Depression and Suicide

In 2021, an estimated 21.0 million adults in the United States had at least one major depressive episode. ^[1] Depressed patients are more likely to develop type 2 diabetes and cardiovascular disease. ^[2] Not counting the effect of secondary disease states, over the next 20 years, unipolar depression is projected to be the second leading cause of disability worldwide and the leading cause of disability in high-income nations, including the United States. ^[3]

Morbidity associated with depression is difficult to quantify, but the lethality of depression takes the measurable form of completed suicide, the eleventh leading reported cause of death in the United States in 2021, with 48,183 deaths. ^[4]

In 2019, the incremental societal economic burden of major depressive disorder (MDD) was estimated at $333.7 billion ($382.4 billion in 2023 US dollars), or $16,854 per adult with MDD. The primary cost drivers were healthcare costs ($127.3 billion; 38.1%), household-related costs ($80.1 billion; 24.0%), presenteeism ($43.3 billion; 13.0%), and absenteeism ($38.4 billion; 11.5%). ^[5] In addition to considerable pain and suffering that interfere with individual functioning, depression affects those who care about the ill person, sometimes destroying family relationships or work dynamics between the patient and others. Therefore, the human cost in suffering cannot be overestimated.

As many as two thirds of people with depression do not realize that they have a treatable illness and do not seek treatment. Only 50% of persons diagnosed with MDD receive any kind of treatment, and only 20% of those individuals receive treatment consistent with current practice guidelines of the American Psychiatric Association (APA). ^{[3, 6]} More alarming, in a large Canadian study, 48% of patients who had suicidal ideation and 24% of those who had made a suicide attempt reported not receiving care or even perceiving the need for care. ^[7]

Persistent ignorance about depression and blatant misperceptions of the disease by the public, and even some health providers, as a personal weakness or failing that can be "willed" or "wished away",  lead to painful stigmatization of sufferers, and avoidance of the diagnosis by many persons who are affected by the disease.

The cause of depression is multifactorial. A family history of depression is common among persons with the disorder, as is a family history of suicides.

In addition to depression, other factors such as alcohol/substance abuse (especially of opiates and cocaine), impulsiveness, and certain familial factors may greatly increase the risk for suicide. These include a past history of mental problems or substance abuse, suicide in the immediate family, family violence of any type, and separation or divorce. ^{[8, 9, 10, 11, 12]}

Other risk factors include prior suicide attempt(s), presence of a firearm in the home, incarceration, and exposure to the suicidal behavior of family members, peers, celebrities, or even highly publicized fictional characters. It is also established that the initiation of treatment for depression with psychotherapeutic agents can temporarily increase the incidence of suicidal ideation as well as energizing motivation, and therefore unfortunately can increase the likelihood of successful suicide attempts. The incidence of depression in healthcare workers is comparable to that in the general population, though the rate of completion of suicide is higher. Therefore, healthcare workers diagnosed with depression, especially when coupled with burnout or substance use disorder, should be considered to be a in higher risk category for attempted or completed suicide. 

Physiologic factors in depression

Depression is thought to involve changes in receptor-neurotransmitter relationships in the limbic system, as well as the prefrontal cortex, hippocampus, and amygdala. Serotonin and norepinephrine are thought to be the primary neurotransmitters involved, but dopamine has also been related to depression.

Typically, neurotransmitters are passed from neuron to neuron; subsequently, either they are reabsorbed into the neuron—where they are either destroyed by an enzyme or actively removed by a reuptake pump and stored until needed—or they are destroyed by monoamine oxidase (MAO) located in the mitochondria.

A decrease in the functional balance of these neurotransmitters causes certain types of depression (ie, decreased norepinephrine causes dullness and lethargy, and decreased serotonin causes irritability, hostility, and suicidal ideation).

Environmental factors, including coexisting illnesses or substance abuse, may affect neurotransmitters and/or have an independent influence on depression.

Alterations in the balance of neurotransmitters and/or their function include the following:

• Impaired synthesis of neurotransmitters

• Increased breakdown or metabolism of neurotransmitters

• Increased pump uptake of neurotransmitters

In addition to localizable brain chemical changes, it is likely that gene-environment interactions, as well as endocrine, immunologic, and metabolic mediators, play a part in the development of depression. ^[13]

Studies have revealed a strong link between depression and migraine with aura, which is explained at least in part by genetic factors. ^[14] In addition, a reciprocal link exists between obesity and depression. ^[15]

Bipolar disorder has a prominent depressive component but is a different clinical entity from depression. There is a possible defect on chromosome II or X, but current genetic research is inconclusive.

Antidepressants and suicide

In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. In September 2004, the results of an FDA analysis suggested that the risk of emergent suicidality in children and adolescents taking selective serotonin-reuptake inhibitors (SSRIs) was real. The FDA advisors—the Psychopharmacologic Drugs and Pediatric Advisory Committees—recommended the following:

• A "black-box" warning label be placed on all antidepressants, indicating that they increase the risk of suicidal thinking and behavior (suicidality)

• A patient information sheet (Medication Guide) be provided to the patient and their caregiver with every prescription

• The results of controlled pediatric trials of depression be included in the labeling for antidepressant drugs

The committees recommended, however, that the products not be contraindicated in the United States, saying that access to the drugs is important for patients who can benefit from them. For more information, see the FDA Statement on Recommendations of the Psychopharmacologic Drugs and Pediatric Advisory Committees.

Some studies have shown that the FDA warnings regarding suicide in children on antidepressants may have had the unintended result of a decrease in the rates of diagnosis and treatment of depression, as well as dosing adjustments by physicians. It has also been noted that monitoring of these patients did not increase following the warnings. ^{[16, 17, 18, 19]}

Occurrence in the United States

An estimated 21.0 million US adults experienced at least one major depressive episode in 2021. ^[1] In the same year, suicide was the 11th leading cause of death in the United States, with 48,183 deaths. This is about one death every 11 minutes. The number of people who think about or attempt suicide is even higher. In 2021, an estimated 12.3 million American adults seriously thought about suicide, 3.5 million planned a suicide attempt, and 1.7 million attempted suicide.13. ^[4]

According to the National Institute of Mental Health, 8.3% of all US adults (21.0 million) had at least one major depressive episode in 2021. Adult females had a higher prevalence of depressive episodes than adult males (10.3% vs 6.2%). Individuals aged 18–25 had the highest prevalence of major depressive episodes at 18.6%. ^[1]

Among adolescents in the United States, an estimated 5.0 million (20.1%) aged 12–17 had at least one major depressive episode in 2021. The prevalence of major depressive episode was higher among adolescent females (29.2%) compared to adolescent males (11.5%). ^[1]

International occurrence

Globally, an estimated 703,000 people take their own lives annually. ^[20] Of these global suicides, 77% occur in low- and middle-income countries. ^[4] However, strong cultural prejudice and stigma resulting from depression or suicide attempts in many countries predicts that these figures are gross underestimates. 

Race-related demographics

African Americans and Mexican Americans are least likely to receive any care, let alone adequate care, for depression. ^[3]

The BRFSS study by the CDC noted that non-Hispanic blacks (4%), Hispanics (4%), and non-Hispanic persons of other races (4.3%) were significantly more likely to report major depression than non-Hispanic whites (3.1%). ^[21]

Suicide rates among American Indian and Alaskan natives aged 15-34 years are almost twice the national average for this age range. Hispanic females make significantly more suicide attempts than their male or non-Hispanic counterparts.

The risk of suicide is increased by concurrent illness, alcohol and drug abuse, access to lethal means, hopelessness, pessimism, isolation, and impulsivity, and the risk is reduced by help-seeking behavior, access to psychiatric treatment, and availability of family and other social supports.

Sex-related demographics

More women than men seek treatment for depression, but this is not necessarily reflective of the true incidence of the disease. The BRFSS study by the CDC determined that women were significantly more likely than men to report major depression (4% vs 2.7%, respectively). ^[21]

Although depression is more often diagnosed in women, more men than women die as a result of suicide by a factor of 4.5:1. White men complete more than 78% of all suicides, with 56% of suicide deaths in males involving firearms. Poisoning is the predominant method among females.

An estimated 8-25 attempted suicides occur for every completion. Many of these are never discovered or never reported. It is critically important to recognize that the majority of suicide attempts are expressions of extreme distress in a very ill individual, and are categorically not, as has often been assumed historically, merely bids for attention.

Age-related demographics

According to the BRFSS study by the CDC, the prevalence of major depression increased with age, from 2.8% among individuals aged 18-24 years to 4.6% among individuals aged 45-64 years; however, incidence declined to 1.6% among those 65 years or older. ^[21] The study also found that "other depression" was highest (8.1%) among individuals aged 18-24 years.

Suicide is estimated to be the eleventh leading cause of death in all age ranges in the United States. Rates of suicide are highest in people ages 85 and older. Men aged 75 and older have the highest rate (42.2 per 100,000) compared to other age groups. Adults aged 35–64 account for 46.8% of all suicides in the United States, and suicide is the 8th leading cause of death for this age group. Youth and young adults ages 10–24 years account for 15% of all suicides, and suicide is the second leading cause of death for this age group, accounting for 7,126 deaths. ^[22]

Occupation-related demographics

Although no profession or occupation is immune to depression, it is recognized that certain occupations and professions may be more susceptible to depression and suicide, either because of pre-existing depressive tendencies upon entering the profession or occupation, or because of occupational hazards encountered. A 2014 claims-based survey of depression in industry analyzed rates for clinical depression in 55 industries and found that they ranged from 6.9 to 16.2%. Industries with the highest rates tended to be those that required frequent or difficult interactions with the public or clients, and had high levels of stress and low levels of physical activity. ^[23]  The medical profession has the highest risk of death by suicide of any profession or occupation for several reasons (see Physician Suicide). In all populations, the existence of depression coupled with knowledge of and access to lethal means dramatically increases the risk for suicide. In addition to medicine, other high control and highly regulated professions such as law enforcement, military, and the legal profession may be more likely to experience depression and less likely to seek intervention because of the associated stigma and possible licensure implications. Certain common conditions, such as PTSD in military, and burnout in healthcare providers, ^[24] may either be confused with or may contribute to the onset of depression. Recent research suggests that suicide is 3 times more likely in individuals who have experienced a concussion, so occupations that might result in head injuries may be predisposed to suicide, with or without concomitant depression. ^[25]

Morbidity associated with depression is difficult to quantify. The lethality of depression, however, in the form of completed suicide, can be measured, with suicide being the eleventh leading cause of death in the United States in 2021.

As previously mentioned, an estimated 703,000 people worldwide take their own lives annually. ^[20]  However, the true incidence of suicide may, as a result of underreporting, be significantly higher. Almost all people who kill themselves intentionally have a diagnosable mental disorder with or without substance abuse, which in itself is often a result of attempted self-treatment for the symptoms of depression. Approximately two thirds of individuals who complete suicide have seen a physician within a month of their death.

Signs of depression in patient history

Depression is a pernicious and all-encompassing disorder that generally affects the body, feelings, thoughts, and behaviors to varying degrees. ^{[26, 27, 28]} However, the condition is often difficult to diagnose because it can manifest in so many different ways. For example, some depressed individuals seem to withdraw into apathy, while others may become irritable or even agitated. Eating and sleeping patterns can be exaggerated to either extreme, either becoming excessive or being almost eliminated. Observable or behavioral symptoms may be minimal despite profound inner turmoil. Symptoms of depression may include the following:

• Persistently sad, anxious, or empty moods

• Loss of pleasure in usual activities (anhedonia)

• Feelings of helplessness, guilt, or worthlessness

• Crying, hopelessness, or persistent pessimism

• Fatigue or decreased energy

• Loss of memory, concentration, or decision-making capability

• Poor abstract reasoning

• Restlessness, irritability

• Sleep disturbances

• Change in appetite or weight

• Physical symptoms that defy diagnosis and do not respond to treatment - (very commonly pain and gastrointestinal complaints)

• Thoughts of suicide, death, or suicide attempts

• Poor self-image or self-esteem - As illustrated, for example, by verbal self-reproach

To establish a diagnosis of major depression, a patient must express 1 of the first 2 items above and at least 5 of the other symptoms listed. Such disturbances must be present nearly daily for at least 2 weeks. Symptoms can last for months or years.

Symptoms can cause significant personality changes and changes in work habits, as well as social withdrawal or consistent irritable moods, making it difficult for others to empathize with the depressed individual. Some symptoms are so disabling that they interfere significantly with the patient's ability to function. In very severe cases, people with depression may be unable to eat, take care of basic hygeine, or even to get out of bed.

Symptomatic episodes may occur only once in a lifetime or may be recurrent, chronic, or longstanding; in some cases, they seem to last forever. Occasionally, symptoms appear to be precipitated by life crises or other illnesses; at other times, they occur at random.

Clinical depression commonly occurs concurrently with, or can be precipitated by, injury or other medical illnesses and worsens the prognosis for these illnesses. Even the diagnosis of concurrent illness is made much more difficult by the presence of depression.

Physical manifestations of depression

There are no inevitable physical findings of depression, although some manifestations may be seen quite often. Signs of depression may include the following:

• Psychomotor retardation or agitation, such as slowed speech, sighs, and long pauses

• Slowed body movements, even to the extent of motionlessness or catatonia

• Pacing, hand wringing, and pulling on hair

• Appearance of preoccupation

• Lack of eye contact

• Tearfulness or sad countenance

• Self-deprecatory manner or belligerence and defiance (especially in adolescents)

• Irritability (especially in high-powered individuals)

The differential diagnosis of depression contains numerous physical, emotional, and psychological disorders, including the following:

• Alcohol and substance abuse

• Anorexia nervosa

• Anxiety disorders

• Burnout (especially in healthcare workers)

• Conversion disorder

• Delirium

• Dementia

• Elder abuse

• Fibromyalgia/Chronic fatigue immune dysfunction (CFIDS)

• Grief reaction

• Human immunodeficiency virus-1 (HIV-1) encephalopathy

• Acquired immunodeficiency virus (AIDS)–related dementia

• Hyperparathyroidism

• Hypothyroidism

• Myopathies

• Panic disorder

• Child abuse and child sexual abuse

• Schizophrenia

• Drug and chemical toxicities

• Withdrawal syndromes

• Postconcussion/Traumatic brain injury

• Posttraumatic stress disorders

• Postpartum depression

• Postpartum psychosis

• Sheehan syndrome/panhypopituitarism

• Liver failure

• Vitamin deficiency

• Medication adverse effects

• Medication abuse/overdose

• Withdrawal from abused substances

• Apathetic thyrotoxicosis (in elderly persons)

Laboratory studies

Depression is a clinical diagnosis. Laboratory tests are primarily used to rule out other diagnoses. Consider the following laboratory tests:

• Complete blood count (CBC)

• Electrolytes, including calcium, phosphate, and magnesium

• Blood urea nitrogen (BUN) and creatinine

• Serum toxicology screen

• Thyroid function tests

• Vitamin B12

An electrocardiogram (ECG) may be indicated for the diagnosis of arrhythmia, particularly heart block. An electroencephalogram (EEG) also may be indicated in selected cases.

Imaging studies

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain is performed if organic brain syndrome or hypopituitarism is included in the differential diagnosis.

Certain psychometric tests can make a diagnosis of depressive disorders with reasonable clinical certainty. They include the following:

• Zung Self-Rating Depression Scale

• Beck Depression Inventory (BDI)

• Criteria for Epidemiologic Studies-Depression (CES-D) scale

• Children's Depression Inventory (CDI)

• Yesavage Geriatric Depression Scale

Emergency department clinicians need to maintain a high index of suspicion for the diagnosis of depression, especially in populations at risk for suicide. ^{[29, 30, 31]}

The emergency department can sometimes be the last opportunity for intervention in the downward spiral of depression, which leads to death for a significant number of persons with the disease. Although the clinician may never see the results of protective intervention, statistics suggest that the presentation of a depressed and suicidal patient to a health-care setting is an opportunity to make a real difference and possibly to save a life.

Few diseases are as lethal, and yet as reversible, as depression. Lives can be and are saved every day as a result of the timely efforts and empathic interventions of skilled and compassionate health-care professionals who are knowledgeable, empathic, and motivated to deal effectively with depression.

Identifying at-risk patients

Although primary at-risk populations include young adults and elderly persons, ^[32] depression and suicidality can occur in any age group, including children.

Depression should be strongly suspected as an underlying factor in drug abuse or overdose (including alcohol) with self-inflicted injury or even in an intentionally inflicted injury by another in which the assailant is known to the victim. In any such patient, screening for diagnostic symptoms of major depression and suicidality is mandatory, in addition to protective custody. 

When a patient has contemplated or attempted suicide, the burden is on the health-care provider to directly explore the situation with the patient in as much detail as possible to determine the current presence of suicidal ideation as well as accessible means and plans for completion of suicide. Discussing these is the most important step emergency department clinicians can take in an attempt to prevent suicide in a patient at risk.

If suicidality is present, hospitalization with the patient's consent or via emergency commitment should be undertaken unless clear-cut means to assure the patient's safety can be assured while outpatient treatment is begun. A child who is suicidal or has made an attempt at suicide should be admitted to a protected environment until all medical and social services can be employed to ensure the child's safety and continued monitoring.

Treatment in the emergency department

Antidepressant therapy generally would not be initiated in the emergency department, although regional variations in this standard exist. A psychiatrist or mental health professional with prescribing privileges should be consulted for definitive pharmaceutical intervention. After consultation, it may be appropriate to provide a small amount of the suggested medication to sustain the patient until follow-up. It may also be appropriate to renew a previously effective medication in small quantities and with the assurance of a follow-up mechanism that is accessible and acceptable to the patient.

A fast-acting intervention in acute depression with suicidality that is currently being reviewed in the emergency medicine literature is the use of a low-dose intravenous bolus of ketamine. ^[33]

Psychotherapeutic interventions act synergistically with pharmacologic therapy. Guidelines for the treatment of patients with major depressive disorder have been updated by the American Psychiatric Association and are available on their Web site. ^[6]

Post–emergency department treatment

Patients may require additional interventions that can be instituted immediately on transfer from the emergency department, but never actually in the emergency department. Electroconvulsive therapy (ECT) is safe and can be quickly effective. It is usually reserved for refractory cases, cases of pharmacologic resistance or adverse effects, and cases in which rapid reversal is indicated. Newer treatment modalities for refractory depression, including electromagnetic transcranial stimulation and repetitive vagal stimulation, are becoming more widely available. For individuals who have previously been given a diagnosis and who have been successfully treated with these modalities, rapid reinstitution can be lifesaving. 

The N-methyl-D-aspartate (NMDA) receptor antagonist esketamine intranasal (Spravato) was approved in 2019 for treatment-resistant depression in conjunction with an oral antidepressant. ^{[34, 35]}  The precise mechanism by which esketamine elicits its antidepressant effect is not fully understood. NMDA is an ionotropic glutamate receptor. 

In August 2020, esketamine intranasal gained approval for treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant. Approval was based on the ASPIRE I and II trials in which esketamine intranasal plus comprehensive standard of care demonstrated a significant, rapid reduction of depressive symptoms within 24 hours, with some patients starting to respond as early as 4 hours. Esketamine intranasal led to a 15.9- and 16.0-point decrease on the Montgomery-Åsberg Depression Rating Scale (MADRS) in each trial at 24 hours after the first dose of study medication. This compared to a reduction of 12.0 and 12.2 points in the placebo plus comprehensive standard of care group. ^{[36, 37]}  

When depression is diagnosed, particularly when suicidality is present or reasonably suspected, the primary care provider, often in consultation with a mental health professional, should design an interim disposition plan appropriate to the diagnosis and degree of risk that is assessed.

This may require legal certification that the patient is in need of emergency evaluation and protective observation, the provision of emergency or short-course medication, contracting for safety with the patient, and/or releasing the patient into the protective custody of his or her family or a law enforcement agency.

While evaluating and securing an appropriate disposition for the patient, all staff members must take measures to ensure the safety and preserve the dignity of the patient.

Transfer is indicated when there is a need for protective custody or intensive intervention that is not available at the present institution.

Consultations

Consult a mental health clinician after a screening evaluation is complete and all acute medical complications are addressed. The protocol for consultation should be established by the institution and should be the same for every patient with presenting symptoms of depression with suicidality.

Patient education

Patients must be told clearly and convincingly that depression is an eminently treatable illness. Carefully inform patients about the critical importance of taking any medications that are prescribed, as well as likely adverse effects and their management. Stress the need for short-term follow-up and continuing treatment.

Recommend reading for patients. A good source of information about depression is the National Alliance on Mental Illness.

For patient education information, see the Depression Center, as well as Depression, Suicidal Thoughts, Antidepressant Medications, and SSRIs and Depression.

Suicidality-associated treatment pitfalls include the following:

• Failure to recognize or appropriately hospitalize a suicidal patient

• Failure to document historical details demonstrating lack of suicidality

• Failure to follow transfer protocols in accordance with the Emergency Medicine Treatment and Active Labor Act (EMTALA) - Note that under current EMTALA interpretations, even a discharge is considered a transfer

• Failure to prescribe suicide precautions for a possibly suicidal patient who is discharged to an institutional setting (such as a correctional facility) rather than a psychiatric setting

• Failure to warn others of any threat made concerning them by a patient who is not to be admitted to protective custody

• Failure to provide a source of follow-up care or to advise on indications to return to the emergency department

• Failure to warn patient and significant others about potential signs of deterioration and suicidality and what to do about them ^[38]