What is a depressive disorder?

Depressive disorders have been with mankind since the beginning of recorded history. In the Bible, King David, as well as Job, suffered from this affliction. Hippocrates referred to depression as melancholia, which literally means black bile. Black bile, along with blood, phlegm, and yellow bile were the four humors (fluids) that described the basic medical physiology theory of that time. Depression, also referred to as clinical depression, has been portrayed in literature and the arts for hundreds of years, but what do we mean today when we refer to a depressive disorder? In the 19th century, depression was seen as an inherited weakness of temperament. In the first half of the 20th century, Freud linked the development of depression to guilt and conflict. John Cheever, the author and a modern sufferer of depressive disorder, wrote of conflict and experiences with his parents as influencing his development of depression.

In the 1950s and '60s, depression was divided into two types, endogenous and neurotic. Endogenous means that the depression comes from within the body, perhaps of genetic origin, or comes out of nowhere. Neurotic or reactive depression has a clear environmental precipitating factor, such as the death of a spouse, or other significant loss, such as the loss of a job. In the 1970s and '80s, the focus of attention shifted from the cause of depression to its effects on the afflicted people. That is to say, whatever the cause in a particular case, what are the symptoms and impaired functions that experts can agree make up a depressive disorder? Although there is some argument even today (as in all branches of medicines), most experts agree on the following:

1. A depressive disorder is a syndrome (group of symptoms) that reflects a sad and/or irritable mood exceeding normal sadness or grief. More specifically, the sadness of depression is characterized by a greater intensity and duration and by more severe symptoms and functional disabilities than is normal.



2. Depressive signs and symptoms are characterized not only by negative thoughts, moods, and behaviors but also by specific changes in bodily functions (for example, crying spells, body aches, low energy or libido, as well as problems with eating, weight, or sleeping). The functional changes of clinical depression are often called neurovegetative signs. This means that the nervous system changes in the brain cause many physical symptoms that result in diminished participation and a decreased or increased activity level.



3. Certain people with depressive disorder, especially bipolar depression (manic depression), seem to have an inherited vulnerability to this condition.



4. Depressive disorders are a huge public-health problem, due to its affecting millions of people. About 10% of adults, up to 8% of teens and 2% of preteen children experience some kind of depressive disorder.

• The statistics on the costs due to depression in the United States include huge amounts of direct costs, which are for treatment, and indirect costs, such as lost productivity and absenteeism from work or school.



• Adolescents who suffer from depression are at risk for developing and maintaining obesity.



• In a major medical study, depression caused significant problems in the functioning of those affected more often than did arthritis, hypertension, chronic lung disease, and diabetes, and in some ways as often as coronary artery disease.



• Depression can increase the risks for developing coronary artery disease, HIV, asthma, and many other medical illnesses. Furthermore, it can increase the morbidity (illness/negative health effects) and mortality (death) from these and many other medical conditions.



• Depression can coexist with virtually every other mental health illness, aggravating the status of those who suffer the combination of both depression and the other mental illness.



• Depression in the elderly tends to be chronic, has a low rate of recovery, and is often undertreated. This is of particular concern given that elderly men, particularly elderly white men have the highest suicide rate.

5. Depression is usually first identified in a primary-care setting, not in a mental health practitioner's office. Moreover, it often assumes various disguises, which causes depression to be frequently underdiagnosed.



6. In spite of clear research evidence and clinical guidelines regarding therapy, depression is often undertreated. Hopefully, this situation can change for the better.



7. For full recovery from a mood disorder, regardless of whether there is a precipitating factor or it seems to come out of the blue, treatment with medication and/or electroconvulsive therapy (ECT) (see discussion below) and psychotherapy are necessary.

What are myths about depression?

The following are myths about depression and its treatment:

• It is a weakness rather than an illness.



• If the sufferer just tries hard enough, it will go away.



• If you ignore depression in yourself or a loved one, it will go away.



• Highly intelligent or highly accomplished people do not get depressed.



• People with developmental disabilities do not get depressed.



• People with depression are "crazy."



• Depression does not really exist.



• Children, teens, the elderly, or men do not get depressed.



• There are ethnic groups for whom depression does not occur.



• Depression cannot look like (present as) irritability.



• People who tell someone they are thinking about committing suicide are only trying to get attention and would never do it, especially if they have talked about it before.



• People with depression cannot have another mental or medical condition at the same time.



• Psychiatric medications are all addicting.



• Psychiatric medications are never necessary to treat depression.



• Medication is the only effective treatment for depression.



• Children and teens should never be given antidepressant medication.

What are the types of depression and their symptoms?

Depressive disorders are mood disorders that come in different forms, just as do other illnesses, such as heart disease and diabetes. Three of the most common types of depressive disorders are discussed below. However, remember that within each of these types, there are variations in the number, timing, severity, and persistence of symptoms. There are also differences in how individuals experience depression based on age. Since babies, toddlers, and preschool children are usually unable to express their feelings in words, they tend to show sadness in their behaviors. For example, they may become withdrawn, resume old, younger behaviors (regress), or fail to thrive. School-age children might develop physical complaints, anxiety, or irritability. In addition to becoming more irritable, teens might lose interest in activities they formerly enjoyed, experience a change in their weight, start abusing substances, and they are more able to complete suicide than their younger counterparts when depressed.

Major depression

Major depression is characterized by a combination of symptoms that last for at least two weeks in a row, including sad and/or irritable mood (see symptom list), that interfere with the ability to work, sleep, eat, and enjoy once-pleasurable activities. Difficulties in sleeping or eating can take the form of excessive or insufficient of either behavior. Disabling episodes of depression can occur once, twice, or several times in a lifetime.

Dysthymia

Dysthymia is a less severe but usually more long-lasting type of depression compared to major depression. It involves long-term (chronic) symptoms that do not disable but yet prevent the affected person from functioning at "full steam" or from feeling good. Sometimes, people with dysthymia also experience episodes of major depression. This combination of the two types of depression is referred to as double-depression.

Bipolar disorder (manic depression)

Another type of depression is bipolar disorder, which encompasses a group of mood disorders that were formerly called manic-depressive illness or manic depression. These conditions show a particular pattern of inheritance. Not nearly as common as the other types of depressive disorders, bipolar disorders involve cycles of mood that include at least one episode of mania and may include episodes of depression as well. Bipolar disorders are often chronic and recurring. Sometimes, the mood switches are dramatic and rapid, but most often they are gradual.

When in the depressed cycle, the person can experience any or all of the symptoms of a depressive disorder. When in the manic cycle, any or all of the symptoms listed later in this article under mania may be experienced. Mania often affects thinking, judgment, and social behavior in ways that cause serious problems and embarrassment. For example, indiscriminate or otherwise unsafe sexual practices or unwise business or financial decisions may be made when an individual is in a manic phase.

A significant variant of the bipolar disorders is designated as bipolar II disorder. (The usual form of bipolar disorder is referred to as bipolar I disorder.) Bipolar II disorder is a syndrome in which the affected person has repeated depressive episodes punctuated by what is called hypomania (mini-highs). These euphoric states in bipolar II do not fully meet the criteria for the complete manic episodes that occur in bipolar I.

Symptoms of depression and mania

Not everyone who is depressed or manic experiences every symptom. Some people experience a few symptoms and some many symptoms. The severity of symptoms also varies with individuals. Less severe symptoms that precede the more debilitating symptoms are called warning signs.

Depression symptoms of major depression or manic depression

• Persistently sad, anxious, angry, irritable, or "empty" mood



• Feelings of hopelessness, pessimism



• Feelings of guilt, worthlessness, helplessness



• Loss of interest or pleasure in hobbies and activities that were once enjoyed, including sex



• Social isolation, meaning the sufferer avoids interactions with family or friends
  
  
• Insomnia, early-morning awakening, or oversleeping



• Decreased appetite and/or weight loss, or overeating and/or weight gain



• Fatigue, decreased energy, being "slowed down"



• Crying spells



• Thoughts of death or suicide, suicide attempts



• Restlessness, irritability



• Difficulty concentrating, remembering, making decisions



• Persistent physical symptoms that do not respond to treatment, such as headaches, digestive disorders, and/or chronic pain

Children and adolescents with depression may also experience the classic symptoms described above but may exhibit other symptoms instead of or in addition to those symptoms, including the following:

• Poor school performance



• Persistent boredom



• Frequent complaints of physical problems such as headaches and stomachaches



• Some of the classic "adult" symptoms of depression may also be more or less obvious in children compared to the actual emotions of sadness, such as a change in eating or sleeping patterns. (Has the child or teen lost or gained weight in recent weeks or months? Does he or she seem more tired than usual?)



• Teen depression may be characterized by the adolescent taking more risks, showing less concern for their own safety.

Mania symptoms of manic depression

• Inappropriate elation



• Inappropriate irritability or anger



• Severe insomnia or decreased need to sleep



• Grandiose notions, like having special powers or importance



• Increased talking speed and/or volume



• Disconnected thoughts or speech



• Racing thoughts



• Severely increased sexual desire and/or activity



• Markedly increased energy



• Poor judgment



• Inappropriate social behavior

What are the causes of depression?

Some types of depression run in families, indicating that a biological vulnerability to depression can be inherited. This seems to be the case, especially with bipolar disorder. Families in which members of each generation develop bipolar disorder have been studied. The investigators found that those with the illness have a somewhat different genetic makeup than those who do not become ill. However, the reverse is not true. That is, not everybody with the genetic makeup that causes vulnerability to bipolar disorder will develop the illness. Apparently, additional factors, possibly a stressful environment, are involved in its onset and protective factors are involved in its prevention.

Major depression also seems to occur in generation after generation in some families, although not as strongly as in bipolar I or II. Indeed, major depression can also occur in people who have no family history of depression.

An external event often seems to initiate an episode of depression. Thus, a serious loss, chronic illness, difficult relationship, financial problem, or any unwelcome change in life patterns can trigger a depressive episode. Very often, a combination of genetic, psychological, and environmental factors is involved in the onset of a depressive disorder. Stressors that contribute to the development of depression sometimes affect some groups more than others. For example, minority groups who more often feel impacted by discrimination and are disproportionately represented. Socioeconomically disadvantaged groups have higher rates of depression compared to their advantaged counterparts. Immigrants to the United States may be more vulnerable to developing depression, particularly when isolated by language.

Regardless of ethnicity, men appear to be particularly sensitive to the depressive effects of unemployment, divorce, low socioeconomic status, and having few good ways to cope with stress. Women who have been the victim of physical, emotional, or sexual abuse, either as a child or perpetrated by a romantic partner are vulnerable to developing a depressive disorder as well. Men who engage in sex with other men seem to be particularly vulnerable to depression when they have no domestic partner, do not identify themselves as homosexual, or have been the victim of multiple episodes of antigay violence. However, it seems that men and women have similar risk factors for depression for the most part.

Nothing in the universe is as complex and fascinating as the human brain. The 100-plus chemicals that circulate in the brain are known as neurochemicals or neurotransmitters. Much of our research and knowledge, however, has focused on four of these neurochemical systems: norepinephrine, serotonin, dopamine, and acetylcholine. In the new millennium, after new discoveries are made, it is possible that these four neurochemicals will be viewed as the "black bile, yellow bile, phlegm, and blood" of the 20th century.

Different neuropsychiatric illnesses seem to be associated with an overabundance or a lack of some of these neurochemicals in certain parts of the brain. For example, a lack of dopamine at the base of the brain causes Parkinson's disease. Alzheimer's dementia seems to be related to lower acetylcholine levels in the brain. The addictive disorders are under the influence of the neurochemical dopamine. That is to say, drugs and alcohol work by releasing dopamine in the brain. The dopamine causes euphoria, which is a pleasant sensation. Repeated use of drugs or alcohol, however, desensitizes the dopamine system, which means that the system gets used to the drugs and alcohol. Therefore, a person needs more drugs or alcohol to achieve the same high feeling. Thus, the addicted person takes more substance but feels less and less high and increasingly depressed.

Certain medications used for a variety of medical conditions are more likely than others to cause depression as a side effect. Specifically, some medications that are used to treat high blood pressure, cancer, seizures, extreme pain, and to achieve contraception can result in depression. Even some psychiatric medications like some sleep aids and medications to treat alcoholism and anxiety can contribute to the development of depression.

Many mental-health conditions or developmental disabilities are associated with depression as well. Individuals with anxiety, substance abuse, and developmental disabilities may be more vulnerable to developing depression.

The different types of schizophrenia are associated with an imbalance of dopamine (too much) and serotonin (poorly regulated) in certain areas of the brain. Finally, the depressive disorders appear to be associated with altered brain serotonin and norepinephrine systems. Both of these neurochemicals may be lower in depressed people. Please note that depression is "associated with" instead of "caused by" abnormalities of these neurochemicals because we really don't know whether low levels of neurochemicals in the brain cause depression or whether depression causes low levels of neurochemicals in the brain.

What we do know is certain medications that alter the levels of norepinephrine or serotonin can alleviate the symptoms of depression. Some medicines that affect both of these neurochemical systems appear to perform even better or faster. Other medications that treat depression primarily affect the other neurochemical systems. The most powerful treatment for depression, electroconvulsive therapy (ECT), is certainly not specific to any particular neurotransmitter system. Rather, ECT, by causing a seizure, produces a generalized brain activity that probably releases massive amounts of all of the neurochemicals.

Women are twice as likely to become depressed as men. However, scientists do not know the reason for this difference. Psychological factors also contribute to a person's vulnerability to depression. Thus, persistent deprivation in infancy, physical or sexual abuse, clusters of certain personality traits, and inadequate ways of coping (maladaptive coping mechanisms) all can increase the frequency and severity of depressive disorders, with or without inherited vulnerability.

The effect of maternal-fetal stress on depression is currently an exciting area of research. It seems that maternal stress during pregnancy can increase the chance that the child will be prone to depression as an adult, particularly if there is a genetic vulnerability. It is thought that the mother's circulating stress hormones can influence the development of the fetus' brain during pregnancy. This altered fetal brain development occurs in ways that predispose the child to the risk of depression as an adult. Further research is still necessary to clarify how this happens. Again, this situation shows the complex interaction between genetic vulnerability and environmental stress, in this case, the stress of the mother on the fetus

Postpartum depression

Postpartum depression (PPD) is a condition that describes a range of physical and emotional changes that many mothers can have after having a baby. PPD can be treated with medication and counseling. Talk with your health-care practitioner right away if you think you have PPD.

There are three types of PPD women can have after giving birth:

1. The so called "baby blues" happen in many women in the days right after childbirth. A new mother can have sudden mood swings, such as feeling very happy and then feeling very sad or angry. She may cry for no reason and can feel impatient, irritable, restless, anxious, lonely, and sad. The baby blues may last only a few hours or as long as one to two weeks after delivery. The baby blues do not always require treatment from a health-care provider. Often, joining a support group of new moms or talking with other moms helps.



2. Postpartum depression (PPD) can happen a few days or even months after childbirth. PPD can happen after the birth of any child, not just the first child. A woman can have feelings similar to the baby blues -- sadness, despair, anxiety, irritability -- but she feels them much more strongly than she would with the baby blues. PPD often keeps a woman from doing the things she needs to do every day. When a woman's ability to function is affected, this is a sure sign that she needs to see her health-care provider right away. If a woman does not get treatment for PPD, symptoms can get worse and last for as long as one year. While PPD is a serious condition, it can be treated with medication and counseling.



3. Postpartum psychosis is a very serious mental illness that can affect new mothers. This illness can happen quickly, often within the first three months after childbirth. Women can experience psychotic depression, in that the depression causes them to lose touch with reality, have auditory hallucinations (hearing things that aren't actually happening, like a person talking), and delusions (seeing things differently from what they are in reality). Visual hallucinations (seeing things that aren't there) are less common. Other symptoms include insomnia (not being able to sleep), feeling agitated (unsettled) and angry, strange feelings and behaviors, as well as having suicidal or homicidal thoughts. Women who have postpartum psychosis need treatment right away and almost always need medication. Sometimes women are put into the hospital because they are at risk for hurting themselves or someone else, including their baby

How is depression diagnosed?

People who wonder if they should talk to their health professional about whether or not they have depression may consider taking a depression self-test, which asks questions about depressive symptoms. In thinking about when to seek medical advice about depression, the sufferer can benefit from considering if the sadness lasts more than two weeks or so or if the way they are feeling significantly interferes with their ability to function at home, school, or work and in their relationships with others. The first step to obtaining appropriate treatment is accurate diagnosis, which requires a complete physical and psychological evaluation to determine whether the person may have a depressive illness, and if so, what type. As previously mentioned, certain medications, as well as some medical conditions, can cause symptoms of depression. Therefore, the examining physician should rule out (exclude) these possibilities through an interview, physical examination, and laboratory tests. Many primary-care doctors use screening tools for depression, which are usually questionnaires that help identify people who have symptoms of depression and may need to receive a full mental-health evaluation.

A thorough diagnostic evaluation includes a complete history of the patient's symptoms:

1. When did the symptoms start?

2. How long have they lasted?

3. How severe are they?

4. Have the symptoms occurred before, and if so, were they treated and what treatment was received?

The doctor usually asks about alcohol and drug use and whether the patient has had thoughts about death or suicide. Further, the history often includes questions about whether other family members have had a depressive illness, and if treated, what treatments they received and which were effective.

A diagnostic evaluation also includes a mental-status examination to determine if the patient's speech, thought pattern, or memory has been affected, as often happens in the case of a depressive or manic-depressive illness. As of today, there is no laboratory test, blood test, or X-ray that can diagnose a mental disorder. Even the powerful CT, MRI, SPECT, and PET scans, which can help diagnose other neurological disorders such as stroke or brain tumors, cannot detect the subtle and complex brain changes in psychiatric illness. However, these techniques are currently useful in research on mental health and perhaps in the future they will be useful for diagnosis as well.

What treatments are available for depression?

Regardless of the medication that may be used to treat depression, practitioners have become more aware that different ethnic groups may have different responses and have different risks for side effects than others.

Antidepressant medications

Selective serotonin reuptake inhibitors (SSRIs) are medications that increase the amount of the neurochemical serotonin in the brain. (Remember that brain serotonin levels are often low in depression.) As their name implies, the SSRIs work by selectively inhibiting (blocking) serotonin reuptake in the brain. This block occurs at the synapse, the place where brain cells (neurons) are connected to each other. Serotonin is one of the chemicals in the brain that carries messages across these connections (synapses) from one neuron to another.

The SSRIs work by keeping serotonin present in high concentrations in the synapses. These drugs do this by preventing the reuptake of serotonin back into the sending nerve cell. The reuptake of serotonin is responsible for turning off the production of new serotonin. Therefore, the serotonin message keeps on coming through. It is thought that this, in turn, helps arouse (activate) cells that have been deactivated by depression, thereby relieving the depressed person's symptoms.

SSRIs have fewer side effects than the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), which are discussed below. SSRIs do not interact with the chemical tyramine in foods, as do the MAOIs, and therefore do not require the dietary restrictions of the MAOIs. Also, SSRIs do not cause orthostatic hypotension (sudden drop in blood pressure when sitting up or standing) and heart-rhythm disturbances, like the TCAs do. Therefore, SSRIs are often the first-line treatment for depression. Examples of SSRIs include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), fluvoxamine (Luvox), and escitalopram (Lexapro).

SSRIs are generally well tolerated, and side effects are usually mild. The most common side effects are nausea, diarrhea, agitation, insomnia, and headache. However, these side effects generally go away within the first month of SSRI use. Some patients experience sexual side effects, such as decreased sexual desire (decreased libido), delayed orgasm, or an inability to have an orgasm. Some patients experience tremors with SSRIs. The so-called serotonergic (meaning caused by serotonin) syndrome is a serious neurologic condition associated with the use of SSRIs. It is characterized by high fevers, seizures, and heart-rhythm disturbances. This condition is very rare and has been reported only in very ill psychiatric patients taking multiple psychiatric medications.

All patients are unique biochemically. Therefore, the occurrence of side effects or the lack of a satisfactory result with one SSRI does not mean that another medication in this group will not be beneficial. However, if someone in the patient's family has had a positive response to a particular drug, that drug may be the preferable one to try first.

Dual-action antidepressants: The biochemical reality is that all classes of medications that treat depression (MAOIs, SSRIs, TCAs, and atypical antidepressants) have some effect on both norepinephrine and serotonin, as well as on other neurotransmitters. However, the various medications affect the different neurotransmitters in varying degrees.

Some of the newer antidepressant drugs, however, appear to have particularly robust effects on both the norepinephrine and serotonin systems. These medications seem to be very promising, especially for the more severe and chronic cases of depression. (Psychiatrists, rather than family practitioners, see such cases most frequently.) Venlafaxine (Effexor) and duloxetine (Cymbalta) are two of these dual-action compounds. Effexor is a serotonin reuptake inhibitor that, at lower doses, shares many of the safety and low side-effect characteristics of the SSRIs. At higher doses, this drug appears to block the reuptake of norepinephrine. Thus, venlafaxine can be considered an SNRI, a serotonin and norepinephrine reuptake inhibitor. Cymbalta tends to act as an equally powerful serotonin reuptake inhibitor and norepinephrine reuptake inhibitor regardless of the dose. It is therefore also considered an SNRI.

Mirtazapine (Remeron), another newer antidepressant, is a tetracyclic compound (four-ring chemical structure). It works at somewhat different biochemical sites and in different ways than the other drugs. It affects serotonin, but at a postsynaptic site (after the connection between nerve cells). It also increases histamine levels, which can cause drowsiness. For this reason, mirtazapine is given at bedtime and is often prescribed for people who have trouble falling asleep. Like venlafaxine, it also works by increasing levels in the norepinephrine system. Other than causing sedation, this medication has side effects that are similar to those of the SSRIs but to a lesser degree in many cases.

Atypical antidepressants are so named because they work in a variety of ways. Thus, atypical antidepressants are not TCAs, SSRIs, or SNRIs, but they are effective in treating depression for many people nonetheless. More specifically, they increase the level of certain neurochemicals in the brain synapses (where nerves communicate with each other). Examples of atypical antidepressants include nefazodone (Serzone), trazodone (Desyrel), and bupropion (Wellbutrin). The United States Food and Drug Administration (FDA) has also approved bupropion for use in weaning from addiction to cigarettes. This drug is also being studied for treating attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD). These problems affect many children and adults and restrict their ability to manage their impulses and activity level, focus, or concentrate on one thing at a time.

Lithium (Eskalith, Lithobid), valproate (Depakene, Depakote), carbamazepine (Epitol, Tegretol), neurontin (Gabapentin), and lamictal (Lamotrigine) are mood stabilizers and anticonvulsants. They have been used to treat bipolar depression. Certain antipsychotic medications, such as ziprasidone (Geodon), risperidone (Risperdal), quetiapine (Seroquel), aripiprazole (Abilify), and paliperdone (Invega), may treat psychotic depression. They have also been found to be effective mood stabilizers and are therefore sometimes been used to treat bipolar depression, usually in combination with other antidepressants.

Monoamine oxidase inhibitors (MAOIs) are the earliest developed antidepressants. Examples of MAOIs include phenelzine (Nardil) and tranylcypromine (Parnate). MAOIs elevate the levels of neurochemicals in the brain synapses by inhibiting monoamine oxidase. Monoamine oxidase is the main enzyme that breaks down neurochemicals, such as norepinephrine. When monoamine oxidase is inhibited, the norepinephrine is not broken down and, therefore, the amount of norepinephrine in the brain is increased.

MAOIs also impair the ability to break down tyramine, a substance found in aged cheese, wines, most nuts, chocolate, and some other foods. Tyramine, like norepinephrine, can elevate blood pressure. Therefore, the consumption of tyramine-containing foods by a patient taking an MAOI drug can cause elevated blood levels of tyramine and dangerously high blood pressure. In addition, MAOIs can interact with over-the-counter cold and cough medications to cause dangerously high blood pressure. The reason for this is that these cold and cough medications often contain drugs that likewise can increase blood pressure. Because of these potentially serious drug and food interactions, MAOIs are usually only prescribed after other treatment options have failed.

Tricyclic antidepressants (TCAs) were developed in the 1950s and '60s to treat depression. They are called tricyclic antidepressants because their chemical structures consist of three chemical rings. TCAs work mainly by increasing the level of norepinephrine in the brain synapses, although they also may affect serotonin levels. Doctors often use TCAs to treat moderate to severe depression. Examples of tricyclic antidepressants are amitriptyline (Elavil), protriptyline (Vivactil), desipramine (Norpramin), nortriptyline (Aventyl, Pamelor), imipramine (Tofranil), trimipramine (Surmontil), and perphenazine (Triavil).

Tetracyclic antidepressants are similar in action to tricyclics, but their structure has four chemical rings. Examples of tetracyclics include maprotiline (Ludiomil) and mirtazapine (Remeron), a drug that was discussed above under dual-action antidepressants.

TCAs are safe and generally well tolerated when properly prescribed and administered. However, if taken in overdose, TCAs can cause life-threatening heart-rhythm disturbances. Some TCAs can also have anticholinergic side effects, which are due to the blocking of the activity of the nerves that are responsible for control of the heart rate, gut motion, visual focus, and saliva production. Thus, some TCAs can produce dry mouth, blurred vision, constipation, and dizziness upon standing. The dizziness results from low blood pressure that occurs upon standing (orthostatic hypotension). Anticholinergic side effects can also aggravate narrow-angle glaucoma, urinary obstruction due to benign prostate hypertrophy, and cause delirium in the elderly. TCAs should also be avoided in patients with seizure disorders or a history of strokes.

Stimulants such as methylphenidate (Ritalin) or dextroamphetamine (Dexedrine) are used primarily for the treatment of depression that is resistant to other medications. The stimulants are most commonly used along with other antidepressants or other medications, such as mood stabilizers, antipsychotics, or even thyroid hormone. They are sometimes used alone but rarely. The reason they are usually used sparingly and with other medications for depression is that unlike the other medications, they may induce an emotional rush and a high in both depressed and nondepressed people. Therefore, the stimulants are potentially addictive drugs.

Electroconvulsive therapy (ECT)

In the ECT procedure, an electric current is passed through the brain to produce controlled convulsions (seizures). ECT is useful for certain patients, particularly for those who cannot take or have not responded to a number of antidepressants, have severe depression, and/or are at a high risk for suicide. ECT often is effective in cases where trials of a number of antidepressant medications do not provide sufficient relief of symptoms. This procedure probably works, as previously mentioned, by a massive neurochemical release in the brain due to the controlled seizure. Highly effective, ECT relieves depression within one to two weeks after beginning treatments in many people. After ECT, some patients will continue to have maintenance ECT, while others will return to antidepressant medications or have a combination of both treatments.

In recent years, the technique of ECT has been much improved. The treatment is given in the hospital under anesthesia so that people receiving ECT do not feel pain. Most patients undergo six to 10 treatments. An electrical current is passed through the brain to cause a controlled seizure, which typically lasts for 20 to 90 seconds. The patient is awake in five to 10 minutes. The most common side effect is short-term memory loss, which resolves quickly. ECT can usually be safely done as an outpatient procedure.

Psychotherapies

Many forms of psychotherapy are effectively used to help depressed individuals, including some short-term (10 to 20 weeks) therapies. Talking therapies (psychotherapies) help patients gain insight into their problems and resolve them through verbal give-and-take with the therapist. Behavioral therapists help patients learn how to obtain more satisfaction and rewards through their own actions. These therapists also help patients to unlearn the behavioral patterns that may contribute to their depression.

Interpersonal and cognitive/behavioral therapies are two of the short-term psychotherapies that research has shown to be helpful for some forms of depression. Interpersonal therapists focus on the patient's disturbed personal relationships that both cause and exacerbate the depression. Cognitive/behavioral therapists help patients change the negative styles of thinking and behaving that are often associated with depression.

Psychodynamic therapies are sometimes used to treat depression. They focus on resolving the patient's internal psychological conflicts that are typically thought to be rooted in childhood. Long-term psychodynamic therapies are particularly important if there seems to be a lifelong history and pattern of inadequate ways of coping (maladaptive coping mechanisms) in negative or self-injurious behavior

What is the general approach to treating depression?

In general, the severe depressive illnesses, particularly those that are recurrent, will require antidepressant medications (or ECT in severe cases) along with psychotherapy for the best outcome. If a person suffers one major depressive episode, he or she has a 50% chance of a second episode. If the individual suffers two major depressive episodes, the chance of a third episode is 75%-80%. If the person suffers three episodes, the likelihood of a fourth episode is 90%-95%. Therefore, after a first depressive episode, it might make sense for the patient to gradually come off medication. However, after a second and certainly after a third episode, most clinicians will have a patient remain on a maintenance dosage of the medication for an extended period of years, if not permanently.

Patience is required because the treatment of depression takes time. Sometimes, the doctor will need to try a variety of antidepressants before finding the medication or combination of medications that is most effective for the patient. Sometimes, the dosage must be increased to be effective.

In choosing an antidepressant, the doctor will take into account the patient's age, his/her other medical conditions, and medication side effects. Doctors often use one of the SSRIs initially because of their lower severity of side effects compared to the other classes of antidepressants. Side effects of SSRI medications can be further minimized by starting them at low doses and gradually increasing the doses to achieve full therapeutic effects. For those patients who do not respond after taking a SSRI at full doses for six to eight weeks, doctors generally switch to a different SSRI or another class of antidepressants. For patients whose depression failed to respond to full doses of one or two SSRIs or whom could not tolerate those medications, doctors will then try medications from another class of antidepressants. Some doctors believe that antidepressants with dual action (action on both serotonin and norepinephrine), such as duloxetine (Cymbalta), mirtazapine (Remeron), and venlafaxine (Effexor), may be effective in treating patients with severe depression that are treatment resistant. Other options include bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban), which has action on dopamine (another neurotransmitter). Sometimes doctors may use a combination of antidepressants from different classes. Also, new types of antidepressants are constantly being developed, and one of these may be the best for a particular patient.

If the depressed person is taking more than one medication for depression or medications for any other medical problem, each of the patient's doctors should be made aware of the other prescriptions. Many of these medications are cleared from the body (metabolized) in the liver. This means that the multiple treatments can interact competitively with the liver's biochemical clearing systems. Therefore, the actual blood levels of the medications may be higher or lower than would be expected from the dosage. This information is especially important if the patient is taking anticoagulants (blood thinners), anticonvulsants (seizure medications), or heart medications, such as digitalis (Crystodigin). Although multiple medications do not necessarily pose a problem, all of the patient's doctors may need to be in close contact to adjust dosages accordingly.

Patients often are tempted to stop their medication too soon, especially when they begin feeling better. It is important to keep taking medication until the doctor says to stop, even if the patient feels better beforehand. Doctors often will continue the antidepressant medications for at least six to 12 months because the risk of depression quickly returning when treatment is stopped decreases after that period of time in those people experiencing their first depressive episode. Some medications must be stopped gradually to give the body time to adjust (see discontinuation of antidepressants below). For individuals with bipolar disorder or chronic major depression, medication may have to become a part of everyday life for an extended period of years in order to avoid disabling symptoms.

Antidepressant medications are not habit-forming, so there need not be concern about that. However, as is the case with any type of medication prescribed for more than a few days, antidepressants must be carefully monitored to ensure that the patient is getting the correct dosage. The doctor will want to check the dosage and its effectiveness regularly.

If the patient is taking MAOIs, certain aged, fermented, or pickled foods must be avoided, like many wines, processed meats, and cheeses. The patient should obtain a complete list of prohibited foods from the doctor and keep it available at all times. The other types of antidepressants require no food restrictions. Remember that some over-the-counter cold and cough medicines can also cause problems when taken with MAOIs.

People should never mix medications of any kind (prescribed, over-the-counter, or borrowed) without consulting their doctor. The dentist or any other medical specialist who prescribes a drug should be informed that the patient is taking antidepressants. Some drugs that are harmless when taken alone can cause severe and dangerous side effects when taken with other drugs. This may also be the case for individuals taking supplements or herbal remedies. Some drugs, such as alcohol (including wine, beer, and hard liquor), tranquilizers, narcotics or marijuana, reduce the effectiveness of antidepressants and should be avoided. These and other drugs can also be dangerous when the person's body is either intoxicated with or withdrawing from their effects due to increasing the risk of seizure in combination with antidepressants medications.

Antianxiety drugs such as diazepam (Valium), alprazolam (Xanax), and lorazepam (Ativan) are not antidepressants but they are occasionally prescribed alone or with antidepressants for a brief period of anxiety. However, they should not be taken alone for depressive disorder. Furthermore, the antianxiety drugs should be phased out as soon as the antidepressant and antianxiety effects of the antidepressant medications begin to work, which is usually in four to six weeks.

Finally, the doctor should be consulted concerning any questions about a medication or problem that the patient believes is medication-related.

What about sexual dysfunction related to antidepressants?

The SSRI antidepressants can cause sexual dysfunction. SSRIs have been reported to decrease sex drive (libido) in both men and women. SSRIs have been reported to cause inability to achieve orgasm or delay in achieving orgasm (anorgasmia) in women and difficulty with ejaculation (delay in ejaculating or loss of ability to ejaculate) in men. Sexual dysfunction with SSRIs is common though the exact incidence is not clearly known. Furthermore, sexual side effects have also been reported with the use of other antidepressant classes such a MAOIs, TCAs, and dual-action antidepressants.

Management of sexual dysfunction due to SSRIs includes the following options:

• Decrease the SSRI dose. This option may be appropriate if the patient is on high doses of an SSRI. Reducing the SSRI dose may also diminish the antidepressant effect. Remember, patients should never change medications and medication doses on their own without permission and monitoring by his/her doctor.



• Trial of sildenafil (Viagra) or other sexual-enhancement medication. Studies in men whose depression has responded to SSRI but have developed sexual dysfunction showed improvement in sexual function with Viagra. Men taking Viagra reported significant improvements in arousal, erection, ejaculation, and orgasm as compared to men who were taking placebo, although Viagra generally does not increase one's libido.



• For men who do not respond to Viagra (and for women with sexual dysfunction due to SSRI), switching from SSRI to another class of antidepressants may be helpful. For example, bupropion, mirtazapine, and duloxetine may have no sexual side effects or significantly less sexual side effects than SSRIs.



• For patients who are unable to switch from SSRIs to another class of antidepressants either because of lack of tolerance or lack of therapeutic response to the other antidepressants, the doctor may consider adding another medication to the SSRI. For example, some doctors have reported success by adding bupropion to SSRI to improve sexual function. However, more clinical trials are needed to determine whether this strategy really works.



• Some doctors also may use buspirone to improve sexual function in patients treated with SSRI. More clinical studies are needed to determine whether this strategy works

What about discontinuing antidepressants?

Antidepressants should be gradually tapered and should not be abruptly discontinued. Abruptly stopping an antidepressant in some patients can cause discontinuation syndrome.

For example, abruptly stopping an SSRI such as paroxetine can cause dizziness, nausea, flu-like symptoms, body aches, anxiety, irritability, fatigue, and vivid dreams. These symptoms typically occur within days of abrupt cessation, and can last one to two weeks (up to 21 days). Among the SSRIs, paroxetine and fluvoxamine cause more pronounced discontinuation symptoms than fluoxetine, sertraline, and citalopram. Some patients experience discontinuation symptoms despite gradual tapering of the SSRI. Abrupt cessation of venlafaxine or duloxetine can cause discontinuation symptoms similar to those of SSRIs.

Abruptly stopping MAOIs can lead to irritability, agitation, and delirium. Similarly, abruptly stopping a TCA can cause agitation, irritability, and abnormal heart rhythms.

What about self-help?

Depressive disorders make those afflicted feel exhausted, worthless, helpless, and hopeless. Such negative thoughts and feelings make some people feel like giving up. It is important to realize that these negative views are part of the depression and typically do not accurately reflect the actual situation. It should be remembered that negative thinking fades as treatment begins to take effect. In the meantime, the following are helpful tips for coping with depression:

• Eat healthy foods and make time to get enough rest to physically promote improvement in your mood.



• Express your feelings, either to friends, in a journal, or using art to help release some negative feelings.



• Do not set difficult goals for yourself or take on a great deal of responsibility.



• Break large tasks into small ones, set some priorities, and do what you can when you can.



• Do not expect too much from yourself too soon as this will only increase feelings of failure.



• Try to be with other people, which is usually better than being alone.



• Participate in activities that may make you feel better.



• You might try exercising mildly, going to a movie or a ball game, or participating in religious or social activities.



• Don't rush or overdo it. Don't get upset if your mood is not greatly improved right away. Feeling better takes time.



• Do not make major life decisions, such as changing jobs or getting married or divorced without consulting others who know you well. These people often can have a more objective view of your situation. In any case, it is advisable to postpone important decisions until your depression has lifted.



• Do not expect to "snap out" of your depression. People rarely do. Help yourself as much as you can, and do not blame yourself for not being up to par.



• Remember, do not accept your negative thinking. It is part of the depression and will disappear as your depression responds to treatment.



• Plan how you would get help for yourself in an emergency, like calling friends, family, your physical or mental-health professional or a local emergency room if you were to develop thoughts of harming yourself or someone else.



• Limit your access to things that could be used to hurt yourself or others (for example, do not keep excess medication of any kind, firearms, or other weapons in the home)

How can someone help a person who is depressed?

Family and friends can help! Since depression can make the affected person feel exhausted and helpless, he or she will want and probably need help from others. However, people who have never had a depressive disorder may not fully understand its effect. Although unintentional, friends and loved ones may unknowingly say and do things that may be hurtful to the depressed person. It may help to share the information in this article with those you most care about so they can better understand and help you.

The most important thing anyone can do for the depressed person is to help him or her get an appropriate diagnosis and treatment. This help may involve encouraging the individual to stay with treatment until symptoms begin to go away (usually several weeks) or to seek different treatment if no improvement occurs. On occasion, it may require making an appointment and accompanying the depressed person to the doctor. It may also mean monitoring whether the depressed person is taking medication for several months after symptoms have improved. Always report a worsening depression to the patient's physician or therapist.

The second most important way to help is to offer emotional support. This support involves understanding, patience, affection, and encouragement. Engage the depressed person in conversation and listen carefully. Do not disparage feelings expressed, but point out realities and offer hope. Do not ignore remarks about suicide. Always report them to the depressed person's therapist.

Invite the depressed person for walks, outings, and to the movies and other activities. Be gently insistent if your invitation is refused. Encourage participation in activities that once gave pleasure, such as hobbies, sports, or religious or cultural activities. However, do not push the depressed person to undertake too much too soon. The depressed person needs company and diversion, but too many demands can increase feelings of failure.

Do not accuse the depressed person of faking illness or of laziness. Do not expect him or her "to snap out of it." Eventually, with treatment, most depressed people do get better. Keep that in mind. Moreover, keep reassuring the depressed person that, with time and help, he or she will feel better.

Where can one seek help for depression?

A complete physical and psychological diagnostic evaluation by professionals will help the depressed person decide the type of treatment that might be best for him or her. However, if the situation is urgent because a suicide seems possible, taking the patient to the emergency room is the appropriate course of action. If the patient makes a suicide gesture or attempt, a 911 call is warranted. The patient might not realize how much help he or she needs. In fact, he or she might feel undeserving of help because of the negativity and helplessness that is a part of depressive illness.

Listed below are the types of people and places that will make a referral or provide diagnostic and treatment services. Check the Yellow Pages under "mental health," "health," "social services," "suicide prevention," "hospitals," or "physicians" for phone numbers and addresses.

• Family doctors



• Mental-health specialists, such as psychiatrists, psychologists, social workers, pastoral or mental-health counselors



• Health maintenance organizations



• Community mental-health centers



• Hospital psychiatry departments and outpatient clinics



• Community support groups, often hospital-affiliated



• University or medical school-affiliated programs



• State hospital outpatient clinics



• Family service/social agencies



• Private clinics and facilities



• Employee assistance programs



• Local medical and/or psychiatric societies

What is in the future for depression?

The future is very bright for the treatment of depression. In response to the customs and practices of their patients from a variety of cultures, physicians are becoming more sensitized to and knowledgeable about natural remedies. Vitamins and other nutritional supplements like vitamin D, folate, and vitamin B12 may be useful in alleviating depression, either alone or in combination with an antidepressant medication. Another intervention from alternative medicine is St. John's wort (Hypernicum perforatum). This herbal remedy has been found to be helpful for some individuals who suffer from mild to moderate depression. However, St. John's wort being an herbal remedy is no guarantee against developing complications. For example, its chemical similarity to many antidepressants disqualifies it from being given to people who are taking those medications. We are close to having genetic markers for bipolar disorder. Soon after, we hope to also have them for major depression. That way, we can know of a child's vulnerability to depression from birth and try to create preventive strategies. For example, we can teach parents early warning signs so that they can get treatment for their children, if necessary, to ward off future problems.

The new world of pharmacogenetics holds the promise of actually keeping the genes responsible for depression turned off so as to avoid the illnesses completely. Also, by studying genes, we are learning more about the matching of patients with treatment. This kind of information will be able to tell us which patients do well on which types of drugs and psychotherapy regimens.

We are learning more about the interactions of the neurochemicals, the chemical messengers in the brain, and their influence on depression. Moreover, new categories of neurochemicals, such as neuropeptides and substance P, are being studied. As a result, we will soon be able to develop new drugs that should be more effective with fewer side effects. We are also learning startling things about how maternal stress early in pregnancy can profoundly affect the developing fetus. For example, we now know that maternal stress can greatly increase the risk for the fetus to develop depression as an adult.

Further information is also being discerned about how to most effectively make treatment of depression available and acceptable to all who need it. This is particularly important for children and adolescents, minorities, individuals who are economically disadvantaged or live in rural areas, the elderly and for people with developmental disabilities, who are known to suffer from lack of adequate access to mental-health treatment that is knowledgeable and respectful of what may be their unique needs and preferences. While sadness will always be part of the human condition, hopefully we will be able to lessen or eradicate the more severe mood disorders from the world to the benefit of all of us

Where can people find more information about depression?

For further information about depression, please visit the following sites:

Suicide Awareness Voices of Education (SAVE)
http://www.save.org/

APA: Women and Depression (American Psychological Association)
http://www.apa.org/ppo/issues/
pwomenanddepress.html

For additional information, you can write or call the following organizations:

D/ART/Public Inquiries; National Institute of Mental Health
Room 15C-05
5600 Fishers Lane
Rockville, MD 20857

National Foundation for Depressive Illness
20 Charles Street
New York, NY 10014

National Depressive and Manic Depressive Association
730 N. Franklin
Suite 501
Chicago, IL 60601
(800) 826-3632
(312) 642-0049
(312) 642-7243--fax
http://www.ndmda.org/

National Mental Health Association
1021 Prince Street
Alexandria, VA 22314-2971
(800) 969-NMHA (6642)
http://www.nmha.org/

National Alliance for the Mentally Ill
2101 Wilson Boulevard
Suite 302
Arlington, VA 22201
HelpLine: 1-800-950-NAMI [6264]
http://www.nami.org/

National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD)
60 Cutter Mill Road, Suite 404
Great Neck, NY 11021 USA
Infoline: 1-800-829-8289
http://www.narsad.org/

Substance Abuse and Mental Health Services Administration (SAMHSA)
5600 Fishers Lane
Rockville, MD 20857
http://www.samhsa.gov/

Surgeon General's Report on Mental Illness
To receive a copy of this report, write or call:
Mental Health
Pueblo, Co 81009
1-800-789-2647
http://www.surgeongeneral.gov/library/mentalhealth/home.html

The National Institute of Mental Health (NIMH) for the Depression Awareness, Recognition, and Treatment (DART) program furnished a portion of the foregoing information.

Depression At A Glance

• A depressive disorder is a syndrome (group of symptoms) that reflects a sad, blue mood exceeding normal sadness or grief.
• Depressive disorders are characterized not only by negative thoughts, moods, and behaviors but also by specific changes in bodily functions (for example, eating, sleeping, and sexual activity).
• One in 10 people will have a depressive disorder in their lifetime, and in one of 10 cases, the depression is a fatal disease as a result of suicide.
• Some types of depression, especially bipolar depression, run in families.
• While there are many social, psychological, and environmental risk factors for developing depression, some are particularly prevalent in one gender or the other, or in particular age or ethnic groups.
• Depression is diagnosed only clinically in that there is no laboratory test or X-ray for depression. Therefore, it is crucial to see a health practitioner as soon as you notice symptoms of depression in yourself, your friends, or family.
• The first step in getting appropriate treatment is a complete physical and psychological evaluation to determine whether the person, in fact, has a depressive disorder.
• Depression is not a weakness but a serious illness with biological, psychological, and social aspects to its cause, symptoms, and treatment. A person cannot will it away. Untreated, it will worsen. Undertreated, it will return.
• There are many safe and effective medications, particularly the SSRIs, that can be of great help in depression.
• For full recovery from a mood disorder, regardless of whether there is a precipitating factor or it seems to come out of the blue, treatments with medications and/or electroconvulsive therapy (ECT) and psychotherapy are necessary.
• In the future, through depression research and education, we will continue to improve our treatments, decrease society's burden, and hopefully develop preventive measures.

Previous contributing author and editor:

Medical Author: Peter J. Panzarino Jr., MD, FAPA
Medical Editor: Leslie J. Schoenfield, MD, PhD

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sourceLast Editorial Review: 12/1/2009

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