Pilot investigation of isradipine in the treatment of bipolar depression motivated by genome-wide association

Authors

  • Michael J Ostacher,

    1. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
    Search for more papers by this author
  • Dan V Iosifescu,

    1. Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
    Search for more papers by this author
  • Aleena Hay,

    1. Department of Psychology, Yale University, New Haven, CT, USA
    Search for more papers by this author
  • Sarah R Blumenthal,

    1. Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA
    Search for more papers by this author
  • Pamela Sklar,

    1. Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
    Search for more papers by this author
  • Roy H Perlis

    Corresponding author
    1. Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA
    • Corresponding author:

      Roy H. Perlis, M.D., M.Sc.

      Department of Psychiatry

      Center for Experimental Drugs and Diagnostics

      Massachusetts General Hospital

      Simches Research Building

      185 Cambridge Street, 6th Floor

      Boston, MA 02114

      USA

      Fax: 617-643-3080

      E-mail: rperlis@chgr.mgh.harvard.edu

    Search for more papers by this author

Abstract

Objectives

Motivated by genetic association data implicating L-type calcium channels in bipolar disorder liability, we sought to estimate the tolerability, safety, and efficacy of isradipine in the adjunctive treatment of bipolar depression.

Methods

A total of 12 patients with bipolar I or II depression entered this pilot, proof-of-concept eight-week investigation and 10 returned for at least one post-baseline visit. They were initiated on isradipine at 2.5 mg and titrated up to 10 mg daily, with blinded assessments of depression using the Montgomery–Åsberg Depression Rating Scale (MADRS) as well as adverse effects.

Results

Among the 10 patients, three had bipolar II disorder; all but two reported current episode duration longer than six months. In all, four of 10 completed the study; no significant adverse events were observed, although one subject discontinued treatment per protocol because of possible hypomanic symptoms which had resolved prior to study visit. In a mixed-effects model, mean improvement in depression severity, assessed by MADRS, was 2.1 (standard error = 0.36) points/week (p < 0.001). Two of the 10 subjects remitted and four of the 10 subjects experienced 50% or greater symptomatic improvement with treatment.

Conclusions

Isradipine merits further investigation for the treatment of bipolar depression. This preliminary trial illustrates the potential utility of genetic investigation in identifying psychiatric treatment targets.

Ancillary