Psychopharmacology: From serendipitous discoveries to rationale design, but what next?

Abstract

Psychopharmacology really developed as a discipline from the mid-20th century with the discovery of a number of new classes of psychoactive drugs which could modify behaviour. These drugs were discovered as a consequence of clinical observations of patients, often being treated for other conditions. These serendipitous discoveries were the start of an era of drug development which has led to the antidepressants, antipsychotics, anxiolytics and mood stabilisers used today. Subsequent research focused on understanding why these drugs were effective, and used this information to develop a second generation of drugs that were more selective for their therapeutic targets, and therefore had reduced side effects and improved safety and tolerability. After a period of decline in new discoveries and withdrawal of the majority of the major pharmaceutical companies from active development programmes in psychiatry, new avenues are emerging fuelling renewed interest in this area.

Keywords: Psychiatry; animal models; antidepressants; antipsychotics; behaviour.

Figure 1.

Drugs have been used to modify behaviour throughout humanity; however, the clinical use of drugs for specific conditions really developed from the start of the 20th century. This overview illustrates the timeline associated with the major classes of drugs used to treat psychiatric disorders. Although defined by their therapeutic target, the figure also indicates (arrows) where the same drugs have multiple therapeutic indications. An alternative approach to classification of psychiatric drugs is based on their psychopharmacology. Referred to as ‘Neuroscience-Based Nomenclature’ (http://www.nbn2.com/), this initiative has recategorised these drug treatments based on their pharmacology and mode of action rather than their first therapeutic indication.

Box 1.

Role of animal models in psychopharmacology.

Box 2.

Examples of some of the new methods and areas of development relevant to the future of psychopharmacology.

Figure 2.

Overview of an approach to develop better translational behavioural methods to study relevant neuropsychological characteristics of psychiatric disorders and improve integration of fundamental biology, preclinical drug discovery and development, and clinical studies. See also discussion in Robinson, 2018 in relation to major depressive disorder.