How tricyclic antidepressants work

If you haven't read a preface, I'd strongly recommend you to look through it: Part 1, 2, 3.

THE TRICYCLIC ANTIDEPRESSANTS

What are the tricyclics used for ?
Tricyclic antidepressants are used to improve mood in people who are feeling low or depressed. The tricyclics may also be used to help the symptoms of anxiety and a number of other symptoms. The tricyclics are the most commonly prescribed antidepressants but there are many other antidepressants. All these drugs seem to be equally effective at the proper dose but have different side effects to each other. If one drug does not suit you, it may be possible to try another.

How do the tricyclics work ?
The brains has many naturally occurring chemical messengers. Two of these are called serotonin (sometimes called 5-HT) and noradrenaline. Both are important in the areas of the brain that control or regulate mood and thinking. It is known that these two chemical messengers are not as effective or active as normal in the brain when someone is depressed. Tricyclic antidepressants increase the amount of these chemical messengers in the brain. This can help correct the lack of action of these messengers and help to improve mood. The tricyclics can also effect another chemical in the brain called "acetylcholine" and this is the cause of some of their side-effects.

"Reduced" nerve activity but with recycling blocked, and increased messages passes:

Side-effects:
Some antidepressants e.g. the tricyclics and venlafaxine, block the reuptake of serotonin and noradrenaline.
Unfortunately, these antidepressant drugs also affect other transmitter systems e.g. acetylcholine, dopamine, histamine etc. Some are a bit like "blunderbuss" treatments i.e. they hit the part that seems to be wrong, but also hit lots of other parts which aren't wrong. The side effects you get from drugs are from these extra "hits". The amount that these drugs effect different transmitters varies between drugs and is the reason you get slightly different side effects from each of the different drugs. These can include:

- If you block acetylcholine receptors, it may blunt your reactions, can produce mild sedation and confusion etc. as well as producing a dry mouth, blurred vision etc.
- Affecting your noradrenaline may also sometimes upset your blood pressure e.g. you may feel dizzy when you stand up etc.
- Too much serotonin and you may feel sick, less hungry, get headaches or migraines
If you block histamine receptors, it can make you feel drowsy (just the same as if you take an antihistamine tablet such as "Piriton" for hay fever or allergy).

Source

reade more... Résuméabuiyad

How SSRI antidepressants work

We continue listing different types of antidepressants. If you missed the preface, I'd strongly recommend you to read it here: PART 1, 2, 3

SPECIFIC SEROTONIN RE-UPTAKE INHIBITORS

"What are the SSRI's used for ?

SSRIs are antidepressants which are used to help to improve mood in people who are feeling low or depressed. Fluoxetine ("Prozac") may also be used to help treat the eating disorder "Bulimia nervosa". In addition to this, the SSRIs are now widely used to help a variety of other symptoms. These include anxiety (where a lower starting dose often helps), social phobia and social anxiety, obsessive-compulsive disorder, post-traumatic stress disorder, panic, pre-menstrual syndrome and agoraphobia. Some drugs are "licensed" (ie officially approved) for some of these conditions (e.g. paroxetine for social phobia) but this does not necessarily mean the others do not help, just one manufacturer can prove it and has applied for a licence.
Trazodone ("Molipaxin") and nefazodone ("Dutonin") are not strictly pure "SSRIs" but have many of the same effects and so are included in this group for convenience.
The SSRIs are now one of the most commonly prescribed antidepressants but there are many other similar drugs. All these antidepressants seem to be equally effective at the proper dose but have different side effects to each other. Apart from nausea, the SSRIs generally have less side effects than the older drugs. If one drug does not suit you, it may be possible to try another. Starting with a lower dose for a week or so may also help the drugs to be more tolerable or have less side effects.

How do the SSRI's work ?
The brains has many naturally occurring chemical messengers. One of these are called serotonin (sometimes called 5-HT) and is important in the areas of the brain that control mood and thinking. It is known that this serotonin is not as effective or active as normal in the brain when someone is feeling depressed. The SSRI antidepressants increase the amount of this serotonin chemical messenger in the brain. This can help correct the lack of action of serotonin and help to improve mood."

"Reduced" nerve activity but with recycling blocked, and increased messages passes:

Side-effects:
SSRI antidepressants mainly block the reuptake of just serotonin. This why they are called the SSRIs ie. Selective Serotonin Reuptake Inhibitors.
Many other antidepressant drugs also affect other transmitter systems e.g. acetylcholine, dopamine, histamine etc. and have many side effects. SSRIs really only block the reuptake of serotonin, and so have less side effects. However, they still have some side effects ;-
- Too much serotonin in some parts of the brain can make you feel sick, less hungry and get headaches or migraines.

Source

reade more... Résuméabuiyad

How MAOI Antidepressants work

Now let us look carefully at different types of antidepressants. But before doing this, I'd strongly recommens you to read the preface (Parts 1, 2, 3) before you continue to specific types of medicines.

Mono-Amine Oxidase Inhibitors

As we understood from the preface,

"There are many chemical messengers (or "neurotransmitters") called "monoamines" which occur naturally in the body. One of the effects that monoamines have is on mood. If the levels of monoamines in the body are high we may feel 'high', and if they are low we may feel 'low'. MAOIs stop the breakdown of these monoamines. They block the monoamine oxidase enzyme which breaks down the transmitter, so the next time an impulse comes along, there is more transmitter, a stronger message is passed, and activity in that part of the brain is increased. By stopping the breakdown of these, the MAOIs may bring back the amounts of monoamines to normal. This helps to improve mood in people who are feeling low or depressed."

"Reduced" nerve activity but with (mono-amine oxidase) enzyme blocked (or inhibited), and increased messages passed:

Side-effects:
Some antidepressants e.g. the tricyclics, block the reuptake of serotonin and noradrenaline. Others mainly block the reuptake of just serotonin e.g. the SSRIs. The MAOIs block the monoamine enzyme which breaks down noradrenaline, serotonin and some other transmitters. They are Monoamine Oxidase Inhibitors.
Unfortunately, the MAOIs also block an enzyme in the body which breaks down other compounds. One of these is an amino acid called tyramine. Tyramine is an essential compound which the body needs, and is found in many foods. However, if you have too much tyramine in the body, it can make your blood pressure rise. Foods such as cheese, yeast and meat extracts etc contain lots of tyramine. If you eat any of these foods while taking an MAOI, your body can not break down (or metabolise) the tyramine. You then get an excess of tyramine in the body, which increases your blood pressure very quickly. This can at cause headaches initially but can be very dangerous and has caused many deaths.
The MAOIs also affect other transmitters which are broken down by the MAO enzyme.
- Affecting your noradrenaline may also sometimes upset your blood pressure e.g. you may feel dizzy when you stand up etc.

Source.

reade more... Résuméabuiyad

How antidepressants work. PART 3

Here is the last part of the material about Antidepressants and it is actually about them. After 2 long and sweet parts of a preface here is the last one which describes depression build-up process.

"5. Depression

People with depression usually have problems with poor sleep, low mood and appetite, loss of energy and interest or pleasure etc. It is a common illness, affecting 3% of the population per year. The main theory about why this happens is the so-called "monoamine hypothesis".

We know that serotonin and noradrenaline in the brain are involved with control of sleep/wake, emotions, mood, arousal, emotion, drive, temperature regulation, feeding etc. Thus, if a person has too little serotonin and noradrenaline in the part of the brain that controls mood, this will produce too little activity, and that part of the brain become slower and less effective. This will lower mood.

In depression, it is known that there are reduced levels of serotonin and noradrenaline. These reduced levels lead to a lowering of mood. The full reasons are not fully known but stress may well play a part in causing this.

"Normal" communication between cells:

"Reduced" nerve activity e.g. as in depression:

There are lots of other theories about how depression occurs e.g. genetics, how the brain develops, stress etc. There may in fact be many causes and in each person there may be a combination of these. Stress may in fact cause changes in the brain which then result in reduced levels of serotonin and noradrenaline. Transmitters other than much serotonin and noradrenaline are probably also involved.

reade more... Résuméabuiyad

How antidepressants work. PART 2

Here goes the second part of the material. This one is about neurotransmitters's and receptors' work.

"3. What happens when a message is passed from one cell to another.

1. A brain cell decides to send a message to another cell in order to make something happen e.g. tighten a muscle, release a hormone, think about something, pass on a message etc.

2. An electrical impulse is sent from the brain cell down one of the nerve fibres/neurones towards the end. It travels at about 120 miles per hour.

3. This message or impulse arrives at the end of the nerve fibre. When it arrives, a chemical ("transmitter") is released from the nerve end.

4. The transmitter is then released and travels across the gap between the first nerve fibre and the next/receiving one.

5. The transmitter hits a receptor on the other side. It fits into it just like a key fitting into a lock.

6. When the transmitter hits the receptor, the receptor changes shape. This causes changes inside the nerve ending which sets off an electrical message in that nerve fibre on to the next brain/nerve cell. This sequence then carries on until the effect occurs e.g. the muscle moves etc.

7. The transmitter is either broken down by enzymes (10%) and removed or taken back up again into the nerve ending (i.e. recycled) - a process known as re-uptake.

8. The nerve fibre and synapse is then ready for next message

Important points:- The passage of messages only works one way or one direction- There is only one type of transmitter per synapse- The transmitter allows an electrical message to be turned into a chemical message and back into an electrical message.

4. "Transmitters"

Although there are over 80 known different "transmitters" in the brain, each nerve ending only has one type. These "neurotransmitters" tend to be grouped together and each seems to have specific roles e.g.:

Serotonin or 5-HT - In the brain, it controls mood, emotions, sleep/wake, feeding, temperature regulation, etc.Too much serotonin and you feel sick, less hungry, get headaches or migraines.Too little and you feel depressed, drowsy etc.

Dopamine - there are three main groups (or pathways) of dopamine neurones in the brain.In the brain, one group controls muscle tension and another controls e.g. emotions, perceptions, sorting out what is real/important/imaginary etc.Not enough dopamine in the first group and your muscles tighten up (e.g. as in Parkinson's Disease).Too much dopamine in the second group gives you an overactive brain i.e. too much "perception e.g. you may see, hear or imagine things that are not real

Noradrenaline (NA) - (sometimes called "norepinephrine" or NE)In the brain, it controls sleep, wakefulness, arousal, mood, emotion and drive.Too much noradrenaline and you may feel anxious, jittery etc.Too little and you may feel depressed, sedated, dizzy, have low blood pressure etc.

Acetylcholine (ACh) - In the brain, it controls arousal, the ability to use memory, learning tasks etc.Too much in your body and your muscles tighten up.Too little can produce dry mouth, blurred vision and constipation, as well as becoming confused, drowsy, slow at learning etc.

Glutamate - Acts as an "accelerator" in the brainToo much and you become anxious, excited and some parts of your brain may become overactive.Too little and you may become drowsy or sedated

GABA - Acts as a "brake" in the brainToo much and you become drowsy or sedated.Too little and you may become anxious and excited

In many mental health problems, it is known that some of these transmitters get out of balance e.g. you have too much or too little of a particular transmitter."

Seems like now you should understand the basic processes in your brain. Now let's head to PART 3 and see how depression develops.

reade more... Résuméabuiyad

How antidepressants work. PART 1

Today I searched for some clear explanation on how SSRI antidepressants work, that will not resemble an encyclopedic article with dozens of medical terms on top of each other.

And I’ve found it. Call it love from the first sight if you wish but the article I am quoting below is amazingly clear and simple for understanding. I am dividing it into 3 parts + several separate posts about each type of antidepressants. First part explains how our brain works. Second part gives a basic review on neuron transmitters. Third part – and depression develops.
If you have a clear picture on these subjects you may then skip these parts and move to medications descriptions.

PART 1

1. The brain

“In order to try to understand a little about how drugs work, it is best to first learn a few facts about the brain. Each human being has: One head. One brain. Each brain has somewhere around 10,000,000,000 brain cells. Each brain cell has lots of connections with other brain cells by means of nerve fibres (the wiring connecting brain cells together). There are about 4 million miles of nerve fibres in each brain. Some fibres may have up to 10,000 branches in them. Each brain cell has lots of connections with other cells, possibly over 25,000! The junctions at the end of the neurones are called synapses.

2. A Synapse

Synapses are very important because:
They are the route by which brain cells talk to each other
Synapses are of the same basic design in the brain, the heart, the legs etc.
There are a lot of them If we can get chemicals (e.g. drugs) into the gap between them in the brain, we can affect the way in which brain cells talk to each other e.g. we can slow the messages down, speed the up etc.

A synapse looks like this:

In the drawing you will see the following:

- Axon - A neurone (or cell body) has many axons (or nerve fibres).
- Vesicles - these contain the transmitter.
- Transmitters - these are small chemicals used by brain cells as messengers. They are stored in the vesicles in the nerve ending ready to be released
- Receptors - these are structures on the surface of the receiving cell which have a space designed just for the transmitter (if the transmitter is a key, receptors are the lock into which they fit)
- Enzymes - these surround the synapse and break down any spare transmitter that might leak out to other synapses nearby. - Electrical signal - This is the way in which one brain cell sends a message to another. The signal travels down the nerve fibre rather like an electrical "Mexican Wave".”

Sounds pretty simple, huh? Let’s move to PART 2

reade more... Résuméabuiyad

Sleeping disorders and depression

Sleeping disorders are known to be one of the common symptoms of depression. However, the relationship between insomnia and depression is more complicated where one effects another and vise versa.

The key factor is Melatonin - "the hormone of darkness".

"What is Melatonin

Melatonin is a naturally occurring hormone secreted by the pineal gland, a pea-size structure at the center of the brain. As our eyes register the fall of darkness and the onset of night melatonin is produced. It signals to our body to prepare for sleep, our blood pressure dips, there is a decrease in body temperature and we start to feel sleepy

Melatonin & Depression

Melatonin is an important nighttime hormone associated with sleep and regeneration. However, excessive levels or daytime melatonin can cause depressive disorders. Medical research confirms the relationship between melatonin and mood disorders. The following paragraphs explain how melatonin works and why it causes depression.

Darkness & Melatonin

Melatonin is normally released by the pineal gland in the evening as sunlight is diminishing. Melatonin causes us to feel tired and withdraw. This helps us to sleep, but if we have to be awake when melatonin is in our system, we become lethargic, disoriented, irritable and moody. This explains why shift work and jet lag can be so debilitating, and why depression rates are highest in darker climates. Almost everyone with a mood disorder suffers worse in the winter because of excess melatonin in his or her system."

Source

Thus you are right to make a conclusion that sunlight is one of the tips on how to cure depression. It may sound simple yet be difficult to follow. When depressed we tend to seek for dark colors. Even subconsciously you will wear dark-colored clothes, sit at home with drawn curtains, place dark-colored furniture in your room and think that you feel comfortable, while your melatonin levels grow higher and worsen your state little by little. All you need to stop it is to go for a walk. Shopping can be a nice idea if you decide to buy some bright-colored clothes. Especially it will be useful to take some friends with you which is both fun and can help to improve your mood.

reade more... Résuméabuiyad

Principles of depression

Low mood, Anxiety, Delusions, Memory and concentration problems, Loss of interest in things you used to enjoy - one may think these are no big deal but just a normal reaction to stress at work, overdue bills, taxes, family quarrels or whatever.

However, when these symptoms are followed by sleep problems (either insomnia or oversleeping), eating disorders (increase or decrease in appetite), constipation, period irregularities, decreased libido, constant feeling of tiredness - one of the most possible diagnosis’ is depression.

It is obvious that to get over negative symptoms of a sickness one should understand it's origin. In this post I would like to quote one of the clearest yet simple explanations on how depression occurs I've ever read:

"The stress system relies on two key hormones: adrenaline and cortisol. In short, adrenaline works in the short term, while cortisol has large momentum and works in the long term.

It is important to realize that the stress system can also be activated if your brain perceives danger or any kind of threat. In the first stage, this triggers the release of adrenaline into the bloodstream to prepare the body for action. As a result, your heart beats faster, you begin to sweat, your breath becomes shallower, and your senses become more acute. This is the so-called fight or flight response to the stressor event, and was quite adequate during most of our evolution, when these events were quite specific and usually short-term. Problems with chronic stress arise because in a modern society we cannot escape easily from the stressor, be it an overbearing boss, crowded cities, or traffic jams.

The effect of the stress hormones on the brain is curious and not what you might expect. The initial surge of adrenaline will make you feel good, though not quite in the same way as with serotonin. The difference is that adrenaline will make you feel euphoric and accelerated, whereas serotonin produces a state which could be described as that of quiet bliss. However, as far as the communication between neurons is concerned, adrenaline can compensate for low levels of serotonin. There is, alas, a serious drawback of adrenaline: together with it comes cortisol, the yang of the stress hormones.

Just as your levels of adrenaline start coming down, so rises the amount of cortisol flowing through your veins. Moreover, cortisol has a much larger momentum than adrenaline, which means that even though it builds up slowly, it also takes a long time to go back to normal. And should you constantly be engaging in activities which require adrenaline, so will your levels of cortisol slowly increase. Together with the rise of cortisol and the decrease of adrenaline, come the nasty side-effects of the stress hormones. It is at this moment that you feel bad, anxious, and having lots of negative thoughts.

To complete the picture of how chronic stress causes depression, there remains one critical factor to be explained: high-levels of stress hormones will over time diminish your brain's ability to produce serotonin. The exact mechanism by which this happens is still subject to discussion, but the general consensus is that sleep is the key. The reason is that higher levels of stress hormones mean less sleep, which is fundamental for the brain to restore its ability to produce serotonin".

from: Demystifying Depression by Name of Feather

If you came this far, I hope you have understood the basics of how the depression build-up works: More stress hormones mean less happiness hormones which means depression. Now as we know the roots of evil we may proceed to cure methods.

reade more... Résuméabuiyad