Discovery Patterns of Drugs Approved for Treating Bipolar Disorder by Applying Operational Criteria of Serendipity: A Historical Analysis

Abstract

While the scientific community has long acknowledged the significant role of serendipity in shaping the field of contemporary psychopharmacology, its impact has not undergone a comprehensive analysis using operational methodologies. Serendipity, originally defined as discoveries stemming from a blend of luck and astuteness by Walpole, has been operationalized by our research group. Our definition builds upon Walpole’s notion of fortuitous accidents and keen insight leading to the unexpected revelation of something unintended. We have discerned four unique serendipitous attributability patterns. In this paper, we delve into the historical aspect of how serendipity has played a role in the discovery and advancement of drugs approved for addressing different stages of bipolar disorder. The revelation of valproate’s antimanic properties aligns with the pure serendipitous pattern (type I). Conversely, the discovery of lithium’s antimanic effects corresponds to the mixed type II pattern, where the initial serendipitous observation of sedation in research animals, prompted by adding lithium salts to enhance uric acid solubility, led to the planned discovery of its calming impact on manic patients. On the contrary, the recognition of the mood-stabilizing attributes of lamotrigine aligns with the type III archetype. This particular pattern is defined by serendipity emerging as a consequence of a discovery that was initially nonserendipitous, as mood-stabilizing efficacy was incidentally observed during the treatment of epileptic patients for whom the drug was originally developed. Finally, carbamazepine and, notably, atypical antipsychotics fall within the type IV pattern. In this category, serendipity is entirely absent, as the antimanic use of carbamazepine was a straightforward extension of the use of other antiepileptic drugs. Atypical antipsychotics were introduced into bipolar disorder therapy through a deliberate and targeted design process, seeking drugs capable of acting on specific biological targets.