Last updated: December 2019
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If you’re struggling with depression or if you know someone who is: You’re not alone. There are resources and support networks, new therapies and emerging research, and a wide range of interventions, tools, and medical-care options. We’ll cover many of them in this article—as always, talk to your doctor about what’s best for you.
For Immediate Help
If you are in crisis, please contact the National Suicide Prevention Lifeline by calling 800.273.TALK (8255) or the Crisis Text Line by texting HOME to 741741 in the United States. If you’re outside the United States, please visit iasp.info.
The World Health Organization (WHO) estimates that 4.4 percent of the global population suffers from depression. Eight percent of American adults have depression, and women are twice as likely to be depressed as men (Brody, Pratt, & Hughes, 2018).
Depression is a wide-ranging disorder that can affect many aspects of your life beyond your mood. It can be associated with lower energy levels and substance disorders. It can affect work performance and interpersonal relationships, and it can lead to physical manifestations of illness, such as heart problems (Kessler, 2012; Wells et al., 1989). Depression can cause more impairment than other chronic diseases, such as diabetes or arthritis (Wells et al., 1989). At its worst, depression can lead to suicide, killing nearly 45,000 people per year in the US (NIH, 2018a).
It’s shocking that depression can be overlooked and even stigmatized in our society, which can contribute to a culture of shame. There is still more work to do, but we’re grateful that many gains have been made in recent years toward destigmatizing depression and starting important conversations about mental health.
Depression can take many forms, including major depression, seasonal affective disorder, situational depression, postpartum depression, and bipolar disorder. We will focus mainly on major depressive disorder (MDD), also called clinical depression or unipolar depression.
Symptoms of Depression
Depression can come and go in bouts or be more persistent, as is the case with major depression. Symptoms vary from person to person and may include changes in sleep, appetite, and energy; loss of interest in daily activities; and thoughts of suicide.
One of the leading depression theories since the 1990s has been that depression is biological: that it is caused in part by changes in the brain and chemical imbalances . This theory has been debated, and today much of the medical community believes that a wide range of factors—biological, emotional, physical, environmental, etc.—could be at the root of depression and that this could look different for different people. Research has looked at genetic susceptibility (depression runs in families) and the impact of trauma, stress, a lack of social connection, illnesses, and medical conditions.
The Diagnostic and Statistical Manual of Mental Disorders (the DSM) defines psychological disorders such as depression with various diagnostic criteria. Major depressive disorder is defined by the DSM-5 as at least two weeks of depressed mood or lack of pleasure in everyday activities, as well as several other symptoms. These symptoms include: weight loss or appetite change, insomnia or hypersomnia, psychomotor agitation, fatigue, feelings of worthlessness or guilt, lack of concentration, and recurrent thoughts of death or suicide (American Psychiatric Association, 2013).
While the DSM has been used since the 1970s to aid with diagnosis, it lumps all depressed individuals into one category for treatment, which is not necessarily useful. Even the National Institute of Health (NIH) acknowledges that not all symptoms need to be present and that subsymptomal depression may also be distressing and require treatment. The bottom line: Seek help if you feel you may need it or want it, regardless of whether you meet the DSM-5 criteria for clinical depression.
A healthy, well-rounded Mediterranean diet is ideal for mental and physical health. Moderating caffeine and alcohol intake is also key.
Food is important to nearly every aspect of our health and well-being. Researchers in Australia determined that a Mediterranean diet intervention consisting of nutritious food, cooking workshops, and social eating was a cost-effective treatment for depression compared to a social support group intervention (Segal et al., 2018). Additionally, a recent meta-analysis of twenty-one studies found that eating a Western diet (red and processed meats, refined grains, sweets, high-fat dairy products, and potatoes) was associated with a greater risk of depression than a Mediterranean diet (fruit, vegetables, whole grains, fish, olive oil, and low-fat dairy) (Li et al., 2017). Researchers have questioned whether this is due to the more well-rounded diet or if the key here is increased omega-3 intake from fish.
Coffee lovers: Research has suggested that coffee, which is a major source of caffeine, may modulate neurotransmitters in the brain such as dopamine and serotonin, and consumption has been associated with decreased risk of depression and suicide (Wang, Shen, Wu, & Zhang, 2016). Scientists in Finland wanted to see how the amount of coffee people drink might affect risk of suicide, and they found that there is a J-shaped association with coffee drinking and risk of suicide. People who were moderate coffee drinkers (two or three cups per day) had the lowest risk of suicide, while the highest risk of suicide was among heavy coffee drinkers (eight or more cups per day) (Tanskanen et al., 2000). If you like coffee and tolerate it well, stick to a couple cups a day.
While a glass of wine suits some people, excess drinking can be particularly hard on people with depression. Several studies have shown that increased alcohol use (as well as misuse of drugs) has been linked to higher risk of depression and suicide (Hawton, Casañas i Comabella, Haw, & Saunders, 2013). According to the CDC, moderate alcohol consumption is one drink per day for women and two drinks per day for men (CDC, 2018). If you drink much more than that, consider whether it’s good for you and seek help if you need it. The National Institutes of Health (NIH) has a guide for seeking help and treatment for alcohol issues.
Nutrients and Supplements for Depression
Proper intake of omega-3 fatty acids, folate, and vitamin D through diet or supplementation may be beneficial for people with depression.
Omega-3 polyunsaturated fatty acids (PUFAs) include alpha-linolenic acid (which is found in flaxseed, chia seeds, and walnuts), eicosapentaenoic acid (EPA, which is found in seafood) and docosahexaenoic acid (DHA, which is also found in seafood) (NIH, 2018b). There is a debate among researchers about whether or not omega-3 supplementation is beneficial for major depression and whether the type of omega-3 makes a difference. A 2012 meta-analysis by researchers at Yale found that omega-3 treatment for depression was not effective and that most of the published studies showing benefits were biased (Bloch & Hannestad, 2012). However, a more recent, 2016 meta-analysis, which included many of the same studies as the 2012 meta-analysis, found a beneficial effect of omega-3s that was similar to the effect of antidepressants. The researchers also found that benefits were greater in participants also taking antidepressants and for higher doses of EPA (Mocking et al., 2016).
Overall, it seems the answer isn’t quite clear yet on whether omega-3s are beneficial for all people with depression, but there is no evidence that supplementation is harmful. Many Americans probably do not get enough omega-3s from their diet alone, so find a good fish oil or algae supplement containing both EPA and DHA.
Sometimes referred to as vitamin B9, folate can be found in several foods such as spinach, black-eyed peas, asparagus, Brussels sprouts, romaine lettuce, avocado, broccoli, and kidney beans. Your body needs folate in order to transform protein into important chemicals messengers called neurotransmitters—these include serotonin, dopamine, and norepinephrine. Low folate status has been associated with depression and poor response to antidepressant treatment in some studies (Huang et al., 2018; Morris, Fava, Jacques, Selhub, & Rosenberg, 2003; Papakostas et al., 2004).
Some evidence suggests that supplementation with folate or methylfolate (a specific form of folate) may be helpful, although this evidence is limited. A 2018 meta-analysis concluded that less than five milligrams per day of folate or fifteen milligrams per day of methylfolate may be a good add-on to SSRI antidepressant therapy (Roberts, Carter, & Young, 2018). Whether folate is beneficial across the board for depression treatment is not clear, but it’s worth making sure your multivitamin contains folate.
Low levels of vitamin D (the “sunshine vitamin”) are associated with depression, and some studies have shown that supplements may be helpful (Anglin, Samaan, Walter, & McDonald, 2013). A 2014 meta-analysis of seven clinical trials found that vitamin D supplementation didn’t improve depressive symptoms, but when the researchers looked at just the two studies on clinically depressed patients, they found that vitamin D did improve depression (Shaffer et al., 2014). Another meta-analysis published in 2014 found that vitamin D supplementation (800 IU per day or more) among people who were deficient improved depression as much as antidepressants (Spedding, 2014).
While there is not general agreement among researchers about whether supplementation may be beneficial for depression, many people may not be getting enough vitamin D from their diet or the sun, so supplementation may be advised regardless. People who live far from the equator may be especially low in vitamin D and have increased risk of depression (see the light therapy section for more) (Melrose, 2015). If you always cover up with clothing or sunblock when are you are outside or if you have dark skin, you may be low in vitamin D.
S-adenosylmethionine (SAMe) is involved in the synthesis and metabolism of neurotransmitters and has been used in Europe to treat depression (Galizia et al., 2016). In the US, it is available as a dietary supplement. A 2016 systematic review of eight clinical trials found that SAMe alone was not better than a placebo but provided some evidence that SAMe combined with antidepressants was more effective than a placebo (Galizia et al., 2016). The most recently published meta-analysis on SAMe reported only modest benefits and was based on just a few small studies (Hardy et al., 2003). There has been relatively little research into SAMe for depression, so hopefully more well-controlled trials will be carried out in the near future to determine if there is promise for its use in treating depression (Sharma et al., 2017).
Tryptophan and 5-Hydroxytryptophan
You may have heard about these amino acids and their mood-lifting effects. Tryptophan is an amino acid found in all protein foods but most associated with Thanksgiving turkey. It is the primary building block for serotonin: With the help of vitamin B6, the body converts tryptophan to 5-hydroxytryptophan (5-HTP), which is then made into serotonin. Both tryptophan and 5-HTP are available as nonprescription dietary supplements. The results that support using these supplements are primarily from small, uncontrolled studies; however, tryptophan continues to be a popular supplement for many people (Lindseth, Helland, & Caspers, 2015; Shaw, Turner, & Mar, 2002).
Lifestyle Changes for Depression
Exercise, social support, and sleep are all necessary ingredients for good mental health. Managing stress, spending time in nature, and using social media consciously may also be helpful.
Exercising regularly is one of the best things you can do for your overall health. A meta-analysis of twenty-three clinical trials found that exercise itself is an effective treatment for depression—so for people who don’t want to (or can’t) try more-aggressive treatment options, exercising alone may be enough. The authors also found that exercise is an effective add-on treatment to antidepressant medications (Kvam, Kleppe, Nordhus, & Hovland, 2016).
Which types of exercise are best? Two separate studies, a meta-analysis and a systematic review, found that moderate-intensity aerobic exercise supervised by a trainer or group fitness leader was beneficial (Schuch et al., 2016; Stanton & Reaburn, 2014). Our recommendation: Find something you like that you can stick with.
Social support has been shown to be protective against depression. A meta-analysis of one hundred studies found that among children, parental support is most important, whereas spousal support is most important for adults, especially for men, followed by friendships (Gariépy, Honkaniemi, & Quesnel-Vallée, 2016). While pushing family and friends away can be common with depression, it’s important to keep your loved ones close or find emotional support from other avenues (a therapist, group activities, etc.).
Depression can affect your ability to get a good night’s rest or, on the other hand, you may be sleeping all the time. A recent meta-analysis found that it’s important to be somewhere in the middle: Individuals with short sleep duration and those who got too much sleep had increased risk for depression compared to those who got a normal night’s rest. The researchers’ explanation was that light sleepers may be tired through the next day, while heavy sleepers may not get a good workout in the next day. One issue is that researchers define “short” versus “long” sleep duration differently—some say less than five hours is too little, and others say less than seven may be too little. Some say more than eight hours is too much, and others say more than nine hours is too much (Zhai, Zhang, & Zhang, 2015). It seems that moderate sleep is the best way to go, but studies have also shown that wake therapy may help some people with MDD (for more on that, see the clinical trials section).
The UN estimates that by 2050, 68 percent of the world will live in urbanized areas, with less access to green space and nature. It’s more important than ever to reconnect with nature in whatever way is available to you. Being immersed in nature—in a park, on a hike, staring out at the ocean from your beach chair—can make you feel small, in a good way. You might relax; your ego might drip away; you might notice that you’re a part of something much greater than yourself. At least, that’s what researchers studying the benefits of nature on mental health believe. In 1981, a University of Michigan architect found that at the State Prison of Southern Michigan, prisoners who occupied cells without access to windows with a view of nature had more frequent sick-call visits than those with nature views (Frumkin, 2001).
Since then, several preliminary studies have shown that more contact with nature improves individuals’ mental health and cognition (Berman et al., 2012; Gascon et al., 2015). A 2017 study of over 23,000 Korean citizens found that greater access to green space was associated with decreased depressive symptoms (Kim & Kim, 2017). While the research is still new and emerging, it’s enough for us to want to unplug and get outdoors.
A cruel irony of depression is that people often feel like they’re alone, when in reality depression is something that they share with millions of other people. We’re also in the age of social media, connected with more people than ever, yet many of us still feel disconnected. Technology gives us opportunities to connect with people online (and in potentially meaningful ways) but has resulted in less face-to-face time with others in which we could have meaningful conversations and interactions. Studies have shown that among both adolescents and adults, more frequent social media users had higher measures of depression, whereas frequent adolescent social media users also had worse anxiety, self-esteem, and sleep (Lin et al., 2016; Woods & Scott, 2016). It’s possible that people with depression may be using social media more often; it isn’t clear yet if social media can cause depression or mental health issues. If using social media causes you to feel lonely, upset, or sad, try to limit your use and take some time to disconnect from your phone.
Stressful life events can increase your likelihood for recurring depression and physical illness (Burcusa & Iacono, 2007; Holmes & Rahe, 1967). It might be that stress accumulates over time, eventually triggering major issues. There is also evidence that stress reactivity (how you respond to everyday stressful events) impacts the development of depression (Booij, Snippe, Jeronimus, Wichers, & Wigman, 2018; Felsten, 2004). Learning to cope with stressful life events is important to both mental and physical well-being. Incorporating mindfulness, yoga, meditation, and social activities may help with stress. For more on this, see the alternate treatments section. You can also take the Stress Test, which was developed in the 1960s to measure social and life events that can have a meaningful impact on a person’s stress and well-being. The tests asks you to recount the number of stressful life events you’ve had in the past year (Holmes & Rahe, 1967).
Conventional Treatment Options for Depression
The most common treatment options for depression are psychotherapy and antidepressants. There are many different styles of therapy and types of antidepressants, and they have varying potential benefits and potential side effects. Treatment is entirely individual, and it may take some time to find what works best.
Cognitive Behavioral Therapy (CBT)
Cognitive behavioral therapy (CBT) is among the most popular evidence-based treatments for depression. It’s usually delivered in hour-long one-on-one sessions with a patient and their therapist. The theory behind it is that psychological problems are rooted in unhelpful ways of thinking and behaving. With CBT, people learn new coping mechanisms and work on changing negative patterns going forward. Several studies have shown that CBT is as effective as antidepressants at treating mild to moderate depression and is even more effective as a combined therapy with antidepressants (Cuijpers et al., 2013). New research into smartphone-delivered CBT has shown favorable results as well, giving hope for more convenient alternatives to in-person therapy for those who are time-strapped (Mantani et al., 2017; Webb, Rosso, & Rauch, 2017).
What’s the Difference between Psychiatrists, Psychologists, and Therapists?
A psychiatrist has a medical degree and can prescribe medications. A psychologist has a doctorate in psychology and cannot prescribe medications. “Therapist” is an umbrella term for any health professional a person sees to talk through their issues—a therapist can have a background in psychology, social work, or other forms of counseling. Some individuals may see both a psychiatrist and therapist, while others may see just one or the other. It depends on whether the person is interested in taking antidepressants or other prescribed medications.
It’s important to find someone you feel you can talk to and that you jibe with. It may take some time to find a therapist you like, but it can be well worth it in the long run to find a good fit. See our article with psychotherapist Satya Doyle Byock, MA, LPC, on how to find a therapist that’s right for you.
Interpersonal Therapy (IPT)
Interpersonal therapy (IPT) is a type of talk therapy that is delivered in three phases across a twelve- to sixteen-week period. The first phase focuses on targeting the clinical diagnosis as well as any interpersonal context around it (for example, the patient’s parent may have recently passed away). The second phase focuses on working through interpersonal problems, such as properly mourning the death of a loved one or resolving a marital dispute. The last phase focuses on helping the patient feel more capable solving interpersonal problems and more empowered moving forward post-treatment (Markowitz & Weissman, 2004).
IPT has been shown in several studies to be effective at treating acute depression and may also help prevent new disorders and relapse (Cuijpers, Donker, Weissman, Ravitz, & Cristea, 2016).
Problem-Solving Therapy (PST)
Another common type of psychotherapy is called problem-solving therapy (PST), which focuses on training people in attitudes and skills to solve daily problems in two phases. In the first phase, which is called “problem orientation,” the therapist explores how the client views their problem and helps them identify and restructure the problem based on their strengths. The second phase focuses on the client’s problem-solving style, creating strategies to overcome it (Gellis & Kenaley, 2008).
A recent meta-analysis found that PST may be an effective treatment for adult depression, with similar success as other types of psychotherapy (Cuijpers, de Wit, Kleiboer, Karyotaki, & Ebert, 2018).
There are many different types of medications that can be taken for depression, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and selective serotonin noradrenaline reuptake inhibitors (SSNRIs). Less commonly used medications include monoamine oxidase inhibitors (MAOIs), trazodone, and lithium.
A recent meta-analysis of 522 clinical trials of twenty-one different antidepressants found that every antidepressant was more effective than a placebo in adults with major depression, although the improvement in symptoms as a result of each antidepressant was only slightly greater than the improvement as a result of the placebo (Cipriani et al., 2018).
Each antidepressant has its own considerations and side effects (such as sexual dysfunction, sleep disturbances, and weight gain), so your doctor or psychiatrist will generally prescribe a low dose at first, and it may take some tweaking to find the right medication and dose for you (Ferguson, 2001). Keep in mind that antidepressants are not an immediate fix; they take several weeks to kick in and are generally prescribed for nine months or even longer to prevent relapse.
A strong warning: Use of antidepressants may increase suicidal thoughts in teenagers and young adults, so they should see a therapist for frequent checkups when beginning a new antidepressant (Turnipseed & Magid, 2008). A meta-analysis considering the risk-benefit trade-off of antidepressants concluded that antidepressants are not worth the risks for children and teenagers (Cipriani et al., 2016).
A Critical Look at Antidepressants
Antidepressants seem to be the norm now for depression treatment. An analysis of NIH data by The New York Times found that the rate of antidepressant use in the US has tripled since 2000, and those who take antidepressants for two or more years has increased by 60 percent since 2010. One proposed cause of this increase in use may be that users simply don’t stop taking them. Stopping antidepressants too suddenly can cause severe symptoms and depressive relapse. If you are considering going off of antidepressants—which is possible for some people—please talk to your doctor and taper off with the help of medical professionals. Severe problems are commonly associated with antidepressant withdrawal, including anxiety, sleep disturbances, sadness, fatigue, and brain zaps (people literally feel as if their brain is being shocked)—which many patients are not warned about and researchers haven’t studied thoroughly enough (Cartwright, Gibson, Read, Cowan, & Dehar, 2016; Ostrow, Jessell, Hurd, Darrow, & Cohen, 2017).
Antidepressants work for some people, and many credible psychiatrists will tell you that they have saved their patients’ lives. There is no shame in taking medication. It just might not be right for everyone (nothing is). Some researchers suggest that antidepressants may benefit only severely depressed people and that antidepressants are no better than a placebo for mild to moderate depression (Fournier et al., 2010; Kirsch et al., 2008). Other researchers suggest they’re no better than a placebo for any depressed person at all. A particularly well-known researcher at Harvard, Irving Kirsch, has published several studies showing that the benefits of antidepressants are so small, in reality they may be no better than a placebo. He and other psychologists have written about how the serotonin theory of depression is unfounded—because nobody really knows how SSRIs work or why—and has been perpetuated by pharmaceutical companies (Healy, 2015; Kirsch et al., 2008; Kirsch, Moore, Scoboria, & Nicholls, 2002; Kirsch & Sapirstein, 1998).
It’s true that many of the “positive” studies on antidepressants are often sponsored by pharmaceutical companies. And that studies that find antidepressant use to have insignificant results or no benefit may not be published at all. This is called publication bias (Jakobsen et al., 2017; Khan & Brown, 2015). Even the STAR*D study, the longest and largest study of depression treatment published by the National Institute of Mental Health, has been subject to much criticism about the validity of the study and how the researchers presented their results (NIH, 2006; Pigott, 2011). (An in-depth analysis and critique of the STAR*D study can be found here.)
As the larger debate continues over antidepressants, it’s important for individuals to be able to make informed decisions about what’s best for them with their doctors. The potential side effects and withdrawal symptoms should be taken into account along with the potential benefits. If you’ve tried other treatment options first (exercise, therapy, etc.) to no avail or are severely depressed and need more help, antidepressants may be the right choice for you.
Brain Stimulation Therapy
You’ve probably seen horror movies about psych wards giving electric shocks to unwilling patients: Brain stimulation therapy is definitely not that. It’s done under general anesthesia. Electric currents are sent through the brain, which triggers a brief seizure that can change the brain chemistry and often reverse depressive symptoms.
There are various types of brain stimulation therapy, including electroconvulsive therapy (ECT), vagus nerve stimulation, repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy, and deep brain stimulation. These types of therapies are generally used when other treatments, like therapy and antidepressants, fail; this is called treatment-resistant depression.
Of all of these therapies, ECT has been shown to be the most effective for depression, specifically showing benefits for people with severe treatment-resistant depression and older adults (Khalid, Atkins, Tredget, Champney-Smith, & Kirov, 2008; Weiner & Reti, 2017).
These therapies do have side effects that warrant serious consideration, including memory issues in the months following treatment. However, memory generally returns after a while.
Alternate Treatment Options for Depression
Mind-body therapies, such as meditation and yoga, have been shown to be effective for depression treatment. Light therapy may be helpful, especially for those with seasonal affective disorder. Herbal protocols and supplements such as St. John’s wort and saffron have been well-researched for their antidepressant activity.
As nature ebbs and flows with the change of seasons, so can our moods if we don’t get enough sunshine. Seasonal affective disorder (SAD) is a type of depression with recurring seasonal patterns, typically appearing in the fall and winter and passing come summer. Women and those who live farther from the equator are more likely to be diagnosed with SAD (NIH, 2016). Light therapy (a bright light box that mimics sunlight without as many harmful UV rays) is a low-cost treatment that has been shown to be as effective as CBT in treating SAD (Golden et al., 2005; Rohan et al., 2015). A recent meta-analysis found that light therapy may also be beneficial for nonseasonal depression, although evidence was limited (Perera et al., 2016).
Overall, the small cost seems well worth it if you live in a colder climate. Try putting one on your vanity for twenty minutes as you get ready in the morning for some added sunshine. Find one specifically made for SAD that has an intensity of 10,000 lux and avoid looking directly into the light as it could cause eye damage (Mayo Clinic, 2016).
While mindfulness is starting to become more mainstream, your doctor probably won’t prescribe ten minutes of sitting per day for depression. But this might help. Developed by Jon Kabat-Zinn, a professor at the University of Massachusetts Medical School and the author of numerous books on mindfulness, mindfulness-based stress reduction (MBSR), and its spin-off developed by psychologists, mindfulness-based cognitive therapy (MBCT), have been thoroughly studied since the late 1990s for their impact of various aspects of mental health and well-being.
Sara Lazar, a professor at Harvard who studies the neuroscience of yoga and meditation, has published several studies showing how mindful meditation can improve mental flexibility and reduce depressive symptoms among individuals with depression (Shapero et al., 2018). A 2014 meta-analysis found that both MBSR and MBCT were beneficial for individuals with depressive disorder, but MBCT may be more effective due to its emphasis on depression treatment (Strauss, Cavanagh, Oliver, & Pettman, 2014). A meta-analysis by researchers at Johns Hopkins found that eight weeks of a mindfulness meditation program can result in small improvements in anxiety, depression, pain, and stress. The researchers also found that mindfulness meditation and antidepressants may be similarly effective (Goyal et al., 2014). Organizations such as Insight LA offer mindfulness workshops, and you can also find a mindfulness-based therapist or practice using online guided meditations or meditation phone apps.
The practice of yoga extends beyond just the physical postures (asanas) through its emphasis on mindfulness, nonattachment, and equanimity, which may improve the negative mental aspects of depression. Several studies have shown that long-time yogis have greater cortical thickness and activation in certain areas of the brain (Afonso et al., 2017; Desai, Tailor, & Bhatt, 2015). It also has been shown in several meta-analyses to be an effective treatment alone and as an add-on for depression, with a similar effect to antidepressants (Cramer, Anheyer, Lauche, & Dobos, 2017; Cramer, Lauche, Langhorst, & Dobos, 2013; Gong, Ni, Shen, Wu, & Jiang, 2015). You can find a local studio or practice on your own; there are many free tutorials and videos online. For more on the benefits of yoga, particularly hot yoga, see the clinical trials section below.
A growing number of people are seeking out Eastern modalities to help treat depression. A meta-analysis of thirteen clinical trials found that acupuncture was an effective add-on to antidepressant treatment over a six-week period (Chan, Lo, Yang, Chen, & Lin, 2015). Another systematic review found that acupuncture helped improve depression-related insomnia, especially when acupuncture was given as an add-on to regular antidepressant medication (Dong et al., 2017). While more high-quality evidence is needed to examine acupuncture as a long-term treatment option for depression, there is promising short-term evidence for its benefits.
St. John’s Wort
Currently sold as a dietary supplement in the US, St. John’s wort has been shown to be an effective short-term treatment for mild to moderate depression. A 2016 meta-analysis found that it is similarly effective to antidepressants with fewer side effects (Cui & Zheng, 2016). Although commonly used in Europe by medical professionals for mild to moderate depression, it is not used as frequently in the US, and studies vary in consistency and quality, so it’s hard to reach a definite conclusion (NIH, 2017).
Important warning: St. John’s wort should never be used in combination with prescription antidepressants as it can lead to potentially life-threatening levels of serotonin in your brain. It may also decrease the effectiveness of certain medications, such as birth control, some HIV drugs, and other medications (NIH, 2017). If you are undergoing an organ transplant, avoid taking St. John’s wort (Ernst, 2002).
Used in Greece, the Middle East, and in traditional Chinese medicine, saffron is a both a spice and medicinal herb that has been shown to be quite effective at improving moderate depression, with several studies showing its efficacy is similar to that of antidepressants (Lopresti & Drummond, 2014). A 2011 systematic review of saffron found that six studies showed beneficial effects when extracts of both the stigma and the petal of the saffron flower were consumed (Dwyer, Whitten, & Hawrelak, 2011). This is promising because the saffron stigma that has traditionally been studied is much more expensive than its petal. Saffron extracts are sold as dietary supplements, and at least thirty milligrams of a saffron extract containing 2 percent safranal is considered an active daily dose (Ann Hausenblas, Heekin, Mutchie, & Anton, 2015).
While getting a massage is typically considered a luxury, research suggests that regular massage with aromatherapy may be beneficial for depression treatment in older adults. A small study in China found that both aromatherapy massage and inhalation of an essential oil consisting of lavender, sweet orange, bergamot, and almond oil reduced depression in a group of older adults when given twice weekly for two weeks (Xiong et al., 2018). Other small studies have found that both aromatherapy massage and regular massage can reduce depression in patients with illnesses such as cancer and HIV (Chang, 2008; Poland et al., 2013). While large-scale studies are needed to confirm these findings, getting massages more regularly could be a great way to improve your mood, relax, or simply treat yourself.
Music as a healing modality dates back to ancient times (Apollo was the ancient god of both music and medicine). Music can affect your mood and energy levels, by lulling you to sleep or waking you up. Recently, there has been a surge of research into music therapy delivered in a one-on-one or group session with a therapist as an adjunct treatment for chronic pain, cancer, mental health disorders, and a variety of other condition. A 2017 meta-analysis found that music therapy is beneficial for short-term treatment of depression and can be a good add-on to other treatment options (Aalbers et al., 2017).
The type of music therapy that is beneficial seems to differ from person to person, but studies have shown that sixty minutes of group music therapy is particularly beneficial, especially for older people (Leubner & Hinterberger, 2017). When music is combined with meditation, it may further improve well-being. One study by researchers at UCSD found that Tibetan sound bowl meditation reduced participants’ tension, anger, fatigue, and depressed mood while increasing their sense of spiritual well-being (Leubner & Hinterberger, 2017).
New and Promising Research on Depression
In recent years, there has been an exciting resurgence in research on the therapeutic usage of psychedelics for mental health conditions such as depression. And new research has drawn a connection between our gut microbiome and mental health.
How Do You Evaluate Clinical Studies and Identify Promising Results?
The results of clinical studies are described throughout this article, and you may wonder which treatments are worth discussing with your doctor. When a particular benefit is described in only one or two studies, consider it of possible interest, or perhaps worth discussing, but definitely not conclusive. Repetition is how the scientific community polices itself and verifies that a particular treatment is of value. When benefits can be reproduced by multiple investigators, they are more likely to be real and meaningful. We’ve tried to focus on review articles and meta-analyses that take all the available results into account; these are more likely to give us a comprehensive evaluation of a particular subject. Of course, there can be flaws in research, and if by chance all of the clinical studies on a particular therapy are flawed—for example with insufficient randomization or lacking a control group—then reviews and meta-analyses based on these studies will be flawed. But in general, it’s a compelling sign when research results can be repeated.
Certain cultures have a long history of using hallucinogenic plants as part of their rituals and ceremonies. In the 1950s, the golden age of psychedelics began in the Western world with researchers and psychologists alike studying the drugs. Numerous studies around this time found benefits of these drugs and therapists began administering them to their patients, including several high-profile celebrities. As use began to increase outside of the laboratories and sweep across college campuses, there was a mass fear that a cultural resistance had begun. In 1970, President Nixon signed the Controlled Substances Act which lumped marijuana, psilocybin, LSD, and MDMA together with heroin and other Schedule 1 drugs (illegal drugs that have high abuse potential, no medical use, and severe safety concerns). With that, the field of psychedelic research became illegal and was pushed underground save for a few academic institutions that still had the green light to continue their studies.
Recently, there has been a resurgence of psychedelic research, with several FDA-funded studies looking at their effects on depression, addiction, PTSD, and other mental health disorders—with very promising findings. Please be advised that while the research is exciting, these studies have been carried out by experienced therapists using carefully calibrated doses, and many of these drugs are still illegal in the United States. To read more about the science and shamanism of psychedelics, see our Q&A with Charles Grob, MD, leading researcher in the field of psychedelic-assisted therapy.
Commonly known as magic mushrooms, the active psychedelic chemical psilocybin has been used in Central American culture for hundreds of years and more recently has been studied in the West for its ability to improve depression, addiction, and anxiety. Several recent studies have shown that psilocybin-assisted psychotherapy can drastically reduce depressive symptoms and possibly even treatment-resistant depression (when two or more treatment options do not work for someone) (R. L. Carhart-Harris et al., 2018; Griffiths et al., 2016; Ross et al., 2016). One study at NYU found that a single low dose of psilocybin (0.3 milligrams per kilogram) clinically reduced depression in 60 to 80 percent of patients—even six and half months later. (Ross et al., 2016). There is a phase 2 clinical trial at Johns Hopkins University studying psilocybin for depression as well as a phase 1 clinical trial at Yale that is recruiting.
Historically used in Amazonian culture, ayahuasca is a vine that can be made into a brew, eliciting psychedelic effects when consumed. Several studies by researchers in Brazil have looked into ayahuasca-assisted psychotherapy for treatment-resistant depression, finding a rapid antidepressant effect. However, about half of the patients experienced vomiting in these studies, and in one study, a small number who presented with a “more delicate condition” stayed for a week in the hospital ward (Osório et al., 2015; Palhano-Fontes et al., 2018; Sanches et al., 2016). More well-controlled research is needed on the safety and feasibility of ayahuasca as a depression treatment.
Generally used for anesthesia, ketamine is a dissociative anesthetic that has also been shown to be extremely successful at improving symptoms in individuals with treatment-resistant depression (Kraus et al., 2017; Murrough et al., 2013). A 2014 meta-analysis of thirteen studies found that ketamine exhibits short-term antidepressant effects that last two to three days (Fond et al., 2014). Based on this research and its designation as a breakthrough therapy for depression, the FDA approved esketamine, a derivative of ketamine, as a nasal spray for treatment-resistant depression in early 2019. There are currently twelve different actively recruiting clinical trials on ketamine treatment for depression. See our Q&A with psychiatrist Will Siu, MD, on ketamine-facilitated psychotherapy and listen to The goop Podcast episode with psychiatrist Steven Levine, MD.
MDMA has gained a somewhat negative reputation because of its street forms, ecstasy and molly, which are used as party drugs in rave culture. But there has been interesting research showing that MDMA can be helpful in psychotherapy for people with PTSD and possibly other mental health disorders such as depression. The thought is that MDMA opens individuals up, which helps them form a closer relationship with their therapist and dive into discussions on difficult topics (Yazar‐Klosinski & Mithoefer, 2017). MDMA may also act on the same serotonin receptors as antidepressants, exhibiting a similar effect. However, animal studies have shown that large doses of MDMA can be neurotoxic (Patel & Titheradge, 2015).
The Multidisciplinary Association for Psychedelic Studies (MAPS) is currently recruiting for the first FDA-approved phase 3 clinical trial of MDMA-assisted psychotherapy for PTSD, with the goal of expanding research to other mental health conditions and having MDMA approved as a prescription drug by 2021. To read more about MAPS, see the clinic trials section below. And read our Q&A with psychiatrist Emily Williams, MD, a MAPS-trained MDMA-assisted psychotherapist.
The Default Mode Network
Why might some psychedelics have antidepressant effects? There are several proposed explanations, including this one: Users almost universally report a partial or complete loss of ego or sense of self. Some researchers have found that psychedelics reduce blood flow to the default mode network (DMN), which connects different areas of your brain and creates your ego (Robin L. Carhart-Harris et al., 2012; Lebedev et al., 2015). The theory is that the DMN in depressed individuals may be overactive, which leads to overthinking (rumination) and negative mental patterns; decreased DMN functioning may reduce depressive symptoms (Carhart-Harris et al., 2017). These changes in the DMN following psychedelic experiences may be similar to those that occur during meditation (Brewer et al., 2011). More exciting research in this field is underway to elucidate exactly how psychedelics are seemingly able to jolt the mind of out its old patterns and form new, more positive ways of thinking.
With all the focus on the brain’s function in depression, you may not know that most of your serotonin (the chemical that is thought to be lacking in people with depression) is created in your digestive tract (Yano et al., 2015). Recent research has found that your gut microbiome plays a critical role in regulating this serotonin production, so interventions to promote a healthy gut, such as probiotics, prebiotics, and a healthy diet, may be useful (Cenit, Sanz, & Codoñer-Franch, 2017; Liang, Wu, & Jin, 2018; Yano et al., 2015). A 2019 meta-analysis found that probiotics had small, but significant effects on improving depression as well as anxiety (Liu et al., 2019). A particularly interesting study took fecal samples from depressed patients and transferred them to a rat, which resulted in depressive symptoms in the animal as well (Kelly et al., 2016). More findings from this field could lead to better, individualized depression treatments targeting the gut-brain connection. There is currently a clinical trial being developed in Switzerland to determine whether healthy fecal transplants administered by oral capsules can improve symptoms in people with depression.
Medication Side Effects
A recent study in The Journal of the American Medical Association found that use of prescription medications was common among Americans, and that people who used multiple medications that have depression listed as a potential side effect had a higher likelihood of being depressed. The list of medications that include depression as a side effect is long. It includes antihypertensive drugs, birth control, and antacids, as well as commonly used analgesics, such as ibuprofen (Qato, Ozenberger, & Olfson, 2018). Talk to you doctor if you are consistently taking one of these drugs, especially if you’re on other medications with depression as a side effect.
Clinical Trials for Depression
Clinical trials are research studies intended to evaluate a medical, surgical, or behavioral intervention. They are done so that researchers can study a particular treatment that may not have a lot of data on its safety or effectiveness yet. If you’re considering signing up for a clinical trial, it’s important to note that if you’re placed in the placebo group, you won’t have access to the treatment being studied. It’s also good to understand the phase of the clinical trial: Phase 1 is the first time most drugs will be used in humans, so it’s about finding a safe dose. If the drug makes it through the initial trial, it can be used in a larger phase 2 trial to see whether it works well. Then it may be compared to a known effective treatment in a phase 3 trial. If the drug is approved by the FDA, it will go on to a phase 4 trial. Phase 3 and phase 4 trials are the most likely to involve the most effective and safest up-and-coming treatments. In general, clinical trials may yield valuable information; they may provide benefits for some subjects but have undesirable outcomes for others. Speak with your doctor about any clinical trial you are considering.
Where Do You Find Studies That Are Recruiting Subjects?
You can find clinical studies that are recruiting subjects on clinicaltrials.gov, which is a website run by the US National Library of Medicine. The database consists of all privately and publicly funded studies that are happening around the globe. You can search disease or a specific drug or treatment you’re interested in, and you can filter by country where the study is taking place.
Do you feel great after a hot yoga class? Research suggests this may be more than a post-workout glow. A few studies have shown that whole-body hyperthermia (extreme heat with temperatures of one hundred degrees Fahrenheit or higher) can reduce depressive symptoms in individuals with MDD (Janssen et al., 2016). To confirm these studies, there are a couple clinical trials currently recruiting to assess hyperthermia as a viable depression treatment at Massachusetts General Hospital. David Mischoulon, MD, PhD, the director of the depression clinical and research program, is recruiting subjects for a phase 2 clinical trial of 60- to 120-minute whole-body hyperthermia sessions. They are also conducting a clinical trial of 90 minutes of hyperthermic yoga (hot yoga) to improve depression.
In a phase 3 clinical trial at Yale, ketamine infusions are being studied in adolescents ages thirteen to seventeen who have severe depression. Psychiatrist Michael Bloch, MD, is leading the study, in which adolescents will be randomized to either ketamine treatment with 0.5 milligrams per kilogram of body weight per forty minutes through an IV or a similar dose of midazolam, a sedative, for comparison.
A few studies have suggested that mind-body exercises such as Tai Chi may improve clinical outcomes for mental disorders in older adults (Lavretsky et al., 2011; Siddarth, Siddarth, & Lavretsky, 2014). At UCLA, psychiatry professor Helen Lavretsky, MD, is recruiting adults sixty years or older for a clinical trial to evaluate the effects on depressive symptoms, quality of life, and cognition of twelve weekly 120-minute Tai Chi sessions versus health and wellness classes.
A few studies have suggested that chronotherapeutics (wake and light therapy) may alleviate depression (Martiny et al., 2012; Wirz-Justice et al., 2005). Jonathan Stewart, MD, a psychiatrist at the New York State Psychiatric Institute, is conducting a clinical trial to study sleep deprivation. Subjects will undergo one week of wake therapy, staying awake on alternating nights, along with light box therapy and/or lithium treatment concurrently.
Help in Crisis
If you are in crisis, please contact the National Suicide Prevention Lifeline by calling 800.273.TALK (8255) or the Crisis Text Line by texting HOME to 741741 in the United States. If you’re outside the United States, please visit iasp.info.
• The National Alliance on Mental Illness (NAMI) provides educational programs, resources, presentations, awareness events, and support for mental health.
• The National Institute of Mental Health provides information on how to find a provider or treatment.
• The Child Mind Institute has resources for parents and information about children’s mental health detection, care, and treatment.
• Active Minds is a nonprofit aimed at starting conversations about mental health and promoting advocacy and action.
• Healthy Minds is a PBS series by Dr. Jeffrey Borenstein that explains psychiatric conditions, speaks with patients and experts, and shares new information on research and treatment.
• Wherever You Go, There You Are: Mindfulness Meditation in Everyday Life by Jon Kabat-Zinn
• Peace Is Every Step by Thich Nhat Hanh
• Lost Connections by Johann Hari
• How to Change Your Mind by Michael Pollan
• MindShift is a free app from the nonprofit Anxiety Canada that offers evidence-based mental health tools, tips, and a journal to record thoughts.
• IntelliCare is a hub of several apps, developed by Northwestern University and funded by the National Institutes of Health, that use evidence-based methods to target mental health issues.
• Moodpath tracks your positive and negative emotions each day and offers guided exercises and talks for difficult emotions, a positive attitude, healthy sleep, dealing with conflicts, and more.
• TalkSpace connects users with licensed therapists over messenger.
• Headspace offers guided meditations and exercises for everything from stress to sleep.
• Waking Up provides thorough lessons on mindfulness theory and an introductory meditation course guided by neuroscientist and philosopher Sam Harris.
Related Reading and Listening on goop
Episodes of The goop Podcast
Afonso, R. F., Balardin, J. B., Lazar, S., Sato, J. R., Igarashi, N., Santaella, D. F., … Kozasa, E. H. (2017). Greater Cortical Thickness in Elderly Female Yoga Practitioners—A Cross-Sectional Study. Frontiers in Aging Neuroscience, 9.
Anglin, R. E. S., Samaan, Z., Walter, S. D., & McDonald, S. D. (2013). Vitamin D deficiency and depression in adults: systematic review and meta-analysis. British Journal of Psychiatry, 202(02), 100–107.
Ann Hausenblas, H., Heekin, K., Mutchie, H. L., & Anton, S. (2015). A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes. Journal of Integrative Medicine, 13(4), 231–240.
Berman, M. G., Kross, E., Krpan, K. M., Askren, M. K., Burson, A., Deldin, P. J., … Jonides, J. (2012). Interacting with Nature Improves Cognition and Affect for Individuals with Depression. Journal of Affective Disorders, 140(3), 300–305.
Booij, S. H., Snippe, E., Jeronimus, B. F., Wichers, M., & Wigman, J. T. W. (2018). Affective reactivity to daily life stress: Relationship to positive psychotic and depressive symptoms in a general population sample. Journal of Affective Disorders, 225, 474–481.
Brewer, J. A., Worhunsky, P. D., Gray, J. R., Tang, Y.-Y., Weber, J., & Kober, H. (2011). Meditation experience is associated with differences in default mode network activity and connectivity. Proceedings of the National Academy of Sciences, 108(50), 20254–20259.
Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., … Nutt, D. J. (2018). Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology, 235(2), 399–408.
Carhart-Harris, Robin L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., … Nutt, D. J. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences, 109(6), 2138–2143.
Carhart-Harris, Robin L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., … Nutt, D. J. (2017). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports, 7(1), 13187.
Cartwright, C., Gibson, K., Read, J., Cowan, O., & Dehar, T. (2016). Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Preference and Adherence, 10, 1401–1407.
Chan, Y.-Y., Lo, W.-Y., Yang, S.-N., Chen, Y.-H., & Lin, J.-G. (2015). The benefit of combined acupuncture and antidepressant medication for depression: A systematic review and meta-analysis. Journal of Affective Disorders, 176, 106–117.
Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., … Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. The Lancet, 391(10128), 1357–1366.
Cipriani, A., Zhou, X., Giovane, C. D., Hetrick, S. E., Qin, B., Whittington, C., … Xie, P. (2016). Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. The Lancet, 388(10047), 881–890.
Cui, Y., & Zheng, Y. (2016). A meta-analysis on the efficacy and safety of St John’s wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults. Neuropsychiatric Disease and Treatment, 12, 1715–1723.
Cuijpers, P., Berking, M., Andersson, G., Quigley, L., Kleiboer, A., & Dobson, K. S. (2013). A Meta-Analysis of Cognitive-Behavioural Therapy for Adult Depression, Alone and in Comparison with other Treatments. The Canadian Journal of Psychiatry, 58(7), 376–385.
Cuijpers, P., Donker, T., Weissman, M. M., Ravitz, P., & Cristea, I. A. (2016). Interpersonal Psychotherapy for Mental Health Problems: A Comprehensive Meta-Analysis. American Journal of Psychiatry, 173(7), 680–687.
Dong, B., Chen, Z., Yin, X., Li, D., Ma, J., Yin, P., … Xu, S. (2017). The Efficacy of Acupuncture for Treating Depression-Related Insomnia Compared with a Control Group: A Systematic Review and Meta-Analysis [Research article].
Fond, G., Loundou, A., Rabu, C., Macgregor, A., Lançon, C., Brittner, M., … Boyer, L. (2014). Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology, 231(18), 3663–3676.
Fournier, J. C., DeRubeis, R. J., Hollon, S. D., Dimidjian, S., Amsterdam, J. D., Shelton, R. C., & Fawcett, J. (2010). Antidepressant Drug effects and Depression Severity: A Patient-Level Meta-Analysis. JAMA : The Journal of the American Medical Association, 303(1), 47–53.
Galizia, I., Oldani, L., Macritchie, K., Amari, E., Dougall, D., Jones, T. N., … Young, A. H. (2016). S‐adenosyl methionine (SAMe) for depression in adults. Cochrane Database of Systematic Reviews, (10).
Gariépy, G., Honkaniemi, H., & Quesnel-Vallée, A. (2016). Social support and protection from depression: systematic review of current findings in Western countries. British Journal of Psychiatry, 209(04), 284–293.
Gascon, M., Triguero-Mas, M., Martínez, D., Dadvand, P., Forns, J., Plasència, A., & Nieuwenhuijsen, M. J. (2015). Mental Health Benefits of Long-Term Exposure to Residential Green and Blue Spaces: A Systematic Review. International Journal of Environmental Research and Public Health, 12(4), 4354–4379.
Golden, R. N., Gaynes, B. N., Ekstrom, R. D., Hamer, R. M., Jacobsen, F. M., Suppes, T., … Nemeroff, C. B. (2005). The Efficacy of Light Therapy in the Treatment of Mood Disorders: A Review and Meta-Analysis of the Evidence. American Journal of Psychiatry, 162(4), 656–662.
Goldsby, T. L., Goldsby, M. E., McWalters, M., & Mills, P. J. (2017). Effects of Singing Bowl Sound Meditation on Mood, Tension, and Well-being: An Observational Study. Journal of Evidence-Based Complementary & Alternative Medicine, 22(3), 401–406.
Goyal, M., Singh, S., Sibinga, E. M. S., Gould, N. F., Rowland-Seymour, A., Sharma, R., … Haythornthwaite, J. A. (2014). Meditation Programs for Psychological Stress and Well-being: A Systematic Review and Meta-analysis. JAMA Internal Medicine, 174(3), 357–368.
Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., … Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12), 1181–1197.
Hardy, M. L., Coulter, I., Morton, S. C., Favreau, J., Venuturupalli, S., Chiappelli, F., … Shekelle, P. (2003). S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease. Evidence Report/Technology Assessment (Summary), (64), 1–3.
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Huang, X., Fan, Y., Han, X., Huang, Z., Yu, M., Zhang, Y., … Xia, Y. (2018). Association between Serum Vitamin Levels and Depression in U.S. Adults 20 Years or Older Based on National Health and Nutrition Examination Survey 2005–2006. International Journal of Environmental Research and Public Health, 15(6), 1215.
Jakobsen, J. C., Katakam, K. K., Schou, A., Hellmuth, S. G., Stallknecht, S. E., Leth-Møller, K., … Gluud, C. (2017). Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry, 17.
Janssen, C. W., Lowry, C. A., Mehl, M. R., Allen, J. J. B., Kelly, K. L., Gartner, D. E., … Raison, C. L. (2016). Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry, 73(8), 789–795.
Kelly, J. R., Borre, Y., O’ Brien, C., Patterson, E., El Aidy, S., Deane, J., … Dinan, T. G. (2016). Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. Journal of Psychiatric Research, 82, 109–118.
Khalid, N., Atkins, M., Tredget, J., Champney-Smith, K., & Kirov, G. (2008). The Effectiveness of Electroconvulsive Therapy in Treatment-Resistant Depression: A Naturalistic Study. J ECT, 24(2), 5. Khan, A., & Brown, W. A. (2015). Antidepressants versus placebo in major depression: an overview. World Psychiatry, 14(3), 294–300.
Kirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008). Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Medicine, 5(2).
Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. S. (2002). The emperor’s new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention & Treatment, 5(1), No Pagination Specified-No Pagination Specified.
Kirsch, I., & Sapirstein, G. (1998). Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. Prevention & Treatment, 1(2), No Pagination Specified-No Pagination Specified.
Kraus, C., Rabl, U., Vanicek, T., Carlberg, L., Popovic, A., Spies, M., … Kasper, S. (2017). Administration of ketamine for unipolar and bipolar depression. International Journal of Psychiatry in Clinical Practice, 21(1), 2–12.
Lavretsky, H., Altstein, L., Olmstead, R. E., Ercoli, L., Riparetti-Brown, M., St. Cyr, N., & Irwin, M. R. (2011). Complementary Use of Tai Chi Chih Augments Escitalopram Treatment of Geriatric Depression: A Randomized Controlled Trial. The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry, 19(10), 839–850.
Lebedev, A. V., Lövdén, M., Rosenthal, G., Feilding, A., Nutt, D. J., & Carhart‐Harris, R. L. (2015). Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin. Human Brain Mapping, 36(8), 3137–3153.
Lin, L. yi, Sidani, J. E., Shensa, A., Radovic, A., Miller, E., Colditz, J. B., … Primack, B. A. (2016). Association Between Social Media Use and Depression Among U.s. Young Adults. Depression and Anxiety, 33(4), 323–331.
Liu, R., Walsh, R., & Sheehan, A. (2019). Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neuroscience & Biobehavioral Reviews, 102, 13-23.
Lopresti, A. L., & Drummond, P. D. (2014). Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Human Psychopharmacology, 29(6), 517–527.
Mantani, A., Kato, T., Horikoshi, M., Imai, H., Hiroe, T., Chino, B., … Kawanishi, N. (2017). Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial. Journal of Medical Internet Research, 19(11).
Martiny, K., Refsgaard, E., Lund, V., Lunde, M., Sørensen, L., Thougaard, B., … Bech, P. (2012). A 9-week randomized trial comparing a chronotherapeutic intervention (wake and light therapy) to exercise in major depressive disorder patients treated with duloxetine. The Journal of Clinical Psychiatry, 73(9), 1234–1242.
Mocking, R. J. T., Harmsen, I., Assies, J., Koeter, M. W. J., Ruhé, H. G., & Schene, A. H. (2016). Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Translational Psychiatry, 6(3), e756.
Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. M., Perez, A. M., … Mathew, S. J. (2013). Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial. The American Journal of Psychiatry, 170(10), 1134–1142.
Osório, F. de L., Sanches, R. F., Macedo, L. R., dos Santos, R. G., Maia-de-Oliveira, J. P., Wichert-Ana, L., … Hallak, J. E. (2015). Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Brazilian Journal of Psychiatry, 37(1), 13–20.
Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A., … Araújo, D. B. (2018). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological Medicine, 1–9.
Papakostas, G. I., Petersen, T., Mischoulon, D., Ryan, J. L., Nierenberg, A. A., Bottiglieri, T., … Fava, M. (2004). Serum Folate, Vitamin B12, and Homocysteine in Major Depressive Disorder, Part 1: Predictors of Clinical Response in Fluoxetine-Resistant Depression. The Journal of Clinical Psychiatry, 65(8), 1090–1095.
Perera, S., Eisen, R., Bhatt, M., Bhatnagar, N., Souza, R. de, Thabane, L., & Samaan, Z. (2016). Light therapy for non-seasonal depression: systematic review and meta-analysis. BJPsych Open, 2(2), 116–126.
Poland, R. E., Gertsik, L., Favreau, J. T., Smith, S. I., Mirocha, J. M., Rao, U., & Daar, E. S. (2013). Open-Label, Randomized, Parallel-Group Controlled Clinical Trial of Massage for Treatment of Depression in HIV-Infected Subjects. Journal of Alternative and Complementary Medicine, 19(4), 334–340.
Rohan, K. J., Mahon, J. N., Evans, M., Ho, S.-Y., Meyerhoff, J., Postolache, T. T., & Vacek, P. M. (2015). Randomized Trial of Cognitive-Behavioral Therapy Versus Light Therapy for Seasonal Affective Disorder: Acute Outcomes. American Journal of Psychiatry, 172(9), 862–869.
Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., … Schmidt, B. L. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, 30(12), 1165–1180.
Sanches, R. F., Osório, F. de L., Santos, R. G. dos, Macedo, L. R. h, Maia-de-oliveira, J. P., Wichert-ana, L., … Hallak, J. E. c. (2016). Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A Spect Study. Journal of Clinical Psychopharmacology, 36(1), 77–81.
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Shaffer, J. A., Edmondson, D., Wasson, L. T., Falzon, L., Homma, K., Ezeokoli, N., … Davidson, K. W. (2014). Vitamin D Supplementation for Depressive Symptoms: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Psychosomatic Medicine, 76(3), 190–196.
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Sharma, A., Gerbarg, P., Bottiglieri, T., Massoumi, L., Carpenter, L. L., Lavretsky, H., … Mischoulon, D. (2017). S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. The Journal of Clinical Psychiatry, 78(6), e656–e667.
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