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"Why don't you just pull yourself together?" It is really hard for non-sufferers to appreciate just what effect depression has on every aspect of a sufferer's life.
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| Twice as many women as men suffer from depression |
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Depression is a state of sadness so severe that it interferes with an individual's social functioning and/or activities of daily living. Although the term "depression" is often used more broadly to indicate a low mood, here we will be discussing clinical depression, which is a medical diagnosis.
A depressed state, including overwhelming feelings of sadness, worthlessness and pessimism, can last for weeks, months, even years. In some severe cases, the feelings can lead to thoughts of self-harm or suicide. In milder cases of depression, sufferers lose their interest in food, socialising and other pleasures ('anhedonia'). They have trouble sleeping, and may require extra care and attention from family, friends and colleagues.
Although depression may sometimes run in families, this most likely reflects a weak-moderate genetic predisposition towards developing the illness rather than a more clearly heritable characteristic such as height or eye colour. Depression may be reactive, being triggered by illness, extreme stress or grief. More than one in five of us will experience mild depression at some point in our lives; with women at least twice as susceptible as men. Major depression, known clinically as unipolar disorder, affects 1 in 20 people at any one time in the UK, with an additional 1 in 50 people developing the violent mood swings of bipolar disorder (formerly known as "manic depression"), which affects men and women equally.
Many people do not seek treatment but those who do have a range of treatment options. At the least invasive extreme are lifestyle changes like increasing exercise, a change in diet, light therapy, taking supplements such as St. John's Wort, or meditation. Treatment may also include a "talking therapy" such as counselling, psychotherapy, family therapy, or cognitive-behavioural therapy (CBT). There are a variety of drugs which can be prescribed by a GP or psychiatrist, such as selective serotonin reuptake inhibitors (SSRIs), known widely as being the "Prozac" family of drugs. These have proven efficacy and relatively few side effects. At the most extreme end of the scale, some individuals may need to be hospitalised if they are considered to be a risk to themselves or others. Patients who continue to be unresponsive to medication may benefit from electroconvulsive therapy (ECT). Some forms of depression tend to recur; indeed some psychiatrists describe depression as a chronic disease, like diabetes or asthma. However the risk of relapses can be reduced by continuing to take medication once the major depressive episode appears to have been resolved.
Types of depression
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| Vincent van Gogh suffered from bipolar disorder, which is often associated with creativity and genius. |
Everyone feels a little "down" or "blue" at times, but unipolar depression interferes with work, relaxation and enjoying oneself. Indicators include a persistent sad, anxious or empty mood, decreased energy, sleep disturbances and changes in eating patterns. The name unipolar depression indicates that the mood swing is towards a depressed state only. Dysthymia, a less severe form of unipolar depression, involves long-term feelings that do not necessarily disable sufferers but stop them feeling good about life. Other forms of unipolar depression include seasonal affective disorder (SAD) and postnatal depression. SAD usually only affects sufferers in the winter months when there is less sunlight, and can be more prevalent in areas like Scandinavia or Alaska. This type of depression may be best helped by light therapy (exposure to an artificial light source). "Postnatal depression" is somewhat of a misnomer; mothers can experience abnormally low mood during, as well as after, pregnancy. At the milder end of the scale are the "baby blues. It is quite normal for mothers to experience tearfulness, irritability, hypochondriasis, sleeplessness, impairment of concentration, and headache for hours or even days after childbirth. At the more extreme end of the scale, mothers can experience intrusive thoughts or excessive self-criticism which make them doubt their ability to look after their newborn child. The stress of childbirth itself is an obvious predisposing factor, but a lack of social support, poor marital relationship, or low self-esteem can also be significant. Occasionally, some mothers develop a short-lived (10-14 day) form of psychosis following childbirth, although this is rare. Treatment of postnatal depression is the same as treatment for unipolar depression.
In bipolar affective disorder, patients experience cyclical mood swings. In the manic phase, they can feel elated, and full of energy and grand schemes. In the depressive phase, they experience all the misery felt by patients with unipolar depression. In addition to mood, bipolar disorder affects energy levels, sleep patterns, activity levels, social rhythms and ability to think clearly.
Depression can also be a secondary feature of other illnesses, such as heart disease or cancer, and may be serious enough to hinder recovery from the primary disorder. It is important that medical personnel consider mood in the holistic treatment of any patient.
Thanks are due to the following organisations and people: Dr Mark Tricklebank, Eli Lilly UK; Professor David Nutt, Director of the Psychopharmacology Unit, Faculty of Medicine and Dentistry, University of Bristol; Dr Clare Stanford, Reader in Experimental Psychopharmacology, University College London; the British Neuroscience Association.
Depression - Treatment & Needs
Ancient Greek and Roman physicians recognised and described depression or melancholia (literally meaning an excess of black bile) more than two millennia ago.
Today we know depression is a physical brain disorder, but this insight dates back less than 50 years. For most of human history, sufferers have been regarded with suspicion, often locked up for years in asylums for their own safety. Florence Nightingale and Winston Churchill, who described bouts as his "black dog", both suffered in this way
Before the mildly antidepressant effect of amphetamines was discovered in the late 1930s, nothing could be done to make life better for patients. At about the same time, electroconvulsive therapy (ECT) was used for the first time, becoming the standard treatment by the mid-1950s. ECT is still used today to treat cases of very severe, drug-resistant depression.
What is the cause?
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| Today, patients having ECT are first put to sleep and given a muscle relaxant, so that they don't suffer the side-effects of earlier versions of this treatment. |
The changes in mood, thinking and perception in depressed people are believed to be caused by alterations to brain chemistry. Something, possibly the result of exposure to prolonged, severe stress, upsets the ability of neurotransmitters to pass messages between nerve cells. The activity of the monoamine neurotransmitters serotonin and noradrenaline is particularly important in the brain areas that control mood and emotion, and this activity is thought to be inadequate in the brains of depressed patients.
The first clues implicating neurotransmitters in depression came from studies dating from the early 1950s onwards on reserpine, a drug used to reduce high blood pressure that also causes a depressed state in some patients. Researchers found that reserpine causes a loss of serotonin from the brain and it was already known that serotonin was a neurotransmitter. So the hypothesis became that depression is caused by not enough serotonin.
The first real antidepressant was stumbled upon at about the same time. Iproniazid was being used to treat tuberculosis but it also made patients very elated. Seeing this effect, doctors wondered whether iproniazid might be helpful in depression. It was, but it proved too toxic for routine use. It inhibits brain enzymes called monoamine oxidases, which, as their name suggests, break down the very monoamine neurotransmitters that are implicated in depression. Researchers then developed other medicines that worked in the same way and some of them are still occasionally prescribed today.
The second class of antidepressants - tricyclics - was also discovered by chance. Imipramine is an antihistamine that was used to treat allergies but it too produced elation and so was tested in depressed patients. Subsequent animal research showed that tricyclics also alter monoamine neurotransmitter activities in the brain. However they do it not like iproniazid, by disrupting the brain enzymes, but rather by preventing neurotransmitter removal via uptake by brain cells. Monoamine neurotransmitters are often recycled rather than destroyed. The new treatment meant that the neurotransmitters hung about in the gaps between brain cells for longer than usual, thus helping to counteract any deficiency in neurotransmitter activity.
The monoamine oxidase inhibitors and the tricyclics have many unwanted side effects unrelated to their effects on monoamines. So, in the 1970s, the search for cleaner drugs that blocked only the reuptake of serotonin - the selective serotonin reuptake inhibitors (SSRIs) - began. The first SSRI to be launched in the UK was fluvoxamine in 1987, followed by probably the most famous SSRI, Lilly's Prozac (fluoxetine) in 1989.
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| Spoof ad for the most famous SSRI, Prozac. |
All the medicines mentioned above are primarily treatments for unipolar depression. In bipolar disorder, antidepressants can be used during depressive episodes but patients are more often treated with mood-stabilising medicines such as lithium and anti-epileptics. Care must be taken not to precipitate a manic episode when mixing mood stabilisers and antidepressants.
Fluoxetine and other SSRIs have revolutionised the treatment of depression - they have fewer side-effects than older antidepressants and are much safer if patients overdose. Recent reports that SSRIs increase the risk of suicide in children and adolescents are being investigated; meanwhile psychiatrists emphasise that the risks of not treating depression must not be overlooked. Nevertheless, better antidepressants are needed and to find these we need to understand what causes depression much better. Currently, only 40-50% of patients recover on the first antidepressant they are given and it may be several weeks before patients feel the benefit of their prescription. Moreover, about 10% of patients do not respond to any currently available drug or to non-pharmacological interventions such as ECT or psychotherapy, and most people who recover from depression have relapses.
Depression - Future Prospects
While great advances have been made through specifically targeting serotonin, other neurotramitters are also implicated in depression.
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| Brain scans can help reveal the emotional state of a patient. |
Measurements in people and in animal models indicate that inhibitors of noradrenaline or dopamine reuptake may help people for whom SSRIs are ineffective.
IIn 1997, reboxetine was the first noradrenaline reuptake inhibitor to be launched in the UK; others are in preclinical and clinical trials. Medicines that prevent the selective reuptake of more than one monoamine transmitter may also provide new antidepressants. The recently approved duloxetine blocks the reuptake of both serotonin and noradrenaline, as does venlafaxine. Bupropion has some effects on dopamine reuptake, another monoamine neurotransmitter implicated in depression. Other drugs that affect the reuptake of the three monoamines to varying degrees are in development.
Although monoamine neurotransmitter reuptake inhibitors are good antidepressants, a deficit in the activity of these neurotransmitters is probably not the primary cause of depression.
Another avenue to find better antidepressant drugs has come from work on pain relief. In the search for painkillers that work by targeting a small protein called substance P, scientists discovered that their candidate painkillers were changing the behaviour of rats and mice in the same way as antidepressants. This work too has now progressed into patients.
Researchers are also looking for ways to boost the production of brain-derived neurotrophic factor (BDNF). BDNF keeps brain cells healthy throughout life. They are doing this because established antidepressants increase concentrations of this growth factor while stress decreases it. Thus, depression may be caused or worsened by a gradual loss of brain cells on exposure to stress and boosting production of the growth factor could reverse that loss.
Finally, a better understanding of the mechanism that tells us when to sleep may suggest new ways to deal with depression. Our circadian rhythms, as they are known, tell us not only when to sleep but also when to be active. They are often disrupted in depression. Research in people, other mammals and even fruit-flies and sea-slugs is beginning to throw light on how this aspect of our biology is controlled and may lead to new treatments, particularly for bipolar disorder.
How you can help
If you've read this information sheet and are interested in doing more there are several places you can go. The Institute of Psychiatry in South London, UK, always requires healthy participants for research projects, some of which are investigating depression or other mental illnesses. You can register for their participant database, "PsychPop". To find out more about charities that support people with depression,
You might like to consider joining a local association branch as a volunteer or making a donation to research. If you can contribute in any way you'll be helping us in the fight.
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This information has been generously supplied to the BioTrax Volunteer Support Group by the :
Coalition for Medical Progress
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And
Dr.Paul Wicks at the MRC centre for Neurodegeneration research. From the Institute of Psychiatry
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Medical research studies may be conducted and are carefully designed to answer specific medical questions while protecting participants´ safety. Well conducted medical trials are the fastest and safest way to find improved treatments and preventions for diseases. Clinical trials or interventional trials determine whether experimental preventions, treatments, or new ways of using known therapies are safe and effective under controlled conditions. Observational or natural history studies examine health issues and disease development in groups of people or populations. For more information on current medical trials or to register on the BioTrax database, view the study section at www.biotrax.com .
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