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Until the 1950s, psychiatrists had very few options for dealing with the problem of serious depression. Then, in 1951 came a major breakthrough. Iproniazid, a drug that was developed for the treatment of tuberculosis, was observed to have ameliorative effects on patients with depression. The age of antidepressant medication had begun.

The monoamine oxidase inhibitors (MAOIs), like Iproniazid, were the first widely prescribed antidepressants. Our interest in these is largely historical, although two such medications remain available today--Parnate and Nardil. I will touch on this section briefly as these are very difficult medications to use and have over the years not been demonstrated to be as effective as other medications available.

Later in the 1950s came the second wave of antidepressants, the tricyclic antidepressants (TCAs), and their second generation cousins, the heterocyclic antidepressants (HCAs). These became the mainstay of antidepressant pharmacological treatment from the mid-fifties through the late eighties, when the SSRIs were introduced.

In 1987, however, the whole arena of antidepressant medications underwent a substantial revolution with the advent of the SSRI class of medications. This group includes Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), Luvox (fluvoxamine) and Celexa (citalopram).

SSRI medications, for any reader who may not know, stands for Selective Serotonin Re-uptake Inhibitors. As the name indicates, they are medications who work primarily by inhibiting the re-uptake of serotonin. The antidepressant effect comes from more serotonin being available to work in certain regions of the limbic system, producing changes in mood and level of anxiety, among other possible effects.

These new antidepressants, while not without their own side-effects, seemed to generate very positive responses for certain kinds of depression, without some of the more dangerous, uncomfortable and serious side-effects of earlier generations of antidepressants.

These are the three major groups or families of antidepressants. There are also some medications we will look at that do not fit neatly into any of these three groups. The first of these is Wellbutrin, which is classified as an aminoketone medication. The mechanisms by which this works as an antidepressant, quite frankly, are not fully understood.

Wellbutrin seems to work on depression by increasing norepinephrine and dopamine, instead of serotonin. Wellbutrin is also marketed for use in smoking cessation under the trade name of Zyban. While there are some side effects that show up in use with Wellbutrin, it is a generally safe medication that offers considerable therapeutic effects.

Then there are Effexor (venlafaxine), Serzone (nefazodone) and Remeron (mirtazapine). These are medications that work on both the serotonin mechanisms - in ways similar to the SSRI medications - and on the norepinephrine mechanisms. These are sometimes referred to as dual-effect antidepressants.

Serzone and Remeron also seem to have a chemical blocking effect on certain receptor sites (5-HT2 and 5-HT3, to be technical) in the brain that may be related to some of the side effects from antidepressants. This means that these medications may lead to a better side-effect profile. This is part of the pharmaceutical industry's search for improved antidepressants: families of medicines that are effective on the different kinds of depression with few or no side-effects.

There are already several new drugs in the pipeline that are attempts to move in that direction. While these efforts move forward, however, the task of professionals engaged in the business of helping people is to utilize the tools at hand in a way that best takes care of the needs of the very real people seeking help. This involves careful assessment, close examination of the trade-offs between what works for the symptoms seen, and what uncomfortable effects are caused by the medicines used.
Moving forward from here, we will try to examine the armament of medications available in more detail. This will involve not only the chemical facts of each of the drugs in question, but the whole landscape of very practical experience of prescribing these medications to real people over many years.

While mental health clinicians will not be in the position to make these complicated decisions about which medication to use, they will be partners in working with these very real patients. It is therefore important that they have some familiarity with the antidepressants that are being used, and some knowledge of why they are being used.

Mental health clinicians, armed with this knowledge, become much better partners to the psychiatrists and other doctors who will be required to direct the course of medication. They can speak with greater certainty when they see clients who stray from a well-planned medication regimen, and more authoritatively direct the client back to the prescribing physician for better medical care.

This course will not be comprehensive in the sense that we will not have time to look at every antidepressant medication that has ever been created. Such a list would have over 80 medications on it, with more being added all the time. We will also not delve too deeply into the complex chemistry of depression and the medications used to treat this disorder.

We will provide enough to help the mental health clinician understand his or her role in supporting the purposes of using medication, but not so much that more confusion is created.

To aid in this purpose, we will present pages that will provide a concise and detailed summary of the important information about each medication we will discuss, including the year each medication was introduced. These summary pages are designed so that the trainee can easily print them, and keep them as a resource to be referred to in clinical work.

This will allow something more durable to remain from the training program undertaken, and will support the clinician's ongoing learning. Towards this end, let us proceed.
Review Questions for Section III

At this point in the training, you should be able to answer the following questions:

1. What are the three major kinds of antidepressants?
2. What are dual action antidepressants?
3. What commonly used antidepressant doesn't fit into any of the major groups?