Depression

• Posted on July 12, 2009 at 10:52 am

Major Depression

What is major depression?

Major depression is a serious medical illness affecting 15 million American adults, or approximately 5 to 8 percent of the adult population in a given year. Unlike normal emotional experiences of sadness, loss, or passing mood states, major depression is persistent and can significantly interfere with an individual’s thoughts, behavior, mood, activity, and physical health. Among all medical illnesses, major depression is the leading cause of disability in the U.S. and many other developed countries. Depression occurs twice as frequently in women as in men, for reasons that are not fully understood. More than half of those who experience a single episode of depression will continue to have episodes that occur as frequently as once or even twice a year. Without treatment, the frequency of depressive illness as well as the severity of symptoms tends to increase over time. Left untreated, depression can lead to suicide. Major depression, also known as clinical depression or unipolar depression, is only one type of depressive disorder. Other depressive disorders include dysthymia (chronic, less severe depression) and bipolar depression (the depressed phase of bipolar disorder or manic depression). People who have bipolar disorder experience both depression and mania. Mania involves unusually and persistently elevated mood or irritability, elevated self-esteem, and excessive energy, thoughts, and talking.  

What are the symptoms of major depression?

The onset of the first episode of major depression may not be obvious if it is gradual or mild. The symptoms of major depression characteristically represent a significant change from how a person functioned before the illness. The symptoms of depression include:

• persistently sad or irritable mood
• pronounced changes in sleep, appetite, and energy
• difficulty thinking, concentrating, and remembering
• physical slowing or agitation
• lack of interest in or pleasure from activities that were once enjoyed
• feelings of guilt, worthlessness, hopelessness, and emptiness
• recurrent thoughts of death or suicide
• persistent physical symptoms that do not respond to treatment, such as headaches, digestive disorders, and chronic pain

When several of these symptoms of depressive illness occur at the same time, last longer than two weeks, and interfere with ordinary functioning, professional treatment is needed.  

What are the causes of major depression?

There is no single cause of major depression. Psychological, biological, and environmental factors may all contribute to its development. Whatever the specific causes of depression, scientific research has firmly established that major depression is a biological, medical illness. Norepinephrine, serotonin, and dopamine are three neurotransmitters (chemical messengers that transmit electrical signals between brain cells) thought to be involved with major depression. Scientists believe that if there is a chemical imbalance in these neurotransmitters, then clinical states of depression result. Antidepressant medications work by increasing the availability of neurotransmitters or by changing the sensitivity of the receptors for these chemical messengers. Scientists have also found evidence of a genetic predisposition to major depression. There is an increased risk for developing depression when there is a family history of the illness. Not everyone with a genetic predisposition develops depression, but some people probably have a biological make-up that leaves them particularly vulnerable to developing depression. Life events, such as the death of a loved one, a major loss or change, chronic stress, and alcohol and drug abuse, may trigger episodes of depression. Some illnesses such as heart disease and cancer and some medications may also trigger depressive episodes. It is also important to note that many depressive episodes occur spontaneously and are not triggered by a life crisis, physical illness, or other risks.  

How is major depression treated?

Although major depression can be a devastating illness, it is highly treatable. Between 80 and 90 percent of those diagnosed with major depression can be effectively treated and return to their usual daily activities and feelings. Many types of treatment are available, and the type chosen depends on the individual and the severity and patterns of his or her illness. There are three well-established types of treatment for depression: medications, psychotherapy, and electroconvulsive therapy (ECT). For some people who have a seasonal component to their depression, light therapy may be useful. These treatments may be used alone or in combination. Additionally, peer education and support can promote recovery. Attention to lifestyle, including diet, exercise, and smoking cessation, can result in better health, including mental health. Medication. . It often takes two to four weeks for antidepressants to start having an effect, and 6-12 weeks for antidepressants to have their full effect. The first antidepressant medications were introduced in the 1950s. Research has shown that imbalances in neurotransmitters like serotonin, dopamine, and norepinephrine can be corrected with antidepressants. Four groups of antidepressant medications are most often prescribed for depression:

• Selective serotonin reuptake inhibitors (SSRIs) act specifically on the neurotransmitter serotonin. They are the most common agents prescribed for depression worldwide. These agents block the reuptake of serotonin from the synapse to the nerve, thus artificially increasing the serotonin that is available in the synapse (this is functional serotonin, since it can become involved in signal transmission, the cardinal function of neurotransmitters). SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and fluvoxamine (Luvox).
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) are the second-most popular antidepressants worldwide. These agents block the reuptake of both serotonin and norepinephrine from the synapse into the nerve (thus increasing the amounts of these chemicals that can participate in signal transmission). SNRIs include venlafaxine (Effexor) and duloxetine (Cymbalta).
• Bupropion (Wellbutrin) is a very popular antidepressant medication classified as a norepinephrine-dopamine reuptake inhibitor (NDRI). It acts by blocking the reuptake of dopamine and norepinephrine.
• Mirtazapine (Remeron) works differently from the compounds discussed above. Mirtazapine targets specific serotonin and norepinephrine receptors in the brain, thus indirectly increasing the activity of several brain circuits.
• Tricyclic antidepressants (TCAs) are older agents seldom used now as first-line treatment. They work similarly to the SNRIs, but have other neurochemical properties which result in very high side effect rates, as compared to almost all other antidepressants. They are sometimes used in cases where other antidepressants have not worked. TCAs include amitriptyline (Elavil, Limbitrol), desipramine (Norpramin), doxepin (Sinequan), imipramine (Norpramin, Tofranil), nortriptyline (Pamelor, Aventyl), and protriptyline (Vivactil).
• Monoamine oxidase inhibitors (MAOIs) are also seldom used now. They work by inactivating enzymes in the brain which catabolize (chew up) serotonin, norepinephrine, and dopamine from the synapse, thus increasing the levels of these chemicals in the brain. They can sometimes be effective for people who do not respond to other medications or who have “atypical” depression with marked anxiety, excessive sleeping, irritability, hypochondria, or phobic characteristics. However, they are the least safe antidepressants to use, as they have important medication interactions and require adherence to a particular diet. MAOIs include phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate).
• Non-antidepressant adjunctive agents. Often psychiatrists will combine the antidepressants mentioned above with each other (we call this a “combination”) or with agents which are not antidepressants themselves (we call this “augmentation”). These latter agents can include the atypical antipsychotic agents [aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), risperidone (Risperdal)], buspirone (Buspar), thyroid hormone (triiodothyonine, or “T3”), the stimulants [methylphenidate (Ritalin), dextroaphetamine (Aderall)], dopamine receptor agonists [pramipexole (Mirapex), ropinirole (Requipp)], lithium, lamotrigine (Lamictal), s-adenosyl methionine (SAMe), pindolol, and steroid hormones (testosterone, estrogen, DHEA).

Consumers and their families must be cautious during the early stages of medication treatment because normal energy levels and the ability to take action often return before mood improves. At this time – when decisions are easier to make, but depression is still severe – the risk of suicide may temporarily increase.

• Psychotherapy. There are several types of psychotherapy that have been shown to be effective for depression including cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT). Research has shown that mild to moderate depression can often be treated successfully with either of these therapies used alone. However, severe depression appears more likely to respond to a combination of psychotherapy and medication.
• Cognitive-behavioral therapy (CBT) – helps to change the negative thinking and unsatisfying behavior associated with depression, while teaching people how to unlearn the behavioral patterns that contribute to their illness.
• Interpersonal therapy (IPT) – focuses on improving troubled personal relationships and on adapting to new life roles that may have been associated with a person’s depression.
• Electroconvulsive therapy (ECT). ECT is a highly effective treatment for severe depressive episodes. In situations where medication, psychotherapy, and a combination of the two prove ineffective, or work too slowly to relieve severe symptoms such as psychosis or thoughts of suicide, ECT may be considered. ECT may also be considered for those who for one reason or another cannot take antidepressant medications.

What are the side effects of the medications used to treat depression?

Different medications produce different side effects, and people differ in the type and severity of side effect they experience. About 50 percent of people who take antidepressant medications experience some side effects, particularly during the first weeks of treatment. Side effects that are particularly bothersome can often be treated by changing the dose of the medication, switching to a different medication, or treating the side effect directly with additional medications. Rarely, serious side effects such as fainting, heart problems, or seizure may occur, but they are almost always treatable.

• Tricyclic antidepressants (TCAs) cause side effects that include dry mouth, constipation, bladder problems, sexual problems, blurred vision, dizziness, drowsiness, skin rash, and weight gain or loss.
• Monoamine oxidase inhibitors (MAOIs). Individuals taking MAOIs may have to be careful about eating certain smoked, fermented, or pickled foods, drinking certain beverages, or taking some medications because they can cause severe high blood pressure in combination with the medication. A range of other, less serious side effects occur including weight gain, constipation, dry mouth, dizziness, headache, drowsiness, insomnia, and sexual side effects (problems with arousal or satisfaction).
• SSRIs, and SNRIs tend to have fewer and different side effects, such as nausea, nervousness, insomnia, diarrhea, rash, agitation, or sexual side effects (problems with arousal or orgasm).
• Bupropion generally causes fewer common side effects than TCAs and MAOIs. Its side effects include restlessness, insomnia, headache or a worsening of preexisting migraine conditions, tremor, dry mouth, agitation, confusion, rapid heartbeat, dizziness, nausea, constipation, menstrual complaints, and rash.

Reviewed by Dr. Ken Duckworth, NAMI Medical Director, September 2006

Read about Treatments and Supports for Mental Illness

More Fact Sheets

Understanding Major Depression and Recovery(PDF)  

NAMI’s booklet on Understanding Major Depression and Recovery.

Women and Depression Brochure(PDF)  

Learn more about women and depression in this self-help brochure from The National Alliance on Mental Illness (NAMI) that addresses the causes, symptoms, life stages and treatment of depression.  

Ask the Doctor: Treatment Resistant Depression

NAMI’s Medical Director, Dr. Ken Duckworth, talks about treatment resistant depression and several treatment options.

Depression in Children and Adolescents

NAMI’s Fact Sheet on Depression in Children and Adolescents

More Fact Sheets…

Related Resources 

DepressionIsReal.com

Frustrated and concerned by popular misconceptions that trivialize depression as “just the blues” or dismiss it entirely as an “imaginary disease,” seven prominent physician, patient and civic nonprofit organizations have joined together to launch a public education campaign to tell Americans the truth about depression.

Depression Survey Results(PDF)

Depression is one of the most prevalent mental health conditions in the United States, affecting approximately 19 million American adults each year. The symptoms of depression vary widely and may greatly impact the social and economic well-being of sufferers. The goal of this survey is to document the costs of depression in terms of relationships, professional life, and economic well-being.

The Down and Up Show

The Down & Up Show is dedicated to the reality of depression. Each week the hosts talk with some of the world’s top experts on depression, as well as people who have been impacted by this illness. The reality of depression is that it is a debilitating and potentially deadly medical condition that affects some 19 million Americans every year. The other reality of depression is that there is hope.

Living with Major Depression

Welcome to NAMI’s Living with Major Depression community. Here you will find support, get targeted information and connect with people who understand.

Find Support

Learn more about the full spectrum of programs and services that NAMI provides across the country for people living with mental illnesses, and their families and loved ones.

Related Links

Sequenced Treatment Alternatives to Relieve Depression (STAR*D)

NIMH sponsored multi-center clinical trial and information resource.  

CBS Cares: Depression Web Site

As part of their new public service announcement campaign, CBS-TV has created a Web site on depression that contains information and stories.

Treatment for Adolescents with Depression Study (TADS)

NIMH sponsored multi-center clinical trial and information resource.

National Institute of Mental Health

Information from the NIH institute on depression.

Clinicaltrials.gov

Bipolar disorder research studies identified through the U.S. National Library of Medicine’s link to federally and privately funded studies worldwide.

Depression and Bipolar Support Alliance

Organization to improve lives of people living with mood disorders through support, education, and advocacy.

Mood and Anxiety Disorders Program (MAP)

NIMH intramural research and information program on mood disorders.

Source: NAMI

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Bipolar Disorder

• Posted on July 12, 2009 at 9:45 am

Bipolar Disorder

What is bipolar disorder?

Bipolar disorder, or manic depression, is a medical illness that causes extreme shifts in mood, energy, and functioning. These changes may be subtle or dramatic and typically vary greatly over the course of a person’s life as well as among individuals. Over 10 million people in America have bipolar disorder, and the illness affects men and women equally. Bipolar disorder is a chronic and generally life-long condition with recurring episodes of mania and depression that can last from days to months that often begin in adolescence or early adulthood, and occasionally even in children. Most people generally require some sort of lifelong treatment. While medication is one key element in successful treatment of bipolar disorder, psychotherapy, support, and education about the illness are also essential components of the treatment process.

What are the symptoms of mania?

Mania is the word that describes the activated phase of bipolar disorder. The symptoms of mania may include:

• either an elated, happy mood or an irritable, angry, unpleasant mood
• increased physical and mental activity and energy
• racing thoughts and flight of ideas
• increased talking, more rapid speech than normal
• ambitious, often grandiose plans
• risk taking
• impulsive activity such as spending sprees, sexual indiscretion, and alcohol abuse
• decreased sleep without experiencing fatigue

What are the symptoms of depression?

Depression is the other phase of bipolar disorder. The symptoms of depression may include:

• loss of energy
• prolonged sadness
• decreased activity and energy
• restlessness and irritability
• inability to concentrate or make decisions
• increased feelings of worry and anxiety
• less interest or participation in, and less enjoyment of activities normally enjoyed
• feelings of guilt and hopelessness
• thoughts of suicide
• change in appetite (either eating more or eating less)
• change in sleep patterns (either sleeping more or sleeping less)

What is a “mixed” state?

A mixed state is when symptoms of mania and depression occur at the same time. During a mixed state depressed mood accompanies manic activation.

What is rapid cycling?

Sometimes individuals may experience an increased frequency of episodes. When four or more episodes of illness occur within a 12-month period, the individual is said to have bipolar disorder with rapid cycling. Rapid cycling is more common in women.

What are the causes of bipolar disorder?

While the exact cause of bipolar disorder is not known, most scientists believe that bipolar disorder is likely caused by multiple factors that interact with each other to produce a chemical imbalance affecting certain parts of the brain. Bipolar disorder often runs in families, and studies suggest a genetic component to the illness. A stressful environment or negative life events may interact with an underlying genetic or biological vulnerability to produce the disorder. There are other possible “triggers” of bipolar episodes: the treatment of depression with an antidepressant medication may trigger a switch into mania, sleep deprivation may trigger mania, or hypothyroidism may produce depression or mood instability. It is important to note that bipolar episodes can and often do occur without any obvious trigger.

How is bipolar disorder treated?

While there is no cure for bipolar disorder, it is a treatable and manageable illness. After an accurate diagnosis, most people can achieve an optimal level of wellness. Medication is an essential element of successful treatment for people with bipolar disorder. In addition, psychosocial therapies including cognitive-behavioral therapy, interpersonal therapy, family therapy, and psychoeducation are important to help people understand the illness and to internalize skills to cope with the stresses that can trigger episodes. Changes in medications or doses may be necessary, as well as changes in treatment plans during different stages of the illness.

It is useful to know whether the “mood stabilizing medication” prescribed has been approved by the FDA for use in bipolar disorder:

Medications for Mania:

Currently FDA approved: lithium (Eskalith or Lithobid), divalproex sodium (Depakote), carbamazepine (Tegretol), olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify)

At least one adequate well controlled study with positive data: haloperidol (Haldol)

Medications for bipolar depression:

Currently FDA approved: combination of olanzapine and fluoxetine (Symbyax)

Also at least one adequate well controlled study with positive data: quetiapine (Seroquel) and lamotrigine (Lamictal)

Medications for preventing (or delaying) recurrence:

Currently FDA approved: lithium (Eskalith or Lithobid), lamotrigine (Lamictal), olanzapine (Zyprexa), and aripiprazole (Abilify) 

Frequently a combination of two or more medications is used, especially during severe episodes of acute mania or depression.

Medication specifics and possible side effects:

Lithium has long been used as a first line treatment for acute mania in people with bipolar disorder for more than 50 years. It generally has more positive impact when used earlier, rather than later, in the course of bipolar disorder. Research shows it is most effective in those individuals with a family history of the illness, and in those experiencing the bipolar I sequence of swings between mania and depression with return to normal function between episodes.

Like all medications, lithium treatment produces side effects. The most common ones are dose-related and can be effectively managed, but for about 30 percent of people who try it, lithium is not tolerable. Lithium side effects may include frequent urination, excessive thirst, weight gain, memory problems, hand tremors, gastrointestinal problems, hair loss, acne, and water retention. There are two important lithium side effects, that can be effectively monitored by a simple blood test: 1)hypothyroidism, which mimics depression and can be easily treated, and 2) less commonly, damage to kidney functions.

Anti-convulsants: The Food and Drug Administration (FDA) approved divalproex sodium (Depakote) in 1995 for treating bipolar episodes. Originally approved in 1983 as a drug to treat epilepsy, Depakote was found to be as effective as lithium for treating acute mania, and appears to be better than lithium in treating the more complex bipolar subtypes of rapid cycling and dysphoric mania, as well as co-morbid substance abuse. In addition, Depakote may be safely given in larger doses to treat acute episodes, and works faster in this situation than lithium. The generic version of this drug is valproic acid. Some people find that the generic version produces more gastrointestinal distress than Depakote.

Depakote may also produce sedation and gastrointestinal distress, but these side effects often resolve during the first six months of treatment, or with dose adjustment. Another dose-related side effect is weight gain, and rare liver and pancreatic function problems may develop while taking Depakote. However, Depakote is generally well-tolerated, and is now prescribed far more often then lithium. Recent controlled trials indicate that the combination of Depakote and lithium is more effective in preventing relapse and recurrence than treatment with lithium alone.

Lamictal (lamotrigine), another anti-convulsant, is effective in the treatment of acute depression in bipolar I and II and in promoting remissions between episodes. For most people, Lamictal has a very tolerable side effect profile. Rarely, this medication can cause a rash serious enough to cause a medical emergency. The risk of this one potentially serious side effect can be reduced by starting with a low dose and going slowly in increasing the dose.

Use of Antidepressants

Standard antidepressant medications (those approved for the treatment of unipolar depression) have not yet been proven effective for bipolar depression. Although the evidence supporting their use for bipolar depression is limited to small or less rigorous studies, these medications remain the most commonly used treatment for bipolar depression. The data from larger studies finds neither evidence of benefit nor evidence that these agents cause large numbers of depressed patients to switch into mania.

Use of Antipsychotic Medications as Mood Stabilizers

To control acute episodes, antipsychotic medications may be used alone (monotherapy), or added to anti-convulsant medications (combination therapy). Medication guidelines now recommend the combination of these two medications as most effective for acute manic episodes. Because the older typical antipsychotic medications run the risk of causing permanent movement disorder, and have been associated with depression when used over the long term, the new atypical antipsychotics are now preferred for this purpose. All the new atypicals are effective in the treatment of acute and mixed mania. Olanzapine (Zyprexa) and risperidone (Risperdal) are FDA-approved for this purpose.

Finding the right preventive/maintenance medicine is an art informed by science and your own observations. Not all medicines that work in the acute phase of mania are as strong in preventing the next episode, so this is an area to explore.

Side effects of the atypicals are different than with first-generation antipsychotics (such as Haldol), although sedation, weight gain, and risk of diabetes are problems associated with many of the new antipsychotics. Clozapine and olanzapine, both effective antipsychotics and mood stabilizers, offer the most risk in this area. Weight gain is a serious clinical concern related to all atypical antipsychotics, and to anti-convulsants as well. Not only can weight gain lead to adult onset also known as type 2 diabetes and cardiovascular diseases, but being overweight is also now the leading cause of medication non-adherence. Doctors advise weekly monitoring of weight in the early stages of taking these medications, along with regular exercise and healthy diets, and people must be willing to make lifestyle changes to maintain optimal health. The FDA has noted an association between all atypical antipsychotics and the risk of diabetes. As the science develops in this area, it will continue to inform medicine choices for the person that best reflect their risks and benefits.             

Reviewed by Ken Duckworth, MD, October 2006

Read about Treatments and Support for Mental Illness

More Fact Sheets:

Understanding Bipolar Disorder and Recovery (PDF)
Guide to Understanding Bipolar Disorder and Recovery.

Child and Adolescent Bipolar Disorder
NAMI’s Fact Sheet on Child and Adolescent Bipolar Disorder

Related Resources:

Find Support
Learn more about the full spectrum of programs and services that NAMI provides across the country for people living with mental illnesses, and their families and loved ones.

Living with Bipolar Disorder
Welcome to the NAMI’s Living with Bipolar Disorder community. Here you will find support, get targeted information and connect with people who understand.

Related Links

Child and Adolescent Bipolar Foundation
An on-line support and advocacy organization focused on childhood bipolar disorder.

Clinicaltrials.gov
Bipolar disorder research studies identified through the U.S. National Library of Medicine’s link to federally and privately funded studies worldwide.

Depression and Bipolar Support Alliance
Organization to improve lives of people living with mood disorders through support, education, and advocacy.

Mood and Anxiety Disorders Program (MAP)
NIMH intramural research and information program on mood disorders.

National Institute of Mental Health
Information from the NIH institute on bipolar disorder.

Systematic Treatment Enhancement Program for Bipolar Disorder
NIMH sponsored multi-center clinical trial and information resource.

Source: NAMI

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