Experimental drugs for bipolar psychosis

ABSTRACT

Introduction: Psychotic features are common in bipolar disorder (BD), especially during acute mania. Even when early detected, their long-term management is difficult, essentially due to the unsatisfactory efficacy/tolerability profile of currently available treatments, thus soliciting the development of novel experimental drugs.

Areas covered: Potential drug targets towards the development of experimental drugs in the treatment of bipolar psychosis are yet to be systematically characterized. Among other potential avenues, the kynurenic acid pathway may represent an intriguing opportunity. Safer lithium alternatives should also be investigated in bipolar psychosis models.

Expert opinion: Regardless of the neurobiological pathways potentially worthy of investigation towards the development of experimental drugs in the treatment of bipolar psychosis, a number of unmet needs should be addressed. Primary goals of novel experimental drugs should be a better metabolic and cognitive tolerability profile, ultimately aiming to reduce the burden of acute psychotic mania and BD overall.

KEYWORDS:

• Experimental drugs
• bipolar disorder
• psychosis
• long-term management
• metabolic tolerability
• cognitive tolerability
• neuroprotection

Article highlights

• Bipolar disorder (BD) may present with psychotic features, especially during mania.

• Bipolar psychosis is associated with major clinical and treatment burden, yet both the number and pharmacological modalities are limited, either in terms of efficacy, safety or long-term tolerability, with a special emphasis towards the need for more tolerable cardio-metabolic and cognitive alternatives.

• Multiple experimental drug targets and potential avenues for the pharmacological treatment of bipolar psychosis have been briefly accounted in the text.

• Additional insights are needed about the neurobiology of bipolar psychosis, whereas both animal and clinical studies are virtually absent on the matter with the notable exception of very preliminary, yet encouraging data about the kynurenic acid pathway modulators in rodents.

• Regardless the neurobiological avenue(s) to expand in the future towards the development of experimental drugs for bipolar psychosis, improved metabolic and cognitive profiles should set as a priority for management of post-acute mood episode(s) associated with prominent psychotic features.

This box summarizes key points contained in the article.

Declaration of interest

M. Carta has received grants from Fondazione Banco di Sardegna, Regione Autonomadella Sardegna and the European Union. The authors have no other 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.

Additional information

Funding

This paper was not funded.