•    154 million people across the world suffer from depression
•    25 million suffer from Schizophrenia
•    91 million are affected by alcohol abuse
•    15 million are affected by drug abuse
•    50 million suffer from epilepsy
•    24 million suffer from dementia
•    Around 877,000 people commit suicide each year

These figures are staggering and go to show the extent of mental health problems in the world today. One of the biggest barriers to treating mental health problems on a global level is the lack of recognition about the seriousness of mental illness and lack of understanding as to how treatment can help.

Indeed, most organisations and members of the public make a clear distinction between physical and mental health and as such, some countries devote as little as 1 percent of their expenditure on health specifically to the treatment of mental health. This is tragic.

Facts about Mental Health

The WHO is a valuable source of information about world mental health and here are just some of the facts they have revealed about mental health on a global level.

Around 20 percent of children and young people in the world have a mental health problem and yet most low and middle income countries have just one child psychiatrist for every 1 to 4 million people

Stigma surrounding mental health problems and discrimination against people and families with mental health problems prevents people from seeking help. In South Africa, a survey revealed that most people believed mental illness was related to stress or lack of willpower and stigma was greater in urban areas and in people with a higher level of education.

Eighty six percent of suicides occur in low and middle income countries with more than fifty percent aged between 15 and 44. The highest suicide rates are in men from Eastern European countries.

In most countries there are human rights violations of people will mental health disorders which include denial of basic needs and privacy, physical restraint and seclusion. Few countries have adequate legislation in place to protect the rights of people with mental health disorders.

Tacking Human Rights Violations in people with mental health disorders

First and foremost it is necessary to change the attitude towards mental health and raise awareness of mental health and the issues surrounding mental health on a global level. Only then will human rights in mental health facilities improve, legislation be put in place to protect people with mental health problems and countries will be willing to invest more in the mental health of the people.

The World Health Organisation has initiated a mental health global action programme (mhGAP) in order to help countries combat stigma and improve mental health care in general.

A psychiatrist is a doctor who specialises in diagnosing and treating mental disorders. The main differences between a psychiatrist and other mental health professionals are that a psychiatrist must first have studied medicine, is able to interpret tests and scans and can prescribe drugs. A psychologist for example, cannot. Consequently it can take many years to become qualified in the field of psychiatry.

When a patient with a mental health disorder is referred to a psychiatrist, the first thing a psychiatrist will do is conduct a full assessment of the person’s physical and mental health in order to make a diagnosis.

Diagnosing Schizophrenia

The problems associated with schizophrenia are that no one yet knows what causes it and many psychiatrists now believe it could be more than one disorder, the symptoms vary from person to person and can overlap with other conditions, there is no cure so treatment consists of drugs and therapy, and there are no diagnostic tests available to ascertain for certain that the person is suffering from schizophrenia. Tests can be conducted but they are to rule out other possible causes for the symptoms.

A psychiatrist is therefore likely to diagnose schizophrenia only after making a full assessment of the patient’s medical history and all the symptoms to rule out other possible causes such as drug abuse, medication or an underlying health problem or another mental health disorder.

The diagnostic criteria is long and complex and has to take many things into consideration but if we put it very simply, a person may be diagnosed with schizophrenia if they have been suffering with extremely severe delusions or hallucinations or two or more of the following symptoms for a period of time:

•    Delusions
•    Hallucinations
•    Disorganized Speech
•    Catatonic Behaviour
•    So called Negative symptoms of Schizophrenia which includes flattening of the emotions, slow speech, lack of motivation, apathy, inappropriate social skills and social isolation

There are other cognitive symptoms too such as inability to focus and concentrate poor memory and difficulty in expressing thoughts and feelings. Only a psychiatrist will be able to determine if any or all of these symptoms are a result of schizophrenia.

Teenage Depression is common in teens and younger children. About 5 percent of children and adolescents in the general population suffer from depression at any given point in time.

Children under stress, who experience loss, or who have attentional, learning, conduct or anxiety disorders are at a higher risk for depression. Teenage girls are at especially high risk, as are minority youth.

Depressed youth often have problems at home. In many cases, the parents are depressed, as depression tends to run in families.

Over the past 50 years, teenage depression has become more common and is now recognized at increasingly younger ages. As the rate of depression rises, so does the teen suicide rate.

It is important to remember that the behavior of depressed children and teenagers may differ from the behavior of depressed adults. The characteristics vary, with most children and teens having additional psychiatric disorders, such as behavior disorders or substance abuse problems.

Mental health professionals advise parents to be aware of signs of depression in their children.

If one or more of these signs of depression persist, parents should seek help:

Frequent sadness, tearfulness, crying
Teens may show their pervasive sadness by wearing black clothes, writing poetry with morbid themes, or having a preoccupation with music that has nihilistic themes. They may cry for no apparent reason.

Hopelessness
Teens may feel that life is not worth living or worth the effort to even maintain their appearance or hygiene. They may believe that a negative situation will never change and be pessimistic about their future.

Decreased interest in activities; or inability to enjoy previously favorite activities
Teens may become apathetic and drop out of clubs, sports, and other activities they once enjoyed. Not much seems fun anymore to the depressed teen.

Persistent boredom; low energy
Lack of motivation and lowered energy level is reflected by missed classes or not going to school. A drop in grade averages can be equated with loss of concentration and slowed thinking.

Social isolation, poor communication
There is a lack of connection with friends and family. Teens may avoid family gatherings and events. Teens who used to spend a lot of time with friends may now spend most of their time alone and without interests. Teens may not share their feelings with others, believing that they are alone in the world and no one is listening to them or even cares about them.

Low self esteem and guilt
Teens may assume blame for negative events or circumstances. They may feel like a failure and have negative views about their competence and self-worth. They feel as if they are not “good enough.”

Extreme sensitivity to rejection or failure
Believing that they are unworthy, depressed teens become even more depressed with every supposed rejection or perceived lack of success.

Increased irritability, anger, or hostility
Depressed teens are often irritable, taking out most of their anger on their family. They may attack others by being critical, sarcastic, or abusive. They may feel they must reject their family before their family rejects them.

Difficulty with relationships
Teens may suddenly have no interest in maintaining friendships. They’ll stop calling and visiting their friends.

Frequent complaints of physical illnesses, such as headaches and stomachaches
Teens may complain about lightheadedness or dizziness, being nauseous, and back pain. Other common complaints include headaches, stomachaches, vomiting, and menstrual problems.

Frequent absences from school or poor performance in school
Children and teens who cause trouble at home or at school may actually be depressed but not know it. Because the child may not always seem sad, parents and teachers may not realize that the behavior problem is a sign of depression)

Poor concentration
Teens may have trouble concentrating on schoolwork, following a conversation, or even watching television.

A major change in eating and/or sleeping patterns
Sleep disturbance may show up as all-night television watching, difficulty in getting up for school, or sleeping during the day. Loss of appetite may become anorexia or bulimia. Eating too much may result in weight gain and obesity.

Talk of or efforts to run away from home
Running away is usually a cry for help. This may be the first time the parents realize that their child has a problem and needs help.

Thoughts or expressions of suicide or self-destructive behavior
Teens who are depressed may say they want to be dead or may talk about suicide. Depressed children and teens are at increased risk for committing suicide. If a child or teen says, “I want to kill myself,” or “I’m going to commit suicide,” always take the statement seriously and seek evaluation from a child and adolescent psychiatrist or other mental health professional. People often feel uncomfortable talking about death. However, asking whether he or she is depressed or thinking about suicide can be helpful. Rather than “putting thoughts in the child’s head,” such a question will provide assurance that somebody cares and will give the young person the chance to talk about problems.

Alcohol and Drug Abuse
Depressed teens may abuse alcohol or other drugs as a way to feel better.

Self-Injury
Teens who have difficulty talking about their feelings may show their emotional tension, physical discomfort, pain and low self-esteem with self-injurious behaviors, such as cutting.

Early diagnosis and medical treatment are essential for teenage depression

Depression is a real illness that requires professional help, self-help, and support from family and friends.

Comprehensive treatment often includes both individual and family therapy. Although there are real and frightening concerns about antidepressant medication, most mental health professionals continue to recommend their use.

There are several ways to get referrals of qualified mental health professionals, including the following:
• First, check with your insurance company for any limitations.
• Talk to family members and friends for their recommendations. If you participate in a parent support group, such as Because I Love You and ToughLove, ask other members for their recommendations.
• Ask your child’s primary care physician or your family doctor for a referral. Tell the doctor what is important to you in choosing a therapist so he or she can make appropriate recommendations.
• Inquire at your church, synagogue, or place of worship.
• Call the professional organizations listed on this page for referrals.
• Network the resources listed on your state’s Family Help page.
• Look in the phone book for the listing of a local mental health association or community mental health center and call these sources for referrals.

Ideally, you will end up with more than one therapist to interview. Call each one and request to ask the therapist some questions, either by phone or in person. You may want to inquire about his or her licensing, level of training, their expertise, approach to therapy and medication, and participation in insurance plans and fees. Such a discussion should help you sort through your options and choose someone with whom you believe you and your teen might interact well

1. Have your blood pressure checked at least weekly for the first six weeks, and at least monthly thereafter.
2. Do not eat foods containing tyramine.

Even if you do not have high blood pressure, do not take St. John’s Wort with amino acid supplements (especially phenylalanine and tyrosine). Amino acids are a form of monoamines, which can pose a danger when mixed with St. John’s Wort. The monoamines that you get in your diet (such as the amino acids in meat) are less concentrated and are not a hazard

Depression affects twice as many women as men. Midlife is often considered a period of increased risk for depression in women. It is not known why, but it may be related to having a personal or family history of depression, life stressors, and role changes. Menopause is often believed to be a time when women are more likely to become depressed. Studies actually show that menopause depression is more likely to occur in the years during transition to. This period is associated with gradual declines in estrogen levels. Some studies suggest that changes in estrogen levels are associated with onset of menopuase depression.
Menopause depression

What are the symptoms of depression during midlife?

The symptoms of depression in pregnancy are: two or more weeks of depressed mood, decreased interest or pleasure in activities, change in appetite, change in sleep patterns, fatigue or loss of energy, difficulty concentrating, excessive feeling of guilt or worthlessness, thoughts of suicide, extreme restlessness and irritability. Many symptoms of menopause overlap with symptoms of depression including problems with sleep, physical symptoms such as hot flashes, fatigue, irritability, anxiety and difficulty concentrating. Some women suffer needlessly because they think these discomforts and problems are a natural part of aging. Depression should not be dismissed as a normal consequence of later life for women.

Depression that goes untreated can lead to more severe episodes of depression and even physical complications. For example, depression is associated with increased risk for heart attacks. A recent study suggests that depression leads to loss of bone mineral density, therefore increasing a women’s risk for broken bones.

What is menopause?

Menopause is the time in life when a woman stops having menstrual periods. All women who live long enough will eventually experience menopause. The average age for menopause is 51. As a woman approaches menopause, her body gradually makes less estrogen and progesterone hormone. As a result, most women have symptoms such as hot flashes, vaginal dryness, lower sex drive, urinary incontinence, and depression. Less common symptoms include sleep disorders, dry skin, mood swings, and fatigue.

ertain health problems, such as osteoporosis (brittle bones) and increased heart disease, are associated with menopause. To help prevent such problems, many women choose to take an estrogen replacement therapy (ERT) or hormone replacement therapy (HRT) to replace what their body is no longer producing. Along with over the counter products, this is the primary treatment for the symptoms of menopause.

Lifestyle changes can also help relieve or prevent menopausal symptoms. Avoiding alcohol, caffeine, and spicy foods can help prevent hot flashes. Keeping cool and dressing in loose layers of natural fabrics such as cotton can help reduce the discomfort of a hot flash. Kegel exercises can strengthen pelvic muscles, preventing urine leaks and improving bladder control. Regular exercise can help prevent osteoporosis and heart disease. It can also lessen symptoms of menopause depression.

More than 2 million American adults,1 or about 1 percent of the population age 18 and older in any given year,2 have bipolar disorder. Bipolar disorder typically develops in late adolescence or early adulthood. However, some people have their first symptoms during childhood, and some develop them late in life. It is often not recognized as an illness, and people may suffer for years before it is properly diagnosed and treated. Like diabetes or heart disease, bipolar disorder is a long-term illness that must be carefully managed throughout a person’s life.

What Are the Symptoms of Manic depression- Bipolar Disorder?

Manic depression – Bipolar disorder causes dramatic mood swings—from overly “high” and/or irritable to sad and hopeless, and then back again, often with periods of normal mood in between. Severe changes in energy and behavior go along with these changes in mood. The periods of highs and lows are called episodes of mania and depression.

Signs and symptoms of mania (or a manic episode) include:

• Increased energy, activity, and restlessness
• Excessively “high,” overly good, euphoric mood
• Extreme irritability
• Racing thoughts and talking very fast, jumping from one idea to another
• Distractibility, can’t concentrate well
• Little sleep needed
• Unrealistic beliefs in one’s abilities and powers
• Poor judgment
• Spending sprees
• A lasting period of behavior that is different from usual
• Increased sexual drive
• Abuse of drugs, particularly cocaine, alcohol, and sleeping medications
• Provocative, intrusive, or aggressive behavior
• Denial that anything is wrong

A manic episode is diagnosed if elevated mood occurs with three or more of the other symptoms most of the day, nearly every day, for 1 week or longer. If the mood is irritable, four additional symptoms must be present.

Signs and symptoms of depression (or a depressive episode) include:

• Lasting sad, anxious, or empty mood
• Feelings of hopelessness or pessimism
• Feelings of guilt, worthlessness, or helplessness
• Loss of interest or pleasure in activities once enjoyed, including sex
• Decreased energy, a feeling of fatigue or of being “slowed down”
• Difficulty concentrating, remembering, making decisions
• Restlessness or irritability
• Sleeping too much, or can’t sleep
• Change in appetite and/or unintended weight loss or gain
• Chronic pain or other persistent bodily symptoms that are not caused by physical illness or injury
• Thoughts of death or suicide, or suicide attempts

A depressive episode is diagnosed if five or more of these symptoms last most of the day, nearly every day, for a period of 2 weeks or longer.

A mild to moderate level of mania is called hypomania. Hypomania may feel good to the person who experiences it and may even be associated with good functioning and enhanced productivity. Thus even when family and friends learn to recognize the mood swings as possible bipolar disorder, the person may deny that anything is wrong. Without proper treatment, however, hypomania can become severe mania in some people or can switch into depression.
Sometimes, severe episodes of mania or depression include symptoms of psychosis (or psychotic symptoms). Common psychotic symptoms are hallucinations (hearing, seeing, or otherwise sensing the presence of things not actually there) and delusions (false, strongly held beliefs not influenced by logical reasoning or explained by a person’s usual cultural concepts). Psychotic symptoms in bipolar disorder tend to reflect the extreme mood state at the time. For example, delusions of grandiosity, such as believing one is the President or has special powers or wealth, may occur during mania; delusions of guilt or worthlessness, such as believing that one is ruined and penniless or has committed some terrible crime, may appear during depression. People with bipolar disorder who have these symptoms are sometimes incorrectly diagnosed as having schizophrenia, another severe mental illness.

It may be helpful to think of the various mood states in manic depression – bipolar disorder as a spectrum or continuous range. At one end is severe depression, above which is moderate depression and then mild low mood, which many people call “the blues” when it is short-lived but is termed “dysthymia” when it is chronic. Then there is normal or balanced mood, above which comes hypomania (mild to moderate mania), and then severe mania.

In some people, however, symptoms of mania and depression may occur together in what is called a mixed bipolar state. Symptoms of a mixed state often include agitation, trouble sleeping, significant change in appetite, psychosis, and suicidal thinking. A person may have a very sad, hopeless mood while at the same time feeling extremely energized.
Manic depression – Bipolar disorder may appear to be a problem other than mental illness—for instance, alcohol or drug abuse, poor school or work performance, or strained interpersonal relationships. Such problems in fact may be signs of an underlying mood disorder.

Diagnosis of manic depression – Bipolar Disorder

Like other mental illnesses, bipolar disorder cannot yet be identified physiologically—for example, through a blood test or a brain scan. Therefore, a diagnosis of bipolar disorder is made on the basis of symptoms, course of illness, and, when available, family history. The diagnostic criteria for bipolar disorder are described in the Diagnostic and Statistical Manual for Mental Disorders, fourth edition (DSM-IV).3

Descriptions offered by people with bipolar disorder give valuable insights into the various mood states associated with the illness:

Depression: I doubt completely my ability to do anything well. It seems as though my mind has slowed down and burned out to the point of being virtually useless…. [I am] haunt[ed]… with the total, the desperate hopelessness of it all…. Others say, “It’s only temporary, it will pass, you will get over it,” but of course they haven’t any idea of how I feel, although they are certain they do. If I can’t feel, move, think or care, then what on earth is the point?

Hypomania: At first when I’m high, it’s tremendous… ideas are fast… like shooting stars you follow until brighter ones appear…. All shyness disappears, the right words and gestures are suddenly there… uninteresting people, things become intensely interesting. Sensuality is pervasive, the desire to seduce and be seduced is irresistible. Your marrow is infused with unbelievable feelings of ease, power, well-being, omnipotence, euphoria… you can do anything… but, somewhere this changes.

Mania: The fast ideas become too fast and there are far too many… overwhelming confusion replaces clarity… you stop keeping up with it—memory goes. Infectious humor ceases to amuse. Your friends become frightened…. everything is now against the grain… you are irritable, angry, frightened, uncontrollable, and trapped.

Suicide

Some people with bipolar disorder become suicidal. Anyone who is thinking about committing suicide needs immediate attention, preferably from a mental health professional or a physician. Anyone who talks about suicide should be taken seriously. Risk for suicide appears to be higher earlier in the course of the illness. Therefore, recognizing bipolar disorder early and learning how best to manage it may decrease the risk of death by suicide.

Signs and symptoms that may accompany suicidal feelings include:

• talking about feeling suicidal or wanting to die
• feeling hopeless, that nothing will ever change or get better
• feeling helpless, that nothing one does makes any difference
• feeling like a burden to family and friends
• abusing alcohol or drugs
• putting affairs in order (e.g., organizing finances or giving away possessions to prepare for one’s death)
• writing a suicide note
• putting oneself in harm’s way, or in situations where there is a danger of being killed
If you are feeling suicidal or know someone who is:
• call a doctor, emergency room, or 911 right away to get immediate help
• make sure you, or the suicidal person, are not left alone
• make sure that access is prevented to large amounts of medication, weapons, or other items that could be used for self-harm

While some suicide attempts are carefully planned over time, others are impulsive acts that have not been well thought out; thus, the final point in the box above may be a valuable long-term strategy for people with bipolar disorder. Either way, it is important to understand that suicidal feelings and actions are symptoms of an illness that can be treated. With proper treatment, suicidal feelings can be overcome.

What Is the Course of manic depression – Bipolar Disorder?

Episodes of mania and depression typically recur across the life span. Between episodes, most people with bipolar disorder are free of symptoms, but as many as one-third of people have some residual symptoms. A small percentage of people experience chronic unremitting symptoms despite treatment.4

The classic form of the illness, which involves recurrent episodes of mania and depression, is called bipolar I disorder. Some people, however, never develop severe mania but instead experience milder episodes of hypomania that alternate with depression; this form of the illness is called bipolar II disorder. When four or more episodes of illness occur within a 12-month period, a person is said to have rapid-cycling bipolar disorder. Some people experience multiple episodes within a single week, or even within a single day. Rapid cycling tends to develop later in the course of illness and is more common among women than among men.

People with bipolar disorder can lead healthy and productive lives when the illness is effectively treated (see below—”How Is Bipolar Disorder Treated?”). Without treatment, however, the natural course of bipolar disorder tends to worsen. Over time a person may suffer more frequent (more rapid-cycling) and more severe manic and depressive episodes than those experienced when the illness first appeared.5 But in most cases, proper treatment can help reduce the frequency and severity of episodes and can help people with bipolar disorder maintain good quality of life.
Can Children and Adolescents Have manic depression – Bipolar Disorder?

Both children and adolescents can develop bipolar disorder. It is more likely to affect the children of parents who have the illness.

Unlike many adults with bipolar disorder, whose episodes tend to be more clearly defined, children and young adolescents with the illness often experience very fast mood swings between depression and mania many times within a day.6 Children with mania are more likely to be irritable and prone to destructive tantrums than to be overly happy and elated. Mixed symptoms also are common in youths with bipolar disorder. Older adolescents who develop the illness may have more classic, adult-type episodes and symptoms.

Bipolar disorder in children and adolescents can be hard to tell apart from other problems that may occur in these age groups. For example, while irritability and aggressiveness can indicate bipolar disorder, they also can be symptoms of attention deficit hyperactivity disorder, conduct disorder, oppositional defiant disorder, or other types of mental disorders more common among adults such as major depression or schizophrenia. Drug abuse also may lead to such symptoms.

For any illness, however, effective treatment depends on appropriate diagnosis. Children or adolescents with emotional and behavioral symptoms should be carefully evaluated by a mental health professional. Any child or adolescent who has suicidal feelings, talks about suicide, or attempts suicide should be taken seriously and should receive immediate help from a mental health specialist.

What Causes Bipolar Disorder?

Scientists are learning about the possible causes of bipolar disorder through several kinds of studies. Most scientists now agree that there is no single cause for bipolar disorder—rather, many factors act together to produce the illness.

Because bipolar disorder tends to run in families, researchers have been searching for specific genes—the microscopic “building blocks” of DNA inside all cells that influence how the body and mind work and grow—passed down through generations that may increase a person’s chance of developing the illness. But genes are not the whole story. Studies of identical twins, who share all the same genes, indicate that both genes and other factors play a role in bipolar disorder. If bipolar disorder were caused entirely by genes, then the identical twin of someone with the illness would always develop the illness, and research has shown that this is not the case. But if one twin has bipolar disorder, the other twin is more likely to develop the illness than is another sibling.7
In addition, findings from gene research suggest that bipolar disorder, like other mental illnesses, does not occur because of a single gene.8 It appears likely that many different genes act together, and in combination with other factors of the person or the person’s environment, to cause bipolar disorder. Finding these genes, each of which contributes only a small amount toward the vulnerability to bipolar disorder, has been extremely difficult. But scientists expect that the advanced research tools now being used will lead to these discoveries and to new and better treatments for bipolar disorder.

Brain-imaging studies are helping scientists learn what goes wrong in the brain to produce bipolar disorder and other mental illnesses.9,10 New brain-imaging techniques allow researchers to take pictures of the living brain at work, to examine its structure and activity, without the need for surgery or other invasive procedures. These techniques include magnetic resonance imaging (MRI), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). There is evidence from imaging studies that the brains of people with bipolar disorder may differ from the brains of healthy individuals. As the differences are more clearly identified and defined through research, scientists will gain a better understanding of the underlying causes of the illness, and eventually may be able to predict which types of treatment will work most effectively.
How Is Bipolar Disorder Treated?

Most people with bipolar disorder—even those with the most severe forms—can achieve substantial stabilization of their mood swings and related symptoms with proper treatment.11,12,13 Because bipolar disorder is a recurrent illness, long-term preventive treatment is strongly recommended and almost always indicated. A strategy that combines medication and psychosocial treatment is optimal for managing the disorder over time.

In most cases, bipolar disorder is much better controlled if treatment is continuous than if it is on and off. But even when there are no breaks in treatment, mood changes can occur and should be reported immediately to your doctor. The doctor may be able to prevent a full-blown episode by making adjustments to the treatment plan. Working closely with the doctor and communicating openly about treatment concerns and options can make a difference in treatment effectiveness.
In addition, keeping a chart of daily mood symptoms, treatments, sleep patterns, and life events may help people with bipolar disorder and their families to better understand the illness. This chart also can help the doctor track and treat the illness most effectively.

Medications

Medications for bipolar disorder are prescribed by psychiatrists—medical doctors (M.D.) with expertise in the diagnosis and treatment of mental disorders. While primary care physicians who do not specialize in psychiatry also may prescribe these medications, it is recommended that people with bipolar disorder see a psychiatrist for treatment.

Medications known as “mood stabilizers” usually are prescribed to help control bipolar disorder.11 Several different types of mood stabilizers are available. In general, people with bipolar disorder continue treatment with mood stabilizers for extended periods of time (years). Other medications are added when necessary, typically for shorter periods, to treat episodes of mania or depression that break through despite the mood stabilizer.

• Lithium, the first mood-stabilizing medication approved by the U.S. Food and Drug Administration (FDA) for treatment of mania, is often very effective in controlling mania and preventing the recurrence of both manic and depressive episodes.
• Anticonvulsant medications, such as valproate (Depakote®) or carbamazepine (Tegretol®), also can have mood-stabilizing effects and may be especially useful for difficult-to-treat bipolar episodes. Valproate was FDA-approved in 1995 for treatment of mania.
• Newer anticonvulsant medications, including lamotrigine (Lamictal®), gabapentin (Neurontin®), and topiramate (Topamax®), are being studied to determine how well they work in stabilizing mood cycles.
• Anticonvulsant medications may be combined with lithium, or with each other, for maximum effect.
• Children and adolescents with bipolar disorder generally are treated with lithium, but valproate and carbamazepine also are used. Researchers are evaluating the safety and efficacy of these and other psychotropic medications in children and adolescents. There is some evidence that valproate may lead to adverse hormone changes in teenage girls and polycystic ovary syndrome in women who began taking the medication before age 20.14 Therefore, young female patients taking valproate should be monitored carefully by a physician.
• Women with bipolar disorder who wish to conceive, or who become pregnant, face special challenges due to the possible harmful effects of existing mood stabilizing medications on the developing fetus and the nursing infant.15 Therefore, the benefits and risks of all available treatment options should be discussed with a clinician skilled in this area. New treatments with reduced risks during pregnancy and lactation are under study.

Treatment of Bipolar Depression

Research has shown that people with bipolar disorder are at risk of switching into mania or hypomania, or of developing rapid cycling, during treatment with antidepressant medication.16 Therefore, “mood-stabilizing” medications generally are required, alone or in combination with antidepressants, to protect people with bipolar disorder from this switch. Lithium and valproate are the most commonly used mood-stabilizing drugs today. However, research studies continue to evaluate the potential mood-stabilizing effects of newer medications.

• Atypical antipsychotic medications, including clozapine (Clozaril®), olanzapine (Zyprexa®), risperidone (Risperdal®), quetiapine (Seroquel®), and ziprasidone (Geodon®), are being studied as possible treatments for bipolar disorder. Evidence suggests clozapine may be helpful as a mood stabilizer for people who do not respond to lithium or anticonvulsants.17 Other research has supported the efficacy of olanzapine for acute mania, an indication that has recently received FDA approval.18 Olanzapine may also help relieve psychotic depression.19
• If insomnia is a problem, a high-potency benzodiazepine medication such as clonazepam (Klonopin®) or lorazepam (Ativan®) may be helpful to promote better sleep. However, since these medications may be habit-forming, they are best prescribed on a short-term basis. Other types of sedative medications, such as zolpidem (Ambien®), are sometimes used instead.
• Changes to the treatment plan may be needed at various times during the course of bipolar disorder to manage the illness most effectively. A psychiatrist should guide any changes in type or dose of medication.
• Be sure to tell the psychiatrist about all other prescription drugs, over-the-counter medications, or natural supplements you may be taking. This is important because certain medications and supplements taken together may cause adverse reactions.
• To reduce the chance of relapse or of developing a new episode, it is important to stick to the treatment plan. Talk to your doctor if you have any concerns about the medications.

Thyroid Function

People with bipolar disorder often have abnormal thyroid gland function.5 Because too much or too little thyroid hormone alone can lead to mood and energy changes, it is important that thyroid levels are carefully monitored by a physician.

People with rapid cycling tend to have co-occurring thyroid problems and may need to take thyroid pills in addition to their medications for bipolar disorder. Also, lithium treatment may cause low thyroid levels in some people, resulting in the need for thyroid supplementation.

Medication Side Effects

Before starting a new medication for bipolar disorder, always talk with your psychiatrist and/or pharmacist about possible side effects. Depending on the medication, side effects may include weight gain, nausea, tremor, reduced sexual drive or performance, anxiety, hair loss, movement problems, or dry mouth. Be sure to tell the doctor about all side effects you notice during treatment. He or she may be able to change the dose or offer a different medication to relieve them. Your medication should not be changed or stopped without the psychiatrist’s guidance.

Psychosocial Treatments

As an addition to medication, psychosocial treatments—including certain forms of psychotherapy (or “talk” therapy)—are helpful in providing support, education, and guidance to people with bipolar disorder and their families. Studies have shown that psychosocial interventions can lead to increased mood stability, fewer hospitalizations, and improved functioning in several areas.13 A licensed psychologist, social worker, or counselor typically provides these therapies and often works together with the psychiatrist to monitor a patient’s progress. The number, frequency, and type of sessions should be based on the treatment needs of each person.

Psychosocial interventions commonly used for bipolar disorder are cognitive behavioral therapy, psychoeducation, family therapy, and a newer technique, interpersonal and social rhythm therapy. NIMH researchers are studying how these interventions compare to one another when added to medication treatment for bipolar disorder.

• Cognitive behavioral therapy helps people with bipolar disorder learn to change inappropriate or negative thought patterns and behaviors associated with the illness.
• Psychoeducation involves teaching people with bipolar disorder about the illness and its treatment, and how to recognize signs of relapse so that early intervention can be sought before a full-blown illness episode occurs. Psychoeducation also may be helpful for family members.
• Family therapy uses strategies to reduce the level of distress within the family that may either contribute to or result from the ill person’s symptoms.
• Interpersonal and social rhythm therapy helps people with bipolar disorder both to improve interpersonal relationships and to regularize their daily routines. Regular daily routines and sleep schedules may help protect against manic episodes.
• As with medication, it is important to follow the treatment plan for any psychosocial intervention to achieve the greatest benefit.
Other Treatments
• In situations where medication, psychosocial treatment, and the combination of these interventions prove ineffective, or work too slowly to relieve severe symptoms such as psychosis or suicidality, electroconvulsive therapy (ECT) may be considered. ECT may also be considered to treat acute episodes when medical conditions, including pregnancy, make the use of medications too risky. ECT is a highly effective treatment for severe depressive, manic, and/or mixed episodes. The possibility of long-lasting memory problems, although a concern in the past, has been significantly reduced with modern ECT techniques. However, the potential benefits and risks of ECT, and of available alternative interventions, should be carefully reviewed and discussed with individuals considering this treatment and, where appropriate, with family or friends.20
• Herbal or natural supplements, such as St. John’s wort (Hypericum perforatum), have not been well studied, and little is known about their effects on bipolar disorder. Because the FDA does not regulate their production, different brands of these supplements can contain different amounts of active ingredient. Before trying herbal or natural supplements, it is important to discuss them with your doctor. There is evidence that St. John’s wort can reduce the effectiveness of certain medications.21 In addition, like prescription antidepressants, St. John’s wort may cause a switch into mania in some individuals with bipolar disorder, especially if no mood stabilizer is being taken.22
• Omega-3 fatty acids found in fish oil are being studied to determine their usefulness, alone and when added to conventional medications, for long-term treatment of bipolar disorder.23
A Long-Term Illness That Can Be Effectively Treated
Even though episodes of mania and depression naturally come and go, it is important to understand that bipolar disorder is a long-term illness that currently has no cure. Staying on treatment, even during well times, can help keep the disease under control and reduce the chance of having recurrent, worsening episodes.

Do Other Illnesses Co-occur with Bipolar Disorder?

Alcohol and drug abuse are very common among people with bipolar disorder. Research findings suggest that many factors may contribute to these substance abuse problems, including self-medication of symptoms, mood symptoms either brought on or perpetuated by substance abuse, and risk factors that may influence the occurrence of both bipolar disorder and substance use disorders.24 Treatment for co-occurring substance abuse, when present, is an important part of the overall treatment plan.

Anxiety disorders, such as post-traumatic stress disorder and obsessive-compulsive disorder, also may be common in people with bipolar disorder.25,26 Co-occurring anxiety disorders may respond to the treatments used for bipolar disorder, or they may require separate treatment. For more information on anxiety disorders, contact NIMH (see below).

How Can Individuals and Families Get Help for Bipolar Disorder?

Anyone with bipolar disorder should be under the care of a psychiatrist skilled in the diagnosis and treatment of this disease. Other mental health professionals, such as psychologists, psychiatric social workers, and psychiatric nurses, can assist in providing the person and family with additional approaches to treatment.

Help can be found at:

• University—or medical school—affiliated programs
• Hospital departments of psychiatry
• Private psychiatric offices and clinics
• Offices of family physicians, internists, and pediatricians
• Public community mental health centers
People with bipolar disorder may need help to get help.
• Often people with bipolar disorder do not realize how impaired they are, or they blame their problems on some cause other than mental illness.
• A person with bipolar disorder may need strong encouragement from family and friends to seek treatment. Family physicians can play an important role in providing referral to a mental health professional.
• Sometimes a family member or friend may need to take the person with bipolar disorder for proper mental health evaluation and treatment.
• A person who is in the midst of a severe episode may need to be hospitalized for his or her own protection and for much-needed treatment. There may be times when the person must be hospitalized against his or her wishes.
• Ongoing encouragement and support are needed after a person obtains treatment, because it may take a while to find the best treatment plan for each individual.
• In some cases, individuals with bipolar disorder may agree, when the disorder is under good control, to a preferred course of action in the event of a future manic or depressive relapse.
• Like other serious illnesses, bipolar disorder is also hard on spouses, family members, friends, and employers.
• Family members of someone with bipolar disorder often have to cope with the person’s serious behavioral problems, such as wild spending sprees during mania or extreme withdrawal from others during depression, and the lasting consequences of these behaviors.

What About Clinical Studies for Bipolar Disorder?

Some people with bipolar disorder receive medication and/or psychosocial therapy by volunteering to participate in clinical studies (clinical trials). Clinical studies involve the scientific investigation of illness and treatment of illness in humans. Clinical studies in mental health can yield information about the efficacy of a medication or a combination of treatments, the usefulness of a behavioral intervention or type of psychotherapy, the reliability of a diagnostic procedure, or the success of a prevention method. Clinical studies also guide scientists in learning how illness develops, progresses, lessens, and affects both mind and body. Millions of Americans diagnosed with mental illness lead healthy, productive lives because of information discovered through clinical studies. These studies are not always right for everyone, however. It is important for each individual to consider carefully the possible risks and benefits of a clinical study before making a decision to participate.

In recent years, NIMH has introduced a new generation of “real-world” clinical studies. They are called “real-world” studies for several reasons. Unlike traditional clinical trials, they offer multiple different treatments and treatment combinations. In addition, they aim to include large numbers of people with mental disorders living in communities throughout the U.S. and receiving treatment across a wide variety of settings. Individuals with more than one mental disorder, as well as those with co-occurring physical illnesses, are encouraged to consider participating in these new studies. The main goal of the real-world studies is to improve treatment strategies and outcomes for all people with these disorders. In addition to measuring improvement in illness symptoms, the studies will evaluate how treatments influence other important, real-world issues such as quality of life, ability to work, and social functioning. They also will assess the cost-effectiveness of different treatments and factors that affect how well people stay on their treatment plans.

References

1Narrow WE. One-year prevalence of depressive disorders among adults 18 and over in the U.S.: NIMH ECA prospective data. Population estimates based on U.S. Census estimated residential population age 18 and over on July 1, 1998. Unpublished.

2Regier DA, Narrow WE, Rae DS, et al. The de facto mental and addictive disorders service system. Epidemiologic Catchment Area prospective 1-year prevalence rates of disorders and services. Archives of General Psychiatry, 1993; 50(2): 85-94.

3American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders, fourth edition (DSM-IV). Washington, DC: American Psychiatric Press, 1994.

4Hyman SE, Rudorfer MV. Depressive and bipolar mood disorders. In: Dale DC, Federman DD, eds. Scientific American®; Medicine. Vol. 3. New York: Healtheon/WebMD Corp., 2000; Sect. 13, Subsect. II, p. 1.

5Goodwin FK, Jamison KR. Manic-depressive illness. New York: Oxford University Press, 1990.

6Geller B, Luby J. Child and adolescent bipolar disorder: a review of the past 10 years. Journal of the American Academy of Child and Adolescent Psychiatry, 1997; 36(9): 1168-76.

7NIMH Genetics Workgroup. Genetics and mental disorders. NIH Publication No. 98-4268. Rockville, MD: National Institute of Mental Health, 1998.

8Hyman SE. Introduction to the complex genetics of mental disorders. Biological Psychiatry, 1999; 45(5): 518-21.

9Soares JC, Mann JJ. The anatomy of mood disorders—review of structural neuroimaging studies. Biological Psychiatry, 1997; 41(1): 86-106.

10Soares JC, Mann JJ. The functional neuroanatomy of mood disorders. Journal of Psychiatric Research, 1997; 31(4): 393-432.

11Sachs GS, Printz DJ, Kahn DA, Carpenter D, Docherty JP. The expert consensus guideline series: medication treatment of bipolar disorder 2000. Postgraduate Medicine, 2000; Spec No:1-104.

12Sachs GS, Thase ME. Bipolar disorder therapeutics: maintenance treatment. Biological Psychiatry, 2000; 48(6): 573-81.

13Huxley NA, Parikh SV, Baldessarini RJ. Effectiveness of psychosocial treatments in bipolar disorder: state of the evidence. Harvard Review of Psychiatry, 2000; 8(3): 126-40.

14Vainionpaa LK, Rattya J, Knip M, Tapanainen JS, Pakarinen AJ, Lanning P, Tekay A, Myllyla VV, Isojarvi JI. Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy. Annals of Neurology, 1999; 45(4): 444-50.

15Llewellyn A, Stowe ZN, Strader JR Jr. The use of lithium and management of women with bipolar disorder during pregnancy and lactation. Journal of Clinical Psychiatry, 1998; 59(Suppl 6): 57-64; discussion 65.

16Thase ME, Sachs GS. Bipolar depression: pharmacotherapy and related therapeutic strategies. Biological Psychiatry, 2000; 48(6): 558-72.

17Suppes T, Webb A, Paul B, Carmody T, Kraemer H, Rush AJ. Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania. American Journal of Psychiatry, 1999; 156(8): 1164-9.

18Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KN, Daniel DG, Petty F, Centorrino F, Wang R, Grundy SL, Greaney MG, Jacobs TG, David SR, Toma V. Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group. American Journal of Psychiatry, 1999; 156(5): 702-9.

19Rothschild AJ, Bates KS, Boehringer KL, Syed A. Olanzapine response in psychotic depression. Journal of Clinical Psychiatry, 1999; 60(2): 116-8.

20U.S. Department of Health and Human Services. Mental health: a report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Center for Mental Health Services, National Institutes of Health, National Institute of Mental Health, 1999.

21Henney JE. Risk of drug interactions with St. John’s wort. From the Food and Drug Administration. Journal of the American Medical Association, 2000; 283(13): 1679.

22Nierenberg AA, Burt T, Matthews J, Weiss AP. Mania associated with St. John’s wort. Biological Psychiatry, 1999; 46(12): 1707-8.

23Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, Marangell LB. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Archives of General Psychiatry, 1999; 56(5): 407-12.

24Strakowski SM, DelBello MP. The co-occurrence of bipolar and substance use disorders. Clinical Psychology Review, 2000; 20(2): 191-206.

25Mueser KT, Goodman LB, Trumbetta SL, Rosenberg SD, Osher FC, Vidaver R, Auciello P, Foy DW. Trauma and posttraumatic stress disorder in severe mental illness. Journal of Consulting and Clinical Psychology, 1998; 66(3): 493-9.

26Strakowski SM, Sax KW, McElroy SL, Keck PE Jr, Hawkins JM, West SA. Course of psychiatric and substance abuse syndromes co-occurring with bipolar disorder after a first psychiatric hospitalization. Journal of Clinical Psychiatry, 1998; 59(9): 465-71.

This publication, written by Melissa Spearing of NIMH, is a revision and update of an earlier version by Mary Lynn Hendrix. Scientific information and review were provided by NIMH Director Steven E. Hyman, M.D., and NIMH staff members Matthew V. Rudorfer, M.D., and Jane L. Pearson, Ph.D. Editorial assistance was provided by Clarissa K. Wittenberg, Margaret Strock, and Lisa D. Alberts of NIMH.

ll material in this publication is in the public domain and may be copied or reproduced without permission of the Institute.

The downside is only now emerging. Although studies show that it is effective for mild to moderate depression and two million British people are taking it, you do have to be careful.

The chief drawback is that the remedy, derived from the yellow flowering hedgerow plant, interacts with other drugs causing them to metabolise through the body too quickly. This is obviously very significant for people on the contraceptive pill or the blood-thinning drug warfarin, who are at risk of a stroke.

Herbal remedies for depression. Warnings issued

The Medicines Control Agency issued a warning on March 1st 2000 that patients who are on a long list of drugs should stop taking St John’s wort until they have consulted their GP or pharmacist. Medications for asthma, epilepsy, depression, migraine and heart problems are all implicated.

The authorities in the Irish Republic have gone further by banning the over-the-counter sale of the ancient herbal remedy since January 1st 2000. It is now available only on prescription.

In the United States, the Food and Drugs Administration (FDA) issued a warning in February 2000 that the herb could interfere with drugs used to treat HIV-infected patients. It also raised the possibility of complications for other patients taking similar medication, including those undergoing heart transplants. The FDA cited research showing that for patients taking St John’s wort, the effectiveness of the antiviral drug Indinavir was ‘dulled’.

There have also been some reports from America that St John’s wort can cause nerve damage or cataracts when combined with bright sunlight. This is believable because herbalists have always known that when St John’s wort is used externally, you have to keep out of the sun. Combined with oil, it is used on the skin for paralysis or to treat pain from nerves or shingles.

Researchers have found that hypericin, the active ingredient in St John’s wort, does react with sunlight. This is particularly significant for people who suffer from the ‘winter blues’ or seasonal affective disorder, who might be tempted to combine a course of St John’s wort with light-box therapy – sitting for long periods bathed in bright light.

Herbal remedies for depression

A better alternative to St Johns Wort as an herbal remedy for depression would be high grade EPA fish oil.

EPA fish oil has been scientifically proven to be very effective for depression, bipolar – manic depression and related disorders, and unlike St Johns Wort the side effects are all positive, thick long healthy hair growth, good nails and fantastic skin. High grade omega 3 EPA fish oil taken in the correct dose and strength give count less benefits.

If you are going to use High Grade Omega 3 fish oil EPA as a natural remedy for depression it is imperative that you take the strongest concentrate of EPA fish oil (90%) and in the correct dose daily to give your self the best chance for the EPA to work and give the maximum therapeutic effect.

It has recently been reported that the Epa works best without the DHA , this notion came about from studies that have been performed on people suffering from depression, researchers found that the higher the EPA to DHA ratio the better the results have been.

Welcome to the 21st-century lab, where hormones, brain pacemakers and magnetic coils can be a depression treatment

We’ve come a long way. Some psychiatrists used to think you could cure depression by removing a patient’s colon or teeth. In the late 1800s, there was a doctor who observed his anxious patient become calm on a bumpy train; thereafter treatment consisted of shaking the poor man for greater and greater lengths of time.

In an attempt to cure the ancient malady of melancholia, we have resorted to scads of strategies, some of them plainly stupid or cruel, others, like Prozac, that work. But an estimated 30 percent of depressed patients are what’s called treatment resistant; they don’t respond to pills or talkor even shock. The good news is that there are new treatments making their way into the 21st-century world—treatments that offer hope for the newly diagnosed or for someone who has been suffering without, so far, a cure in sight.

Miracle Meds – depression treatment

It used to be that psychiatrists would try a patient on one antidepressant medication, wait eight weeks and, if it didn’t work, switch to another one. While this is still a viable (if frustratingly slow) tactic, psychiatrists are relying more and more on secondary, and even tertiary, drugs to boost the primary player. One of those booster drugs is Cytomel, a thyroid stimulator. Even women with normal thyroid levels can, under a psychiatrist’s supervision, take Cytomel in addition to an antidepressant. About 50 percent of the time, it helps the primary drug work more effectively. Other popular booster medications are lithium and Ritalin.

Hormone Therapy – depression treatment

Scientists have spent years and years investigating chemicals like serotonin and their effects on mood, while neglecting to study brain chemicals still more common, and abundant, like estrogen and progesterone. Andrew Herzog, M.D., a neuroendocrinologist at the Beth Israel Deaconess Medical Center in Boston, treats many women who don’t respond to Prozac and its chemical cousins with sex steroids. “The future of psychiatry lies largely in the realm of using hormones to regulate brain states,” Herzog says.

He believes many women become depressed either because they have a measurable imbalance of estrogen and progesterone or because their brains are too sensitively tuned to normal fluctuations. “Hormones are psychoactive,” Herzog says, “and there’s no doubt that they can have huge effects on our feelings.” Progesterone, claims Herzog, is seven times stronger than your average barbiturate, and it exerts a strong calming, even sleepy, effect. Estrogen, the opposite, provides pep just as well, if not better, than that Prozac pill you’re taking. For women with agitated depressions that make them nervous and jumpy, Herzog might prescribe progesterone to calm with a bit of estrogen to brighten, in the form of a cream the woman rubs into her skin. For lethargic depressions, Herzog emphasizes the estrogen instead, and he’s had remarkable success treating women who were deemed “untreatable.” “These hormones gave me my life back,” says one of his patients, who became depressed in her 40s and was incapacitated by her 50s.

Hormone treatment for depression requires that you see a knowledgeable neuroendocrinologist and that you undergo a hormone profile, having your levels of progesterone and estrogen measured at the beginning and end of the month. The procedure is new but so far highly promising.

“Get Happy” Pacemakers- depression treatment

The vagal nerve connects your brain stem with your upper body, specifically your lungs, heart and stomach. The nerve is a critical conduit for relaying information to and from your central nervous system, carrying electrochemical signals up its tubing and depositing them directly into your cortex.

Some years ago researchers began implanting a small pacemaker into the vagal nerves of epileptics to see if tiny pulses might help stop the seizures. The pacemakers did indeed reduce or eliminate seizures in some epileptics, but they did something else, as well, something surprising and critical. Epileptics with vagal-nerve pacemakers got happy. Their moods improved. That’s when researchers decided to try using them in people with treatment-resistant depression.

No one quite knows how or why they work. Some doctors hypothesize that vagal-nerve stimulation (VNS) instigates changes in norepinephrine and serotonin, two neurotransmitters closely associated with mood. John Rush, M.D., at the University of Texas Southwestern Medical Center at Dallas, and colleagues did a study of 30 people with treatment-resistant depression. They implanted the pacemakers into those people and, over a two-week period, gradually increased the amount of stimulation current to levels the patients could tolerate comfortably.

Forty percent of these patients showed a substantial decrease in depression as measured by a verbal test asking them about their thoughts and feelings; 17 percent had a complete remission.

After one year of VNS, more than 90 percent of the patients who benefited from the initial treatment continued to show a decrease in depression.

Magnetic Healing

Transcranial magnetic stimulation (TMS) may someday replace electroconvulsive therapy (ECT) altogether. In TMS, an electrical current passes through a handheld wire coil that a doctor then moves over your scalp. The electrical current makes a powerful magnetic pulse, which passes straight through your scalp and stimulates nerve cells in the brain.

TMS is in part remarkable because of its specificity. Researchers now believe they can target brain structures that they know are involved in the creation and maintenance of depression and anxiety.

Many studies indicate that magnetic brain stimulation once daily for two or more weeks may relieve depression (a typical patient’s symptoms are reduced by almost 30 percent). Although TMS is still considered an experimental form of treatment, various hospitals and clinics offer it. Within five to ten years, TMS may become a common form of treatment for people with depression.

And this is just the beginning. Twenty years ago we had only the crudest psychiatric drugs; in the space of two short decades, we’ve developed an arsenal, and more important than that, we’ve shown we’re capable of ever more complex and innovative treatment strategies. The next few decades will bring as-yet-unheard-of kinds of cures, for us, for our children and so on down the line.

What is depression?

Most people, children as well as adults, feel low or `blue’ occasionally. Feeling sad is a normal reaction to experiences that are stressful or

upsetting.

When these feelings go on and on, or dominate and interfere with your whole life, it can become an illness. This illness is called `depression’. Depression probably affects one in every 200 children under 12 years old and two to three in every 100 teenagers.

What are the signs of depression in children

• Being moody and irritable – easily upset, `ratty’ or tearful

• Becoming withdrawn – avoiding friends, family and regular activities

• Feeling guilty or bad, being self-critical and self-blaming – hating yourself

• Feeling unhappy, miserable and lonely a lot of the time

• Feeling hopeless and wanting to die

• Finding it difficult to concentrate

• Not looking after your personal appearance

• Changes in sleep pattern: sleeping too little or too much

• Tiredness and lack of energy

• Changes in appetite

• Frequent minor health problems, such as headaches or stomach-aches

• Some people believe they are ugly, guilty and have done terrible things.

If you have all or most of these signs and have had them over a long period of time, it may mean

that you are depressed. You may find it very

difficult to talk about how you are feeling.

What causes depression in children

Depression in children is usually caused by a mixture of things, rather than any one thing alone.

Events or personal experiences

can be a trigger. These include family breakdown, the death or loss of a loved one, neglect, abuse, bullying and physical illness. Depression can also be triggered if too many changes happen in your life too quickly.

Risk factors

People are more at risk of becoming depressed if they are under a lot of stress, have no one to share their worries with, and lack practical support.

Biological factors

Depression may run in families due to genetic factors. It is also more common in girls and women compared to boys.

Depression seems to be linked with chemical changes in the part of brain that controls mood. These changes prevent normal functioning of the brain and cause many of the symptoms of

depression.

Where can I get help?

There are a lot of things that can be done to help people who suffer from depression.

Helping yourself

Simply talking to someone you trust, and who you feel understands, can lighten the burden. It can also make it easier to work out practical solutions to problems. For example, if you are stressed out by exams, you should talk to your teacher or school counsellor.

If you are worried about being pregnant, you should go and see your general practitioner or family planning clinic. Here are some things to remember:

• talk to someone who can help

• keep as active and occupied as possible, but don’t overstress yourself

• you are not alone – depression is a common problem and can be overcome.

How parents and teachers can help

It can be very hard for young people to put their feelings into words. You can help by asking sympathetically how they are feeling, and listening to them.

When specialist help is needed

If the depression is dragging on and causing serious difficulties, it’s important to seek treatment. Your general practitioner will be able to advise you about what help is available and to arrange a referral to the local child and adolescent mental health service.

Many young people will get better on their own with support and understanding. For those whose symptoms are severe and persistent, the most effective forms of treatment include cognitive behavioural therapy (CBT) and sometimes antidepressant medication. CBT is a type of talking treatment that helps someone understand their thoughts, feelings and behaviour (see Royal College of Psychiatrists Factsheet on CBT).

Antidepressant medication may help and usually has to be taken for several months. They are not addictive, but there may be some withdrawal symptoms for a short time when you stop taking them. All medicines have side-effects, but if you are concerned about these, you should talk to your general practitioner or psychiatrist (see Royal College of Psychiatrists’ Factsheet on antidepressants; www.rcpsych.ac.uk).

References

• Carr, A. (ed.) (2000) ‘What Works with Children and Adolescents?’ – A Critical Review of Psychological Interventions with Children, Adolescents and their Families. London: Brunner-Routledge.

• Rutter, M. & Taylor, E. (eds) (2002) ‘Child and Adolescent Psychiatry’ (4th edn). London: Blackwell.

• Scott, A., Shaw, M. & Joughin, C. (eds) (2001) ‘Finding the Evidence’ – A Gateway to the Literature in Child and Adolescent Mental Health (2nd edn). London: Gaskell

Depression is one of the most widespread illnesses in the Western world, yet it is also one of the most misunderstood and under treated health problems. Approximately 10-14 million people are medically depressed in the U.S. in any given year, yet only one third of depressives receive treatment (1). “Depression is just as socially debilitating as coronary artery disease, and more debilitating than diabetes mellitus or arthritis. Up to 15% of severely ill depressed patients will ultimately commit suicide” (1).

Untreated depression carries a huge list of costs: up to 30,000 suicides/year in the U.S., fatal accidents due to impaired concentration and attention; alcohol and drug abuse; lost jobs and productivity; job related injuries; and dysfunctional families, to name just a few (1).

Psychiatrists normally define major depression as including 5 or more of the following 9 symptoms, lasting two weeks or more (1):

1. Depressed mood 2. Diminished interest or pleasure in normal daily activities 3. Significant weight loss without dieting, or rapid weight gain; loss or excess of appetite 4. Insomnia or hypersomnia 5. Psychomotor retardation or agitation 6. Fatigue, loss of energy 7. Feelings of worthlessness or inappropriate guilt 8. Diminished ability to think or concentrate, indecisiveness 9. Recurrent thoughts of death, recurrent suicidal ideation, specific suicide plan or attempt

Public misunderstanding of depression is widespread. “A recent survey of the general population revealed that 71% thought that mental illnesses were due to emotional weakness; 65% thought it was caused by bad parenting; 45% thought it was the victim’s fault and they could will it away; 43% thought mental illness was incurable; 33% thought it was the consequence of sinful behavior; and only 10% thought it had a biological basis or involved the brain.” (1) During the past 50 years neuroscience, psychiatry and pharmacology have demonstrated unequivocally that compromised brain function plays a key role in depression, and that proper therapeutic manipulation of brain chemistry can frequently alleviate or “cure” depression, without resorting to years of psychoanalysis. Researcher Paul Willner, in his massive work Depression: A Psychobiological Synthesis, summarizes the chief neurochemical difficulties in depression: “The major changes in neurotransmission associated with severe depression are (1) a reduced level of DA [dopamine] function, related to psychomotor retardation, and reflecting a reduced level of incentive motivation; (2) a retarded level of 5-HT [serotonin] function, related to psychomotor agitation, and reflecting an inability to relax; (3) a reduced level of NA [noradrenalin] function, … reflecting inability to maintain effort; and (4) cholinergic [acetylcholine] hyperactivity, … reflecting a high level of stress. Antidepressants reverse these changes, primarily by actions on NA and 5-HT neurons.” (2)

5-HT, DA, and NA are each made from a single amino acid – 5-HT from tryptophan, and DA/NA from either phenylalanine or tyrosine. Hence they are called “monoamine” (MA) neurotransmitters. Since the 1950′s various types of drugs have been used by doctors and psychiatrists to enhance brain MA neurotransmitter function. The first medical antidepressant (since retired due to toxic side effects) was iproniazid, a monoamine oxidase inhibitor (MAOI). MAO enzymes are present inside neurons, as well as other cells including the liver, where they serve to break down MA neurotransmitters. Some MAs are broken down by MAOs as soon as they’re formed, even before they can be released into the synaptic gap to “fire” the next neuron. MAs which are discharged into the synaptic gap are sooner or later re-taken up by the neuron that secreted them. They are then either repackaged for re-use, or destroyed by MAO enzymes. MAOI drugs thus act to increase the synaptic availability of MAs by preventing their breakdown by MAO enzymes. This may increase the intraneuronal levels of 5-HT and other MAs by 300% (3). However, MAOIs can also increase the neuronal and blood levels of another substance called “tyramine”, found in many common foods, and induce severe, even fatal, high blood pressure reactions unless a rigid low-tyramine diet is followed, as well other side effects, such as postural hypotension, sexual dysfunction, heart problems and insomnia (4). The next generation of drugs believed to enhance brain 5-HT and NA became available in the 1960s: the tricyclic antidepressants (TCA), such as imipramine and amitryptilene. TCAs seem to attach to and inhibit the neuronal re-uptake sites for 5-HT and NA, preventing the return of the MAs to the neuron which secreted them. This enhances MA action in two ways. Since most MAs returned to their source neuron are broken down by MAO enzymes, TCAs slow MA breakdown. TCAs also cause more 5-HT and NA to remain in the synaptic gap, thereby increasing 5-HT/NA neuro-transmission. However, TCAs also affect other receptors on neurons which respond to acetylcholine, histamine, and DA. TCAs thus suffer from a wide range of unpleasant side effects, ranging from drowsiness, confusion and blurred vision to hypotension and movement disorders (5). TCAs are now considered “antiquated” by, most psychiatrists, yet many general practice physicians still favor them.

The 1980s spawned the current favorites among antidepressant drugs: the serotonin-specific reuptake inhibitors (SSRIs). The first and most famous of these is fluoxetine (Prozac®). Other SSRIs such as paroxetine (Paxil®), sertaline (Zoloft®) and fluroxamine (Luvox®) are also now in vogue in America and Europe. These drugs are used to treat eating disorders and obsessive-compulsive disorders as well as depression. They have put 5-HT (serotonin) “on the map” with the general public as “the mood molecule.” 5-HT drugs were the cover story for Time magazine on September 29, 1997. The Time article noted: “So far, the [drug] tools used to manipulate serotonin in the brain are more like machetes than scalpels-crudely effective but capable of doing plenty of collateral damage.” Robert Julien, in his text A Primer of Drug Action, notes that side effects of Prozac® may include nervousness, anxiety, sexual dysfunction, insomnia, nausea, loss of appetite, motor restlessness and muscle rigidity (5). Psychiatrist Peter Breggin, in Talking Back To Prozac, also provides evidence that Prozac® may actually damage serotonergic nerves and create an addictive-necessity for long-term Prozac® use, as well as incline some users to sudden suicide with no prior warning (6).

Thus, given their side effect profiles, their xenobiotic nature (they’re molecules foreign to normal brain metabolism), and their need for rigid special diets and/or careful medical monitoring to insure safe usage, the MAOIs, TCAs and SSRIs cannot reasonably be considered the ideal remedies for depression. Fortunately, neuroscience over the past 40 years has also uncovered some simpler and more natural remedies for depression, as well as several “life-extension” drugs with far more safe and gentle antidepressant effect.

TRYPTOPHAN AND 5HTP – NATURE’S ANSWER TO PROZAC®

Studies with humans and animals over the past 35 years have shown that 5-HT (serotonin) nerve circuits promote feelings of well-being, calm, personal security, relaxation, confidence and concentration (7). 5-HT neural circuits also help counterbalance the tendency of overactive (e.g. due to genetics, stress or drugs) DA and NA circuits to encourage over arousal, fear, anger, tension, aggression and violence, obsessive compulsive actions, anxiety and sleep disturbance (7). A deficiency of 5-HT nerve action has been shown to manifest as a broad array of emotional and behavioral problems, ranging from depression, premenstrual syndrome, anxiety, alcoholism and overeating to compulsive gambling, fire-starting, thrill-seeking through violence and suicide.

There is rarely a problem with the structure or “wiring” of the brain’s 5-HT circuits. Rather the problem is caused by a chronic deficit of 5-HT in the nerves which use it as their neurotransmitter. It is no coincidence that the most popular psychiatric drugs in history are the SSRIs, and the common thread connecting MAOIs, TCAs, and SSRIs is their 5-HT neural effects. 5-HT is the “Achilles heel” of the human brain. Yet no neuron suffered a literal deficiency of these xenobiotic drug molecules. 5-HT neurons can, and frequently do, however, suffer a deficit of the raw material from which neurons normally produce 5-HT: the essential amino acid tryptophan (Tryp).

In any normal diet, animal or vegetarian protein based, Tryp is the least plentiful of the 22 dietary amino acids. A typical diet provides only 0.75 to 1.5 grams Tryp/day, yet there is much competition in the body for this scarce amino. It is used to make various proteins, and in people with low to moderate intakes of vitamin B3 (niacin/niacinamide), Tryp may be used by the liver to make the coenzyme form of B3-NAD- at the expensive ratio of 60mg Tryp to one mg niacin (8). In people who are even marginally vitamin B6 deficient, Tryp may be immediately degraded by the liver into the mildly toxic metabolites hydroxykynurenine, xanthurenic acid, and hydroxyanthranilic acid, then excreted in urine (9). Thus, the brain typically receives less than 1% of ingested Tryp.

Yet even getting its modest share of dietary Tryp is difficult for the brain, due to the blood-brain barrier (BBB). The BBB serves as a protection to prevent many toxins, as well as excesses of nutrients which might temporarily overwhelm and dysregulate brain function, from entering the brain. 5-HT itself cannot penetrate the BBB, although Tryp can. Yet the BBB creates difficulties even for essential nutrients to enter the brain. Amino acids must be carried through the BBB by a special transport protein, like passengers on a bus. Unfortunately for 5-HT using neurons, Tryp must share its “transport bus” with 5 other amino acids: phenylalanine, tyrosine, valine, leucine and isoleucine. Tryp is typically outnumbered about 9:1 in its competition to secure its transport through the BBB into the brain.

Eating a high protein diet to provide more Tryp only worsens the problem, by increasing even more the intake of the 5 competing aminos. Ironically the only dietary strategy which increases brain Tryp is to eat a high carbohydrate/low protein diet. When large amounts of carbos are eaten, the body secretes large amounts of the hormone insulin to lower the ensuing high blood sugar. Insulin also clears from the blood much of the 5 aminos that compete with tryp for entry through the BBB. Insulin has relatively little effect on clearing Tryp from the blood, however, thus allowing Tryp more space on the BBB “transport bus,” and thus more Tryp reaches the brain. R. and J. Wurtman reported in 1988 and 1989 that women suffering from PMS-related depression were found to spontaneously increase their carbo food and snack intake, without increasing protein, during their depressive phase, with a consequent significant decrease in measured depression ratings, presumably through the insulin-Tryp-5-HT mechanism (10,11). Unfortunately, insulin also promotes conversion of the incoming food to stored body fat. Hence the high carbohydrate diet method of enhancing brain Tryp/5-HT merely trades depression for obesity and chronic carbo addiction/over consumption.

35 years of research has provided a pair of alternatives to enhance brain 5-HT levels with consequent lessening of 5-HT related depression. Many studies have shown both Tryp and its metabolite, 5-hydroxytryptophan (5-HTP), to be capable of enhancing brain serotonin and relieving depression when taken as supplements (12-21).

TRYPTOPHAN SUPPLEMENTS

Taking Tryp as a dietary supplement is the most natural way to solve the brain’s 5-HT production problems. A Tryp supplement, unlike a high protein diet, will not increase blood levels of Tryp’s 5 amino competitors. Since the normal dietary intake of tryp is only a gram or so, even a modest amount of supplemental Tryp (1 to 3 grams) will have a significant effect in boosting blood and brain Tryp, and hence brain 5-HT levels. Under normal conditions, the brain enzyme Tryp hydroxylase (TpH) is only 50% saturated (22). TpH is the rate-limiting factor in 5-HT production, converting Tryp to 5HTP. This means that an increase in brain Tryp will automatically tend to increase brain 5HTP production. After TpH converts Tryp to 5HTP, a vitamin B6-dependent carboxylase enzyme then rapidly converts 5HTP to 5-HT.

However, increased brain production of 5-HT through Tryp supplementation does not automatically increase 5-HT nerve activity. At low levels of psychobiologic arousal, there will be adequate serotonin to support the correlative low 5-HT nerve activity, even when neuron levels of Tryp and 5-HT are low (22). This more apathetic, vegetative quiescent variety of depression (“I’m so depressed I can’t even get out of bed”) is referred to as the “apathetic-inhibited” type (22). This form of depression represents more of a deficiency of activity of the DA/NA “yang” “get-up-and-go”, activating neural circuits, and so Tryp/5-HT may offer little relief to, or even worsen, this type of depression.

At higher levels of arousal, however, the more rapid turnover of 5-HT in the synaptic gap will require higher levels of 5-HT production to adequately maintain the greater activity of 5-HT circuits. Thus Young and Teff suggest that Tryp will be most effective as an anti-depressant in those suffering from “anxious-agitated” depression, with its high state of stress arousal, combined with the depression (22). Anxious, agitated depression occurs when a person’s DA/NA activating (“yang”) neural circuits are functioning strongly, without the calming, relaxing, mellowing 5-HT circuits (“yin”) functioning strongly as a complementary counterbalance.

The biggest drawback to using Tryp to solve 5-HT deficiency depression is the activity of the liver Tryp degrading enzyme, Tryp pyrrolase (TP). TP is known to be activated by two factors (23). The first is the hormone cortisol. Cortisol, the “state of siege” stress hormone, is known to be frequently elevated in the very conditions, such as depression and insomnia, for which Tryp might be helpful. Taking Gerovital-H3®, low dose Dilantin, or 7-Keto-DHEA may provide an anti-cortisol activity to prevent cortisol activation of tryp-destroying TP.

The other TP-activating factor is- Tryp itself! Tryp is known to induce and stabilize TP, thus keeping it active in destroying Tryp as it passes through the liver. Thus Yuweiler and colleagues point out that successful Tryp antidepressant studies have generally used low doses (3 grams or less) compared with Tryp studies having negative results, which have often used high doses (6-9 grams) (23). The higher doses could ironically lessen the antidepressant effect of Tryp by hyper activating liver TP, which would then catabolize incoming Tryp with great efficiency, canceling out any hoped-for increase in blood/brain Tryp.

5HTP: TRYPTOPHAN PLUS!

European and Japanese depression research over the past 30 years has focused on 5HTP (Oxitriptan) as a natural solution to enhance brain 5-HT activity. 5HTP is the intermediate between Tryp and serotonin. Since the rate-limiting, or problematic, step in 5-HT production is the conversion of Tryp to 5HTP, using 5HTP as an antidepressant simply bypasses the production bottleneck. As Zmilacher and co-authors also note: “L-5-HTP is not degraded by the tryptophan pyrrolase to kynurenine, the major pathway for peripheral degradation of L-Tryptophan (about 98%). Furthermore, L-5-HTP easily crosses the blood-brain barrier….” (24). Byerley and his co-workers also point out another key advantage of 5HTP over Tryp: “…administration of 5-HTP enhances synthesis of serotonin in the brain, but may also effect noradrenergic [NA] and dopaminergic [DA] neurotransmission. In laboratory animals as well as human subjects, increased turnover of dopamine and norepinephrine [NA] occurs after 5-HTP administration.” (25)

In a 1984 paper, van Praag also noted the different effects of tryp and 5HTP on DA/NA neurotransmission. Van Praag found significant increases in the spinal fluid concentration of 5HIAA, the serotonin-metabolite, after giving both Tryp and 5HTP to different test subjects. Unlike Tryp, which only raised spinal fluid 5HIAA, 5HTP also raised spinal fluid metabolites of DA and NA, indicating an activating effect of 5HTP of DA/NA neurotransmission as well as 5-HT neurotransmission (26). In a 1983 report, van Praag also demonstrated that among patients who maintained their antidepressant effect from 5HTP over the long term, there was evidence from spinal fluid metabolites of continuing DA/NA activation as well as 5-HT activation. Among patients whose initial positive response to 5HTP dropped off after several months, van Praag found a drop in their initial high levels of DA/NA spinal fluid metabolites as the 5HTP antidepressant effects decreased. When van Praag then gave these patients supplements of tyrosine, the amino acid from which DA and NA are made, along with their 5HTP, their depression once again cleared, while their spinal fluid metabolites of DA/NA also again increased (27). Van Praag thus demonstrated that 5HTP is more than just a better Tryp-it is a “Tryp plus” due to its DA/NA neuroactivation.

In their 1988 review of 5HTP antidepressant studies, Zmilacher and co-writers report that “Out of the 17 reviewed studies… 60.5% of all the patients (342 out of 565) showed a good or very good improvement of their depressive state…. A tendency indicating that L-5-HTP was especially effective in patients with an anxious agitated depressive syndrome was observed…. An important finding is the very rapid onset of action (within 3-5 days) in patients responding to treatment.” (24).

The main drawback to 5HTP use is its gastrointestinal side effects. “…gastrointestinal symptoms, such as abdominal cramping, nausea, and diarrhoea, appear to be the most common adverse effect…. Adverse effects reported infrequently after oral doses include insomnia, headache and [heart] palpitations.” (25) Zmilacher suggests taking 5HTP with a meal to reduce GI side effects. Some researchers have suggested that enteric coated 5HTP, which doesn’t dissolve until it reaches the small intestine, will also reduce GI side effects. (Ed- IAS Oxitriptan is enteric coated). Some 5HTP researchers give drugs called “peripheral decarboxylase inhibitors” along with 5HTP, both to reduce GI side effects as well as allegedly to increase treatment efficacy, yet Zmilacher notes that “A review of the literature on this subject revealed that L-5-HTP with a peripheral decarboxylase inhibitor (93 out of 176 patients, 52.9%).” (24) “… psychopathological side effects [swings from depression to mania or hypomania] have mainly been reported in patients receiving L-5-HTP in combination with a peripheral decarboxylase inhibitor.” (24)

In 1991 Poeldinger and colleagues reported a landmark double-blind study that compared 5HTP with the popular SSRI, fluvoxamine (a Prozac® “cousin”). Not only did 5HTP prove to be slightly superior to fluvoxamine in antidepressant action, but 5HTP patients had significantly fewer and less serious side effects (mostly GI) than patients receiving fluvoxamine (28). Thus, not only is 5HTP an effective and more natural alternative to the SSRIs, but it is also less side-effect prone.

Tryp and 5HTP may be used separately or together to improve serotonin metabolism. Tryp may best be taken at bedtime, 1-3 grams. 5HTP may be taken with meals, 50-100 mg, once or twice daily. Initial GI symptoms from 5HTP, if they occur, will frequently disappear with continued use. If not, then using only Tryp may still provide adequate 5HT antidepressant effect.

Tryp and 5HTP will potentate the effects of MAOI, TCA and SSRI drugs, and they may possibly precipitate the “serotonin syndrome” if combined with these drugs. The fortunately rare 5-HT syndrome, as reported by H. Sternbach in 1991 (29), involves extreme hyperactivity of 5-HT neural circuits and may include confusion, hypomania. agitation, “feeling drunk,” as well as extreme restlessness, muscle twitches, hyperactive reflexes, intense sweating, shivering, tremor, diarrhoea, fever and in coordination. Occasionally coma or death may result. Thus, although Tryp or 5HTP may be useful to lessen the needed dosage fro those wishing to remain on standard antidepressant drugs, combining Tryp or 5HTP with antidepressant drugs, or altering current drug dosages, should be done ONLY under expert medical supervision to avoid inducing the serotonin syndrome. Also, one should never suddenly stop antidepressant drugs and replace them with Tryp or 5HTP. Any cessation of current antidepressant drug therapy should be done gradually, and only under expert medical supervision, to avoid possible depression relapse.

L-DEPRENYL

L-deprenyl (DPR) is a drug developed in the 1960s by Dr. Joseph Knoll. Research has shown DPR to be a safe and multi-faceted drug. At doses of 10-15mg/day or less for humans, DPR is a selective MAO-B inhibitor. MAO-A enzymes break down 5-HT and NA, while MAO-B enzymes break down DA and phenylethylamine (PEA). Classic MAOIs, such as phenelzine and tranylcypromine, inhibit both MAO-A and MAO-B. Classic MAOIs also routinely suffer from the “cheese effect” – the tendency to promote serious, even fatal high blood pressure crises from ingestion of tyramine-rich foods such as aged cheeses and wines. DPR is remarkably free from the “cheese effect” even at typically high daily doses of 30-60mg (4,30). DPR also suppresses the free radical/oxidant stress associated with increased DA neuron activity, as occurs in Parkinson’s disease (31). DPR protects DA neurons in monkeys from MPTP, a neurotoxin that has caused rapid-onset Parkinson’s disease in humans who unwittingly consumed it in recreational drugs (32). DPR has extended the average life span of male rats beyond the maximum age of death of the species. And DPR has been successfully used as an antidepressant.

In 1980 Mendelwicz and Youdin reported results from a double-blind study comparing placebo, 300mg 5HTP, and 5HTP plus DPR. The 18 patients receiving DPR plus 5HTP experienced depression relief significantly greater than those receiving placebo or 5HTP alone (34).

Quitkin and co-workers found DPR to be superior to placebo in a 6 week trial with 17 atypical depressive patients, and relatively free of side effects. 9/10 positive DPR responders required a 30mg/day DPR dosage. At doses above 20mg, DPR is no longer a selective MAO-B inhibitor, but also begins to suppress MAO-A activity as well, as do standard MAOIs. Nonetheless, Quitkin noted: “There were no reported hypertensive ["cheese effect"] episodes…. L-deprenyl’s relative freedom from other MAOI side effects may prove to be of major importance…. Several patients on a regimen of standard MAOIs tolerated a six-week regimen of L-deprenyl quite well.” (4)

J. Mann and colleagues reported positive antidepressant effect with DPR in a 44-patient double blind study in 1989. “…after six weeks and at higher doses (averaging about 30mg/d fro the second three weeks), [DPR] was superior to placebo in antidepressant effect with a positive response rate of 50% vs. 13.6% and with a 41% reduction in the Hamilton depression Rating Scale mean score vs. 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with [DPR] was no greater than with placebo…. [DPR] is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of the nonselective MAO inhibitors.” (33)

Based on a double blind, crossover study of placebo vs. 3 weeks of DPR at 60mg/day dosage, T. Sunderland and co-workers reported in 1994 that “Selegiline [DPR] appears to be an effective antidepressant in older patients with treatment-resistant depression…. No serious side effects were noted during our study…. there was… an overall reduction in anxiety, and a decrease in self-reported irritability.” (30)

All of the preceding studies were relatively short-term, typically 3 to 6 weeks. Although only minimal side effects were noted, even at the unusually high DPR doses of 30-60 mg/day, the researchers did express concern about possible side effects at these higher doses with more typical long-term (months to years) antidepressant usage. Two successful studies with treatment-resistant depressives have been done, however, that used very modest DPR doses of 5-10mg/day. At this low dose, DPR remains a purely MAO-B inhibitor and is normally fairly side-effect free, even with long-term use.

In 1984 W. Birkmayer and colleagues reported their results from an open study of 155 serious, treatment-resistant depressives. “…102 unipolar [out-] patients… had depression for 3 to 15 years (range); only patients with at least five depressed phases were studied. Usual antidepressant treatment was not successful before the start of a combined L-deprenyl – L-phenylalanine treatment. L-phenylalanine (250mg) and L-deprenyl (5-10mg) were given orally as a single morning dose for 28 to 96 days…. [53 inpatients] had severe unipolar depression for 3 to 15 years; again only patients with at least five episodes of depression were included…. Moreover, usual antidepressants were not effective in this group. L-phenylalanine (250mg) and L-deprenyl (10mg) were given intravenously as morning dose. The duration of this combined treatment was between 14 and 28 days…. After 10 daily infusion we reduced to twice weekly and continued later with oral treatment. In a few patients this [oral] treatment was continued up to 24 months… without any loss of antidepressant effect.” (35)

Sleeplessness, tension and anxiety were noted as adverse reactions – these are symptoms of DA/NA over-activation uncompensated for by counterbalancing serotonin activation – Tryp would have been appropriate to complement the DPR/phenylalanine treatment. Birkmayer reports surprisingly excellent results based on modified Hamilton depression rating scale and global clinical impressions: 68.5% full remission and 21.5% moderate effect in the outpatients, with 69.5% full remission and 11% mild and moderate effects in the outpatients.

In 1991 H.C. Sabelli described his results from a small study with 10 treatment-resistant major depressives. Treatment consisted of 5 mg DPR/day, 100 mg vitamin B6/day, and 1 gram phenylalamine a.m. and p.m., with gradual increase to 6 gm/day if needed. “Nine out of 10 patients experienced mood elevation within hours of phenylalamine administration, and 6 viewed their episodes of depression as terminated within 2 to 3 days. Global Assessment Scale scores were significantly lowered after 3 days… and the improved scores were still observed 6 weeks later.” (36)

Both the Birkmayer group and Sabelli relate the combined DPR/phenylalamine treatment to enhancement of phenylethylamine (PEA) metabolism. PEA and DA are the main substrates for MÅO-B, which DPR inhibits. PEA is formed from phenylamine with the help of a B6-activated enzyme. PEA is a trace amine that may potentate neuronal firing rates of NA/DA neurons, especially when they’re underactive (37). Sabelli has shown that depressives have significantly lower blood and urine levels of PAA (the chief PEA breakdown product) than non-depressed controls. He also notes that effective antidepressant treatment usually increases urinary PAA excretion, while antidepressant treatment that fails to successfully ameliorate depression also fails to increase urinary PAA excretion. Low values of PAA excretion were observed in both retarded and agitated depressives (38). In addition to being converted to PEA, phenylalamine can also be converted into the two “yang” neurotransmitters, NA and DA (39). Thus, a low dose DPR (5-10 mg), moderate dose l-phenylalamine (250 – 500 mg once or twice daily) and 50 -100 mg dose of vitamin B6 regimen may serve to enhance mood, drive, and energy in the “apathetic-inhibited” type of depression, while Tryp may serve to inhibit potential “overactivation” side effects of insomnia, anxiety and irritability.

NADH

J.G. and W. Birkmayer are pioneers in the use of NADH. NADH is the active, reduced (electron-rich) coenzyme from of vitamin B3 – nicotinamide. NAD/NADH is the most plentiful coenzyme in the human brain. NADH is the key in converting food into ATP bioenergy. During normal oxidative metabolism, NADH is formed in both the glycolytic and citric acid (Krebs’) cycles, and transferred to the electron transport chain, where each NADH can generate 3 ATPs. NADH is the “lynch-pin” of oxidative energy metabolism (40).

NADH is also the indirect activator of tyrosine hydroxylase (TH), the rate-limiting enzyme in the formation of DA and NA. TH converts the amino acid tyrosine into L-dopa. It can also convert phenylalamine into tyrosine. DA neurons convert L-dopa into DA, while NA neurons convert L-dopa first to DA, then into NA.

The coenzyme that activates TH is tetrahydrobiopterin (H4BP), which is produced from the B vitamin folic acid through an enzyme called H2 pteridine reductase (DHPR). NADH activates DHPR, and thus is able to indirectly activate TH an dDA/NA metabolism. In a study of more than 400 Parkinson’s patients, the Birkmayers demonstrated that NADH improved the symptoms of Parkinson’s patients. “Biochemical analysis showed that the improvement of clinical symptoms was paralleled by an increase of the dopamine metabolites HVA and VMA in the urine which provides indirect evidence that NADH is increasing the endogenous dopamine production. Direct support for our hypothesis have been gained from tissue culture-experiments. NADH added to the culture medium increased the production of dopamine in phaeochromocytoma cells up to 6 times. Furthermore, tyrosinehydroxylase activity was stimulated by NADH to 175%.” (41)

The Birkmayers and others had noticed that many Parkinson’s patients suffer from depression, and the Birkmayers also observed their depressive symptoms disappear when successfully treating Parkinson’s patients with NADH. They therefore decided to use NADH in an open label (non-double blind) trial with 205 patients suffering depression with various symptoms. NADH was given orally, intramuscularly or intravenously, with doses of 5 to 12.5 mg. Duration of therapy ranged from 5 to 310 days. 93% of the patients exhibited some degree of a beneficial clinical effect (41). Gabriel Cousens, M.D. has also successfully used NADH to treat depression in his practice, based on Birkmayers’ work. He states that “About 85% of my clients with depression seem to benefit from taking NADH…. they may feel results from it within three weeks, sometimes sooner. I’m very pleased with its antidepressant effect.” (41A) Because of its combined energy-enhancing role (the brain produces and uses 20% of the body’s ATP energy total) and its ability to stimulate DA/NA production, 5-10 mg NADH, taken once or twice daily on an empty stomach, may serve as a useful complement to the DPR/phenylalanine program or may be simply used as a single therapy.

GEROVITAL: GH3

Gerovital-H3® (GH3) (specially stabilized procaine) was developed in the 1940s by Ana Aslan in Romania. It is the original “anti-aging” drug. In addition to its various physical benefits, such as improved joint mobility and pain relief, it was known by the 1960s that GH3 possessed antidepressant effect. By the 1970s at least part of the basis of GH3′s antidepressant effect was known, GH3 was discovered to be a weak, reversible, fully competitive MAO inhibitor (42, 43). The more toxic and dangerous MAOIs, such as iproniazid and phenelzine, are strong, irreversible, non-competitive MAO inhibitors. It is this difference which makes them prone to the “cheese effect,” i.e. potentially fatal hypertensive crises in patients who eat a tyramine-rich diet while taking them. GH3 researchers M.D. MacFarlane and H. Besbris noted that in contrast, “…the use of GH3 for the treatment of depression and for other manifestations of aging has not been associated with any significant adverse reactions and there are no restrictions regarding the type of food the GH3 patient can enjoy.” (42) And contrary to the claims of critics that there is no difference between GH3 and ordinary procaine, MacFarlane noted that “when the ability of GH3 to inhibit MAO was compared with that of procaine hydrochloride (Novocain), it was found that GH3 produced a significantly greater inhibition of MAO than did procaine.” (43) Zung and colleagues also remarked on the difference between GH3 and procaine: “Procaine when injected in the human body is rapidly hydrolysed by cholinesterase into para-aminobenzoic acid (PABA) and diethylaminoethanol (DEAE). In the case of procaine in the GH3 formula, metabolic studies… show that the intact molecules of procaine can be found in blood or urine after six hours of administration of the drug.” (44) Being a safe and effective (albeit mild) MAOI, GH3 can be expected to help raise DA, NA, and 5 HT through inhibition of their neuronal MAO destruction, with consequent antidepressant effect.

Several studies in the 1970s found an antidepressant effect from GH3. Cohen and Ditman reported in 1974 that “Eighty five percent of 41 subjects reported some improvement from a series of 12 GH3 intramuscular injections…. Their response was prompt and dramatic, but mainly subjective. Most felt a greater sense of well-being and relaxation, slept better at night, and mainly obtained some relief from depression and the discomforts of chronic inflammatory or degenerative disease.” (45)

W. Zung and co-workers reported a successful double-blind, placebo trial comparing GH3 with the TCA imipramine in 1974. They concluded that “… the results of this study showed that using the clinical global impression and the Zung self depression scale, the change scores obtained from calculating pre-treatment to post-treatment differences showed GH3 to be superior to imipramine, since the GH3-placebo differences were significantly different, while the imipramine-placebo differences were not.” (44) The table listing side effects in the Zung study also shows that GH3 produced fewer side effects than both imipramine and placebo!

In 1984 paper pharmaceutical researcher Alfred Sapse expounded the disease-promoting power of chronic, excessive, stress-released cortisol. He gave a short list of substances that could oppose cortisol’s negative actions. GH3 was one of five anti-cortisol agents Sapse recommended (46). And as Murphy and Wolkowitz point out, “Major depression is associated with a high incidence of cortisol hypersecretion…. this hypercorisolism is the most well-replicated biological abnormality in major depression….” (47) Thus, GH3′s anti-cortisol action may also enhance its antidepressant effect. Because of cortisol’s power to induce liver Tryp pyrrolase, the Tryp-destroying enzyme, GH3′s ability to reduce cortisol may also provide antidepressant effect through enhancing brain Tryp, and hence, brain 5-HT status. Thus, one tablet of GH3, taken once or twice daily (AM/PM) on an empty stomach may be a safe yet effective antidepressant, alone or in a combination with others in this article.

SAMe

S-adenosylmethionine (SAMe) has recently become known to the public as an antidote for one of the most important heart disease risk factors, homocysteine. A large number of studies have also shown SAMe to be an excellent and rapid-acting (often 3-7 days) antidepressant (48-53). As SAMe research pioneer G. Stramentinoli has stated, “[SAMe] is an important physiologic compound that occurs in every living cell…. SAMe is probably second only to ATP [the basic energy molecule of life] in the variety of reactions in which it serves as a cofactor.” (54) SAMe is the linchpin of all the body’s transmethylation reactions. “…methyltransferase reactions… shift the ‘active’ methyl group of SAMe to a wide variety of methyl ‘acceptor’ molecules, including … biogenic amines [neurotransmitters], fatty acids and phospholipids, proteins, nucleic acids, polysaccharides and porphyrins. In this role SAMe is the most important methyl group donor in mammalian tissue.” (48) SAMe’s methyl group makes possible the production of neuronutrient acetyl-l-carnitine, the stress hormone and neuro-transmitter adrenalin, and the neuronutrient and chief neuronal membrane fluidizer phosphatidye choline (55). SAMe has been shown to significantly increase cerebrospinal fluid levels of HVA and 5HIAA, the chief metabolites of DA and 5-HT. SAMe has been shown in antidepressant studies to possess mood-elevating and behaviorally arousing effects due to the SAMe-increased DA and 5-HT activity, and due to a selective excitatory action on cortical neurons in the brain (48).

In 1994 G.M. Bressa reported a meta-analysis of 31 prior studies of SAMe’s antidepressant effects. “The average [antidepressant] effect size of SAMe… derived from our meta-analysis of placebo-controlled trials is therefore slightly higher than that obtained by Greenberg et al … for both standard tricyclic antidepressants and relatively newer antidepressants…. Since SAMe is a naturally occurring compound with relatively few side effects, its antidepressant effect makes it a potentially important tool [for treatment of depression].” (53) In general, side effects in SAMe studies are few and mild. In some studies SAMe induced fewer or less serious side effects than placebo! For example, in a double blind study with 734 people comparing SAMe with the painkiller naproxen and placebo, 10 people withdrew from the study due to side effects from SAMe, compared with 13 from placebo and 17 from naproxen side effects (56). The most commonly reported side effects are gastrointestinal – primarily heartburn, nausea, and stomach ache (57). However, the GI effects seem to be mediated through the brain – they are not the result of direct GI tract irritation. SAMe actually inhibits and protects against GI lining damage and irritation. The other occasionally reported side effect of SAMe is mania or hypomania – i.e. excessive mood elevation and over stimulation. This side effect is reported far more rarely than the GI side effects. SAMe-induced mania may on occasion be serious enough to warrant lithium treatment to end the mania. Bipolar (manic) depressives should therefore use SAMe with caution.

SAMe has been given orally in doses ranging from 400 mg/day to 1600 mg/day. SAMe is usually given in two or three doses daily, with 10 AM and 3 PM being a common time for twice daily administration (57). Starting with low dose (200 – 300 mg) once or twice daily and working up to higher doses if necessary is the best strategy. Because SAMe tablets are (or should be) enteric-coated, they should not be cut in half to achieve a lower dose – the SAMe may then break down before absorption.

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