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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 a, Sección Deptal. de Farmacología y Toxicología (Veterinaria), Depto. de Farmacología y Toxicología, Fac. de Veterinaria, Fac. de Farmacia, TRUE, pub

[Abstract] Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient’s disability and quality of life. However, mostly due to the heterogeneity of symptoms and the complexity of the underlying comorbidities, depression can be difficult to diagnose, resulting in limited recognition and in undertreatment. The early detection and treatment of depression simultaneously with the neurological disorder is key to avoiding deterioration and further disability. Although the neurologist should be able to identify and treat depression initially, a neuropsychiatry team should be available for severe cases and those who are unresponsive to treatment. Neurologists should be also aware that in neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, different depression symptoms could develop at different stages of the disease. The treatment options for depression in neurological diseases include drugs, cognitive-behavioral therapy, and somatic interventions, among others, but often, the evidence-based efficacy is limited and the results are highly variable. Here, we review recent research on the diagnosis and treatment of depression in the context of Alzheimer’s disease, Parkinson’s disease, and strokes, with the aim of identifying common approaches and solutions for its initial management by the neurologist.

The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature. In its original meaning (Walpole), serendipity refers to discoveries made through a combination of accidents and sagacity. We have implemented an operational definition of serendipity based on finding something unexpected or unintended, regardless of the systematic process that led to the accidental observation, and we have established four different patterns of serendipitous attributability. In this paper, we have analyzed the role of serendipity in the discovery and development of classical antidepressant drugs, tricyclic antidepressants and monoamine oxidase inhibitors as well as heterocyclic, “atypical” or “second generation” antidepressants. The discovery of the antidepressant properties of imipramine and iproniazid, the prototypes of tricyclic antidepressants and monoamine oxidase inhibitors, respectively, fits the mixed type II pattern; initial serendipitous discoveries (imipramine was an antipsychotic and iproniazid was an anti-tuberculosis agent) led secondarily to non-serendipitous discoveries. But the other components of these two families of drugs were developed specifically as antidepressants, modifying the chemical structure of the series leaders, thereby allowing all of them to be included in the type IV pattern, characterized by the complete absence of serendipity. Among the heterocyclic drugs, mianserin (originally developed as an antihistamine) also falls into the type II pattern., Depto. de Farmacología, Farmacognosia y Botánica, Fac. de Farmacia, TRUE, pub