Innovative approaches to bipolar disorder and its treatment.
All psychiatric disorders have suffered from a dearth of truly novel pharmacological interventions. In bipolar disorder, lithium remains a mainstay of treatment, six decades since its effects were serendipitously discovered. The lack of progress reflects several factors, including ignorance of the disorder's pathophysiology and the complexities of the clinical phenotype. After reviewing the current status, we discuss some ways forward. First, we highlight the need for a richer characterization of the clinical profile, facilitated by novel devices and new forms of data capture and analysis; such data are already promoting a reevaluation of the phenotype, with an emphasis on mood instability rather than on discrete clinical episodes. Second, experimental medicine can provide early indications of target engagement and therapeutic response, reducing the time, cost, and risk involved in evaluating potential mood stabilizers. Third, genomic data can inform target identification and validation, such as the increasing evidence for involvement of calcium channel genes in bipolar disorder. Finally, new methods and models relevant to bipolar disorder, including stem cells and genetically modified mice, are being used to study key pathways and drug effects. A combination of these approaches has real potential to break the impasse and deliver genuinely new treatments.
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.|Oxford Health NHS Foundation Trust, Oxford, United Kingdom.
Paul J
PJ
Harrison
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.|Oxford Health NHS Foundation Trust, Oxford, United Kingdom.
Andrea
A
Cipriani
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.|Oxford Health NHS Foundation Trust, Oxford, United Kingdom.
Catherine J
CJ
Harmer
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.|Oxford Health NHS Foundation Trust, Oxford, United Kingdom.|Oxford Centre for Human Brain Activity, Warneford Hospital, Oxford, United Kingdom.
Anna C
AC
Nobre
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.|Oxford Health NHS Foundation Trust, Oxford, United Kingdom.
Kate
K
Saunders
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.|Oxford Health NHS Foundation Trust, Oxford, United Kingdom.
Guy M
GM
Goodwin
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.|Oxford Health NHS Foundation Trust, Oxford, United Kingdom.
John R
JR
Geddes
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods* / Q000639:trends; D006801:Humans; D035703:Therapies, Investigational / Q000379:methods / Q000639:trends; D016896:Treatment Outcome
D000928:Antidepressive Agents; D014150:Antipsychotic Agents
bipolar disorder; clinical; genetics; mood; therapy