Updated in September 2009
Fact Sheet content was reviewed by a member of NARSAD's Scientific Council
Overview
Clinical depression is a serious condition that negatively affects how a person thinks, feels, and behaves. In contrast to normal sadness, clinical depression is persistent, often interferes with a person's ability to experience or anticipate pleasure, and significantly interferes with daily life. Clinical depression, which psychiatrists call major depression, cannot be "willed away" or "shaken off"-common misconceptions that prevent people from seeking treatment. Untreated, symptoms can last for weeks, months, or years; and if inadequately treated, depression can lead to significant impairment, other health-related issues, and in rare cases, suicide.
Clinical depression, which can be mild, moderate or quite severe, can strike at any age. It is estimated depression affects 17 million to 20 million Americans a year, or one in 10 adults, and twice as many women as men. It often first appears during the late teens to mid-20s; episodes may recur throughout life. Late-onset depression, affecting the elderly, is underdiagnosed and undertreated.
Depression tends to run in families - especially for people with bipolar disorder, which includes both mania and depressive episodes - but in many cases there is no family history. Traumatic events early in life increase the chances of experiencing depression as an adult. Stressful events throughout life, such as divorce, job loss, or loss of a loved one, increase the near-term risk of depression.
Mood disorders related to depression include:
• Dysthymia, which is less severe than major depression, but involves long-term, chronic symptoms that decrease functioning and quality of life and increase the risk of a major depressive episode.
• Seasonal Affective Disorder (SAD), depression brought on by seasonal changes.
• Postpartum Depression, which results from hormonal changes after childbirth and its attendant stresses.
• Adjustment Disorders, which occur when a depressed mood follows a particularly stressful event.
• Bipolar Disorder, formerly called manic-depressive illness, which is marked by extreme mood swings, including severe highs (mania) and/or lows (depression).
What are the symptoms of depression and how is depression diagnosed?
A person is diagnosed with a major depression when he or she experiences at least five of the symptoms listed below for two consecutive weeks. At least one of the five symptoms must be either (1) depressed mood or (2) loss of interest or pleasure.
• Depressed mood most of the day, nearly every day
• Markedly diminished interest or pleasure in activities most of the day, nearly every day
• Changes in appetite that result in weight losses or gains unrelated to dieting
• Changes in sleeping patterns
• Loss of energy or increased fatigue
• Restlessness or irritability
• Feelings of anxiety
• Feelings of worthlessness, helplessness, or hopelessness
• Inappropriate guilt
• Difficulty thinking, concentrating, or making decisions
• Increased use of alcohol or drug use (although true, usually not a criteria for the diagnosis)
• Thoughts of death or suicide or attempts at suicide
For a person to be considered depressed, these symptoms must cause significant distress or impairment in social and work life, and must not be due to medical conditions, substance abuse or the loss of a loved one.
New NARSAD-funded research to improve the diagnosis of depression includes:
• Developing new and more sensitive brain imaging methods to understand the brain circuitry of depression .
• Studying key chemicals in the blood of children exposed to trauma to determine if they increase the likelihood of developing depression later in life
• Using cognitive testing and brain imaging to assess whether people with depression have problems in thinking and remembering, particularly in recalling positive things about their own lives.
• Assessing whether blood levels of certain chemicals in pregnant women and after birth can predict postpartum depression .
• Identifying genetic factors associated with a high risk of suicide as a potential screen for suicide risk .
How is depression treated?
The most common and effective treatments for clinical depression are antidepressant medications and psychotherapy.
Antidepressants correct chemical imbalances in the brain, while psychotherapy helps an individual cope with ongoing problems and specific issues that may contribute to depression. The two most often-used forms of psychotherapy are cognitive behavioral therapy and interpersonal therapy. A combination of medication and psychotherapy currently is the most effective treatment for severe depression, while either medication or psychotherapy alone is effective for mild to moderate cases.
• Antidepressants are prescribed based on the severity of the depression, a patient's drug history, and drug side effects. Antidepressants include:
• The selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil) and sertraline (Zoloft).
• The serotonin/norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor)
• Bupropion (Wellbutrin)
• Tricyclic antidepressants, such as amitriptyline (Elavil) and Tofranil (imipramine)
• Tetracyclics, such as mirtazapine (Remeron)
• Monoamine oxidase inhibitors (MAOIs), such as phenelzine (Nardil)
• Stimulants, lithium, and other mood stabilizers.
Newer antidepressants, such as SSRIs, SNRIs, and bupropion, a drug that targets the brain chemical dopamine, are often prescribed as a first line treatment because they have fewer side effects than older medications. Older drugs, including tricyclics, tetracyclics and MAOIs, however, may still be the best option for some people. If someone is severely depressed, stimulants may be prescribed initially since antidepressants are slow to work. Lithium and mood stabilizers are used primarily to treat bipolar disorder.
People who take antidepressants should keep several points in mind:
• Most side effects of antidepressants are not medically serious and do not last long. Physicians and the drug packaging list what reactions might occur and alert patients to report any unusual responses. The side effects for some SSRIs include loss of libido, weight gain and sleeping problems; for venlafaxine, high blood pressure, and for extended-release bupropion, a rare possibility of seizure. The adverse reactions do not occur in every person taking the medication. But if the side effects interfere with daily life, doctors may lower a medication's dose or try a different one.
• Drugs should not be stopped without the assistance of a physician. People need to be weaned off some antidepressants slowly because stopping too quickly can cause withdrawal symptoms.
• If one medication doesn't work to treat the depressive symptoms, others are available. People often need to try different medications, or different doses of one medication, to find the drug or combination that works best for them.
• While antidepressants are deemed safe and effective, research by the Food and Drug Administration has shown that children and adolescents taking antidepressants have an increased risk of suicidal thinking and even attempts. Actual suicides are rare, making it difficult to establish scientifically if they are more common. The Food and Drug Administration has required a warning label stating that people of all ages taking these drugs should in the first few weeks of their use watch closely for any unusual thoughts or behavior, which should be reported to a physician.
• Psychotherapy
• Cognitive Behavioral Therapy is a treatment approach that focuses on reversing negative patterns of thinking and behavior, and changing the beliefs that underlie such thoughts and activities. A person with depression, for example, may sincerely believe he or she is a failure. But with a therapist's help a depressed person can learn to view such an idea as harmful and self-destructive, and can learn to challenge the validity of pessimistic or harmful thoughts. Part of the therapy involves monitoring negative and self-defeating views and developing methods to minimize this kind of thinking.
• Interpersonal Psychotherapy is a short-term therapy that teaches a person with depression how to understand and adapt to the emotional aspects of relationships. In the therapeutic process, people learn how to identify, understand and communicate about emotional issues in their lives and in their relationships and how to manage their interpersonal problems more effectively.
• Electroconvulsive Therapy (ECT) is used for treatment-resistant depression or when someone is suffering from psychotic depression (for example, with hallucinations or delusions) or is at risk of suicide. ECT is generally safe and highly effective for severe depressive episodes. Long-lasting memory problems, although a concern in the past, have been significantly reduced with modern ECT techniques.
• Vagus Nerve Stimulation (VNS) is a medical procedure that has had some success in treatment-resistant depression. It was approved for depression by the Food and Drug Administration in 2005. VNS employs an implanted device that sends electrical pulses to the left vagus nerve in the neck. Doctors do not yet understand how the treatment leads to improvement.
• Transcranial Magnetic Stimulation (TMS) and repetitive Transcranial Magnetic Stimulation (rTMS) are noninvasive treatments that deliver magnetic pulses over the frontal regions of the brain for a few minutes a day, over several weeks. The treatment appears to affect different biochemical processes and certain areas of the brain and has been shown to be effective in some people with treatment-resistant depression. Although TMS received approval by the Food and Drug Administration in 2008 for treatment-resistant depression, it is still being studied extensively in clinical research. Magnetic Seizure Therapy (MST) uses high-intensity repetitive rTMS to induce focal seizures in specific regions of the brain. The goal of MST is to focus the induced seizures in the parts of the brain believed to be involved in the antidepressant response, while limiting side effects.
A new treatment under investigation for treatment-resistant depression is Deep Brain Stimulation (DBS), a technique that uses minute electrical pulses to stimulate a tiny region in the brain believed to play a key role in depressive symptoms. DBS is approved by the Food and Drug Administration for use in Parkinson's disease.
Recurring bouts of depression are common in many people who have had one episode, so continuing treatment for at least six months greatly reduces the risk of relapse. If someone has had three or more previous episodes of depression, long-term treatment with antidepressants is often recommended to reduce the risk of recurrence. Once depression is identified, more than 80 percent of people respond well to some form of treatment.
New NARSAD-funded research about depression treatment includes:
• How variations in genes that affect the brain chemical serotonin influence response to antidepressants. Animal studies of these genes may help explain why certain antidepressants do not work in some people
• Using brain imaging to monitor the effectiveness of traditional and novel antidepressant therapies .
• Understanding how brain circuitry gets rewired by deep brain stimulation .
• Characterizing how brain circuitry gets rewired by electroconvulsive therapy, and finding ways to minimize memory loss that can accompany the treatment
• Determining what other neurotransmitters and brain chemicals, such as glutamate, galanin, norepinephrine, dopamine and others, might be targets in the development of new drugs to treat depression .
• Exploring how ketamine, which has been used as an anesthetic, might be a very fast acting antidepressant .
• Analyzing how nerve cell growth and development can reduce depression in animal models of depression and in humans
• Figuring out what additional drugs might help improve the effects of antidepressants
• Studying the possibility that a newly studied biological chemical, called microRNA, might exert an antidepressant effect.
Living with depression, from diagnosis to treatment to daily life
"Depression" is a potentially confusing term because it refers both to the symptom of sadness and the syndrome of depression. While sadness is simply an emotion that most people experience from time to time, the syndrome of depression is a serious illness that has a constellation of symptoms, runs a somewhat typical course and usually responds to medical and psychological treatment. In fact, people who are depressed do not usually say they are "sad," but instead might say for an extended period of time that they are extremely worried, that something very serious is wrong with them, that their life is a complete failure or that they have lost confidence in the future.
Additionally, they often have low energy and difficulty concentrating or focusing attention. Approximately half of people with clinical depression never seek treatment; they may try to tough out their symptoms or self-medicate with drugs of abuse or alcohol. For those who do seek treatment or have a loved one bring them for care, the majority respond to drugs, psychotherapy, or a combination of the two.
Because people have depressive episodes of shorter or longer duration, ranging from 6 months to 18 months, clinicians work with patients to determine how long they will need medication or psychotherapy. Some people want to try to stop drug treatment if they can, while others prefer continuing treatment because they feel much better on medication and in psychotherapy. By and large serious side effects are rare with SSRIs. The two most common difficulties with chronic SSRI treatment are sexual difficulties and tiredness. For patients resistant to the commonly used antidepressants, combination treatments or MAOIs inhibitors can be effective.
What causes depression?
While there is no single cause of depression, those with a family history are at a higher risk of suffering from it. Experts also believe depression can be caused by one or a combination of factors including
• brain biochemistry, such as imbalances in neurotransmitters, the brain chemicals that send and receive messages
• environment, such as continuous exposure to neglect, abuse, and stressful life events
• personality, such as a tendency to be self-critical, overly dependent, or have low self-esteem and chronic medical conditions, such as cancer or diabetes.
New NARSAD-supported research is focusing on the causes of depression:
• Trying to understand how severe stress and immune factors impact brain chemistry and the development of depression
• Studying how stress affects neurogenesis, the ability of new nerve cells in the brain to grow. Reduced neurogenesis in certain brain regions occurs in the brains of depressed people .
• Understanding the role of brain cells other than neurons, such as glial cells, in depression .
• Determining the role of the brain chemical BDNF in depression
• Studying how epigenetic changes -- chemical changes that affect the function of DNA but not the DNA sequence itself -- lead to depression .
Help support NARSAD's research on depression
For the past 23 years, NARSAD has been at the forefront of research on mental illness. From 1987 through 2009, NARSAD has given more than $252 million in grants to support innovative research by more than 2,800 scientists at leading universities, medical centers and research institutions around the world. Besides depression, NARSAD funds research on schizophrenia, bipolar disorder, anxiety disorders, and childhood mental illness.
NARSAD supports research on all aspects of depression and other mental illnesses-the causes and nature of the disease, structural and functional changes in the brain, chemical abnormalities, genetics, pharmacological and non-pharmacological treatments, and social and behavioral aspects of the illness. NARSAD's grantmaking program is guided by its Scientific Council, a volunteer group of 116 leading neuroscientists, which reviews and recommends research proposals for funding.
NARSAD relies on the generosity of thousands of donors and volunteers to support this research, which has yielded great progress in the understanding, diagnosis and treatment of mental illnesses. Formerly known as the National Alliance for Research on Schizophrenia and Depression, NARSAD is a 501 (c)(3) organization that receives no government support. All donations are tax-deductible. To donate to NARSAD and to learn more about our work, click here.
