Progress in bipolar disorder drug design toward the development of novel therapeutic targets: a clinician’s perspective

ABSTRACT

Introduction: Bipolar disorder (BD) is a considerable burden to the affected individual. The need for novel drug targets and improved drug design (DD) in BD is therefore clear.

Areas covered: The following article provides a brief, narrative, clinician-oriented overview of the most promising novel pharmacological targets for BD along with a concise overview regarding the general DD process and the unmet needs relevant to BD.

Expert opinion: A number of novel potential drug targets have been investigated. With the notable exception of the kynurenine pathway, available evidence is too scarce to highlight a definitive roadmap for forthcoming DD in BD. BD itself may present with different facets, as it is a polymorphic clinical spectrum. Therefore, promoting clinical-case stratification should be based on precision medicine, rather than on novel biological targets. Furthermore, the full release of raw study data to the scientific community and the development of uniform clinical trial standards (including more realistic outcomes) should be promoted to facilitate the DD process in BD.

KEYWORDS:

• Bipolar disorder (BD)
• drug design
• novel therapeutic targets

Article highlights

• Bipolar disorder (BD) is source of significant burden for the suffering patient and his/her caregivers.

• BD neurobiology is complex and largely unknown.

• As consequence, ‘rational’ drug design (DD) and ‘rational’ investigation of novel drug targets is substantially tentative.

• Regrettably, serendipity still play a major role in advancing and broadening the pharmacological portfolio for BD.

• Among other potential novel drug targets, the kynurenine, GSK-inhibition and other lithium-related pathways seems to represent the most promising avenue.

• From a clinical perspective, clear-cut stratification of BD accounting for neuroprogression over the time as well as the age at onset and other clinically-meaningful moderators should be promoted towards rational DD.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. One referee is an employee of Novartis Institutes of Biomedical Research. Novartis produce agents for bipolar disorder.

Additional information

Funding

This manuscript has not been funded.