Depression

DEFINITION: One of the most common psychiatric disorders to occur in most lifetimes, caused by biological, psychological, social, and/or environmental factors

ANATOMY OR SYSTEM AFFECTED: Brain, heart, musculoskeletal system, psychic-emotional system

Causes and Symptoms

The word “depression” is often used to describe many different things. It can define a fleeting mood, or perhaps an outward physical appearance of sadness, or for others, a diagnosable clinical disorder. In any year, millions of adults suffer from clinically diagnosed depression, a mood disorder that often affects personal, vocational, social, and health functioning. The text-revised fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR, 2022) of the American Psychiatric Association delineates a number of mood disorders that include clinical depression, known as major depressive disorder. According to data published in 2022 by the National Institute of Mental Health, 8.3 percent of adults in the US had a major depressive episode in 2021. This rate remained fairly stable in subsequent years, with 8.4 percent of US adults experiencing at least one major depressive episode in 2023.

Major depressive disorder is characterized by a syndrome of symptoms, present during a two-week period and representing a clinically significant change from previous functioning. The symptoms include at least five of the following: depressed or irritable mood for most of the day, diminished interest in previously pleasurable activities, significant unintentional weight loss or weight gain, insomnia or hypersomnia, physical agitation or slowness, loss of energy or fatigue, feelings of worthlessness or excessive guilt, indecisiveness or a diminished ability to concentrate, and recurrent thoughts of death. The clinical depression cannot be initiated or maintained by another illness or condition.

Major depressive disorder is often first recognized in the patient’s twenties, while a major depressive episode can occur at any age. Women are twice as likely as men to be diagnosed with depression.

There are several potential causes of major depressive disorder. Genetic factors may determine a person's susceptibility to developing depression following stressful life events. Genetic studies suggest a familial link with higher rates of clinical depression in first-degree relatives. There also appears to be a relationship between clinical depression and levels of the brain’s neurochemicals, specifically decreased monoamines—the neurotransmitters dopamine, norepinephrine, and serotonin. It is important to keep in mind, however, that anywhere from 15 to 20 percent of adults will experience major depression at some point in their lifetimes. Furthermore, not everyone has a biological cause for this depression.

Common causes of clinical depression also include psychosocial stressors such as the death of a loved one, financial stress, loss of a job and unemployment, interpersonal problems, or traumatic world events such as natural disasters and war. It is unclear, however, why some people respond to a specific psychosocial stressor with a clinical depression and others do not. Finally, certain prescription medications have been noted to cause or be related to clinical depression. These drugs include muscle relaxants, heart medications, hypertensive medications, ulcer medications, oral contraceptives, painkillers, narcotics, and steroids. Thus, there are many causes of clinical depression, and no single cause is sufficient to explain all clinical depressions.

Other likely risk factors for depression include past alcohol dependence, insecure attachment to parents in early adolescence, and the experience of childhood abuse or neglect. Possible risk factors for depression that have been explored include cannabis use, low birth weight, high levels of television viewing and media exposure in adolescence, and head injury.

In the DSM-5-TR, the existence of at least three manic symptoms (which is insufficient to satisfy the diagnostic criteria for a manic episode) within a major depressive episode is acknowledged by the specifier "major depressive disorder with mixed features." The presence of mixed features in an episode of major depressive disorder increases the likelihood that the illness exists in the bipolar spectrum, although separate criteria exist for the diagnosis of bipolar disorder, which can share some symptoms with major depression.

Dysthymic disorder is another persistent depressive disorder characterized by chronic low-level depression. In the United States, the twelve-month prevalence of dysthymic disorder is estimated to be approximately 1.5 percent of the adult population. Dysthymic disorder is characterized by at least a two-year history of depressed mood and at least two of the following symptoms that cause clinically significant impairment in social, work, or other important areas of functioning: poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or decision-making, or feelings of hopelessness. The individual cannot be without the symptoms for more than two months at a time, the disorder cannot be superimposed on another psychotic disorder, and it cannot be initiated or maintained by another illness or condition. Dysthymic disorder is more common in adult women, equally common in both sexes of children, and with a greater prevalence in families. The causes of dysthymic disorder are believed to be similar to those listed for major depressive disorder, but the disorder is less well understood than is depression.

In order to prevent the overdiagnosis of bipolar disorder in children, the DSM-5, first published in 2013 and later revised and republished in 2022, added a new depressive disorder called disruptive mood dysregulation disorder (DMDD). This diagnosis is given to children up to the age of eighteen years who exhibit persistent irritability and frequent episodes of extreme emotional outbursts and behavioral dyscontrol. DMDD is characterized by severe and recurrent temper outbursts that are grossly out of proportion in intensity or duration to the situation at hand, occurring on average three or more times per week for one year or more. Diagnosis of DMDD requires the symptoms to be present in at least two settings (at school, at home, and/or in social settings), and the child cannot have gone three or more consecutive months without symptoms to be diagnosed with DMDD. Onset of DMDD must occur before the age of ten years, and diagnosis cannot be made for the first time before the age of six years or after eighteen years. In many cases, DMDD develops into depressive disorder or anxiety disorder during adulthood.

Also in the category of depressive disorders, the DSM-5-TR includes premenstrual dysphoric disorder (PMDD), which was previously categorized under Appendix B "Criteria Sets and Axes Provided for Further Study" in the DSM-IV, due to a strong body of evidence supporting its existence and the validity of the diagnostic criteria. PMDD is an extreme version of premenstrual syndrome that affects approximately 3 to 8 percent of women of reproductive age. PMDD is characterized by the presence of symptoms for most of the time during the last week of the luteal phase of the menstrual cycle; these symptoms begin to remit within a few days of the onset of the follicular phase and are not present in the weeks following menstruation. For the diagnosis of PMDD, a person must have five or more of the following symptoms for most menstrual cycles during the past one year: markedly depressed mood or feelings of hopelessness, marked anxiety or tension, persistent anger or irritability or increased interpersonal conflicts, sense of difficulty in concentrating, lethargy or fatigue, marked changes in appetite, hypersomnia or insomnia, feelings of being overwhelmed or out of control, and/or physical symptoms such as headache, joint or muscle pain, and breast tenderness. These symptoms must also cause a clinically significant impact on functioning at work, school, and social settings or within personal relationships.

Postpartum depression, also called postnatal depression, is a variant of depression that occurs in some women shortly after giving birth. While certain post-birth symptoms, such as mood swings, melancholy, anxiety, and sleeping difficulties are relatively common and do not necessarily indicate a psychiatric condition, postpartum depression affects anywhere from 6.5 to 20 percent of women after childbirth, according to the National Institutes of Health (NIH). This type of depression, which typically occurs within six weeks of childbirth, can involve symptoms typical of other types of depression, including intense sadness, low energy, and difficulty sleeping. In extreme cases, postpartum depression symptoms can occur alongside postpartum psychosis, a rare but severe condition that presents shortly after childbirth and can involve delusions, hallucinations, and other serious psychiatric issues. Some researchers have also noted instances of postpartum depression symptoms in fathers and other partners who did not give birth. There are a number of risk factors for postpartum depression include a previous history of mental health challenges, financial issues, difficulty breastfeeding, and relationship issues with a spouse or partner. A key tool for diagnosing postpartum depression is the Edinburgh Scale, a screening tool which uses ten questions to determine if a new parent identify is experiencing depression, anxiety, or thoughts of self-harm.

Another variant of clinical depression is known as seasonal affective disorder (SAD). Patients with this illness demonstrate a pattern of clinical depression during the winter, when there is a reduction in the amount of daylight hours. For these patients, the reduction in available light is thought to be the cause of the depression. In the DSM-5-TR, SAD is categorized as a mood disorder with a specifier called "with seasonal pattern."

Treatment and Therapy

Crucial to the choice of treatment for clinical depression is determining the variant of depression being experienced. Each of the diagnostic categories has associated treatment approaches that are more effective for a particular diagnosis. Multiple assessment techniques are available to the health care professional to determine the type of clinical depression. The most valid and reliable is the clinical interview. The health care provider may conduct either an informal interview or a structured, formal clinical interview assessing the symptoms that would confirm the diagnosis of clinical depression. If the patient meets the diagnostic criteria set forth in the most current version of the DSM, then the patient is considered for depression treatments. Patients who meet many but not all diagnostic criteria are sometimes diagnosed with a “subclinical” depression. These patients might also be considered appropriate for the treatment of depression, at the discretion of their health care providers.

Another assessment technique is the “paper-and-pencil” measure, or depression questionnaire. A variety of questionnaires have proven useful in confirming the diagnosis of clinical depression. Questionnaires such as the Beck Depression Inventory, Hamilton Depression Rating Scale, Zung Self-Rating Depression Scale, and the Center for Epidemiologic Studies Depression Scale are used to identify persons with clinical depression and to document changes with treatment. This technique is often used as an adjunct to the clinical interview and rarely stands alone as the definitive assessment approach to diagnosing clinical depression.

Once a clinical depression (or a subclinical depression) is identified, several types of treatment options are available. These options are dependent on the subtype and severity of the depression. They include individual and group psychotherapy, light therapy, family therapy, psychopharmacology (drug therapy), electroconvulsive therapy (ECT), and other less traditional treatments. These treatment options can be provided to the patient as part of an outpatient program or, in certain severe cases of clinical depression in which the person is a danger to the self or others, as part of a hospitalization.

Clinical depression often affects the patient physically, emotionally, and socially. Therefore, before beginning any treatment with a clinically depressed individual, the health care provider will attempt to develop an open and communicative relationship with the patient. This relationship will allow the health care provider to provide patient education on the illness and to solicit the collaboration of the patient in treatment. Supportiveness, understanding, and collaboration are all necessary components of any treatment approach.

For the treatment of mild to moderate depression in adults, the American Psychiatric Association (APA) recommends psychotherapy as the initial treatment choice. The APA also recommends antidepressant medications as an initial treatment choice, whereas the National Institute for Clinical Excellence (NICE) recommends antidepressants only if the patient is unresponsive to initial psychosocial interventions. For moderate to severe depression in adults, the APA and the NICE recommend a combination of psychotherapy and antidepressants. The APA also recommends electroconvulsive therapy (ECT) for the treatment of severe unresponsive major depression in adults.

For the treatment of depression in children and adolescents, the recommended initial treatment choices include education, supportive treatment, and case management. If depression is complicated or chronic, psychotherapy may then be recommended. Interpersonal therapy and cognitive-behavioral therapy have been shown to be among the best psychotherapeutic options for the treatment of depression. If the child or adolescent with depression is unresponsive to psychotherapy, he or she may benefit from some types of antidepressant medications; however, in most children with depression, antidepressants do not appear to be an effective treatment.

Psychotherapy refers to a number of different treatment techniques used to deal with the psychosocial contributors and consequences of clinical depression. In psychotherapy, the patients develop knowledge and insight into the causes of and treatment for their clinical depression. In cognitive psychotherapy, symptom relief comes from assisting patients in modifying maladaptive, irrational, or automatic beliefs that can lead to clinical depression. In behavioral psychotherapy, patients modify their environment such that social or personal rewards are more forthcoming. This process might involve being more assertive, reducing isolation by becoming more socially active, increasing physical activities or exercise, or learning relaxation techniques or other coping skills. Research upholds the effectiveness of these and other psychotherapy techniques for the treatment of depression and other mood disorders.

The primary types of medications used in the treatment of clinical depression in adults include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), mirtazapine (Remeron), and bupropion (Wellbutrin). Monoamine oxidase inhibitors (MAOIs) should be restricted to patients who do not respond to other treatments. The health care professional will select an antidepressant based on side effects, dosing convenience (once daily versus three times a day), and cost.

Cyclic antidepressants represent one class of antidepressant medications. As the name implies, the chemical makeup of the medication contains chemical rings, or “cycles.” There are unicyclic (buproprion and fluoxetine, or Prozac), bicyclic (sertraline and trazodone), tricyclic (amitriptyline, desipramine, and nortriptyline), and tetracyclic (maprotiline) antidepressants. These antidepressants function to either block the reuptake of neurotransmitters by the neurons, allowing more of the neurotransmitter to be available at a receptor site, or increase the amount of neurotransmitter produced. The side effects associated with the cyclic antidepressants—dry mouth, blurred vision, constipation, urinary difficulties, palpitations, and sleep disturbance—vary and can be quite problematic. Some of these antidepressants have deadly toxic effects at high levels, so they are not prescribed to patients who are at risk of dying by suicide. Furthermore, in some patients, antidepressants such as SSRIs are associated with increased suicidal ideation, so patients should be carefully monitored as they begin an antidepressant treatment regimen.

Newer drugs are more specific in terms of the drug action. For instance, fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and works specifically on the neurotransmitter serotonin. Similarly, buproprion is a norepinephrine and dopamine reuptake inhibitor (NDRI) and works specifically on the neurotransmitters norepinephrine and dopamine. More specific drugs generally create fewer side effects. Fewer side effects can be associated with greater medication compliance, making these drugs a more effective treatment for many individuals.

Monoamine oxidase inhibitors (isocarboxazid, phenelzine, and tranylcypromine) are another class of antidepressants. They function by slowing the production of the enzyme monoamine oxidase. This enzyme is responsible for breaking down the neurotransmitters norepinephrine and serotonin, which are believed to be responsible for depression. By slowing the decomposition of these transmitters, more of them are available to the receptors for a longer period of time. Restlessness, dizziness, weight gain, insomnia, and sexual dysfunction are common side effects of the MAOIs. MAOIs are most notable because of the dangerous adverse reaction (severely high blood pressure) that can occur if the patient consumes large quantities of foods high in tyramine (such as aged cheeses, fermented sausages, red wine, foods with a heavy yeast content, and pickled fish). Because of this potentially dangerous reaction, MAOIs are not usually the first choice of medication and are more commonly reserved for depressed patients who do not respond to other treatment options.

Electroconvulsive or shock therapy is one of the most effective treatments for severe and persistent depression that does not respond to other treatments. If the clinically depressed patient fails to respond to medications or psychotherapy and the depression is life-threatening, electroconvulsive therapy is considered. It is also considered if the patient cannot physically tolerate antidepressants, as with elderly patients who have other medical conditions. This therapy involves inducing a seizure in the patient by administering an electrical current to specific parts of the brain. The therapy has become quite sophisticated and much safer than when it was introduced in the mid-twentieth century, and it involves fewer risks to the patient. Patients undergo several treatments over a period of time. Some temporary memory impairment is a common side effect of this treatment.

A special treatment used for individuals with seasonal affective disorder is light therapy, or phototherapy. Light therapy involves exposing patients to bright light for a period of time each day during seasons of the year when there is decreased light. This may be done as a preventive measure and also during depressive episodes. The manner in which this treatment approach modifies the depression is unclear and awaits further research, but some believe it affects the internal clock of the body, or circadian rhythm. Studies of the effectiveness of light therapy have been mixed, but interest in this promising treatment is strong, as it may prove useful for working with nonseasonal mood disorders as well. It should be noted, however, that light therapy does have some risks associated with it. Caution must be used to protect the eyes and to use the light as directed. Additionally, the intensity of light must be correct to achieve therapeutic effects and not cause other problems. Finally, some individuals can experience manic episodes if they are exposed to too much light, so caution must be exercised in terms of the length of time for light exposure treatment sessions.

Surgery, the final treatment option for severe depression, is quite rare. Psychosurgery is used only after all treatment options have failed and the clinical depression is life-threatening. Vagus nerve stimulation (VNS) is a form of surgery that implants a stimulus generator on the vagus nerve; it is approved by the FDA for the treatment of severe unresponsive depression. Nonsurgical methods of creating similar stimuli have been explored as well.

Twenty-first century research into alternative treatment options for depression has shown promising initial results. Numerous studies have pointed toward the effectiveness of ketamine treatments in fighting long-term depression. For example, 2019 study published in the Indian Journal of Psychiatry examined the effectiveness of ketamine treatments in fighting long-term depression. The study, which administered intravenous doses of ketamine to patients with severe depressive disorders, found that ketamine had a significant improvement on depression symptoms after two weeks of treatment which persisted one month after the treatments ended. In addition to ketamine, research into the application of psychedelics in fighting depression has been equally promising. A 2021 meta-analytical study published in Psychopharmacology reviewed a series of studies that examined the effectiveness of serotonergic psychedelics (a subclass of psychedelics found in psilocybin, LSD, and DMT, among others) against a placebo and found that patients who were treated with serotonergic psychedelics showed a marked improvement in the reduction of depression symptoms compared to those that were administered a placebo. Experiments on ketamine and psychedelic treatments have opened the door to less invasive treatment alternatives for those that do not respond to classical treatment options.

Perspective and Prospects

Depression, or the more historical term “melancholy,” has had a history predating modern medicine. Writings from the time of the ancient Greek physician Hippocrates refer to patients with a symptom complex similar to the present-day definition of clinical depression.

The rates of clinical depression have increased since the early twentieth century, while the age of onset of clinical depression has decreased. Women appear to be at least twice as likely as men to suffer from clinical depression.

While most psychiatric disorders are nonfatal, clinical depression can lead to death. About 60 percent of individuals who die by suicide have a mood disorder such as depression at the time. In a lifetime, however, only about 7 percent of men and 1 percent of women with lifetime histories of depression will die by suicide. Though these numbers are high, what this means is that not everyone who is depressed will die by suicide. In fact, many receive help and recover from depression. There are, however, other costs of clinical depression. Billions of dollars are spent on clinical depression, divided among the following areas: treatment, suicide, and absenteeism. Clinical depression obviously has a significant economic impact on society, and major personal impacts on the lives of individuals suffering from depression.

Studies have shown a marked increase in depression among those in their twenties and thirties in the early twenty-first century. The Center for Collegiate Mental Health reported in 2015 that there had been an average increase of 30 percent in visits to mental health counselors on college campuses between 2009 and 2015. A reported 20 percent of college students experienced depression symptoms in 2019, according to the American College Health Association.

Amid the coronavirus disease 2019 (COVID-19) pandemic, a household survey by the Kaiser Family Foundation showed that adults were reporting an increase in negative impacts on mental health. In January 2021, 41.1 percent of adults reported experiencing symptoms of anxiety disorder and/or depressive disorder, an increase from the 11 percent reported in January–June 2019. The survey also reported that the pandemic had disproportionately affected the mental health of communities of color; 48 percent of non-Hispanic Black adults and 46 percent of Hispanic or Latino adults reported anxiety and/or depression symptoms, while 41 percent of non-Hispanic White adults reported symptoms.

In the United States, in 2023, about 21 million adults (8.4 percent) had experienced a major episode involving depression. An estimated 50 million Americans were believed to struggle with mental illness. About 10 percent of young people reported having depression severe enough to disrupt their school, work, or home life. By 2030, the World Health Organization projects that depression will be the most prevalent disease globally, with an estimated 5 percent of adults worldwide projected to experience the condition.

Another major risk associated with depression are the types of dependencies it can induce. These include substance abuse. Suicide is another tragic outcome. In the United States, the most at-risk population of dying by suicide are older generations of adults. The most prevalent rates exist among those 85 and older, followed by those 75 and older. The highest rates of depression in the United States existed in rural areas where poverty, economic fluctuations, opioid abuse, and COVID-19 intersected. These included the states of Louisiana, West Virginia, and Kentucky.

The future of clinical depression lies in early identification and treatment. Identification will involve two areas. The first is improving the social awareness of mental health issues to include clinical depression. By eliminating the negative social stigma associated with mental health treatment, there will be an increased level of the reporting of depression symptoms and thereby an improved opportunity for early intervention, preventing the progression of the disorder. The second approach to identification involves the development of reliable assessment strategies for clinical depression. Data suggests that the majority of those who die by suicide see a physician within thirty days of their death. The field of psychology will continue to strive to identify biological markers and other methods to predict and identify clinical depression more accurately. Treatment advances will focus on the further development of non-pharmacological and pharmacological strategies to increase effectiveness.

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