Depression and suicide.

Morbidity associated with depression is difficult to quantify, but the lethality of depression takes the measurable form of completed suicide, the eighth leading reported cause of death in the United States.

Depression is a potentially life-threatening mood disorder that affects 1 in 6 persons in the United States, or approximately 17.6 million Americans each year. Depressed patients are more likely to develop type 2 diabetes and cardiovascular disease.[1] 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.[2]

See Posttraumatic Stress Disorder (PTSD), a Critical Images slideshow, to help recognize the symptoms of PTSD and depression, and to determine effective treatment options.

The current economic cost of depressive illness is estimated to be $30-44 billion annually in the United States alone. 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 major depression receive any kind of treatment, and only 20% of those individuals receive treatment consistent with current practice guidelines of the American Psychiatric Association (APA).[2, 3] 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.[4]

Persistent ignorance about depression and misperceptions of it 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 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.

In addition to depression, other etiologies such as alcohol/substance abuse (especially of opiates and cocaine), impulsiveness, and certain familial factors are highly associated with risk for suicide. These factors include a history of mental problems or substance abuse, suicide in the immediate family, family violence of any type, and separation or divorce.[5, 6, 7, 8, 9]

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 and therefore the likelihood of suicide attempts. The incidence of depression in health-care workers is comparable to that in the general population, though the rate of completion of suicide is higher.

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.[10]

Studies have revealed a strong link between depression and migraine with aura, which is explained at least in part by genetic factors.[11] In addition, a reciprocal link exists between obesity and depression.[12]

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.


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