Bipolar Research: Ketamine, Sleep, Sense of Smell, & Depression

From ketamine for treatment-resistant bipolar depression to the hazards of bright light at night, here are 5 advances in bipolar disorder research.

If someone asks you what bipolar disorder is, what do you tell them? 

You could start with the official symptoms and standard treatments. Those are the basics. But they miss important parts of your bipolar journey. Like how your symptoms might improve while everyday tasks — like writing a text message — are still hard. Or how your personal strengths can be lifelines during the darkest moments. 

Going deep like this is exactly what researchers do. They explore the nitty-gritty of real life with bipolar disorder, using science to go beyond textbook definitions and unpack the complexity of life with this brain-based health condition. 

Here you’ll discover five new studies that dig into questions that have real implications for your daily life — and help you understand yourself better:

• Could the ketamine nasal spray Spravato help with a notoriously stubborn depression symptom?
• Does a little light in your bedroom really make a difference in your sleep?
• Does your sense of smell change during mood episodes?
• Is treating bipolar depression symptoms enough to help you function day to day?
• Could a personal strength like grit help you feel more joy with bipolar disorder?

Ketamine Could Address Hard-to-Treat Bipolar Depression Symptoms

One of the toughest depression symptoms to treat is anhedonia, which the American Psychological Association (APA) defines as the inability to feel pleasure or enjoyment in the things you used to love. 

Anhedonia’s cause isn’t fully understood, but experts think it may be related to problems with your glutamatergic system, one of the reward pathways in the brain. Standard antidepressants don’t directly affect glutamate, but esketamine (Spravato), a nasal spray derived from the anesthetic ketamine, does. 

Does that mean esketamine could help with anhedonia in people living with bipolar disorder and major depressive disorder? New research published in the journal Psychiatry Research investigates. 

What the Research Says

In the United States, esketamine is currently only indicated for treating certain cases of major depressive disorder and is not approved for bipolar disorder, per the U.S. Food and Drug Administration (FDA).

But there’s ongoing research into the potential for ketamine-derived treatments for other uses, including research into intravenous ketamine as an innovative therapy for bipolar depression. The study in Psychiatry Research is part of a multinational project to understand more about how well esketamine works as a therapy for treatment-resistant bipolar and unipolar depression.

In this real-world study, 253 people receiving treatment at Italian mental health centers agreed to try esketamine as an add-on to their existing medications. All participants were considered treatment-resistant, in that their symptoms hadn’t improved after trying at least two medications. Participants were diagnosed with either bipolar disorder (54 people) or major depressive disorder (199 people). 

The participants were given esketamine nasal spray in line with the indications from Agenzia Italiana del Farmaco, the Italian drug regulatory agency, according to another paper from the same study describing the protocol. In general, participants received doses of esketamine twice a week for four weeks. For the next four weeks, they received a single weekly dose. And for the last four weeks, they either continued at one weekly dose or dropped back to one dose every other week.

The researchers measured participants’ anhedonia symptoms during that time and compared the results to see if the treatments made a difference. Here’s what they found:

• More than half of the participants with bipolar disorder felt better after esketamine treatment. After the first month, about 17 percent had experienced a decrease in anhedonia of at least 50 percent. After three months, the number of people who benefited had tripled to almost 52 percent.
• For major depressive disorder, more than one-third improved with esketamine. A higher percentage responded right away (roughly 22 percent), and 38 percent responded by the end of the study period. 

Why It Matters

If future research confirms that esketamine is safe and effective at treating anhedonia, it could be a game-changer for managing hard-to-treat depressive symptoms in bipolar disorder and major depressive disorder. 

What This Means for You

• There’s new hope for anhedonia. This study is a reminder that just because existing treatments aren’t working for you doesn’t mean no treatments ever will. Scientists are continually studying new therapies, including those that work in entirely new ways, like how esketamine works on glutamate. If you’ve been struggling with the inability to feel pleasure, this study suggests that esketamine may someday offer a way to get that feeling back, alongside the broader message that new treatments are always possible.
• Esketamine still isn’t FDA-approved for bipolar disorder. These results are encouraging, but more work is needed before this medication is approved for use in bipolar. Some of its known side effects — which, according to Mayo Clinic, include agitation and depression — may be particularly concerning for people living with the condition, so additional research involving more people and a placebo group would be needed before it’s considered safe and useful enough to be formally recommended for these cases.

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How Does Light Affect Sleep in Bipolar Disorder?

No one feels their best after a bad night’s sleep. But when you live with bipolar disorder, the consequences of sleeping poorly can be serious, potentially triggering episodes of mania and depression.

Research already suggests that light is a key factor in regulating sleep patterns for people without bipolar disorder. For example, studies suggest that exposure to morning light can help you sleep better that night, while light at night appears to have the opposite effect, per Harvard Health Publishing.

But when you have bipolar, things can affect you differently than they would someone else. So, how do light during the day and at night work together to impact sleep in individuals with bipolar disorder? New findings published in Translational Psychiatry shed light on the relationship. 

What the Research Says

To understand the connection between light and sleep, researchers in Japan and California asked 204 people with bipolar disorder to wear a special device on their wrists for seven days. The wearable measured their movement (a proxy for sleep) and the daytime light level, allowing researchers to collect objective data on sleep patterns and brightness. The researchers also placed a portable light meter in the participants’ bedrooms to measure nighttime light since blankets and bedclothes might interfere with getting an accurate reading via the wearable. 

Here’s what they discovered: 

• In general, people exposed to brighter light during the day slept better. They fell asleep faster, spent more time in bed actually sleeping, spent a higher percentage of their time in bed asleep, and slept more minutes overall. 
• But the picture got more complicated when researchers analyzed nighttime light exposure, too. The researchers divided the participants into two groups: those who slept in brighter environments and those who slept in darker ones. Darker rooms had light levels below 2.28 lux, which is very dark. For context, e-readers provide an illumination of about 30 lux, according to one study. 
• People in the dark bedroom group slept even better. The contrast of bright days and dark nights was linked with improvements in all the sleep metrics. Participants fell asleep more quickly, woke up less frequently, spent a higher percentage of time asleep while in bed, and had a higher total sleep time. 
• When researchers looked only at people who experienced bright light during the day but also had bright bedrooms, the benefits of daytime light mostly disappeared. For this group, there was no longer a meaningful association between most of the measures of good sleep and daytime light. The only benefit that remained was that this group still slept a bit longer overall. 

Why It Matters

These findings affirm that light seems to impact sleep management for people living with bipolar disorder, just like it does for those without the diagnosis. It also suggests that the positive effects of daytime light on sleep can be undone if your bedroom is too bright. 

Key Highlights

• If you want to sleep better, seek out daytime light. The results of this study suggest that if you do, you’ll have better quality sleep, logging more minutes of rest and waking up less in the middle of the night.
• But don’t forget about nighttime light. The benefits of daytime light might be canceled out by too much light at night, the results suggest. Make sure your bedroom is truly dark to help manage your sleep and protect against mood episodes. 

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Sense of Smell May Change During Bipolar Episodes, Study Finds

Could your sense of smell be linked to bipolar disorder symptoms? 

It might sound like a stretch, but there’s already scientific evidence that smell and emotion use similar brain pathways, according to a review of the research. 

Building on these findings, a new study published in BMC Psychiatry examined whether sense of smell and inflammation levels changed alongside mood states for people living with bipolar 1 disorder.

What the Research Says

If your sense of smell and inflammation were markedly different during episodes, it would mean they could be used as biomarkers for bipolar disorder. 

Biomarkers are measurable signs of a condition, and they can help with diagnosis and management. One of the challenges of addressing mental health conditions, including bipolar, is that clear biomarkers haven’t been discovered yet, though there’s active research into many possibilities.

For this study, the Chinese research team focused on two potential biomarkers for bipolar disorder: 

• Sense of Smell Researchers tested olfactory function using a standard test called Sniffin’ Sticks. Participants smelled a group of pens and had to figure out which one had a scent. Then, they’d do it again, but with a scented pen that had a weaker scent. After several rounds, each person got a score reflecting the lowest level of scent they could detect. 
• Inflammation Researchers used a blood test to check levels of a protein called interleukin-6 (IL-6). Higher IL-6 levels indicate higher inflammation in the body. 

The study involved 81 people with bipolar 1 disorder — some in a manic episode (50) and some in a depressive episode (31) — and 59 people who didn’t have the condition. 

Everyone had their sense of smell and inflammation levels measured at the beginning of the study. Participants with bipolar did both tests again once their mood stabilized, and they were no longer in a manic or depressive episode.

When the researchers analyzed the data, they found:

• Sense of smell was reduced during bipolar episodes. During manic and depressive episodes, people with bipolar 1 disorder had a harder time detecting and naming smells than their counterparts without the diagnosis.
• Ability to detect smells rebounded during remission. After mood episodes resolved, people with bipolar 1 had a similar ability to detect smells as those without the condition. 
• But difficulty identifying smells lingered. Although it improved from baseline, even when their moods had stabilized, people in the study who lived with bipolar weren’t quite as good at naming smells as those who didn’t have the diagnosis. 
• Inflammation and the sense of smell were connected in manic episodes. For people in manic episodes, levels of IL-6 and the ability to detect smells were linked. They moved in opposite directions, so individuals with increased levels of IL-6 also tended to have a decreased ability to detect smells. This suggests a potential connection between inflammation and the sense of smell. 
• Inflammation was higher during manic episodes. IL-6 levels decreased once the episode resolved, but it wasn’t as low as those in the group that didn’t have bipolar disorder. 

These findings match up with some existing studies and differ from others, the researchers note. This variation suggests that more research is needed to untangle the relationship between bipolar symptoms, smell, and inflammation. 

Why It Matters

This research suggests that changes in your sense of smell and inflammation levels might be connected to mood changes in bipolar disorder. 

These findings are a reminder that this condition affects your whole body, and researchers are still learning about what that really means and how measuring those changes could help with your care. 

What This Means for You

• If you’ve noticed changes in your sense of smell during mood episodes, this research suggests you’re not imagining it. This study adds to the growing evidence that bipolar isn’t just about mood — it involves physical changes in the body. Even though the results aren’t definitive, they suggest that it’s possible that your sense of smell is one of those physical changes.
• Someday down the line, a sniff test might be part of a workup for bipolar disorder. It’s potentially meaningful that people with bipolar had a worse sense of smell during and after a mood episode compared with people without a mental health condition in this study. If this finding is replicated — and ends up being unique to bipolar disorder — measuring your sense of smell could be a way to diagnose or track bipolar disorder’s progress. But more studies are needed before your care provider will monitor how you’re doing by asking you to smell something.

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Study Reveals Gap Between Symptom Relief and Real-Life Improvement in Bipolar Depression

After a bout of bipolar depression, you’re feeling better in some ways, but life still doesn’t feel quite right. Meeting all of your daily responsibilities still feels harder than it used to. Could lingering bipolar symptoms be to blame?

A new study published in the Journal of Affective Disorders looked into how often people recovering from bipolar depression still struggle with daily life tasks even when their symptoms improve, and whether two popular treatments can help bridge that gap.

What the Research Says

A team of researchers in the United States wanted to understand how well different types of treatment worked to help people experiencing bipolar depression feel like themselves again. 

A group of 92 volunteers who had bipolar 2 disorder and were in a depressive episode tried two different treatment tracks:

• Therapy Alone The 45 people in this group received a type of talk therapy called Interpersonal and Social Rhythm Therapy (IPSRT) along with a placebo (sugar pill). The 45-minute weekly IPSRT sessions focused on maintaining regular daily routines (like sleep and eating) and improving relationships. 
• Therapy Plus Medication The 47 people in this group also participated in IPSRT and took a daily pill, but theirs contained an antipsychotic medication that’s FDA-approved for treating bipolar depression called quetiapine (Seroquel).

This study was a double-blind placebo-controlled trial, the gold standard for testing whether a treatment works. During the treatment period, neither the participants nor the researchers knew who was getting the real medicine and who wasn’t, which helped reduce bias in the results. 

During the 20 weeks of the study, the research team asked participants to complete surveys that revealed how they were doing in three main areas:

• Improved Bipolar Depression Symptoms Participants were considered improved if their depression symptoms had reduced by half. 
• Bipolar Depressive Episode Remission If depression symptoms were low enough for three weeks in a row, the depressive episode was considered over, and IPSRT sessions decreased to every other week.
• Improved Day-to-Day Functioning If participants said that bipolar disorder didn’t interfere much with their ability to do everyday things, this was considered improved, too.

When researchers unblinded the data and analyzed the results, they discovered two key findings:

• Most people’s depressive symptoms got better. This was true for both groups, regardless of whether they were on the medication or the placebo. The two treatment groups had about the same level of improvement, suggesting short-term IPSRT may be enough on its own to address a depressive episode in some people diagnosed with bipolar 2 disorder. 
• But regaining their ability to do day-to-day tasks took longer. Unfortunately, even at the end of the study, most people said they still had difficulty doing all the things they wanted to at work and at home. The only exception was for leisure activities, like hobbies and other activities people do for fun, which started to feel easier around the time that people’s depression symptoms lifted. 

Why It Matters

Studies testing treatment for bipolar depression tend to only measure whether symptoms improve. Part of what makes this study important is that it also examined how well treatments helped participants handle day-to-day activities, which can come back more slowly. 

What This Means for You

• Just because your depressive symptoms improve doesn’t mean life is back to normal. This study suggests that having meaningful symptom improvement but still not feeling like yourself is common among people being treated for bipolar depression. Even when doctors say a depressive episode is over, low-grade symptoms can linger, interfering with your daily life. 
• Functional recovery is a separate treatment goal. Clinical symptoms are often the first focus of bipolar disorder treatment. But treatment doesn’t have to stop there. Talk to your bipolar care team about how the condition is affecting your work, relationships, and other daily activities so you can work together to fine-tune your treatment plan.
• IPSRT may be a medication-free way to treat depressive episodes. For some people who have an episode of bipolar depression, a course of IPSRT may be sufficient to help address depressive symptoms without adjusting medications, per these findings. These results reinforce IPSRT’s use as a go-to therapy for bipolar disorder, per Cleveland Clinic. 

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Study Finds Grit May Help You Find Joy With Bipolar

When you’re dealing with depressive episodes in bipolar disorder and major depressive disorder, treatment usually focuses on reducing the hard feelings, like hopelessness, sadness, and exhaustion. 

This can help, but it’s not the only way. You can also take the opposite tack by building up positive feelings, like reconnecting with joy and finding meaning.

New research published in the Journal of Affective Disorders examines how personal strengths like grit and mindfulness might help you live well — even when depression symptoms are flaring — by boosting these sorts of positive emotions.

What the Research Says

An international research team wanted to understand how grit and mindfulness affected the daily mental health of people living with bipolar disorder and major depressive disorder. 

To do this, the researchers decided to use real-time surveys to see the relationship between these traits and mental health over a two-week period for three groups of people: those living with bipolar disorder, those living with major depressive disorder, and those who didn’t have any mental health diagnosis. 

At the beginning of the study period, the roughly 100 participants answered questions about:

• Mental Health Symptoms This included clinical symptoms of depression and mania in addition to questions about how much joy and pleasure they experienced.
• Grit Grit is your ability to keep going despite setbacks. To understand the participant’s grit, the grit survey ranks people on what research calls the short grit scale by asking them how much they agree with statements like, “I finish whatever I begin.” 
• Mindfulness Mindfulness, the researchers noted, is your ability to pay attention without judgment. The mindfulness survey asks questions like, “When I take a shower or a bath, I stay alert to the sensations of water on my body.”

For the next two weeks, participants used their smartphones to check in five times per day about their mental health. They answered a mix of questions about depression symptoms, enjoyment, and whether their life felt meaningful. When researchers analyzed the data, they found: 

• For people with bipolar disorder, higher grit was linked with more joy. The study found that when people living with bipolar had higher levels of grit, they also said they felt more joy, even when they also experienced a lot of negative feelings. This boost didn’t happen for people with depression or without mental health conditions. The researchers think that grit might help you keep up with the meaningful activities and goals that unlock good feelings, even when your energy or motivation dips.
• For people with major depression, mindfulness and meaning went hand in hand. Mindfulness seemed to help people with major depression feel a sense of purpose despite their negative feelings. It wasn’t as helpful for people in the bipolar or no-diagnosis groups.

Why It Matters

These findings suggest that personal strengths help people who experience depressive episodes feel more positive emotions and thrive. Which strengths are most helpful seems to differ depending on your diagnosis. For people with bipolar, grit seems to be especially useful for enhancing joy. Alternatively, for those with major depression, mindfulness practice fostered a greater sense of meaning. 

What This Means for You

• You don’t have to get rid of negative feelings to start feeling better. This study suggests that, for people with bipolar disorder, grit may act like an umbrella. Even when bipolar depression is storming, grit can help protect your ability to find pockets of joy in your life. 
• Future mental health treatments could focus on your unique strengths. This study affirms that personal strengths, like grit and mindfulness, can help unlock positive feelings, like joy and meaning, even and especially when you’re living with mental health conditions. While more research is still needed, future therapies might build on these insights to help you harness grit for greater pleasure in your day-to-day life. 
• In the meantime, to find more joy while living with bipolar, try cultivating grit. This research aimed to understand what already helps people thrive. While grit isn’t a cure-all, these results suggest that this mindset can help you stick with the activities that bring you happiness, even during challenging periods.

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