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

AbstractOBJECTIVES:
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.
AuthorsMichael J Ostacher, Dan V Iosifescu, Aleena Hay, Sarah R Blumenthal, Pamela Sklar, Roy H Perlis
JournalBipolar disorders (Bipolar Disord) Vol. 16 Issue 2 Pg. 199-203 (Mar 2014) ISSN: 1399-5618 [Electronic] Denmark
PMID24372835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Chemical References
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Isradipine
Topics
  • Adult
  • Bipolar Disorder (drug therapy)
  • Calcium Channel Blockers (therapeutic use)
  • Calcium Channels, L-Type (genetics)
  • Female
  • Genome-Wide Association Study
  • Humans
  • Isradipine (therapeutic use)
  • Male
  • Middle Aged
  • Pilot Projects
  • Psychiatric Status Rating Scales

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