Depression

    Last Updated: August 10, 2023

    Depression is a chronic state of low mood often associated with hopelessness, apathy, and fatigue. Unlike sadness, depression is a disorder that persists for weeks or months and interferes with daily life.

    Depression falls under the Mental Health category.

    What is depression?

    Depression is a state of low mood that can persist for weeks or months.[1] The symptoms of depression interfere with daily life and are often present during adolescence and young adulthood but may not be diagnosed until adulthood. As of 2019, The National Center for Health Statistics reports that 4.7% of U.S. adults over 18 years of age have regular feelings of depression.

    What are the main signs and symptoms of depression?

    The symptoms of depression vary widely, such as sleeping too much or too little. This is one reason why diagnosing depression can be a challenge. Other symptoms include lost interest in favorite activities, feeling hopeless, and under-or overeating.[1] Symptoms may also vary by sex. For example, men with depression report higher rates of anger, aggression, substance use, and risk-taking compared to women.[2]

    How is depression diagnosed?

    Depression is diagnosed by a healthcare provider who usually uses questionnaires that assess symptom severity. For more information on diagnosing depression, please refer to the American Psychiatric Association.[3]

    What are some of the main medical treatments for depression?

    Today, antidepressants (chiefly SSRIs and SNRIs) are still the first-line treatment for depression, but their effects vary across individuals, so one may need to try different antidepressants to find the correct one.[1] Talk therapy is usually used in conjunction with antidepressants. If antidepressants fail to improve symptoms, brain stimulation therapies such as electroconvulsive therapy and transcranial magnetic stimulation can be effective tools for medication-resistant depression.[4]

    How could diet affect depression?

    It appears that a Mediterranean diet or a diet consisting of foods with a low Dietary Inflammatory Index (DII) has been associated with a reduced risk of depression.[5] However, more research is needed before a specific diet can be recommended. With that being said, current research suggests that improving one's diet by replacing "junk" foods with nutrient-dense, higher fiber foods, such as vegetables, fruits, whole grains, and nuts reduce the risk and symptoms of depression.[6]

    Have any supplements been studied for depression?

    If you are using an antidepressant, consult your physician before taking any supplement, as cases of harmful interactions between certain supplements and antidepressants have been reported (e.g., between S-Adenosyl methionine and clomipramine[7]).

    With that in mind, several supplements and herbal remedies have been examined for depression including fish oil, saffron, curcumin, and zinc.

    St. John's wort (Hypericum perforatum, or HP) has shown promise as an effective treatment for mild-to-moderate depression. Several studies have investigated its clinical impact by comparing the Hamilton Depression Rating Scale (HAMD) scores of people taking HP with those of people taking a placebo or traditional antidepressant medications. Some of these studies found that HP extracts have similar antidepressant properties and remission rate to serotonin reuptake inhibitors (SSRIs), with a lower rate of treatment discontinuation due to side effects.[8][9][10] When compared to tricyclic antidepressants (TCAs), HP appears to cause fewer side effects and have lower dropout rates.[10] However, it’s important to note that St. John’s Wort can adversely interact with many pharmaceuticals, including some antidepressants.[8][11][12]

    Are there any other treatments for depression?

    Although alternative treatments such as acupuncture, herbal medicines, and meditation are commonly used for depression, it is not recommended to use alternative medical treatments without seeking approval from a healthcare professional.

    What causes depression?

    The causes of depression are complex, including prenatal factors, genetics, environment, biology, age, and sociocultural and psychological factors.[13]

    Examine Database: Depression

    Research FeedRead all studies

    Frequently asked questions

    What is depression?

    Depression is a state of low mood that can persist for weeks or months.[1] The symptoms of depression interfere with daily life and are often present during adolescence and young adulthood but may not be diagnosed until adulthood. As of 2019, The National Center for Health Statistics reports that 4.7% of U.S. adults over 18 years of age have regular feelings of depression.

    Why is depression more prevalent in women?

    Hard to say, but there’s some evidence that hormones could play a role. One line of evidence suggesting this is that young women are at the greatest risk[20] for major depression and mental disorders starting at puberty, when prevalence of depression[21] is doubled in women compared to men for ages 14-25. However, other social factors around this age could equally play a role. What’s more confusing is that a reduction in estrogen also looks to be linked to depression. In the time right before menopause, when estrogen levels begin to decrease in an irregular fashion, the risk of depression[22] appears to increase, and studies[23] suggest that hormone replacement therapy (particularly estrogen) may prevent or alleviate depression experienced during the transition. In fact, women using oral contraceptives[24], especially the monophasic (same amount of hormones in each pill) type, reported reduced rates of depression and anxiety in comparison to non-users. Unfortunately, since researchers suspect hormonal fluctuations can influence depression, most studies tend to avoid women participants for this reason, so not much human data is available.

    What are the main signs and symptoms of depression?

    The symptoms of depression vary widely, such as sleeping too much or too little. This is one reason why diagnosing depression can be a challenge. Other symptoms include lost interest in favorite activities, feeling hopeless, and under-or overeating.[1] Symptoms may also vary by sex. For example, men with depression report higher rates of anger, aggression, substance use, and risk-taking compared to women.[2]

    How is depression diagnosed?

    Depression is diagnosed by a healthcare provider who usually uses questionnaires that assess symptom severity. For more information on diagnosing depression, please refer to the American Psychiatric Association.[3]

    What are some of the main medical treatments for depression?

    Today, antidepressants (chiefly SSRIs and SNRIs) are still the first-line treatment for depression, but their effects vary across individuals, so one may need to try different antidepressants to find the correct one.[1] Talk therapy is usually used in conjunction with antidepressants. If antidepressants fail to improve symptoms, brain stimulation therapies such as electroconvulsive therapy and transcranial magnetic stimulation can be effective tools for medication-resistant depression.[4]

    How could diet affect depression?

    It appears that a Mediterranean diet or a diet consisting of foods with a low Dietary Inflammatory Index (DII) has been associated with a reduced risk of depression.[5] However, more research is needed before a specific diet can be recommended. With that being said, current research suggests that improving one's diet by replacing "junk" foods with nutrient-dense, higher fiber foods, such as vegetables, fruits, whole grains, and nuts reduce the risk and symptoms of depression.[6]

    Is there a best diet for depression?

    Dietary trends appear to emerge across dietary intervention trials investigating changes in depressive symptoms, and several align with the Mediterranean diet. Increases in fruit and vegetables, nuts and seeds, and fish intake appear to be the way to go[17], and that’s not just for[18] depressive symptoms. In addition, decreases in processed meats, refined carbohydrates, and other inflammatory foods[19] have previously been found to be associated with a greater mental well-being. Even though the state of the evidence isn’t ideal, there is some evidence that certain food groups may impact depression.

    image

    Have any supplements been studied for depression?

    If you are using an antidepressant, consult your physician before taking any supplement, as cases of harmful interactions between certain supplements and antidepressants have been reported (e.g., between S-Adenosyl methionine and clomipramine[7]).

    With that in mind, several supplements and herbal remedies have been examined for depression including fish oil, saffron, curcumin, and zinc.

    St. John's wort (Hypericum perforatum, or HP) has shown promise as an effective treatment for mild-to-moderate depression. Several studies have investigated its clinical impact by comparing the Hamilton Depression Rating Scale (HAMD) scores of people taking HP with those of people taking a placebo or traditional antidepressant medications. Some of these studies found that HP extracts have similar antidepressant properties and remission rate to serotonin reuptake inhibitors (SSRIs), with a lower rate of treatment discontinuation due to side effects.[8][9][10] When compared to tricyclic antidepressants (TCAs), HP appears to cause fewer side effects and have lower dropout rates.[10] However, it’s important to note that St. John’s Wort can adversely interact with many pharmaceuticals, including some antidepressants.[8][11][12]

    Will creatine supplementation help prevent depression?

    Major depressive disorder (MDD) appears to have a genetic component to it, but it’s unknown how much of the disease is preventable. Along with other predictive markers of depression[16] (e.g. income) we can predict to some extent which individuals may be at higher risk of developing MDD. While numerous methods are used as preventive approaches, the brain-energetics side remains largely unexplored.

    Overall, the current evidence is insufficient to recommend supplementation for MDD prevention. Nevertheless, because creatine supplementation is quite safe (with minimal to no side effects), it may prove to be a candidate for those at risk of depression, and the dose would also be relatively easy to titrate (always making sure you discuss your supplementation with your physician or health professional).

    Can vitamin D cure depression?

    Many people get depressed during the winter months, when we produce less vitamin D. So, can supplemental vitamin D cure seasonal depression, and maybe other types of depression? No, alas — but it may help.

    Vitamin D is the “sunshine vitamin”,[29] and sunshine is implicated in mood. So it makes sense that researchers have intently explored vitamin D supplementation for depression. But depression is complex, and the mechanisms at work are not well-understood. However, careful analysis of the trials testing the effects of vitamin D on depression and mood-related pathways will help provide some insight into whether, or if, vitamin D may be helpful for depression in different contexts or populations.

    Two reviews of observational studies and intervention trials reached the same conclusions: When parsing the observational data, both reviews found a correlation between depression and low levels of vitamin D (≤20 ng/mL). When parsing the trial data, both reviews found benefits from supplementation, but also assessed some of the included studies as having low methodological quality and high risk of bias.[30][31]

    Those two reviews were published in 2017 and 2016, so shortly after a 2015 meta-analysis of randomized controlled trials (RCTs) reported finding no significant reduction in depression after vitamin D supplementation. Its authors, however, mentioned that “most of the studies focused on individuals with low levels of depression and sufficient serum vitamin D at baseline”.[32] In other words, they didn’t rule out the possibility that in people with higher levels of depression or lower levels of vitamin D, supplementation might be more effective.

    This hypothesis lines up with the conclusions of a 2014 meta-analysis, which found that, if one considered only the studies whose subjects had low levels of vitamin D at baseline (≤20 ng/mL) and were then given enough vitamin D to achieve sufficiency over the course of the trial, then supplemental vitamin D was about as effective as antidepressant medication.[33] However, this meta-analysis did not account for publication bias.

    A 2018 meta-analysis focused on major depression and found a moderate benefit from vitamin D. However, it stresses the low number of qualifying studies (four trials) and, like the 2017 and 2016 reviews, deplores the low methodological quality of some of the studies.[34] Additionally, a 2016 randomized controlled trial of vitamin D supplementation in people with major depressive disorder purportedly saw an antidepressant effect,[35] but this study was retracted in 2021 due to concerns over the validity of the participant data.[36]

    Finally, let’s mention a 2016 RCT that found that pregnant women who took a daily dose of 2,000 IU (50 μg) of vitamin D3 during late pregnancy had lower scores on a postpartum depression screening scale than those who did not supplement.[37] However, this study only addressed postpartum depression in healthy women with a low-to-moderate pre-partum risk of depression; it may not have wider applicability, and further research is needed.

    Vitamin D insufficiency (≤20 ng/mL) has been associated with depression. If your depression is severe, you are more likely to benefit from correcting an insufficiency. If your levels of vitamin D are sufficient, however, then whether your depression is severe or not, supplementation isn’t likely to help. (Due to the poor overall methodological quality of the studies, those conclusions are at best preliminary.)

    In support of this, a number of observational studies have found that people with depression are more likely to have low vitamin D levels.[38] However, randomized controlled trials don’t consistently find beneficial effects of vitamin D supplementation on depression.[39][40] One reason for this could be that benefits only occur if a person has sufficiently severe depression symptoms. In support of this, two meta-analyses of randomized controlled trials found that vitamin D supplementation reduced the severity of depression symptoms in people with depression but had no effect on depression symptoms in people without depression.[41][42]

    Vitamin D receptors can be found pretty much everywhere in the human body, so the ways in which vitamin D might affect your mood are innumerable. One of those mechanisms could be hormonal, since vitamin D helps regulate testosterone levels,[43][44] and since low testosterone can impair the mood of both men[45][46][47][48] and women.[49]

    We should remember, however, that correlation is not causation. As stated above, the observational data suggests a correlation between depression and low levels of vitamin D, but that doesn’t mean that low levels of vitamin D cause the depression. It might be that depressed people go outside less, thus getting less sunlight, thus producing less vitamin D: the depression would then be the cause of the low vitamin D levels, rather than its consequence.

    Even if depression is a consequence, not a cause, it doesn’t mean that low levels of vitamin D aren’t also a consequence. People who go outside less get less sunlight, but also probably less exercise — and we know that exercise benefits mood,[50] both directly and by promoting better sleep.

    And of course, a consequence can have more than one cause. For instance, a decrease in vitamin D production during the winter months is a possible factor in seasonal affective disorder (SAD),[51] but so is a decrease in illumination,[52] since one meta-analysis[53] and a more recent RCT[54] found that light therapy (using visible light, free of the UVB rays that allow your skin to produce vitamin D) can improve SAD symptoms, often as much as can pharmaceuticals. It should be noted, however, that a few trials with small sample sizes make for rather weak evidence, especially since the meta-analysis didn’t account for publication bias.

    The findings on vitamin D are less consistent. One study found an association between depression and seasonal changes in vitamin D,[55] but another study found no effect of supplemental vitamin D on SAD.[56] And compounding the uncertainty, the researchers of both studies stressed that potential confounders were numerous.

    To summarize:

    • Low levels of vitamin D have been associated with depression, but it doesn’t follow that low levels of vitamin D are the cause of the depression. They’re probably one of the factors at play in seasonal depression, but so is the decrease in illumination.
    • If your vitamin D levels are not low, supplementation isn’t likely to benefit your mood. If they are low, supplementation is more likely to help if you suffer from major depression.
    • If you suspect your vitamin D levels are low, you can have them assessed through a 25-hydroxyvitamin D blood test. Assessing your vitamin D levels twice in a year — in midsummer and midwinter, when there is the most and least sunlight — is an efficient way of estimating what your levels are around the year.
    Are there any other treatments for depression?

    Although alternative treatments such as acupuncture, herbal medicines, and meditation are commonly used for depression, it is not recommended to use alternative medical treatments without seeking approval from a healthcare professional.

    Is there a best type of exercise to protect against depression?

    A large-scale observational study of nearly 18,000 individuals compared self-reported moderate to vigorous-intensity aerobic physical activity, muscle-strengthening exercise, and a combination of the two.[14] The researchers observed that individuals who met Centers for Disease Control and Prevention (CDC) guidelines for both aerobic and muscle-strengthening exercise[15] had the lowest prevalence ratios for depressive symptom severity. The results can be seen below, which are sorted by depression severity.

    Impact of meeting CDC activity guidelines on depression

    image

    Reference: Bennie et al. Prev Med. 2019.[14]

    Despite the considerable number of individual studies on this topic, further work is needed to refine potential recommendations to account for the following.

    • Aerobic versus non-aerobic physical activity versus a combination of the two
    • The type(s) of physical activity that may confer the greatest benefit
    • Differences between males and females
    • Differences across age groups
    • The severity of the depression
    • Comorbidities

    Furthermore, it would be helpful to know the minimum duration and intensity of physical activity that still exerts a meaningful level of protection from depression.

    How does exercise compare to antidepressant medication or psychotherapy for treating depression?

    Exercise seems to compare at least comparably with the current medical standard of care for depression.[25][26] In one clinical trial, researchers randomly assigned 156 moderately depressed males and females to an exercise intervention, medication, or a combined exercise and medication group.[27]

    • The exercise group walked or jogged on a treadmill for thirty minutes, three times per week for sixteen weeks.
    • The medication group received the common selective serotonin reuptake inhibitor (SSRI) sertraline (Zoloft)
    • The combination group received the medication and performed the exercise program concurrently.

    Results showed that the medication worked more quickly to reduce symptoms of depression, but exercise was equally effective at the end of the sixteen-week program and created more lasting alleviation of depression at a ten-month follow-up.[28]

    What causes depression?

    The causes of depression are complex, including prenatal factors, genetics, environment, biology, age, and sociocultural and psychological factors.[13]

    Update History

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    1. Postpartum Depression Symptoms - Juliana Dos Santos Vaz, Dayana Rodrigues Farias, Amanda Rodrigues Amorim Adegboye, Antonio Egidio Nardi, Gilberto KacOmega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: a randomized placebo-controlled trialBMC Pregnancy Childbirth.(2017 Jun 9)
    2. Postpartum Depression Symptoms - Su KP, Huang SY, Chiu TH, Huang KC, Huang CL, Chang HC, Pariante CMOmega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trialJ Clin Psychiatry.(2008 Apr)
    3. Depression Symptoms - Peet M, Horrobin DFA dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugsArch Gen Psychiatry.(2002 Oct)
    4. Depression Symptoms - Sarris J, Mischoulon D, Schweitzer IOmega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depressionJ Clin Psychiatry.(2012 Jan)
    5. Depression Symptoms - Nahas R, Sheikh OComplementary and alternative medicine for the treatment of major depressive disorderCan Fam Physician.(2011 Jun)
    6. Depression Symptoms - Appleton KM, Sallis HM, Perry R, Ness AR, Churchill ROmega-3 fatty acids for depression in adultsCochrane Database Syst Rev.(2015 Nov 5)
    7. Depression Symptoms - Su KP, Huang SY, Chiu CC, Shen WWOmega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trialEur Neuropsychopharmacol.(2003 Aug)
    8. Depression Symptoms - Katherine M Appleton, Philip D Voyias, Hannah M Sallis, Sarah Dawson, Andrew R Ness, Rachel Churchill, Rachel PerryOmega-3 fatty acids for depression in adultsCochrane Database Syst Rev.(2021 Nov 24)
    9. Depression Symptoms - Maike Wolters, Annkathrin von der Haar, Ann-Kristin Baalmann, Maike Wellbrock, Thomas L Heise, Stefan RachEffects of n-3 Polyunsaturated Fatty Acid Supplementation in the Prevention and Treatment of Depressive Disorders-A Systematic Review and Meta-AnalysisNutrients.(2021 Mar 25)
    10. Depression Symptoms - Nemets B, Stahl Z, Belmaker RHAddition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorderAm J Psychiatry.(2002 Mar)
    11. Depression Symptoms - Grenyer BF, Crowe T, Meyer B, Owen AJ, Grigonis-Deane EM, Caputi P, Howe PRFish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trialProg Neuropsychopharmacol Biol Psychiatry.(2007 Oct 1)
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    13. Depression Symptoms - Martins JGEPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trialsJ Am Coll Nutr.(2009 Oct)
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