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Depression

Depression

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:

 

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.

 

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.

 

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

 

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. Other complications of depression include its tendency to 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 healt hillness, 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.

 

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.

 

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

 

 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.

 

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.

 

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 or hypomania 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

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 or pessimism.
  • Feelings of worthlessness, helplessness, or excessive guilt.
  • 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, or making decisions.
  • Persistent physical symptoms that do not respond to treatment, such asheadaches, digestive disorders, and/or chronic pain.
  • 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.

Causes

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 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, attention deficit hyperactivity disorder (ADHD), 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.

Treatment

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) andmonoamine 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.

 

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), duloxetine (Cymbalta) and desvenlafaxine (Pristiq) are three 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 and Pristiq tend to act as equally powerful serotonin reuptake inhibitors and norepinephrine reuptake inhibitors regardless of the dose. They are, therefore, also considered SNRIs.

 

Mirtazapine (Remeron), another 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 the SNRIs, 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) and trazodone (Desyrel) 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), and lamotrigine (Lamictal) are mood stabilizers and anticonvulsants. They have been used to treat bipolar depression.

 

Certain antipsychotic medications, as ziprasidone (Geodon), quetiapine (Seroquel), aripiprazole (Abilify), asenapine (Saphris), and paliperidone (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.

 

Often 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.

 

Over the 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 hurt themselves or 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. Talkingtherapies (psychotherapies) help patients gain insight into their problems and resolve them through verbal give-and-take with the therapist. Behavioraltherapists 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.

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