History of the Treatment of Depression:

The history of the treatment of depression is hard to put a date on. In the early years of treatment there was little or no distinction between mental disorders as we know them today. Depression was not recognized as a unique problem and therefore did not receive unique treatment.

One of the earliest forms of depression specific treatment was psychoanalysis, a method developed by Sigmund Freud in the late 1800's. In the 1930's electroconvulsive therapy was utilized, but again, there was not always a distinction made between persistent mental disorders. In 1949 the National Institute of Mental Health (NIMH) was founded to conduct research into mind, brain, and behavior and thereby reduce mental illness.

There are now several major types of antidepressant drugs, but the earliest found to successfully treat depression were the monoamine oxidase inhibitors (MAO-Is) and tricyclic antidepressants. Like many pharmacological breakthroughs, the first major antidepressant was discovered by accident.

Iproniazid (the first MAO inhibitor) itself was originally developed to fight tuberculosis. In addition to effectively treating tuberculosis, Iproniazid was observed to elevate mood and stimulate activity in many patients. These effects led researchers to investigate the ability of Iproniazid to treat the symptoms of depression.

The evolution of MAOI antidepressants has been primarily one of increasing specificity of action. As our knowledge of brain chemistry and physiology advances were are increasingly able to target increasingly specific areas of monoamine dysfunction while eliminating side effects. The term "selective" is often heard here, denoting the ability of a drug to alter the properties of desired brain circuits while leaving others intact.

Around the same time Iproniazid and the early tricyclic antidepressants were being studied. Imipramine, the first Tricyclic antidepressant, was discovered in 1950 by clinicians searching for new antipsychotics. The drugs were marketed as antidepressants in the 1960's. While they were some of the earliest antidepressants released, they now play second fiddle to the much safer SSRIs.

The development of SSRIs happened in a very short period of time beginning in the 1970's. How SSRIs were developed is acknowledged as a major scientific breakthrough. SSRIs were the first purposefully designed class of psychotropic medications and are credited with marking a new era in psychotropic drug development. Prior to SSRIs, all psychotropic medications, including MAO-Is and Tricyclics, were the result of chance observation. The rational used to develop SSRIs was to design a new drug that could target a specific neural site of action, in this case uptake pumps, while avoiding effects on other sites such as receptors. The idea was to produce agents that are more selective and therefore more effective, safer, and better tolerated than older medications. The marketing of SSRIs began in the 80's with Prozac and has been booming ever since.