Preventative efforts may result in decreases in rates of the condition of between 22 and 38%. Eating large amounts of fish may also reduce the risk.

Behavioral interventions, such as interpersonal therapy and cognitive-behavioral therapy, are effective at preventing new onset depression. Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet.

However, an earlier meta-analysis found preventive programs with a competence-enhancing component to be superior to behavior-oriented programs overall, and found behavioral programs to be particularly unhelpful for older people, for whom social support programs were uniquely beneficial. In addition, the programs that best prevented depression comprised more than eight sessions, each lasting between 60 and 90 minutes, were provided by a combination of lay and professional workers, had a high-quality research design, reported attrition rates, and had a well-defined intervention.

The Netherlands mental health care system provides preventive interventions, such as the "Coping with Depression" course (CWD) for people with sub-threshold depression. The course is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies.

There is some evidence that omega-3 fatty acids fish oil supplements containing high levels of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) are effective in the treatment of, but not the prevention of major depression. However, a Cochrane review determined there was insufficient high quality evidence to suggest Omega-3 fatty acids were effective in depression. There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D deficient. There is some preliminary evidence that COX-2 inhibitors have a beneficial effect on major depression. Lithium appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression to nearly the same levels as the general population. There is a narrow range of effective and safe dosages of lithium thus close monitoring may be needed. Low-dose thyroid hormone may be added to existing antidepressants to treat persistent depression symptoms in people who have tried multiple courses of medication. Limited evidence suggests stimulants such as amphetamine and modafinil may be effective in the short term, or as add on therapy.

Both psychotherapy as well as different drugs (e.g. serotonin reuptake inhibitors - SSRIs or mood stabilizers, e.g. lithium, antiepileptics) have been suggested as treatments. However, no randomized controlled treatment trial of RBD has been conducted.

Individuals suffering from endogenous depression require treatment plans that focus on the internal, cognitive thought processes since internal stressors are the root of somatic symptoms. Individual cognitive therapy (ICT) is therefore a common treatment used to gain insight to the individual's internal conflicts or thoughts that are motivating their distressing symptoms. Once the cause of the symptoms are identified, sessions are used to develop new coping skills, behavior modification, and changes in beliefs.

As preventative measures, pharmaceuticals such as SSRI's and antidepressants may also be utilized to avoid further development or progression to Major Depressive Disorder. There have been few treatments targeted specifically toward Endogenous Depression; therefore, symptoms are often managed similarly to Major Depressive Disorder. One such treatment is electroconvulsive therapy (ECT). ECT is used as a treatment option for endogenous depression in adults, however, practitioners avoid the use of ECT in young adolescents due to rates of injury.

Depressed mood may not require professional treatment, and may be a normal temporary reaction to life events, a symptom of some medical condition, or a side effect of some drugs or medical treatments. A prolonged depressed mood, especially in combination with other symptoms, may lead to a diagnosis of a psychiatric or medical condition which may benefit from treatment. Different sub-divisions of depression have different treatment approaches.

In the United States, it has been estimated that two thirds of people with depression do not actively seek treatment. The World Health Organisation (WHO) has predicted that by 2030, depression will account for the highest level of disability accorded any physical or mental disorder in the world (WHO, 2008).

The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor. A recent meta-analysis also indicated that most antidepressants, besides fluoxetine, do not seem to offer a clear advantage for children and adolescents in the acute treatment of major depressive disorder.

A combination of antidepressant medication and psychotherapy has consistently been shown to be the most effective line of treatment for people diagnosed with dysthymia. Working with a psychotherapist to address the causes and effects of the disorder, in addition to taking antidepressants to help eliminate the symptoms, can be extremely beneficial. This combination is often the preferred method of treatment for those who have dysthymia. Looking at various studies involving treatment for dysthymia, 75% of people responded positively to a combination of cognitive behavioral therapy (CBT) and pharmacotherapy, whereas only 48% of people responded positively to just CBT or medication alone.

In a meta-analytic study from 2008, researchers found an effect size of -0.07 (Cohen's d) between pharmacologic treatments and psychological treatments for depressive disorders, suggesting pharmacologic treatments to be slightly more effective, though the results were not found to be statistically significant. This small effect is true only for SSRIs, with TCAs and other pharmacologic treatments showing no differences from psychological treatments. Additionally, there have been several studies yielding results that indicate that severe depression responds more favorably to psychotherapy than pharmacotherapy.

Psychologic therapies are recommended for elderly patients with depression because of this group’s vulnerability to adverse effects and high rates of medical problems and medication use. Psychotherapeutic approaches include cognitive behavioral therapy, supportive psychotherapy, problem-solving therapy, and interpersonal therapy. The potential benefit of psychotherapy is not diminished by increasing age. Older adults often have better treatment compliance, lower dropout rates, and more positive responses to psychotherapy than younger patients. Consultation with a clinical geropsychologist is useful.

The first line of pharmacotherapy is usually SSRIs due to their more tolerable nature and reduced side effects compared to the irreversible monoamine oxidase inhibitors or tricyclic antidepressants. Studies have found that the mean response to antidepressant medications for people with dysthymia is 55%, compared with a 31% response rate to a placebo. The most commonly prescribed antidepressants/SSRIs for dysthymia are escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine. It often takes an average of 6–8 weeks before the patient begins to feel these medications' therapeutic effects. Additionally, STAR*D, a multi-clinic governmental study, found that people with overall depression will generally need to try different brands of medication before finding one that works specifically for them. Research shows that 1 in 4 of those who switch medications get better results regardless of whether the second medication is an SSRI or some other type of antidepressant.

In a meta-analytic study from 2005, it was found that SSRIs and TCAs are equally effective in treating dysthymia. They also found that MAOIs have a slight advantage over the use of other medication in treating this disorder. However, the author of this study cautions that MAOIs should not necessarily be the first line of defense in the treatment of dysthymia, as they are often less tolerable than their counterparts, such as SSRIs.

Tentative evidence supports the use of amisulpride to treat dysthymia but with increased side effects.

Treatment of minor depressive disorder has not been studied as extensively as major depressive disorder. Although there are often similarities in the treatments used, there are also differences in what may work better for the treatment of minor depressive disorder. Some third-party payers do not pay to cover treatment for minor depressive disorder.

The leading treatment techniques for minor depressive disorder are the use of antidepressants and therapy. Typically, patients with minor depression were treated by watchful waiting, prescribed antidepressants, and given brief supportive counseling, but Problem-Solving Treatment for Primary Care (PST-PC) is a Cognitive-Behavioral Therapy that has gained popularity. In one study, Problem-Solving Treatment for Primary Care (PST-PC) and Paroxetine, an antidepressant, were shown to be equally effective in significantly reducing symptoms. In another study, PST-PC was compared with the more typical care of the time and shown to reduce symptoms more quickly. Although the use of antidepressants has been widely used, not all agree that it is an appropriate treatment for some minor depression disorder settings.

Another alternative that has been researched is the use of St. John's wort ("Hypericum perforatum"). This herbal treatment has been studied by various groups with various results. Some studies show evidence of the treatment being helpful to treat minor depression, but others show that it does no better than the placebo.

Pharmacotherapy for acute episodes of depression usually is effective and free of complications. Underuse or misuse of antidepressants and prescribing inadequate dosages are the most common mistakes physicians make when treating elderly patients for depression. Only 10 to 40 percent of depressed elderly patients are given medication. Antidepressants, in general, may also work by playing a neuroprotective role in how they relieve anxiety and depression. It's thought that antidepressants may increase the effects of brain receptors that help nerve cells keep sensitivity to glutamate which is an organic compound of a nonessential amino acid. This increased support of nerve cells lowers glutamate sensitivity, providing protection against the glutamate overwhelming and exciting key brain areas related to depression. Antidepressant medications are often the first treatment choice for adults with moderate or severe depression, sometimes along with psychotherapy. Although antidepressants may not cure depression, they can lead to remission, which is the disappearance or nearly complete reduction of depression symptoms.

Treatment typically includes three things: the treatment of acute hypomania, the treatment of acute depression, and the prevention of the relapse of either hypomania or depression. The main goal is to make sure that patients do not harm themselves.

The most common treatment for reducing bipolar II disorder symptoms is medication, usually in the form of mood stabilizers. However, treatment with mood stabilizers may produce a flat affect in the patient, which is dose-dependent. Concurrent use of SSRI antidepressants may help some with bipolar II disorder, though these medications should be used with caution because it is believed that they may cause a hypomanic switch.

The pharmaceutical management of bipolar II disorder is not generally supported by strong evidence, with limited randomised controlled trials (RCTs) published in the literature. Some medications used are:

- Lithium - There is strong evidence that lithium is effective in treating both the depressive and hypomanic symptoms in bipolar II. In addition, its action as a mood stabilizer can be used to decrease the risk of hypomanic switch in patients treated with antidepressants.

- Anticonvulsants - there is evidence that lamotrigine decreases the risk of relapse in rapid cycling bipolar II. It appears to be more effective in bipolar II than bipolar I, suggesting that lamotrigine is more effective for the treatment of depressive rather than manic episodes. Doses ranging from 100–200 mg have been reported to have the most efficacy, while experimental doses of 400 mg have rendered little response. A large, multicentre trial comparing carbamazepine and lithium over two and a half years found that carbamazepine was superior in terms of preventing future episodes of bipolar II, although lithium was superior in individuals with bipolar I. There is also some evidence for the use of valproate and topiramate, although the results for the use of gabapentin have been disappointing.

- Antidepressants - there is evidence to support the use of SSRI and SNRI antidepressants in bipolar II. Indeed, some sources consider them to be one of the first line treatments. However, antidepressants also pose significant risks, including a switch to mania, rapid cycling, and dysphoria and so many psychiatrists advise against their use for bipolar. When used, antidepressants are typically combined with a mood stabilizer.

- Antipsychotics - there is good evidence for the use of quetiapine, and it has been approved by the FDA for this indication. There is also some evidence for the use of risperidone, although the relevant trial was not placebo controlled and was complicated by the use of other medications in some of the patients.

- Dopamine agonists - there is evidence for the efficacy of pramipexole from one RCT.

There are different types of treatments available for mood disorders, such as therapy and medications. Behaviour therapy, cognitive behaviour therapy and interpersonal therapy have all shown to be potentially beneficial in depression. Major depressive disorder medications usually include antidepressants, while bipolar disorder medications can consist of antipsychotics, mood stabilizers, anticonvulsants and/or lithium. Lithium specifically has been proven to reduce suicide and all causes of mortality in people with mood disorders. If mitochondrial dysfunction or mitochondrial diseases are the cause of mood disorders like bipolar disorder, then it has been hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.

Depression is a treatable illness. Treatments for a major depressive episode may be obtained in one or more of the following settings: mental health specialists (i.e. psychologist, psychiatrists, social workers, counselors, etc.), mental health centers or organizations, hospitals, outpatient clinics, social service agencies, private clinics, peer support groups, clergy, and employee assistance programs. The treatment plan could include psychotherapy alone, antidepressant medications alone, or a combination of medication and psychotherapy.

For major depressive episodes of severe intensity (multiple symptoms, minimal mood reactivity, severe functional impairment), combined psychotherapy and antidepressant medications are more effective than psychotherapy alone. Patients with severe symptoms may require outpatient treatment or hospitalization.

Psychotherapy, also known as talk therapy, counseling, or psychosocial therapy, is characterized by a patient talking about their condition and mental health issues with a trained therapist. Different types of psychotherapy can be effective for depression. These include cognitive behavioral therapy, interpersonal therapy, dialectical behavior therapy, acceptance and commitment therapy, and mindfulness techniques.

Medications used to treat depression include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and atypical antidepressants such as mirtazapine, which do not fit neatly into any of the other categories. Different antidepressants work better for different individuals. It is often necessary to try several before finding one that works best for a specific patient. Some people may find it necessary to combine medications, which could mean two antidepressants or an antipsychotic medication in addition to an antidepressant. If a person's close relative has responded well to a certain medication, that treatment will likely work well for him or her.

Sometimes, people stop taking antidepressant medications due to side effects, although side effects often become less severe over time. Suddenly stopping treatment or missing several doses may cause withdrawal-like symptoms. Some studies have shown that antidepressants may increase short-term suicidal thoughts or actions, especially in children, adolescents, and young adults. However, antidepressants are more likely to reduce a person's risk of suicide in the long run.

If left untreated, a typical major depressive episode may last for about six months. About 20% of these episodes can last two years or more. About half of depressive episodes end spontaneously. However, even after the major depressive episode is over, 20% to 30% of patients have residual symptoms, which can be distressing and associated with disability.

Among the psychological assessments for identifying whether or not children and adolescents are experiencing depression and/or depressive symptoms is the Children's Depression Inventory. In early 2016, the USPSTF released an updated recommendation for the screening of adolescents ages 12 to 18 years for major depressive disorder (MDD). Appropriate treatment and follow-up should be provided for adolescents who screen positive.

Several studies have suggested that omega 3 fatty acids may have beneficial effects on depressive symptoms, but not manic symptoms. However, only a few small studies of variable quality have been published and there is not enough evidence to draw any firm conclusions.

Depression may also be iatrogenic (the result of healthcare), such as drug induced depression. Therapies associated with depression include interferon therapy, beta-blockers, Isotretinoin, contraceptives, cardiac agents, anticonvulsants, antimigraine drugs, antipsychotics, and hormonal agents such as gonadotropin-releasing hormone agonist.

There are multiple treatments that can be effective in treating children diagnosed with depression. Psychotherapy and medications are commonly used treatment options. In some research, adolescents showed a preference for psychotherapy rather than antidepressant medication for treatment. For adolescents, cognitive behavioral therapy and interpersonal therapy have been empirically supported as effective treatment options. The use of antidepressant medication in children is often seen as a last resort; however, studies have shown that a combination of psychotherapy and medication is the most effective treatment. Pediatric massage therapy may have an immediate effect on a child's emotional state at the time of the massage, but sustained effects on depression have not been identified.

Treatment programs have been developed that help reduce the symptoms of depression. These treatments focus on immediate symptom reduction by concentrating on teaching children skills pertaining to primary and secondary control. While much research is still needed to confirm this treatment program’s efficacy, one study showed it to be effective in children with mild or moderate depressive symptoms.

Several treatment guidelines recommend either the combination of a second-generation antidepressant and atypical antipsychotic or tricyclic antidepressant monotherapy or electroconvulsive therapy (ECT) as the first-line treatment for unipolar psychotic depression.

Pharmaceutical treatments can include tricyclic antidepressants, atypical antipsychotics, or a combination of an antidepressant from the newer, more well tolerated SSRI or SNRI categories and an atypical antipsychotic. Olanzapine may be an effective monotherapy in psychotic depression, although there is evidence that it is ineffective for depressive symptoms as a monotherapy; and olanzapine/fluoxetine is more effective. Quetiapine monotherapy may be particularly helpful in psychotic depression since it has both antidepressant and antipsychotic effects and a reasonable tolerability profile compared to other atypical antipsychotics. The current drug-based treatments of psychotic depression are reasonably effective but can cause side effects, such as nausea, headaches, dizziness, and weight gain. Tricyclic antidepressants are particularly dangerous in overdose due to their potential to cause potentially-fatal cardiac arrhythmias.

In the context of psychotic depression, the following are the most well-studied antidepressant/antipsychotic combinations

"First-generation"

- Amitriptyline/perphenazine

- Amitriptyline/haloperidol

"Second-generation"

- Venlafaxine/quetiapine?

- Olanzapine/fluoxetine

- Olanzapine/sertraline

In modern practice of ECT a therapeutic clonic seizure is induced by electric current via electrodes placed on an anaesthetised, unconscious patient. Despite much research the exact mechanism of action of ECT is still not known. ECT carries the risk of temporary cognitive deficits (e.g., confusion, memory problems), in addition to the burden of repeated exposures to general anesthesia.

This type of depression often occurs due to biological reasons. Since symptoms are due to an internal phenomena, prevalence rates tend to be higher in older adults and more prevalent among women. Although endogenous depression has been associated with increased age, there has been few attempts to evaluate this fully. More research is needed to indicate factual prevalence rates on this type of depression in society.

Short courses of benzodiazepines may be used in addition to other medications until mood stabilizing become effective. Electroconvulsive therapy (ECT) is an effective form of treatment for acute mood disturbances in those with bipolar disorder, especially when psychotic or catatonic features are displayed. ECT is also recommended for use in pregnant women with bipolar disorder.

There are three basic categories of drug treatment that can be used when a medication course is found to be ineffective. One option is to switch the patient to a different medication. Another option is to add a medication to the patient’s current treatment. This can include combination therapy: the combination of two different types of antidepressants, or augmentation therapy: the addition of a non-antidepressant medication that may increase the effectiveness of the antidepressant.

Increasing the dosage of an antidepressant is a common strategy to treat depression that does not respond after adequate treatment duration. Practitioners who use this strategy will usually increase the dose until the patient reports intolerable side effects, symptoms are eliminated, or the dose is increased to the limit of what is considered safe.

Treatments for classic (winter-based) seasonal affective disorder include light therapy, medication, ionized-air administration, cognitive-behavioral therapy and carefully timed supplementation of the hormone melatonin.

Photoperiod-related alterations of the duration of melatonin secretion may affect the seasonal mood cycles of SAD. This suggests that light therapy may be an effective treatment for SAD. Light therapy uses a lightbox which emits far more lumens than a customary incandescent lamp. Bright white "full spectrum" light at 10,000 lux, blue light at a wavelength of 480 nm at 2,500 lux or green (actually cyan or blue-green) light at a wavelength of 500 nm at 350 lux are used, with the first-mentioned historically preferred.

Bright light therapy is effective with the patient sitting a prescribed distance, commonly 30–60 cm, in front of the box with her/his eyes open but not staring at the light source for 30–60 minutes. A study published in May 2010 suggests that the blue light often used for SAD treatment should perhaps be replaced by green or white illumination. Discovering the best schedule is essential. One study has shown that up to 69% of patients find lightbox treatment inconvenient and as many as 19% stop use because of this.

Dawn simulation has also proven to be effective; in some studies, there is an 83% better response when compared to other bright light therapy. When compared in a study to negative air ionization, bright light was shown to be 57% effective vs. dawn simulation 50%. Patients using light therapy can experience improvement during the first week, but increased results are evident when continued throughout several weeks. Most studies have found it effective without use year round but rather as a seasonal treatment lasting for several weeks until frequent light exposure is naturally obtained.

Light therapy can also consist of exposure to sunlight, either by spending more time outside or using a computer-controlled heliostat to reflect sunlight into the windows of a home or office. Although light therapy is the leading treatment for seasonal affective disorder, prolonged direct sunlight or artificial lights that don't block the ultraviolet range should be avoided due to the threat of skin cancer.

SSRI (selective serotonin reuptake inhibitor) antidepressants have proven effective in treating SAD. Effective antidepressants are fluoxetine, sertraline, or paroxetine. Both fluoxetine and light therapy are 67% effective in treating SAD according to direct head-to-head trials conducted during the 2006 Can-SAD study. Subjects using the light therapy protocol showed earlier clinical improvement, generally within one week of beginning the clinical treatment. Bupropion extended-release has been shown to prevent SAD for one in eight people, but has not been compared directly to other preventive options in trials.

Negative air ionization, which involves releasing charged particles into the sleep environment, has been found effective with a 47.9% improvement if the negative ions are in sufficient density (quantity).

Depending upon the patient, one treatment (e.g., lightbox) may be used in conjunction with another (e.g., medication).

Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression.

Another explanation is that vitamin D levels are too low when people do not get enough Ultraviolet-B on their skin. An alternative to using bright lights is to take vitamin D supplements. However, studies did not show a link between vitamin D levels and depressive symptoms in elderly Chinese nor among elderly British women.

Physical exercise has shown to be an effective form of depression therapy, particularly when in addition to another form of treatment for SAD. One particular study noted marked effectiveness for treatment of depressive symptoms when combining regular exercise with bright light therapy. Patients exposed to exercise which had been added to their treatments in 20 minutes intervals on the aerobic bike during the day along with the same amount of time underneath the UV light were seen to make quick recovery.

In general, atypical depression tends to cause greater functional impairment than other forms of depression. Atypical depression is a chronic syndrome that tends to begin earlier in life than other forms of depression—usually beginning in the teenage years. Similarly, patients with atypical depression are more likely to suffer from personality disorders and anxiety disorders such as borderline personality disorder, avoidant personality disorder, generalized anxiety disorder, obsessive-compulsive disorder, and bipolar disorder.

Recent research suggests that young people are more likely to suffer from hypersomnia while older people are more likely to suffer from polyphagia.

Medication response differs between chronic atypical depression and acute melancholic depression. Some studies suggest that the older class of antidepressants, monoamine oxidase inhibitors (MAOIs), may be more effective at treating atypical depression. While the more modern SSRIs and SNRIs are usually quite effective in this illness, the tricyclic antidepressants typically are not. The wakefulness-promoting agent modafinil has shown considerable effect in combating atypical depression, maintaining this effect even after discontinuation of treatment. Antidepressant response can often be enhanced with supplemental medications, such as buspirone, bupropion, or aripiprazole. Psychotherapy, whether alone or in combination with medication, is also an effective treatment.