light therapy to patients who had bipolar depression were maintained on mood stabilizers. Intriguingly, 3 out of the 4 patients who were first enrolled in this study experienced an induction of hypomania and mixed symptoms rapid‑cycling within days after starting treatment.

Upon careful literature review and consultation with experts, we made adjustments to our protocol, adjusted the timing of light therapy to a midday time period. By doing so, we recruited 5 more patients, of which 3 experienced a full response, and 1 responded fully to the transition of morning light.

What we did find in our earlier case series trial is that mid‑day light may produce a promising therapeutic effect for bipolar‑depressed patients. Given the promising findings, we then conducted a randomized controlled trial to confirm the efficacy of adjunctive midday bright light for bipolar depression.

We compared patients randomized to bright light therapy at midday with patients who were administered a placebo‑controlled comparator. We'll discuss that more in the talk.

After 4 to 6 weeks, we discovered that 67% of patients given bright light therapy experienced a full response and remission compared to only 33% who were randomized to the placebo comparator.

In this talk, we will look at not only the primary outcomes, which included remission rates, changes in functioning, and the risk of mood polarity switch, which was very minimal to none. Also, we'll examine secondary outcome measures that may or may not be as predictive of the response that we're looking for, things like sleep quality and the patients' baseline chronotype.

We will explore this a little bit more in‑depth and discuss not only the methods but some of the primary and secondary outcome measures that may be of interest.

Q: Are you working on other research in this area? (5:49)

The other component of the work I've done in my research career involves a focus on the phenomenology, pathophysiology, and pharmacological responses in women across their life cycle. Some of the work that I have done has encompassed studies that examined the changes in antidepressant concentrations across pregnancy.

What these studies have accomplished is to illustrate the mean drug concentration to dose ratios. So, the drug concentration's control for dose for the common antidepressants used for the treatment of depression and anxiety that include fluoxetine, sertraline, citalopram, and escitalopram.

The concentration or the drug concentration‑to‑dose ratios for these drugs seem to decrease in the second and third trimesters of pregnancy. It's presumably from the changes in the induction of hepatic metabolism.

When we looked at pregnant women treated with citalopram, the parent drug and its metabolite, the drug concentration decreased substantially. In fact, looking at the ratios first of sertraline in the earlier publications, the concentrations of sertraline decreased by an average of 60% between 20 weeks of pregnancy and delivery.

By 4 to 6 weeks postpartum, the ratios of sertraline were similar to that in early pregnancy. When we looked at fluoxetine, the mean ratios of the parent drug to the metabolite—the parent drug, meaning fluoxetine, and the metabolite, norfluoxetine—concentrations decreased across pregnancy.

In fact, there was a negative relationship or a negative association between the depression scores and the dose‑corrected concentrations, meaning that as the scores were higher, the concentrations on corrected for dose were lower.

Thirdly, pregnant women treated with citalopram or escitalopram, the drugs and the metabolite concentrations decreased between 20 weeks gestation and delivery and returned to baseline by the 12th week postpartum.

What these studies illustrate is that the concentration‑to‑dose ratios for these drugs—sertraline, fluoxetine, and citalopram or escitalopram—would in the second half of pregnancy, in the third trimester presumably due to an increased hepatic metabolism.

What this translates to in clinical care is that we need to monitor the dosing and the treatment's response very carefully in pregnancy and postpartum and be aware that when mood symptoms start to increase and depression scores increase, it may be a time to up the dose and increase the dose of antidepressant treatment to compensate for the reduction in this concentration‑to‑dose ratio that we were seeing in these earlier studies.

That has also translated into upcoming and ongoing studies that are building on these earlier findings. From our group, we have investigators that include my mentor, Dr. Katherine Wisner, Northwestern University Feinberg School of Medicine, Chicago, Illinois our colleagues, Dr. Catherine Stika, State University of New York, Syracuse, and Dr. Alfred George, Northwestern University Feinberg School of Medicine.

Together, they are conducting a National Institutes of Health, Bethesda, Maryland, sponsored study, sponsored by the National Institute of Child Health and Human Development, Bethesda, Maryland, and the Obstetric-Fetal Pharmacology Research Center, Galveston, Texas, to examine optimal medication management of mothers with depression. This is also known as the OptiMUM study.

In this study, they're examining data, collecting data that can be used to construct a guideline for optimal antidepressant drug dosing across pregnancy and postpartum to reduce disease burden and minimize adverse effects looking at these specific drugs.

In future studies, exploring the possibility of developing a center of excellence through the p50 structure to examine more carefully and to map the activities of the cytochrome hepatic enzymes throughout childbearing, with a particular careful attention at examining the progressive changes in drug and metabolite concentrations across pregnancy in the first 3 to 6 months after birth.

To determine, longitudinally, the monthly concentrations of drugs that should be used in obstetrical and psychiatric care, particularly with respect to the antidepressant drugs.

Q: What are the practical implications of your findings for clinicians treating patients with bipolar disorder? (11:14)

What are some of the practical implications from our findings for clinicians who are treating patients with bipolar disorder? The important several implications with bipolar disorder, just being aware that patients may be experiencing depression in a vast majority of the mood episodes that they're having.

They can present as purely major depressive episodes with bipolar disorder or mixed episodes, so a mixture of depression, but also hypomanic and manic symptoms.

Knowing this, because bright light therapy is primarily an antidepressant response and there's no indication that it produces a mood‑stabilizing effect, it will be important for patients and their clinicians to be aware that they should be optimally treated with their antimanic drug therapy before adding in an antidepressant somatic therapy such as bright light or antidepressant drug. Ensuring that the mixed symptoms and the hypomanic residual symptoms are under good control before adding bright light.

In the study, exclusion criteria included patients who had any form of hypomania who are not maintained on a proper antimanic treatment, other patients who had any type of psychotic features.

Keep in mind that this is a study that recruited patients who have purely bipolar depression. Also know that with this approach, we introduce midday light as a safer option. We will discuss a little bit more about ways to manipulate the dose, the timing, and other aspects of the dosing of light therapy to improve outcome.

The understanding is that light therapy is primarily effected through the circadian system. However, we do not have sufficient data to support that we are making changes or producing changes in the circadian rhythms of patients who are receiving light therapy.

Even so, it may provide a benefit to improve the sleep phase, possibly the consolidation sleep quality.

The other aspect to this is that we still need replication data, particularly for our study. This is the one clinical trial conducted on midday light for this type of patient population. We definitely need replication studies.

We'll talk about what other groups have found and compare their outcomes to provide a more balanced understanding of the outcomes to expect and also the possible avenues for future research related to what we discovered.

Q: Based on your findings, briefly describe the different approaches in the management of antidepressant therapy in perinatal women. (14:35)

To address, based on our findings, briefly describing the different approaches in the management of antidepressant therapy in perinatal women.

Important to remember that with women during pregnancy, who have a history of major depression, but they are currently in remission or patients who have active symptoms of depression or anxiety, it will be important to monitor mood symptoms carefully and repeatedly across the perinatal, the pregnancy period, and also the postpartum period.

Throughout pregnancy, and definitely for the first 6 to 12 months postpartum, carefully monitor, and manage symptoms, and examine the dosing, the depression levels repeatedly during this time period.

Knowing that patients who experience relapsing symptoms, worsening symptoms, or the new onset of depression symptoms in pregnancy may need to have a careful discussion of the risks and the benefits of treatments, including antidepressants, in pregnancy.

The risks and benefits, in general, will be quite reassuring. We will go into more detail during this discussion. The risks and benefits, particularly of the serotonin reuptake inhibitors, we have ample data to suggest that the treatment of depression using these agents is more reassuring than ever.

It will be important to also understand that some patients have a preference to restart treatment at the time of delivery to prevent postpartum depression. We'll go into some of the strategies for that: the dosing strategies based on our published reports from our group on the changes in pregnancy and changes in the second and third trimester of the concentration dose ratios of some of the antidepressants. We study what that implies in dosing during the second and third trimester.

Also, knowing that there are other treatment options that some patients may decide upon, like nondrug therapies. Even so, bright light therapy can provide a very reasonable somatic treatment option for the management of depression in pregnancy.

We'll go through some of the literature, and early findings, and recent pubs that provide support for using bright light therapy in perinatal women who have depression. Please, join the talk to learn more about this.

Q: Are there any misconceptions on this topic that you would like to clear up? (17:40)

Misconceptions on this topic. No real misconceptions, but intriguingly, bright light therapy is gaining a lot of traction in the marketplace, and in the lay public, gaining a lot of interest as a novel treatment that people can do themselves.

We, light therapy experts, clinicians in the field, are trying to advocate that patients implement, initiate, and continue light therapy treatment under the receiving guidance from a clinician who's been trained.

Knowing that bright light therapy can produce adverse effects on their mood, their physical well‑being, cause sleep disruptions in ways that they do not anticipate.

We strongly urge clinicians to enter into discussion about this possibility if they feel comfortable but to also encourage patients on the proper selection of the lightbox and work closely with their patients on monitoring their response to treatment and expectations of treatment.

In this talk, I will also go over some of the details related to the clinical approach to implementing and following patients who are receiving bright light therapy, some of the strategies to help improve the adherence or to improve engagement in treatment.

Trying to help patients and clinicians find the optimal approach to implementing light therapy as a viable clinical option for the management of their depression and anxiety.

Dorothy Sit, MD, received her medical degree at the University of Toronto, School of Medicine, Canada. She completed residencies in family medicine and general psychiatry, and a fellowship in psychopharmacology. Dr. Sit is an associate professor at Northwestern University, Feinberg School of Medicine, Chicago, Illinois. She provides clinical care and training of residents, fellows, and medical students at the Asher Center for the Research and Treatment of Depressive Disorders, Chicago, Illinois. Dr. Sit studies the phenomenology, pathophysiology, and pharmacologic responses of women across the lifespan, especially in the perinatal period. She investigates novel somatic therapies including bright light therapy for patients with bipolar illness, epilepsy, and complex mood disorders.

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