Schizophrenia is a major problem in the field of psychiatric diseases, with a lifetime prevalence of 0.8% to 1% in the general population. It induces feelings of helplessness, illustrated by a suicidal rate in this group of patients 10 to 12 times higher than in the general population.

Antipsychotics have proven valuable in the management of patients with schizophrenia, both in the relief of acute symptoms of psychosis and in the prevention of recurrence of illness. However, the "typical" antipsychotics (such as haloperidol) are far from ideal. Typical antipsychotics appear largely ineffective against the negative and depressive features of schizophrenia, they are of limited value in relieving the cognitive impairments that result from prolonged illness, and are associated with severe side effects such as extrapyramidal symptoms (EPS), tardive dyskinesia and prolactin increase.

The development of the thienobenzodiazepines was part of a large program within Lilly to investigate benzodiazepine analogues. These tricyclic derivatives form a large and diverse group of compounds, many of which have pronounced and varied central nervous system activity. Zyprexa^® (olanzapine, LY170053, 2-methyl-4-(4-methyl-1-piperazinyl)-10 H-thieno-[2,3-b][1,5]benzodiazepine) possesses nanomolar affinity at a range of neurotransmitter receptors recently implicated in the pathophysiology of schizophrenia. The dose of olanzapine needed to affect conditioned avoidance response was found to be significantly lower than the dose that causes catalepsy. These data predict that olanzapine would be an effective antipsychotic with minimal EPS liability. Clinical data have confirmed that olanzapine is effective against both positive and negative symptoms of schizophrenia and that the compound causes minimal EPS and no increase in prolactin levels.

In September 1995, the European Union (centralised process) and US registrations of olanzapine were submitted. This event represented a historic achievement for Eli Lilly and Company’s development and regulatory organisations. The EU decision granting the marketing authorisation for Zyprexa was signed in Brussels on September 27, 1996, one working day before the FDA approved the New Drug Application in the US. The first sales of olanzapine were made in both territories during September.

Since its launch over 3.5 million patients have been treated with olanzapine in nearly 80 countries worldwide. As a result of this rapid market penetration, the launch has proven to be the most successful for an antipsychotic ever recorded with sales to date in excess of $3.5 billion.