What is depression………….?

An illness that involves the body, mood, and thoughts, that affects the way a person eats and sleeps, the way one feels about oneself, and the way one thinks about things.

DEPRESSION may be described as feeling sad, blue (fed up), unhappy, miserable, or down in the dumps. Most of us feel this way at one time or another for short periods. True clinical depression is a mood disorder (affective disorder) in which feelings of sadness, loss, anger, or frustration interfere with everyday life for weeks or longer.

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Common Sign of Depression• Sad , anxious or ‘empty’ mood • Feeling of hopelessness• Feeling of guilt, helplessness• Difficulty in concentrating, remembering, making decisions.• Oversleeping• Appetite and/or weight changes• Thoughts of death, suicide or suicide attempts• Restlessness, irritability• Loss of interest or pleasure in hobbies and activities that

were once enjoyed, including sex.

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Depression in Men

• According to the statistics, men are less likely to suffer from depression than women.

• Depression typically shows up in men, not as feelings of helplessness and vulnerability, but as being irritable, angry and uncooperative. Depression may therefore be difficult to recognize as such in men.

• Even if a man realizes that he is depressed, he is perhaps less willing than a woman to seek help. Encouragement and support from a partner and/or family members can make a big difference here.

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Depression in Women

• Women are about twice as likely as men to experience depression. A number of factors may explain this.

• Hormonal factors • Changes in menstrual cycle• Pregnancy • Miscarriage• The time immediately after the birth of a baby• Pre-menopause and menopause are all associated with

hormonal changes.

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Causes of depression• The exact cause of depression is not known. Many

researchers believe it is caused by chemical changes in the brain. This may be due to a problem with your genes, or triggered by certain stressful events. More likely, it's a combination of both.

• Some types of depression run in families. But depression can also occur if you have no family history of the illness. Anyone can develop depression, even kids.

The following may play a role in depression:• Alcohol or drug abuse• Certain medical conditions, including underactive thyroid, cancer, or

long-term pain• Certain medications such as steroids• Sleeping problems• Stressful life events, such as:

– Breaking up with a boyfriend or girlfriend– Failing a class– Death or illness of someone close to you– Divorce– Childhood abuse or neglect– Job loss– Social isolation (common in the elderly)

TREATMENT FOR DEPRESSION• Psychotherapy• Electroconvulsive therapy (ECT)• Natural alternatives (natural and herbal remedies)• Medication

• SSRIs (Selective-Serotonin Reuptake Inhibitors)• MAOIs (Monoamine Oxidase Inhibitors)• TCAs (Tricyclic Antidepressants)• SNRIs (Selective Nor-epinephrine Reuptake Inhibitors)• NDRIs (Nor-epinephrine Dopamine Reuptake Inhibitors)

• Psychotherapy/talk therapy – especially useful when combined with medications. Goal is to teach good coping skills for every day stressors

• ECT – electric shock is applied to scalp through electrodes, results in seizure (convulsion) in the brain. Fast and effective in patients with depression or suicidal thoughts. Usually given up to three times a week for two to four weeks.

• Natural alternatives – sold in teas and tablets, and in diet pills-not good for severe depression but can help mild depression (omega-3 fatty acids, folic acid, diets, exercise etc.)

Bipolar Disorder• Bipolar disorder is a mood disorder that causes radical

emotional changes and mood swings, from manic highs to depressive lows.

Depression and mania are considered to be the polar opposites of human emotion. The term "bipolar" describes the swings between these two emotional "poles."

• During a "manic phase," people with bipolar disorder experience feelings of euphoria (elation), happiness, and hyperactivity. During a "depressed phase," feelings of sadness and depression are the normal.

• When the person experiences a depressive episode only, then it is called a unipolar disorder. When the episode occurs between the two poles of depression and mania (obsession, craze), it is called bipolar disorder.

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There are two subtypes of bipolar disorder:

1.Bipolar disorder type I: episode of mania with or without depression.

2.Bipolar disorder type II : episode of depression with episode of hypomania or mania.

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Depression can appear as anger and discouragement, rather than feelings of sadness. If depression is very severe, there may also be psychotic symptoms, such as hallucination (nightmare, imagined thing).

Causes of bipolar disorder

1.Genetic: bipolar disorder is higher (7 times more) among the people whose parents have this disorder.

2. Biochemical: a number of neurotransmitters have been responsible for this disorder. Drugs like cocaine exacerbate mania and tricyclic antidepressant triggers mania.

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• Antidepressant drugs are medicines that relieve symptoms of depressive disorders.

• Depressive disorders may be unipolar or bipolar.• These agents act by increasing the levels of excitatory

neurotransmitters. The main types of antidepressants are:1. Tricyclic antidepressants- amitriptyline ,imipramine,

nortriptyline2. Monoamine oxidase inhibitors (MAOIs)-

phenelzine ,tranylcypromine.3. Selective Serotonin reuptake inhibitors (SSRIs)-fluoxetine,

paroxetine, and sertraline.4. Tetracyclic compounds and atypical antidepressants which

do not fall into any of the above categories.

Classification

• Divided into 3 groups: 1st generation: Block the

oxidative deamination of various biogenic monoamines-Iproniazid

2nd generation: Act selectively-cimoxatone

3rd generation: act reversibly & selectively-Metralindole

Iproniazid

Metralindole

Structural references: Aryl moiety(X) Alkyl moiety(Y) Hydrazine part1.Variation of aryl moiety:I. If phenyl ring is mono-

substituted with polar group will increase anti-depressant activity.

II.If benzene ring is replaced by other heterocyclic ring reduces activity.

X Y-NH-NH2

2.Variation of alkyl moiety:I. If X=CH2,comp is benzyl hydrazine.II. If X=CH2-CH2, comp is phenethyl

hydrazine or Phenelzine which is active.

III. If X=CH2CH2CH2,comp is 3-phenylpropyl hydrazine which is

less potent than Iproniazid.I. If Y=branching (CH2-CH-CH3), comp is

Pheniprazine(most potent MAOI)II. If Y=further branching, causes loss of

activity.3.Variation of Hydrazine part:I. H2 atom on hydrazine nitrogen

bearing alkyl group is essential for MAOI activity.

X Y-NH-NH2

• Depression linked to an imbalance of chemicals within the brain.

• In brain there are chemical messengers\neurotransmitters, called monoamines-noradrenalin , serotonin.

• Neurotransmitters control or regulate bodily functions, & noradrenalin and serotonin control and regulate mood.

• During depression, there may be a decrease in amount of these monoamines released from nerve cells in the brain. Monoamines are broken down by an enzyme called monoamine oxidase.

• MAOIs prevent monoamine oxidase from breaking down the monoamines. This results in an increased amount of active monoamines in the brain.

• By increasing the amount, the imbalance of chemicals, important in causing depression, is altered. This helps relieve the symptoms of depression.

• Moclobemide is a more selective type of MAOI, called a reversible inhibitor of monoamine oxidase type A (RIMA).

Many drugs should be avoided when taking an MAOI antidepressant. The most common are:

• Allergy, cold, cough and sinus medications • Antihistamines • Antipsychotics • Asthma drugs • Blood pressure medications Other antidepressants not specifically listed,

including other MAOIs • Tryptophan Often interact with certain foods; e.g. Alcoholic

beverages, fermented foods, soya sauce.

• A class of compounds typically used as antidepressants in the treatment of:– depression,– anxiety disorders,– personality disorders.

• Typically effective and used in treating some cases of insomnia.

• 1967-Research for alternative drugs to help depressed patients began.

• At the time, most scientists believed that norepinephrine was the chemical messenger that was really involved in the depression.

• However, interest began to develop in serotonin as well.• Due to that increasing interest, as well as interest in

finding antidepressants that would have more tolerable side effects, the serotonin-specific reuptake inhibitors, or SSRIs, came about.

• The first drug in this class was fluoxetine (Prozac).• Researchers suggest that these drugs work by only

blocking the reuptake of serotonin, thereby reducing side effects.

1. SSRI antidepressants are believed to involve a chemical in the brain called serotonin. Serotonin is one of the "neurotransmitter" chemicals important in communication between nerve cells.

2. SSRIs reduce the amount of serotonin that is reabsorbed by the presynaptic neuron. As a result, more of this neurotransmitter remains in the synaptic gap for a longer time, which gives Pharmacological effect of some depressed people.

3. SSRIs are different from tricyclics, because they block only the reuptake pumps for serotonin, and not those for norepinephrine..

Beginning with the combination of SSRIs with other antidepressants, the following can occur:

I.Combining SSRIs with tricyclic and tetracyclic antidepressants can result in abnormal heart rhythms.

II.Combining SSRIs with monoamine oxidase inhibitors (MAOI's) can result in a very serious disease called serotonin syndrome.

A few examples....

Paroxetine

Fluoxetine

Sertraline

Escitalopram

Fluvoxamine

Citalopram

Tricyclic Antidepressants (TCAs)

Monoamine Oxidase Inhibitors (MAOIs)

Selective Serotonin Reuptake Inhibitors (SSRIs)

TCAs work mainly by increasing the level of norepinephrine in the brain synapses, although they also

may affect serotonin levels.

MAOIs elevate the levels of neuro-chemicals in the brain

synapses by inhibiting monoamine oxidase.

Selective serotonin reuptake inhibitors (SSRIs) are medications

that increase the amount of serotonin neuro-chemical in the

brain.TCAs impair the ability to break

down tyramine which cause dangerously high blood pressure

MAOIs impair the ability to break down tyramine which cause

dangerously high blood pressure

SSRIs do not interact with tyranine in food

TCAs produce severe side effects MAOIs produce severe side effectsSSRIs are generally well tolerated and side effects are usually mild

TCAs have more anticholinergic and

cardiovascular side effects

MAOIs have more anticholinergic and

cardiovascular side effects

SSRIs have fewer anticholinergic and

cardiovascular side effects

TCAs have fewer sexual and gastrointestinal side effects

MAOIs have fewer sexual and gastrointestinal side

effects

SSRIs have severe sexual and gastrointestinal side effects

TCAs are more toxic than SSRIs but less toxic than MAOIs.

MAOIs are the most toxic among the three.

SSRIs are the least toxic among the three.