Major depressive disorder
Specialty	Psychiatry

Clinical Depression is state of sadness or melancholia that has advanced to the point of being disruptive to an individual's social functioning and/or activities of daily living (ADLs). The diagnosis may be applied when an individual meets a sufficient number of the symptomatic criteria for the Depression spectrum as suggested in the DSM-IV-TR or ICD-9/10. It is important to note that an individual may suffer from what is termed a "clinical depression" without fully meeting the criteria for a specific diagnosis on the Depression spectrum. Clinically, this is referred to as a "depressed mood". This state is typically psycho-social in nature, as opposed to organic (chemical). A strict clinical diagnosis of Depression, and/or its various corollaries, almost invariably maintains the presence of a biological component.

Although a mood characterized by sadness is often colloquially referred to as depression, clinical depression is something more than just a temporary state of sadness. Symptoms lasting two weeks or longer, and of a severity that begins to interfere with typical social functioning and/or activities of daily living, are considered to constitute clinical depression.

Clinical depression affects about 16%^[1] of the population on at least one occasion in their lives. The mean age of onset, from a number of studies, is in the late 20s. About twice as many females as males report or receive treatment for clinical depression, though this imbalance is shrinking over the course of recent history; this difference seems to completely disappear after the age of 50 - 55, when most females have passed the end of menopause. Clinical depression is currently the leading cause of disability in the US as well as other countries, and is expected to become the second leading cause of disability worldwide (after heart disease) by the year 2020, according to the World Health Organization^[2].

According to the DSM-IV-TR criteria for diagnosing a major depressive disorder (see also: DSM cautionary statement) one or both of the following two required elements need to be present:

• Depressed mood, or
• Loss of interest or pleasure.

It is sufficient to have either of these symptoms in conjunction with four of a list of other symptoms. These include:

• Feelings of overwhelming sadness or fear, or the seeming inability to feel emotion.
• A decrease in the amount of pleasure derived from what were previously pleasurable activities.
• Changing appetite and marked weight gain or weight loss.
• Disturbed sleep patterns, such as insomnia or excessive sleep.
• Changes in activity levels, such as restlessness or a slowing of movement.
• Fatigue, both mental and physical.
• Feelings of guilt, helplessness, anxiety, and/or fear.
• A decrease in self-esteem.
• Trouble concentrating or making decisions.
• Self-harm or ruminating on self-harm.
• Ruminating on death and/or suicide.

Depression in children is not as obvious as it is in adults. Here are some symptoms that children might display:

• Loss of appetite.
• Sleep problems, such as recurrent nightmares.
• Learning or memory problems where none existed before.
• Significant behavioural changes; such as withdrawal, social isolation and aggression.

In older children and adolescents, an additional indicator could be the excessive use of drugs or alcohol. Depressed adolescents are at particular risk of further destructive behaviours, such as eating disorders and self-harm.

One of the most widely used instruments for measuring depression severity is the Beck Depression Inventory, a 21 question multiple choice survey.

It is hard for people who have not experienced clinical depression, either personally or by regular exposure to people suffering it, to understand its emotional impact and severity, interpreting it instead as being similar to "having the blues" or "feeling down". As the list of symptoms above indicates, clinical depression is a syndrome of interlocking symptoms which goes far beyond sad or painful feelings. A variety of biological indicators, including measurement of neurotransmitter levels, have shown that there are significant changes in brain chemistry and an overall reduction in brain activity.^{[citation needed]}

One consequence of a lack of understanding of clinical depression is that the depressed individual will often feel extreme guilt over their inability to recover; and that guilt can be aggravated by those close to them.^{[citation needed]}

Because of this profound and often overwhelmingly negative outlook, the depressed individual is unlikely to recover on their own without some sort of treatment.^{[citation needed]} Untreated depression is typically characterized by progressively worsening episodes separated by plateaux of temporary stability or remission.^{[citation needed]} If left untreated it will generally resolve within six months to two years although occasionally depression becomes chronic and lasts for many years or indefinitely.^{[citation needed]} In many cases (but not all) treatment can shorten the period of distress to a matter of weeks.^{[citation needed]}

While depressed, the person may damage themselves socially (e.g. break up relationships), occupationally (e.g. lose his job), financially, and physically. Treatment of depression can significantly reduce the incidence of this damage, including reducing the likelihood of suicide which is otherwise a common outcome^{[citation needed]}. For all of these reasons, treatment of clinical depression is seen by many as very useful and at times life-saving.

Some people can experience anhedonia for long periods of time before they discover it is a mental illness.^{[citation needed]} The inability to feel pleasure can advance negativity already present in a depressed person's mental state.

The modern idea of depression seems to be the same as the much older concept of melancholia. The name melancholia derives from 'black bile', one of the 'four humours' postulated by Galen.

The Ebers papyrus (ca 1550 BC) contains a short description of clinical depression. Though full of incantations and foul applications meant to turn away disease-causing demons and other superstition, it also evinces a long tradition of empirical practice and observation.

1. Major depression. Also referred to as 'major depressive disorder' or biochemical, clinical, endogenous, unipolar, or biological depression. It is characterized by a severely depressed mood that persists for at least two weeks. Episodes of depression may start suddenly or slowly and can occur several times through a person's life. Major depressive disorder may be categorized as "single episode" or "recurrent" depending on whether previous episodes have been experienced before. Major depression may also be referred to as unipolar affective disorder, a term which emphasizes its relatedness to bipolar disorder.

   Clinicians recognise several subtypes of Major Depression:

   • Melancholic depression (what used to be referred to as endogenous depression) is characterized by insomnia, poor appetite and weight loss, less responsive mood, and morning worsening.
   • Atypical depression is characterized by "reversed vegetative symptoms" which include oversleeping, overeating, leaden paralysis, rejection sensitivity and temporary brightening of mood in response to positive events. It may overlap with anxiety and panic attacks. It is often more chronic than melancholic depression.
   • Psychotic depression is accompanied by hallucinations or delusions.
2. Dysthymia is a long-term, mild depression that lasts for at least two years. By definition the symptoms are not as severe as in major depression, although those with dysthymia are highly likely to have superimposed major depressive episodes (known as "double depression"). It often begins in adolescence and spans several decades.
3. Bipolar disorder is a cyclical illness in which moods fluctuate between mania (extreme happiness or giddiness and frantic activity) and clinical depression. Bipolar disorder has also been commonly called "manic depression", although this usage is now unpopular with psychiatrists, who have standardised on Kraepelin's usage of the term "manic depression" to describe the whole bipolar spectrum that includes both bipolar disorder and unipolar depression; they now usually use the term bipolar disorder. This then leaves the term unipolar depression which is used to differentiate it from bipolar disorder.
4. Unipolar Bipolar disorder is a depression similar to bipolar disorder with the exception of very weak or completely absent maniacal periods. This is often a long-term severe depression with no, or at most very few, good periods.
5. Depressive pseudodementia is a syndrome in which the patient shows symptoms of dementia that are actually caused by depression.

The DSM-IV-TR is largely unchanged since the DSM-III of 1980. Although much has been learned about depression and the brain since then, it is unlikely that future editions will reflect this knowledge, as the DSM by nature is a very conservative document.

There is a case to be made for anxiety-driven depression, and there may be changes to the next DSM to reflect this reality. Anxiety is a frequent co-traveler with depression, either as a co-occurring illness or with any number of anxiety symptoms manifesting in depressive episodes. Researchers such as Robert Sapolsky PhD of Stanford and others argue that stress biologically underpins both anxiety and depression. Pharmaceutical companies are seeking to ward off depression and anxiety by targeting stress hormones such as corticotropin releasing factor (CRF). (See Anxiety in Depression and Bipolar Disorder.)

It can be argued that the DSM fails to account for destructive behaviour identified with males such as aggression and substance use while overemphasising “female” failings such as excessive guilt, feelings of sadness, and overeating or not eating enough. As a result, according to this argument, twice as many women as men are diagnosed with depression. Therapists Terrence Real and Jed Diamond and others are seeking to have psychiatry redress this imbalance. (see Depression in Men.)

Another major behavior the DSM fails to account for is apathy, or the lack of motivation. Motivation is tied mainly to the dopamine system in the brain, rather than the serotonin system that is the target of most antidepressant medications. Apathy is typically discussed in the context of neuropsychiatric illnesses such as Alzheimer’s or Parkinson's Disease, but remains for the present moment terra incognita to psychiatry. (See Apathy Matters.)

Finally, the DSM fails to account for manic or hypomanic features in depression. This is the gray area of the mood spectrum, where clinical (unipolar) depression and bipolar disorder appear to overlap. Some researchers such as Hagop Akiskal MD are in favour of widening the criteria for bipolar disorder to include what they see are “softer forms” of this illness. By the same token, depressed patients with some hypomanic or manic features could be regarded as having a “harder” form of depression. (See Multipolar Depression.)

No specific cause for depression has been identified, but there are a number of factors believed to be involved.

• Heredity The tendency to develop depression may be inherited; there is some evidence that this disorder may run in families.

• Physiology There may be changes or imbalances in chemicals which transmit information in the brain, called neurotransmitters. Many modern antidepressant drugs attempt to increase levels of certain neurotransmitters, like serotonin. While the causal relationship is unclear, it is known that antidepressant medications do relieve certain symptoms of depression- although critics point out that the relationship between serotonin, SSRIs, and depression is usually greatly oversimplified when presented to the public. Seasonal affective disorder (SAD) is a type of depressive disorder that occurs in the winter when daylight hours are short. It is believed that the body's production of melatonin, which is produced at increased levels in the dark, plays a major part in the onset of SAD, and that many sufferers respond well to bright light therapy, also known as phototherapy. High levels of Omega-6 fatty acids in the brain have also been linked to depression.
• Psychological factors Low self-esteem and self-defeating or distorted thinking are connected with depression. While it is not clear which is the cause and which is the effect, it is known that sufferers who are able to make corrections to their thinking patterns can show improved mood and self-esteem. Psychological factors include the complex development of one's personality and how one has learned to cope with external environmental factors, such as stress.

• Early experiences Events such as the death of a parent, abandonment or rejection, neglect, chronic illness, and severe physical, psychological, or sexual abuse can also increase the likelihood of depression later in life. Post-traumatic stress disorder (PTSD) includes depression as one of its major symptoms.

• Life experiences Job loss, financial difficulties, long periods of unemployment, the loss of a spouse or other family member, divorce or the end of a committed relationship, or other traumatic events may trigger depression. Long-term stress, at home, work or school, can also be involved.

• Medical conditions Certain illnesses including cardiovascular pathologies^[3], hepatitis, mononucleosis, and hypothyroidism may contribute to depression, as may certain prescription drugs such as birth control pills and steroids.

• Diet the increase in depression in industrialised societies has been linked to diet; in particular to reduced levels of omega-3 fatty acids in intensively farmed food and processed foods^[4]. This link has been, at least partly, validated by studies using dietry supplements in schools^[5] and by a double blind test in a prison.

• Alcohol and other drugs Alcohol can have a negative effect on mood, and misuse or abuse of alcohol, benzodiazepine-based tranquillizers and sleeping medications, or narcotics can all play a major role in the length and severity of depression. The link between frequent cannabis use and depression is also widely documented, although the direction of causality remains in question.

• Postpartum depression About ten percent of new mothers experience some form of depression after childbirth. When it occurs, the onset is typically within three months after delivery, and it may last for several months. About two new mothers out of a thousand have depression so severe it includes hallucinations or delusions.

• Living with a depressed person Those living with someone suffering from depression experience increased anxiety, and life disruption, increasing the possibility of also becoming depressed.

• Social Environment Evolutionary theory suggests that depression is a protective mechanism: if an individual is involved in a lengthy fight for dominance of a social group and is clearly losing, depression causes the individual to back down and accept the submissive role. In doing so, the individual is protected from unnecessary harm. In this way, depression maintains the social hierarchy.

• Other Evolutionary Theories Another evolutionary theory is that the cognitive response that produces modern day depression evolved as a mechanism that allows people to assess whether they are in pursuit of an unreachable goal. Still others claim that depression can be linked to perfectionism. People that accept satisfactory outcomes in lieu of "the best" outcome tend to lead happier lives.

Treatment of depression varies broadly, and is different for each individual. Various types and combinations of treatments may have to be tried. There are two primary modes of treatment, typically employed in conjunction with one another: medication and psychotherapy. A third treatment, electroconvulsive therapy (ECT) also known as electroshock, may be used where chemical treatment fails. Other alternative treatments used for depression include exercise and the use of vitamins, herbs, or other nutritional supplements.

The effectiveness of treatment often depends on factors such as the amount of optimism and hope the sufferer is able to maintain, the control s/he has over stressors, the severity of symptoms, the amount of time the sufferer has been depressed, the results of previous treatments, and the degree of support of family, friends, and significant others.

While treatment is generally effective, there are some cases where the condition fails to respond. Treatment-resistant depression requires a full assessment which may lead to the addition of psychotherapy, higher medication doses, changes of medication or combination therapy, a trial of ECT/electroshock, or even a change in the diagnosis with subsequent treatment changes. Although this process helps many, some people's symptoms continue unabated.

In emergency situations with suicidal persons, psychiatric hospitalization is used simply to keep suicidal people safe until they cease to be dangers to themselves. Another treatment program is partial hospitalization, in which the patient sleeps at home but spends the day, either five or seven days a week, in a psychiatric hospital setting in intense treatment. This treatment usually involves group therapy, individual therapy, psychopharmacology, and academics (in child and adolescent programs).

Medication which relieves the symptoms of depression has been available for several decades. These drugs are listed in order of historical development. Typical first line therapy for depression is the use of an SSRI type drug, such as sertraline (Zoloft).

Monoamine oxidase inhibitors (MAOIs) such as Nardil may be used if other antidepressant medications are ineffective. Because there are potenially fatal interactions between this class of medication and certain foods and drugs, they are rarely prescribed anymore. A new MAOI has recently been introduced. Moclobemide (Manerix), known as a reversible inhibitor of monoamine oxidase A (RIMA), follows a very specific chemical pathway and does not require a special diet.

Tricyclic antidepressants are the oldest, and include such medications as amitriptyline and desipramine. They are used less commonly now, due to side-effects which may include increased heart rate, drowsiness, dry mouth, and memory impairment. Most importantly, they have a high potential to be lethal in moderate overdose. The reason why tricyclic antidepressants are still used is their high potency, especially in severe cases of clinical depression.

Selective serotonin reuptake inhibitors (SSRIs) comprise the current standard family of antidepressants. It is thought that one cause of depression is that an inadequate amount of serotonin, a chemical which the brain uses to transmit signals between nerve cells, is produced. These drugs are said to work by preventing the reabsorption of serotonin by the nerve cell, thus maintaining the levels the brain needs to function effectively, although two researchers recently demonstrated that this is a marketing technique rather than a scientific portrayal of how the drugs actually work. [6]. Recent research indicates that these drugs may interact with transcription factors known as "clock genes"[7] that may be important for the addictive properties of drugs of abuse and possibly in obesity[8][9].

This family of drugs includes fluoxetine (Prozac), paroxetine (Paxil), escitalopram (Lexapro), and sertraline (Zoloft). These antidepressants typically have fewer adverse side effects than the tricyclics or the MAOIs, though such effects as drowsiness, dry mouth, and decreased ability to function sexually may occur.

Noradrenaline reuptake inhibitors (NARIs) such as reboxetine (Edronax) act via noradrenaline. NARIs are thought to have a positive effect on concentration and motivation in particular.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta) are a newer form of anti-depressant which work both on noradrenaline and on serotonin. They typically have similar side-effects to the SSRIs although there may be a withdrawal syndrome on discontinuation which may require a tapering of the dose.

5-HTP supplements are claimed to provide more raw material to the body's natural serotonin production process. There is a reasonable indication that 5-HTP may not be effective for those who haven't already responded well to an SSRI.

S-adenosyl methionine (SAM-e) is a derivative of the amino acid methionine that is found throughout the human body, where it acts as a methyl donor and participates in other biochemical reactions. It is available as a prescription antidepressant in Europe, and an over-the-counter dietary supplement in the United States. Clinical trials have shown SAM-e to be as effective as standard antidepressant medication, with many fewer side effects.^[10],^[11] Its mode of action is unknown.

Omega-3 fatty acids (found naturally in oily fish, vitamin D, flax seeds, hemp seeds, walnuts, canola oil etc.) have also been found to be effective while used as a dietary supplement.

Some antidepressants have been found to work more effectively in some patients when used in combination with another drug. Such "augmentor" drugs include tryptophan (Tryptan) and buspirone (Buspar).

Tranquillizers and sedatives, typically the benzodiazepines, may be prescribed to ease anxiety and promote sleep. Because of their high potential for fostering dependence, these medications are intended only for short-term or occasional use. Medications are often employed not for their primary function, but to exploit what are normally side effects. Quetiapine fumarate (Seroquel) is designed primarily to treat schizophrenia and bipolar disorder, but a frequently-reported side-effect is somnolence. Hence, this non-addictive drug can be used in place of an addictive anti-anxiety agent such as clonazepam (Klonopin, Rivotril).

Antipsychotics such as risperidone (Risperdal) and olanzapine (Zyprexa), and Quetiapine (Seroquel) are prescribed as mood stabilizers and are also effective in treating anxiety. Antipsychotics (typical or atypical) may be also prescribed in an attempt to augment an antidepressant, to make antidepressant blood concentration higher, or to relieve psychotic or paranoid symptoms often accompanying clinical depression. However, they may have serious side effects, particularly at high doses, which may include blurred vision, muscle spasms, restlessness, tardive dyskinesia, and weight gain.

Antidepressants by their nature are stimulants. Anti-anxiety medications by their nature are depressants. Close medical supervision is critical to proper treatment if a subject is presenting both illnesses as the medications tend to work against each other.

Lithium and Depakote remain the standard treatments for bipolar disorder, but may also be effective for people with depression, particularly in preventing relapse. Lithium's potential side effects include thirst, tremors, light-headedness, and nausea or diarrhea. Some of the anticonvulsants such as carbamazepine (Tegretol), sodium valproate (Epilim), and lamotrigine (Lamictal) are also used as mood stabilisers, particularly in bipolar disorder.

Failure to take medication, or failure to take it as prescribed, is one of the major causes of relapse. Should one feel a change or discontinuation of medication is necessary, it is critical that this be done in consultation with a doctor.

In psychotherapy, or counselling, one receives assistance in understanding and resolving problems which may be contributing to depression. This may be done individually or with a group, and is conducted by health professionals such as psychiatrists, psychologists, social workers, or psychiatric nurses. It is important to enquire about both the therapist's training and approach; a very close bond often forms between practitioner and client, and it is important that the client feel understood by the clinician.

Counsellors can help a person make changes in thinking patterns, deal with relationship issues, detect and deal with relapses, and understand the factors that contribute to depression.

There are many therapeutic approaches, but all are aimed at improving an individual's personal and interpersonal functioning. Cognitive therapy, also known as Cognitive Behaviour Therapy, focuses on how people think about themselves and their relationships to the world. It works to counteract negative thought patterns and enhance self-esteem. Therapy can be used to help a person develop or improve interpersonal skills in order to allow them to communicate more effectively and reduce stress. Behavioral therapy is based on the assumption that behaviors are learned. This type of therapy attempts to teach individuals new and healthier types of behaviours. Supportive therapy encourages people to discuss their problems and provides them with emotional support. The focus is on sharing information, ideas, and strategies for coping with daily life. Family systems therapy helps people live together more harmoniously and undo patterns of destructive behaviour.

Repetitive transcranial magnetic stimulation (rTMS) is currently under study as a possible treatment for depression. Initially designed as a tool for physiological studies of the brain, this technique shows promise as a means of alleviating depression. In this therapy, a powerful magnetic field is used to stimulate the left prefrontal cortex, an area of the brain which typically shows abnormal activity in depressed individuals.

rTMS has been proposed as an alternative to ECT that would have fewer side effects. No sedation is required, and the only reported side effects are a slight headache in some patients, and facial muscle contraction during treatment. However clear evidence that it is an effective treatment is still awaited.^[12]

Recent work in Poland has suggested that weak, variable magnetic fields may offer relief from depression in those that have been unresponsive to medication. However, some of the existing work has been questioned with claims that the effect is not as significant once environmental conditions are controlled for.

Vagus nerve stimulation therapy is a treatment used since 1997 to control seizures in epileptic patients and has recently been approved for treating resistant cases of clinical depression. The VNS device is implanted in a patient's chest with wires that connect it to the vagus nerve, which it stimulates to reach a region of the brain associated with moods. The device delivers controlled electrical doses to the vagus nerve at regular intervals.

Electroconvulsive therapy (ECT), also known as electroshock or electroshock therapy employs short bursts of a controlled current of electricity (this is typically fixed at 0.9 ampere) into the brain to induce a brief, artificial seizure while the patient is under general anaesthesia.

ECT has acquired a fearsome reputation, in part, from its use as a tool of repression in the former USSR, and its fictional depiction in films such as One Flew Over the Cuckoo's Nest, but remains a common treatment where other means of treatment have failed, or where the use of drugs is unacceptable (such as in pregnancy). Also, in contrast to "direct" electroshock of years ago, most countries now only allow ECT to be administered under anaesthesia. In a typical regimen of treatment, a patient receives three treatments per week over three or four weeks. Repeat sessions may be required. Short-term memory loss, disorientation and headache are very common side effects. In some cases, permanent memory loss has occurred, but detailed neuropsychological testing in clinical studies have not been able to prove permanent effects on memory. ECT offers the benefit of a very fast response, however, this response has been shown not to last unless either maintenance electroshock or maintenance medications are used. While antidepressants usually take around a month to take effect, the results of ECT have been shown to be much faster. For this reason, it is the treatment of choice in emergency circumstances (for example in catatonic depression where the patient has ceased oral intake of fluid or nutrients).

There remains much controversy over electroshock. Advocacy groups and scientific critics, such as Dr Peter Breggin[13], call for restrictions on its use or complete abolishment. Like all forms of psychiatric treatment, electroshock can be given without a patient's consent, but this is subject to legal conditions dependent on the jurisdiction.

Bright light (both sunlight and artificial light) is shown to be effective in seasonal (winter) depression, and sometimes may be effective in other types of depression, especially atypical depression or depression with "seasonal phenotype" (overeating, oversleeping, weight gain, apathy). It is wise to recommend to any depressive patient to take as much sunlight as possible by walking at daytime, even if the patient suffers from depression which does not have seasonal pattern or "seasonal symptoms".

Important note: an antidepressant effect is caused by visible light stimulation of retina, not by ultra-violet, so it is not necessary (and may be even dangerous in some cases) to sunburn. It is enough just to walk at daytime or to take light therapy in a light cabin with a special powerful lamp.

It is widely believed that physical activity and exercise helps depressive patients and promotes quicker and better relief from depression. It is also thought to help antidepressants and psychotherapy to work better and faster. It can be difficult to find the motivation to exercise if the depression is severe, but sufferers should be encouraged to take part in some form of regularly-scheduled physical activity if possible. A workout need not be strenuous; many find walking, for example, to be of great help. Exercise produces higher levels of chemicals in the brain, notably dopamine, serotonin, and norepinephrine. In general this leads to improvements in mood, which is effective in countering depression.

Note that prior to beginning an exercise regime, it is wise to consult a doctor. He or she can establish whether a person possesses any health problems that could rule out some types of exercise.

Severe clinical depression is often accompanied by constipation. Tricyclic antidepressants themselves also tend to produce constipation as a side effect. Laxatives reduce the absorption of an antidepressant in the small intestine, thereby reducing its bioavailability and clinical efficacy. Warm water enemas, on the other hand, do not interfere with antidepressant absorption, and may have a slight antidepressive effect by increasing serotonin production in thick bowel wall and temporarily raising serotonin level in the bloodstream.

Meditation is increasingly seen as a useful treatment for depression. The current professional opinion of meditation is that it represents at least a complementary method of treating depression, a view that has been clearly underscored by the Mayo Clinic. Since the late 1990s, much research has been carried out to determine how meditation affects the brain (for more information see the main article on meditation). While the effects on the mind are somewhat complex, they are often quite positive, encouraging a calm, reflective and rational state of mind which can be of great help against depression. It's notable that while many religions actively encourage/use meditative practice, it is not necessary to be a member of any faith to partake in meditation.

Insulin shock treatment is an old and currently mostly abandoned treatment of severe depressions, psychoses, catatonic states and other mental disorders. It consists of induction of hypoglycemic coma by intravenous infusion of insulin. The treatment is potentially unsafe and can be lethal in some cases (about 1% of patients undergoing insulin coma), even with proper monitoring. That was the main reason why it was abandoned from current medical practice. In contrast, ECT is considered to be very safe.

Nevertheless, insulin shock therapy is still officially used in Russia and some other countries, and can be administered to a very treatment-resistant patient under his written consent in many Western countries.

Atropinic shock therapy, also known as atropinic coma therapy, is an old and currently rarely-used method. It consists of induction of atropinic coma by rapid intravenous infusion of atropine.

The atropinic shock treatment is considered relatively safe but the problem with its administration is that it requires prolonged coma (4-5 hours), careful monitoring and preparation, and it has many unpleasant side effects, like blurred vision due to atropine. Thus it is rarely used now. But it can be used under written consent in Western countries in some very treatment-resistant cases, and is still officially used in Russia and some other countries.

Relapse is more likely if treatment has not resulted in the full remission of symptoms.⁴ In fact, current guidelines for antidepressant use recommend 4 to 6 months of continuing treatment following symptom resolution to prevent relapse of depression.

Combined evidence from many randomized controlled trials indicates that continuing antidepressant medications after recovery substantially reduces (halves) the chances of relapse. This preventative effect probably lasts for at least the first 36 months of use.^[14]

Some anecdotal evidence exists to suggest that chronic disease is accompanied by relapses after prolonged treatment with antidepressants (Tachyphylaxis). Psychiatric texts suggest that physicians respond to this by increasing dosage, complementing the medication with a different class, or changing the medication class entirely. The reason for relapse in these cases is as poorly understood as the change in brain physiology induced by the medications themselves. Possible reasons may include ageing of the brain or worsening of the condition. Most SSRI psychiatric medications were developed for short term use (a year or less), but are widely prescribed for indefinite periods.[15]

• Beck Depression Inventory
• Hamilton Depression Rating Scale
• Cyclothymia
• Dysthymia
• Mania
• Bipolar disorder
• Seasonal affective disorder (SAD)
• List of people who have suffered from depression
• Stress
• Hypoadrenia (also covers 'adrenal exhaustion', sometimes called 'adrenal fatigue')
• Learned helplessness
• Wikibooks - Demystifying Depression

• Beck, A. T., Rush, A. J., Shaw, B. F., Emery, G. (1987). Cognitive therapy of depression. New York: Guilford.
• Burns, David D. (1999). Feeling Good : The New Mood Therapy. Avon.
• Klein, D. F., & Wender, P. H. (1993). Understanding depression: A complete guide to its diagnosis and treatment. New York: Oxford University Press.
• Kramer, Peter D (2005). Against Depression. New York: Viking Adult
• Weissman, M. M., Markowitz, J. C., & Klerman, G. L. (2000). Comprehensive guide to interpersonal psychotherapy. New York: Basic Books.
• Sarbadhikari S. N. (2005).Ed, Depression and Dementia:Progress in Brain Research, Clinical Applications and Future Trends. Hauppauge, Nova Science Publishers. [16] ISBN 1-59454-114-0

• Wurtzel, E. (1997) Prozac Nation: Young and Depressed in America: A Memoir. Riverhead Books. ISBN 1573225126
• Lewinsohn, P. M., Munoz, R. F, Youngren, M. A., Zeiss, A. M. (1992). Control your depression. New York: Fireside/Simon&Schuster.
• Nesaule, Agate (1995). A Woman in Amber: Healing the Trauma of War and Exile New York: Penguin Books.

  ISBN 1-56947-046-4 (hc.); 0 14 02.6190 7 (pbk.)

• Rowe, Dorothy (2003). Depression: The way out of your prison. London: Brunner-Routledge.
• Sealey, Robert (2002). Finding Care for Depression, Mental Episodes & Brain Disorders, Toronto: Sear Publications www.searpubl.ca
• Shields, Brooke (2005). Down Came the Rain: My Journey Through Postpartum Depression. Hyperion. ISBN: 1401301894.
• Smith, Jeffery (2001). Where the roots reach for water: A personal and natural history of melancholia. New York: North Point Press.
• Solomon, Andrew (2001). The noonday demon: An atlas of depression. New York: Scribner.
• Styron, William (1992). Darkness visible: A memoir of madness. New York: Vintage Books/Random House.
• Wolpert, Lewis (2001). Malignant sadness: The anatomy of depression. London: Faber and Faber.

1. ^ Bland, R.C. (1997) Epidemiology of Affective Disorders: A Review. Can J Psychiatry, 42:367?377.
2. ^ Murray, C.J.L., Lopez, A.D. 1997. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 349, 1498-1504
3. ^ 5-Lipoxygenase as a putative link between cardiovascular and psychiatric disorders., Manev R, Manev H. Critical Reviews in Neurobiology. 2004; 16(1-2):181-6.
4. ^ . ISBN 0-141-01566-7. {{cite book}}: Missing or empty |title= (help); Unknown parameter |Chapter= ignored (|chapter= suggested) (help); Unknown parameter |Editor= ignored (|editor= suggested) (help); Unknown parameter |First= ignored (|first= suggested) (help); Unknown parameter |Last= ignored (|last= suggested) (help); Unknown parameter |Pages= ignored (|pages= suggested) (help); Unknown parameter |Publisher= ignored (|publisher= suggested) (help); Unknown parameter |Title= ignored (|title= suggested) (help); Unknown parameter |Year= ignored (|year= suggested) (help)
5. ^ "Using Fatty Acids for Enhancing Classroom Achievement". January. {{cite web}}: Check date values in: |date= and |year= / |date= mismatch (help)
6. ^ Roberto Delle Chiaie, Paolo Pancheri and Pierluigi Scapicchio. (2002). Efficacy and tolerability of oral and intramuscular S-adenosyl- L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr, 76 (5): 1172S-1176S
7. ^ Mischoulon D, Fava M. (2002). Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr, 76 (5): 1158S-61S.
8. ^ Keller, M.B. (2003) Past, Present, and Future Directions for Defining Optimal Treatment Outcome in Depression. JAMA, 289:3152-3160.
9. ^ Martin JL, Barbanoj MJ, Schlaepfer TE, Thompson E, Perez V, Kulisevsky J. Repetitive transcranial magnetic stimulation for the treatment of depression. Systematic review and meta-analysis. British Journal of Psychiatry. 2003 Jun;182:480-91. PMID 12777338
10. ^ Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, Goodwin GM. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. 2003 Feb 22;361(9358):653-61. PMID 12606176

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• General Information
  • Depression Information from the US Institute of Mental Health
  • Information and links from the UK National Electronic Library for Mental Health
  • Depression: Clinical and Alternative Treatments
  • Dr. Ivan's depression central - Links to a plethora of information about depression and related disorders by biopsychiatrist Ivan Goldberg, MD.
  • Psych Central: Depression Information and Treatments
  • 100 FAQs about depression
  • A Buddhist View on Depression
  • Mental Health Matters: Depression
  • Symptoms of Clinical Depression (Major Depressive Disorder)
  • Internet Mental Health: Major Depressive Disorder
  • TrappedMinds.org - Depression and Mood Disorder Resources
  • An Analysis of Use of Prozac, Paxil and Zoloft in USA 1988--2002 (pdf file)
  • Depression and Chronic Back Pain
  • Depression Treatment Information, Resources, and Support Forum
• Online Support Groups
  • Secretworld - Mood Disorders and Depression Support
  • Moodgym - Training CBT for preventing depression (ANU)
  • BluePages - evidence-based information about depression (ANU)
  • [17] - Descriptions of effects of psychiatric drugs by people who take them, links to more information on drugs and discussion groups.

• Books and Publications
  • Depression in Children and Adolescents (PDF) Lists books, web sites, support groups and resources on depression in children and adolescents. From Seattle Children's Hospital.
  • The Wave Riders - A book and newsletter with an alternative approach to Bipolar disorder and depression.
  • The Hamilton test - The Hamilton test for evalutating the degree of depression (pdf)
  • The MADRs test - The MADRs test for evaluating the degree of depression (pdf).
  • Against Depression Peter Kramer's exploration of cultural stereotypes of depression and artistic expression.
  • Depression: Mind and Body - A peer-reviewed journal describing advances in the understanding and treatment of depression and its physical symptoms.
  • Bipolar Disorder Proven techniques to help co-manage and cope with bipolar disorder in a loved one. Compiled by a NAMI faculty member from thousands of bipolar victims and co-victims.

• Organizations
  • Depression Alliance website (UK charity)
  • "Philosophy And Depression," Philosophical Society.com
• Discussions
  • Psych Forums: Depression Forum
  • DepressioNet: board for depression sufferers.
  • AuroraMD provides Primary Care screening services
  • Wing of Madness Message Board - Message board and chat for people with mood disorders.
• News
  • Depression News
  • Researchers from the Hebrew university developed a blood test for Anxiety - now working on depression - A web Article

• Evolution and Depression
  • Randolph Nesse's homepage
  • Martin Seligman Seligman was the discoverer of learned helplessness in laboratory mice. He is also the developer of Positive Psychology.

• Philosophy & Depression
  • "Philosophy And Depression," Philosophical Society.com An article which asks whether the depressed state really is a disease that needs to be palliated by drugs.