Depression

Depression is a mood disorder in which feelings of loss, anger, sadness, or frustration interfere with everyday life. Depression affects approximately 17 million Americans each year. It can be mild, moderate, or severe and occur as a single episode, as recurring episodes, or as chronic depression (lasting more than 2 years).

The primary types of depression include:

• Major depression—five or more symptoms must be present; an episode must last at least 2 weeks, but tends to continue for 20 weeks. (A mood disorder is classified as minor depression if less than five depressive symptoms are present for at least 2 weeks.)
• Dysthymia—a chronic, generally milder form of depression; symptoms are similar to major depression but more mild in degree
• Atypical depression—depression accompanied by unusual symptoms, such as hallucinations, delusions, and physical rigidity

Other common forms of depression include:

• Postpartum depression—experienced by 8% to 20% of women following delivery
• Premenstrual dysphoric disorder (PDD)—experienced by 3% to 8% of women; depressive symptoms occur 1 week prior to menstruation and disappear following menstruation
• Seasonal affective disorder (SAD)—experienced by 5% of adults, the majority of whom are women; occurs during the fall-winter season and disappears during the spring-summer season

Depression may also occur with mania (known as manic-depression or bipolar disorder). In this condition, moods cycle between mania and depression.

Signs and Symptoms

While it is normal for most people to feel "down in the dumps" on occasion, a person with major depression feels significantly depressed for a prolonged period of time, has difficulty enjoying acts that were once pleasurable, and experiences at least five of the following symptoms for 2 weeks or more:

• Sleep disturbances—at least 90% of people with depression have either insomnia (sleeplessness) or hypersomnia (excessive sleeping)
• Significant change in appetite (often resulting in either weight loss or weight gain)
• Fatigue and loss of energy
• Feelings of worthlessness, self-hate, and inappropriate guilt
• Extreme difficulty concentrating
• Either agitation, restlessness, and irritability or inactivity and withdrawal
• Recurring thoughts of death or suicide
• Feelings of hopelessness

Although not generally considered to be defining characteristics of depression, many people with the condition report a lack of sex drive and sudden bursts of anger.

Causes

The causes of depression are complex and involve a combination of biologic, genetic, and environmental factors. People with depression may have abnormal levels of certain brain chemicals, including serotonin, acetylcholine, and catecholamines (such as dopamine). The following may alter the levels of these brain chemicals and contribute to development of depression:

• Heredity—a recently identified gene called SERT that regulates the brain chemical serotonin, has been linked to depression
• Chronic stress (such as from loss, abuse, or deprivation in early childhood)
• Amount of exposure to light
• Sleep disturbances
• Social isolation
• Nutritional deficiencies (especially folate [vitamin B9] and omega-3 fatty acids)
• Serious medical conditions, such as heart attack or cancer
• Certain medications, including those for high blood pressure, high cholesterol, or irregular heartbeat

Risk Factors

Although depression is a condition that can affect anyone, regardless of age, race, or gender, the following factors may increase an individual's risk for an initial or recurrent episode of depression:

• Prior episodes of depression
• Family history of depression
• Suicide attempt—a former attempt of suicide during a major depressive episode increases the likelihood of another episode of depression
• Female gender—the incidence of depression appears to be greater in women than in men, however, some researchers speculate that women may simply report their symptoms more frequently than men and that men may be more apt to mask their depressive symptoms with alcohol. Therefore, it is still unclear whether women truly have a greater risk for depression.
• Young adulthood or middle age—the highest occurrence of depression is between the ages of 25 and 44; the elderly are also at particular risk due to death of loved ones, physical illness, and loss of independence
• Stressful life events (such as the death of a loved one), particularly if the event occurs at a young age
• Postpartum period
• Chronic medical or psychological conditions including autoimmune diseases (such as lupus), cancer, heart disease, chronic headaches, chronic pain, anxiety, obsessive-compulsive disorder, and borderline personality disorder; medical conditions that cause shifts in hormones, such as thyroid disorders or menopause, may also contribute to depression.
• History of abuse (such as mental, physical, or sexual)
• Lack of social support system (such as a network of close friends or family)
• Current or past alcohol or drug abuse—25% of people with addictions have depression

Diagnosis

If feelings of depression or any of the related symptoms are present, it is important to address them with a physician or someone who can help direct care appropriately. Unfortunately, many people with depression tend to refrain from disclosing any or all of their symptoms in this setting. Occasionally, even when the symptoms are discussed during an appointment, a physician may try to treat them individually, rather than recognizing the complete picture of depression. Working together with a primary care physician is extremely important, however, because he or she is often the person who makes a referral to a psychiatrist who, in turn, makes a definite diagnosis of depression. Proper diagnosis of depression is the first step toward proper treatment.

Only psychiatrists can prescribe medication, but psychologists and social workers, as well as psychiatrists, use psychotherapy as an important mode of treatment. These specialists will often administer a screening test, such as the Beck Depression Inventory or the Hamilton Rating Scale, which consists of about 20 questions that assess an individual's risk for depression. Even before these psychological screening tests, however, several blood tests will be performed to determine whether nutrient deficiencies or underlying medical conditions (such as a thyroid disorder) may be causing or contributing to depression.

Although the vast majority of people with depression are treated as outpatients, hospitalization is necessary for people who intend or attempt suicide, and may be necessary under other circumstances as well.

Preventive Care

The following steps can help prevent depression or decrease the chances of relapse:

• Adequate sleep, regular exercise, and a balanced, healthy diet may help prevent depression and diminish symptoms of this mood disorder.
• Using mind/body techniques, such as biofeedback, meditation, and tai chi, are effective ways to prevent or reduce symptoms associated with depression.
• Psychotherapy directed at coping skills generally helps prevent relapse.
• Family therapy may prevent children or teens of depressed parents from becoming depressed later in life.
• Compliance with the prescribed treatment regimen decreases the chance of relapse.

Treatment Approach

People with depression have a number of options for treatment, but a combination of psychotherapy and antidepressant medications is the regimen of choice, particularly for people with major depression. Cognitive-behavioral therapy appears to be the most effective type of psychotherapy, particularly for adolescents and people with atypical or postpartum depression. As many as 90% of people with depression improve from a combination of psychotherapy and antidepressants; however, adverse side effects from certain medications make it difficult for many to take their medications. Some complementary and alternative therapies may be helpful in reducing the side effects from such medications; other complementary and alternative therapies may actually diminish the symptoms of depression. The following, in the order indicated, may be considered under the guidance of an appropriately trained specialist such as a psychiatrist or psychologist:

• Physical activity
• Folate supplements
• St. John's wort (Hypericum perforatum)
• Essential fatty acids
• Acupuncture

Lifestyle

Exercise
Studies have consistently shown that regular exercise (either aerobic or strength/flexibility training) significantly reduces depressive symptoms in people with mild to moderate depression and improves the mood of people with major depression. Some even suggest that exercise may be as effective as psychotherapy for people with mild to moderate depression, although additional research is needed to confirm this encouraging finding. In the meantime, exercise can be used safely in conjunction with medication for those with depression.

Diet
Studies suggest that people with depression who eat a healthy diet that includes fatty fish (such as salmon, mackerel, herring, and sardines) two to three times per week may significantly reduce their feelings of depression and anxiety. Fatty fish contain omega-3 polyunsaturated fatty acids (PUFAs), and many individuals with depression are deficient in this substance. Some studies suggest that dietary supplementation with docosahexaenoic acid (DHA), one type of PUFA, may help prevent depression.

Diets rich in fruits and vegetables, particularly leafy green vegetables, are also recommended for people with depression. For those who have difficulty maintaining a balanced diet, supplementation with a multivitamin may also be recommended.

Medications

Antidepressant medications are very effective; reports indicate that they are 90% successful in treating depression. In general, medications are taken for at least 4 to 6 months to assure complete and effective treatment. However, antidepressants often cause adverse side effects, making it difficult for some people to comply with taking their medications. Medications must not be stopped without first discussing this change with a physician. Most antidepressants cause withdrawal symptoms if they are not discontinued slowly over time with guidance from a physician.

There are several classes of antidepressant medications, including:

Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs increase the activity of a chemical in the brain called serotonin. Most healthcare practitioners will prescribe SSRIs before any other antidepressant medication for depression, in part because the side effects associated with SSRIs are generally fewer than for other classes of antidepressants. Typical side effects caused by SSRIs include stomach upset, weight gain or loss, drowsiness, sexual dysfunction (such as impotence, decreased libido, and diminished orgasm), headache, jaw grinding, and apathy. Very unusual side effects from this class of prescription drugs include extreme agitation, impulsivity, tremors, and insomnia. People who discontinue taking SSRIs due to side effects usually attribute their discontent to sexual dysfunction.

Drugs classified as SSRIs include:

• Fluoxetine
• Sertraline
• Paroxetine—most likely in this class to cause sexual dysfunction
• Fluvoxamine
• Citalopram—least likely in this class to cause sexual dysfunction

Another group of antidepressant medications (which are similar to SSRIs, but target other brain chemicals in addition to serotonin) may cause fewer negative sexual side effects. These include:

• Bupropion—should not be used if there is history of or risk for seizure
• Nefazodone—no sexual dysfunction reported; begins to work very quickly; may cause a decrease in blood pressure when going from lying or sitting to standing
• Venlafaxine—may impair sexual function; not recommended in the elderly; may improve quality of life more effectively than other antidepressants, but can cause irregular heart rhythm; withdrawal from the medication is difficult
• Mirtazapine—may be particularly effective if feelings of anxiety are also present; helps with insomnia but may cause drowsiness; other side effects are blurred vision, weight gain, and damage to production of cells in the bone marrow (very rare)
• Maprotiline—may cause dry mouth, drowsiness, sensitivity to the sun, and seizures

Tricyclic Antidepressants
Tricyclics increase the activity of the brain chemicals serotonin and norepinephrine. They are as effective as SSRIs, but are usually prescribed only to those who do not respond well to SSRIs because side effects are quite common and are usually less tolerable. Dry mouth, blurred vision, constipation, sexual dysfunction, weight gain, dizziness, drowsiness, urinary urgency (a sense that one has to urinate even when the bladder is empty), drop in blood pressure when going from lying or sitting to standing (causes dizziness and lightheadedness), and irregular heart rhythm are among the side effects of tricyclics.

Tricyclic antidepressants include:

• Amitriptyline
• Amoxapine—increases risk of seizure in those who are prone to have a seizure
• Clomipramine—used for obsessive/compulsive disorder
• Desipramine
• Doxepin—may help with insomnia
• Imipramine—may cause a rare lung disorder called idiopathic pulmonary fibrosis
• Nortriptyline—less risk of irregular heart rhythm than others in this class
• Protriptyline—less drowsiness than others in this class and may even cause weight loss; may lead to sun sensitivity
• Trimipramine—high risk for irregular heart rhythm

Monoamine Oxidase Inhibitors (MAOIs)
MAOIs boost the levels of norepinephrine, dopamine, and serotonin in the brain. MAOIs are generally prescribed only when other antidepressants have not been effective, which may occur in people with atypical depression. People who take MAOIs may experience a sharp increase in blood pressure after consuming food or drink containing the amino acid tyramine (found in such foods as aged cheeses and red wine). MAOIs also negatively interact with other medications, including ritalin (used for attention deficit hyperactivity disorder) and pseudoephedrine (decongestant in many over the counter and prescription medications), and should not be taken with other classes of antidepressants.

MAOIs include:

• Phenelzine—should be avoided with a history of seizures or bipolar disorder (manic-depression)
• Isocarboxazid—side effects include drowsiness, sexual dysfunction, weakness, trembling, and blurred vision
• Tranylcypromine—should not be used if there is any history of kidney disease or bipolar disorder

Surgery and Other Procedures

• Electroconvulsive Therapy (ECT) for depression is usually reserved for cases in which all other therapies have been unsuccessful. In this procedure, a small electrical current induces a seizure lasting approximately 40 seconds. A muscle relaxant and mild sedative are administered prior to the procedure. ECT is generally repeated every 2 to 5 days for a total of six treatments. It may cause temporary confusion, memory impairment, headache, muscle aches, irregular heart rhythm, or nausea.
• Magnetic Resonance Imaging (MRI)-Guided Cingulotomy involves the application of an electrical current to a specific part of the brain; the MRI is used as a guide for an exact placement. Long-term improvement has been reported using this technique in over 50% of people with depression who have not responded to other modes of therapy.

Nutrition and Dietary Supplements

Certain nutrients and dietary supplements have been associated with depression, including:

Folate (Vitamin B9)
Studies suggest that folate may be associated with depression more than any other nutrient. Between 15% and 38% of people with depression have low folate levels in their bodies and those with very low levels tend to be the most depressed. Having low levels of folate may also affect treatment; some studies report that people with folate deficiencies tend to respond less effectively to the SSRI, fluoxetine, than those with normal amounts of folate. Therefore, folate supplementation (typically between 400 and 800 mg) may be useful in both treating depression and assuring the appropriate effects of some antidepressant medications.

Many healthcare providers start by recommending a multivitamin (MVI) that contains folate, and then monitoring the homocysteine levels in the blood to ensure the adequacy of therapy. Elevated homocysteine levels indicate a deficiency of folate even if the levels of folate in the blood are normal. If the MVI alone is not enough to lower homocysteine and improve folate function, the provider may suggest additional folate along with vitamins B6 and B12.

Omega-3 fatty acids
Essential fatty acids, such as omega-3 and omega-6 fatty acids play a crucial role in the function of brain chemicals, particularly serotonin and dopamine. Studies have shown that low levels of omega-3 fatty acids (found in cold-water fish such as tuna and salmon), or a high ratio of omega-6 fatty acids (found in certain vegetable oils, such as corn and soybean oils) to omega-3 fatty acids, may be associated with depression. A typical American diet is high in omega-6 compared to omega-3 fatty acids. Eating foods rich in omega-3 fatty acids on a regular basis helps maintain an appropriate balance of omega-6 to omega-3 fatty acids, and although unproven, restoring this balance may help with feelings and symptoms of depression.

S-Adenosinemethionine (SAMe)
Some studies suggest that the dietary supplement SAMe may be just as effective as tricyclic antidepressants for treating depression, but with fewer side effects. SAMe appears to boost serotonin levels in the brain, but further research investigating the mechanism of action (how it works), safety, and effectiveness of SAMe for depression is warranted. Until more is understood, it is best to avoid using SAMe in conjunction with other antidepressants. Discuss its use with your healthcare provider who can help tailor your treatment accordingly.

Tryptophan
Tryptophan is an amino acid involved in the production of serotonin. Studies suggest that tryptophan depletion can lead to diminished serotonin levels, and in some cases, may increase a person's susceptibility to depression. Some research indicates that tryptophan, together with tricyclic medications, may produce better results than the medication alone. Tryptophan supplementation alone may not be enough to reduce symptoms of depression. However, while research results are intriguing, tryptophan use has been associated with the development of serious conditions such as liver and brain toxicity, and with eosinophilic myalgia syndrome (EMS), a potentially fatal disorder that affects the skin, blood, muscles, and organs. (An outbreak of EMS caused by a contaminated batch of tryptophan led to the removal of this supplement from the United States market in 1989.) In addition, given the possibility of adverse interactions, tryptophan should not be used in conjunction with MAOIs or SSRIs.

5-Hydroxytryptophan (5-HTP)
Some studies suggest that a by-product of tryptophan known as 5-HTP may be as effective as SSRIs and tricyclic antidepressants in treating depression, but with fewer side effects. As with tryptophan, EMS has been reported in 10 people taking 5-HTP. Further research is necessary to determine whether supplementation with 5-HTP is safe and effective for the treatment of depression.

Selenium
Some reports indicate that the mineral selenium, found in wheat germ, brewer's yeast, liver, fish, shellfish, garlic, sunflower seeds, Brazil nuts, and grains, significantly affects mood. In one study of people with low levels of selenium, those who consumed a diet high in selenium reported decreased feelings of depression after 5 weeks.

Inositol
Inositol is a naturally occurring substance involved in the production of certain brain chemicals. In a few studies, levels of inositol were lower in the cerebrospinal fluid (fluid surrounding the brain and spinal column) of depressed people compared to healthy people. In addition, administration of inositol decreased signs of depression in two animal studies. Several small human studies suggest that inositol may be of value in the treatment of depression, particularly for those who do not respond to antidepressant medications. More clinical trials are necessary to draw definitive conclusions on this substance, however.

Tyrosine
A number of studies conducted in the 1970s showed encouraging results regarding the use of tyrosine to ease symptoms of depression. In one study from 1990, however, tyrosine failed to demonstrate any anti-depressant activity. More studies are needed in order to draw firm conclusions about the use of tyrosine to help treat mild to moderate depression.

Melatonin
In one study of only 10 people with seasonal affective disorder, those who received melatonin supplements had significant improvement in their symptoms compared to those who received placebo. Given the small size of this study, however, more research is needed before conclusions can be drawn regarding use of melatonin for either seasonal affective disorder or any other type of depression.

Vitamin C
Some healthcare professionals recommend vitamin C to reduce the symptom of dry mouth, a side effect experienced by many people taking antidepressant medications.

Herbs

While many herbal remedies have been used traditionally to treat depression, the most substantial amount of scientific research has involved the following herb:

St. John's wort (Hypericum perforatum)
Several studies indicate that St. John's wort may be as effective as tricyclic antidepressants, but with fewer side effects. Reported side effects include gastrointestinal complaints, fatigue, and oversensitivity to sunlight. Because of potential adverse interactions, St. John's wort should not be taken in conjunction with other antidepressants or with certain medications, including indinivir (a protease inhibitor used for HIV), oral contraceptives, theophylline, warfarin, digoxin, reserpine, cyclosporine, and loperamide.

Although they have yet to be scientifically evaluated for their use in treating depression, the following are a few examples of herbs that may be recommended by professional herbalists for depression or its related symptoms:

• Valerian root (Valerian officinalis)—may improve symptoms of insomnia associated with depression
• Damiana (Turnera diffusa)—may reduce sexual dysfunction associated with many antidepressant medications
• Ginseng (Panax ginseng)—may help the body resist stress

Acupuncture

Two randomized, controlled, clinical trials suggest that electroacupuncture may reduce symptoms of depression as effectively as amitryptiline, a tricyclic antidepressant medication. Electroacupuncture involves the application of a small electrical current through acupuncture needles. Other studies suggest that acupuncture may be effective for people with mild depression and for those with depression related to a chronic medical illness. Further research is warranted in this area.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies to alleviate the symptoms of depression based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type. A constitutional type is defined as a person's physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual.

• Ignatia — for a sudden sense of grief or disappointment following the death of a loved one, the end of a romantic relationship, or an unexpected loss of one's job; this remedy is most appropriate for individuals who are very sad and have frequent crying spells
• Natrum muriaticum — for grief following the death of a loved one or sadness from the end of a romantic relationship; this remedy is most appropriate for individuals who grieve silently and desire to be alone, avoid being comforted, and are reluctant to cry in public

Massage and Physical Therapy

Studies of formerly depressed adolescent mothers, children hospitalized for depression, and women with eating disorders, suggest that massage decreases stress hormone levels, feelings of anxiety, and symptoms of depression. Giving massage may also be beneficial for people who are depressed. Elderly volunteers with depression showed notable improvement in their symptoms when they massaged infants.

Aromatherapy, or the use of essential oils in massage therapy, may also be of value as a supplemental treatment for depression. Theoretically, the smells of the oils elicit positive emotions through the limbic system (the area of the brain responsible for memories and emotions). However, the benefits of aromatherapy appear to be related to the relaxation effects of the treatment as well as to the recipient's belief that the treatment will be beneficial. Essential oils used during massage for depression are quite varied and include:

• Basil (Ocimum basilicum)
• Orange (Citrus aurantium)
• Sandalwood (Santalum album)
• Lemon (Citrus limonis)
• Jasmine (Jasminum spp.)
• Sage (Salvia officinalis)
• Chamomile (Chamaemelum nobile)
• Peppermint (Mentha piperita)

Mind/Body Medicine

Mind/body therapies and techniques that may be useful as a part of an overall treatment regimen for depression include:

Psychotherapy
Cognitive-behavioral therapy is a type of psychotherapy in which individuals learn to identify and change distorted perceptions about themselves and adapt new behaviors to better cope with the world around them. This therapy is frequently considered the treatment of choice for people with mild to moderate depression, but it may not be recommended for those with severe depression. Studies of people with depression indicate that cognitive-behavioral therapy is at least as effective as tricyclic antidepressants. Compared to those treated with antidepressants, people treated with cognitive-behavioral therapy demonstrated similar, or better, results and lower relapse rates.

Other therapeutic approaches that may be applied by a psychiatrist, psychologist, or social worker include:

• Psychodynamic psychotherapy—based on Freud's theories about unresolved conflicts in childhood and depression as a grief process
• Interpersonal therapy—acknowledges childhood roots of depression, but focuses on current problems contributing to depression; considered very effective treatment for depression
• Supportive psychotherapy—nonjudgmental advice, attention, and sympathy; this approach may improve compliance with taking medication

Relaxation
One study suggests that relaxation techniques, such as yoga and tai chi, may improve symptoms of depression in people with mild depression.

Meditation
Some researchers theorize that mindfulness meditation may prevent depression from recurring in people who once had the condition.

Other Considerations

Pregnancy

• Postpartum depression is experienced by 8% to 20% of women following delivery.
• The safety of SSRIs and tricyclic antidepressant medications during pregnancy remains uncertain. The physician will provide guidance regarding use or avoidance of antidepressants during pregnancy. The risks and benefits to the mother and the fetus must be weighed in each individual case in order to determine the most appropriate regimen during pregnancy. MAOIs cause birth defects and should be avoided during pregnancy.
• The dietary supplements and herbs mentioned here have not been tested for safety during pregnancy, and should therefore be avoided.

Warnings and Precautions

• SSRIs should be avoided in people with Parkinson's disease.
• Tricyclic antidepressants should be avoided in people with coronary artery disease.
• Several herbal remedies and supplements should not be combined with antidepressant medications. Be sure to inform your healthcare provider of all herbs and supplements you take to avoid adverse interactions.

Prognosis and Complications

Depression is a serious condition that can have a devastating effect on people's lives. It can directly and indirectly contribute to chronic medical conditions, such as heart disease and stroke, because depressed people with these conditions are less likely to engage in healthy behaviors (such as exercise) and more likely to engage in unhealthy behaviors (such as smoking). Suicide is a significant factor in depression; about 15% of people with major depressive disorder commit suicide. Depression also significantly shortens the life-span of the elderly and is associated with the development of memory impairment and dementia.

When left untreated, depression can last up to 2 years. Rates of recurrence are variable: 50% of people who have had one depressive episode will have a second major depressive disorder; 70% will have a third and 90% will have a fourth. Symptoms of depression usually disappear after menopause in women with premenstrual dysphoric disorder or seasonal affective disorder. Fortunately, there are several treatment options available for people with depression and the prognosis improves tremendously for those who seek treatment and comply with their regimen.

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