 | Depression
Depression is the most common psychological problem in the US. Minor Depression can be attributed to normal depressed feelings that arise because of a specific life situation, a side effect of medication, hormonal changes or physical illness, and does not usually require treatment. Major Depression (depressive illness) is a serious condition that result in extreme fatigue, sleep problems and eventually an inability to function.
The exact cause is unknown, but it is thought to be a malfunction of brain neurotransmitters, which are chemicals that modulate moods. Major Depression is usually treated with a combination of psychotherapy and antidepressants which moderate or correct chemical imbalances in the brain. The group of antidepressants most frequently prescribed is the selective serotonin reuptake inhibitors (SSRIs) which regulate the neurotransmitter serotonin.Antidepressant Medications Selective serotonin reuptake inhibitors (SSRIs) are medications that increase the amount of the neurochemical serotonin in the brain. (Remember that brain serotonin levels are low in depression.) As their name implies, the SSRIs work by selectively inhibiting (blocking) serotonin reuptake in the brain. This block occurs at the synapse, the place where brain cells (neurons) are connected to each other. Serotonin is one of the chemicals in the brain that carries messages across these connections (synapses) from one neuron to another.
The SSRIs work by keeping the serotonin present in high concentrations in the synapses. These drugs do this by preventing the reuptake of serotonin back into the sending nerve cell. The reuptake of serotonin is responsible for turning off the production of new serotonin. Therefore, the serotonin message keeps on coming through. This, in turn, helps arouse (activate) cells that have been deactivated by depression, and relieves the depressed person's symptoms.
In the United States, SSRIs have been used successfully for a decade to treat depression. They have fewer side effects than the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), which are discussed below. SSRIs do not interact with the chemical tyramine in foods, as do the MAOIs. Also, SSRIs do not cause orthostatic hypotension and heart rhythm disturbances, like the TCAs do. Therefore, SSRIs are often the first-line treatment for depression. Examples of SSRIs include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft).
Dual Action Antidepressants: The biochemical reality is that all classes of medications that treat depression (MAOIs, SSRIs, TCAs, and atypical antidepressants) have some effect on both norepinephrine and serotonin, as well as on other neurotransmitters. However, the various medications affect the different neurotransmitters in varying degrees.
Some of the newer antidepressant drugs, however, appear to have particularly robust effects on both the norepinephrine and serotonin systems. These drugs seem to be very promising, especially for the more severe and chronic cases of depression. (Psychiatrists, rather than family practitioners, see such cases most frequently.)
Atypical antidepressants are so named because they work in a variety of ways. Thus, atypical antidepressants are not TCAs or SSRIs, but they act like them. More specifically, they increase the level of certain neurochemicals in the brain synapses (where nerves communicate with each other). Examples of atypical antidepressants include nefazodone (Serzone) and bupropion (Wellbutrin). The United States Food and Drug Administration (FDA) has also approved bupropion for use in weaning from addiction to cigarettes. This drug is also being studied for treating attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD). These problems affect many children and adults and restrict their ability to focus or concentrate on one thing at a time.
Monoamine oxidase inhibitors (MAOIs) are the earliest developed antidepressants. MAOIs elevate the levels of neurochemicals in the brain synapses by inhibiting monoamine oxidase. Monoamine oxidase is the main enzyme that breaks down neurochemicals, such as norepinephrine. When monoamine oxidase is inhibited, the norepinephrine is not broken down and, therefore, the amount of norepinephrine in the brain is increased.
MAOIs also impair the ability to break down tyramine, a substance found in aged cheese, wines, most nuts, chocolate, and some other foods. Tyramine, like norepinephrine, can elevate blood pressure. Therefore, the consumption of tyramine-containing foods by a patient taking an MAOI drug can cause elevated blood levels of tyramine and dangerously high blood pressure. In addition, MAOIs can interact with over-the-counter cold and cough medications to cause dangerously high blood pressures. The reason for this is that these cold and cough medications often contain drugs that likewise can increase blood pressure. Because of these potentially serious drug and food interactions, MAOIs are usually only prescribed after other treatment options have failed.
Tricyclic antidepressants (TCAs) were developed in the 1950's and 60's to treat depression. They are called tricyclic antidepressants because their chemical structures consist of three chemical rings. TCAs work mainly by increasing the level of norepinephrine in the brain synapses, although they also may affect serotonin levels. Doctors often use TCAs to treat moderate to severe depression.
Tetracyclic antidepressants are similar in action to tricyclics, but their structure has four chemical rings. Examples of tetracyclics include maprotiline (Ludiomil) and mirtazapine (Remeron), a drug that was discussed above under dual action antidepressants.
TCAs are safe and generally well tolerated when properly prescribed and administered. However, if taken in over-dose, TCAs can cause life-threatening heart rhythm disturbances. Some TCAs can also have anti-cholinergic side effects, which are due to the blocking of the activity of the nerves that are responsible for control of the heart rate, gut motion, and saliva production. Thus, some TCAs can produce dry mouth, constipation, and dizziness upon standing. The dizziness results from low blood pressure that occurs upon standing (orthostatic hypotension). Anti-cholinergic side effects can also aggravate narrow angle glaucoma, urinary obstruction due to benign prostate hypertrophy, and cause delirium in the elderly. TCAs should also be avoided in patients with seizure disorders and a history of strokes.
| |
