Monoamine Oxidase Antidepressant

1.Introduction
The incidentally discovery of monoamine oxidase inhibotor (MAOI) iproniazid and the tricyclic antidepressant (TCA) imipramine in the late 1950s were major breaktroughs in the treatment of depression. The discovery of imipramine initiated a search for new tricyclic antidepressants.
Lundbeck (pharmaceutical company) developed new patentable syntheses three drugs as amitriptyline (1), nortriptyline (2), melitracen (3) and entered the market with these products at early 1960s. However, TCAs has several serious side effects, such as dryness of the mouth, constipation, confusion, dizziness, sedation, orthostatic hypotension and tachycardia.
For that several serious side effects of TCAs chemists started to look for ways to improve TCAs.

The basis was thus established for clinical studies in patients with a view to obtaining marketing authorisation. Normally, studies are carried out to show the relationship between effect/side effects and dosage. However, on the basis of data from earlier studies with citalopram, and the pharmacological studies with escitalopram, it was possible to predict which doses of escitalopram were likely to show a clinically relevant effect. It was therefore not necessary to conduct preliminary studies in patients (phase II), and Lundbeck could move on directly to large-scale studies in patients (phase

In these studies, the effect of escitalopram was compared to that of an inactive control (placebo). The clinical studies were coducted on three continents and in 21 countries. Approximately 170 centres participated in the studies, and recruitment of the more than 2,000 patients was completed in record time. Since SSRIs are mainly perscribed in general practice, it was extremely important for the studies to be conducted in a primary care setting. The studies were therefore conducted in a specialist setting and in general