LDN and Bipolar Disorder 6 FAQs
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casereports.bmj.com/content/13/1/e232502Brown ES, et al. (2006). Naltrexone in patients with bipolar disorder and alcohol dependence.
onlinelibrary.wiley.com/doi/abs/10.1002/da.20213Escelsior A, et al. (2022). Evidence of alterations of beta-endorphin levels and mu-opioid receptor gene expression in bipolar disorder.
sciencedirect.com/science/article/abs/pii/S016517812200381XGrunze H, et al. (2021). Comorbid bipolar and alcohol use disorder - a therapeutic challenge.
frontiersin.org/articles/10.3389/fpsyt.2021.660432/fullGrunze H, et al. (2022). The pharmacotherapeutic management of comorbid bipolar disorder and alcohol use disorder.
tandfonline.com/doi/abs/10.1080/14656566.2022.2083500Label and off-label coverage of outpatient drugs and biologicals. (2019).
cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=33915&ver=17Losekam S, et al. (2013). Letter to the editor: Shopping frenzy induced by naltrexone - a paradoxical effect in bipolar disorder?
cambridge.org/core/journals/psychological-medicine/article/letter-to-the-editor-shopping-frenzy-induced-by-naltrexone-a-paradoxical-effect-in-bipolar-disorder/4C05639F02DCE1B94B5B1D7AFA6AD25CMischoulon D, et al. (2017). Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants.
sciencedirect.com/science/article/abs/pii/S0165032716304499?via%3DihubNaltrexone. (2022).
samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/naltrexoneTeneralli RE, et al. (2021). Exploring real-world evidence to uncover unknown drug benefits and support the discovery of new treatment targets for depressive and bipolar disorders.
sciencedirect.com/science/article/pii/S0165032721004286?via%3DihubToljan K, et al. (2018). Low-dose naltrexone (LDN) - review of therapeutic utilization.
mdpi.com/2076-3271/6/4/82/htmWhat you need to know about low dose naltrexone. (2020).
weillcornell.org/news/what-you-need-to-know-about-low-dose-naltrexoneOur experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Current Version Sep 19, 2022 By Emily Swaim Edited By Crystal Raypole Medically Reviewed By Yalda Safai, MD, MPH Copy Edited By Jill Campbell Share this articleMedically reviewed by Yalda Safai, MD, MPH — By Emily Swaim on September 19, 2022
6 FAQs About Low Dose Naltrexone LDN for Bipolar Disorder
Medically reviewed by Yalda Safai, MD, MPH — By Emily Swaim on September 19, 2022Share on Pinterestljubaphoto/Getty ImagesBipolar disorder is a mental health condition characterized by periods of intense mood symptoms. If you have bipolar disorder, you may experience: episodes of depression during which you feel sad, fatigued, or numbepisodes of mania or hypomania during which you feel euphoric, irritable, or anxiousboth types of episodes Typically, treatment for bipolar disorder involves a combination of therapy and medication — you’ll find more information on those below. Of course, these existing bipolar disorder treatments may not work for everyone, and some medications involve a number of side effects. That’s why researchers continue to explore new potential medications to help treat bipolar disorder. One drug currently undergoing study is naltrexone, a medication typically used to treat substance use disorder (SUD). Some preliminary research suggests that low dose naltrexone (LDN) may help reduce mood episodes. Below, you can find answers to some of the most common questions about naltrexone for bipolar disorder, including why a low dose might be beneficial as part of treatment.1 What is naltrexone
Naltrexone is a medication that the Food and Drug Administration (FDA) has approved to treat alcohol use disorder (AUD) and opioid use disorder (OUD). It works in two main ways: It helps reduce cravings, and it blocks off the endorphin and opioid receptors in your brain. To put it simply, if you drink alcohol or use opioids while taking naltrexone, those substances won’t produce the feelings of euphoria that they typically would. Some research also supports naltrexone as a treatment for bipolar disorder, though existing studies mostly focus on people living with both SUD and bipolar disorder. This is most likely because the two conditions frequently occur together. In fact, between 40% and 70% of people with bipolar disorder have also had AUD at some point in their lives. Although it is common for SUD and bipolar disorder to occur together, only a few studies have explored how treating SUD with naltrexone may affect co-occurring bipolar disorder symptoms. In a small 2006 study, 34 people with bipolar disorder and AUD took naltrexone for 16 weeks. Participants reported improvement in both depression and mania symptoms, as well as decreases in alcohol cravings and days drinking alcohol. What’s more, naltrexone did not appear to cause any major negative effects. A large self-controlled cohort study from 2021 also explored naltrexone as a treatment. In this type of study, participants report on their symptoms before and after a specific treatment. The study authors found that people who took naltrexone to treat either AUD or OUD had a 65% lower rate of bipolar disorder diagnosis than those who didn’t take naltrexone.What do these findings mean
These results may seem encouraging, but it may be worth taking them with a grain of salt. For one thing, neither of these two studies had a traditional control group. So, it’s certainly possible that naltrexone could reduce bipolar disorder symptoms or prevent them from developing in the first place. But cutting back on drinking when taking naltrexone could also make a difference — research suggests that reducing alcohol use can improve bipolar disorder symptoms.2 What about LDN
Naltrexone is a hormetic drug, which means different doses can affect you differently. A regular dose of naltrexone is 50 milligrams (mg) per day. This dose blocks your endorphin and opioid receptors to prevent your brain from releasing too much of those chemicals if you drink alcohol or use other substances. A low dose of naltrexone is 1 to 5 mg per day. At this dose, naltrexone actually boosts endorphin and opioid levels — just not quite as much as alcohol and opioids do. LDN may also reduce inflammation in your brain. LDN is an adjunct therapy. This means that it helps boost the effects of other drugs, so you’ll take it in combination with another type of medication. Since LDN research is in the very early stages, experts still don’t know exactly why LDN affects the brain this way. However, the limited studies that exist show fairly consistent effects.3 Does LDN actually work
Evidence suggests that changes in your endorphin levels can contribute to episodes of both mania and depression. Therefore, LDN may improve bipolar disorder symptoms because it boosts endorphin levels. But again, experts have yet to come to any conclusions about how LDN affects bipolar disorder specifically. Studies exploring use of LDN for other conditions may yield some insight on its potential benefits. For instance, people who take LDN for chronic illness often report improvement in co-occurring mental health issues — including symptoms associated with bipolar disorder, such as:a low or depressed moodfatiguesleep disturbancesdifficulty performing daily tasks Evidence from one small 2017 study also supports the benefits of LDN for major depression. The study included 12 participants who experienced a recurrence of depression symptoms while taking antidepressants. When the treatment group added 1 mg of naltrexone to their medication regimen for 3 weeks, they noticed more improvement in their breakthrough symptoms than the placebo group. So far, no evidence from large clinical trials supports the benefits of LDN for bipolar disorder — but research does suggest that LDN may have promise for treating conditions that don’t always respond to conventional treatments, including:fibromyalgiaCrohn’s diseasemultiple sclerosiscomplex regional pain syndromecancerImportant LDN is intended to support conventional therapies, not to replace them. It’s important to work with a medical or mental health professional to get treatment for any physical or mental health symptoms you experience.4 What are the side effects of naltrexone and LDN
Like any other drug, naltrexone may cause some unwanted side effects. But LDN seems to pose less risk of side effects than regular-dose naltrexone.Naltrexone side effects
Naltrexone is generally considered safe for people with bipolar disorder, but one case report from 2013 suggests that it may, in rare cases, trigger an episode of mania. A regular 50-mg dose of naltrexone can cause side effects like:anxiety and irritabilityvery high energy levelsdifficulty falling asleepconfusion or paranoiahallucinations As you may have noticed, these side effects closely resemble some symptoms of mania. This could make it difficult to determine whether you’re experiencing side effects or a mood episode. If you notice any of these side effects, contact your doctor right away. They can offer personalized guidance on managing these symptoms and finding a replacement medication that better suits your needs.LDN side effects
LDN tends to cause only mild and infrequent side effects. Headaches and vivid dreams are among the most commonly reported effects. What’s more, you might notice these effects only when taking a “higher” LDN dose of 4 to 5 mg. Doses of 3 mg or less typically involve minimal, if any, side effects.5 How can I try LDN
The FDA has approved naltrexone, at a full dose, only to treat SUD. LDN isn’t yet approved as a treatment for bipolar disorder because of the lack of research on its potential benefits and side effects. Therefore, a prescription for LDN is considered off-label use. Taking LDN is still legal with a prescription, but the absence of government approval can make it much harder to get a prescription — or to get coverage from your insurance company. Insurance plans often won’t cover medications prescribed for off-label use. In order to try LDN, you’ll need your doctor to send a prescription to a compounding pharmacy. These places grind up regular tablets of naltrexone into the smaller doses you’ll need. As of 2018, each daily dose of LDN typically costs less than $1.6 What other treatments can help with bipolar disorder
Regular-dose naltrexone and LDN may help reduce bipolar disorder symptoms, but they aren’t intended as stand-alone treatments. In short, it’s still important to work with a mental health professional for bipolar disorder treatment while taking naltrexone. Treatment can depend on your specific symptoms, but your care team may recommend a combination of medication and therapy. Learn more about finding affordable treatment for bipolar disorder.Medication
Common medications for bipolar disorder include:Mood stabilizers: These medications help prevent shifts in mood. Antipsychotics: These medications can help improve mania symptoms. Antidepressants: Certain antidepressants may help relieve feelings of depression. Benzodiazepines: These medications may help treat mania symptoms such as agitation, decreased need for sleep, and racing thoughts. A doctor or psychiatrist can offer more information about medications for bipolar disorder.Therapy
Types of therapy often used to help address bipolar disorder symptoms include:Cognitive behavioral therapy: This approach to therapy can help you learn skills for addressing unhelpful thoughts, feelings, and behaviors.Dialectical behavior therapy: This approach can help you practice mindfulness and emotional regulation skills.Interpersonal and social rhythm therapy: This approach, specifically designed to address bipolar disorder symptoms, may reduce the frequency of mood episodes by helping you create stable routines.Family-focused therapy: Family therapy can help you address conflict and tension in your relationships with loved ones. Psychoeducation: Learning more about bipolar disorder, including your specific triggers and symptoms, can help you better predict and navigate mood episodes. Support groups, which give you a chance to connect with others who have had a similar experience, may also be helpful. Check out our guide to the best bipolar disorder support groups.The bottom line
While research on LDN for bipolar disorder remains in the early stages, some emerging evidence suggests that it could help treat symptoms such as fatigue, sleep problems, and feelings of depression. If you’d like to try naltrexone, at any dose, a good first step is to ask your prescribing clinician about the possibility of adding it to your treatment plan. Emily Swaim is a freelance health writer and editor who specializes in psychology. She has a BA in English from Kenyon College and an MFA in writing from California College of the Arts. In 2021, she received her Board of Editors in Life Sciences (BELS) certification. You can find more of her work on GoodTherapy, Verywell, Investopedia, Vox, and Insider. Find her on Twitter and LinkedIn. Last medically reviewed on September 19, 2022How we vetted this article
SourcesHistoryHealthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. We avoid using tertiary references. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.Bolton MJ, et al. (2020). Low-dose naltrexone as a treatment for chronic fatigue syndrome.casereports.bmj.com/content/13/1/e232502Brown ES, et al. (2006). Naltrexone in patients with bipolar disorder and alcohol dependence.
onlinelibrary.wiley.com/doi/abs/10.1002/da.20213Escelsior A, et al. (2022). Evidence of alterations of beta-endorphin levels and mu-opioid receptor gene expression in bipolar disorder.
sciencedirect.com/science/article/abs/pii/S016517812200381XGrunze H, et al. (2021). Comorbid bipolar and alcohol use disorder - a therapeutic challenge.
frontiersin.org/articles/10.3389/fpsyt.2021.660432/fullGrunze H, et al. (2022). The pharmacotherapeutic management of comorbid bipolar disorder and alcohol use disorder.
tandfonline.com/doi/abs/10.1080/14656566.2022.2083500Label and off-label coverage of outpatient drugs and biologicals. (2019).
cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=33915&ver=17Losekam S, et al. (2013). Letter to the editor: Shopping frenzy induced by naltrexone - a paradoxical effect in bipolar disorder?
cambridge.org/core/journals/psychological-medicine/article/letter-to-the-editor-shopping-frenzy-induced-by-naltrexone-a-paradoxical-effect-in-bipolar-disorder/4C05639F02DCE1B94B5B1D7AFA6AD25CMischoulon D, et al. (2017). Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants.
sciencedirect.com/science/article/abs/pii/S0165032716304499?via%3DihubNaltrexone. (2022).
samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/naltrexoneTeneralli RE, et al. (2021). Exploring real-world evidence to uncover unknown drug benefits and support the discovery of new treatment targets for depressive and bipolar disorders.
sciencedirect.com/science/article/pii/S0165032721004286?via%3DihubToljan K, et al. (2018). Low-dose naltrexone (LDN) - review of therapeutic utilization.
mdpi.com/2076-3271/6/4/82/htmWhat you need to know about low dose naltrexone. (2020).
weillcornell.org/news/what-you-need-to-know-about-low-dose-naltrexoneOur experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Current Version Sep 19, 2022 By Emily Swaim Edited By Crystal Raypole Medically Reviewed By Yalda Safai, MD, MPH Copy Edited By Jill Campbell Share this articleMedically reviewed by Yalda Safai, MD, MPH — By Emily Swaim on September 19, 2022