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Inositol augmentation of lithium or valproate for bipolar depression

Authors

  • A Eden Evins,

    1. Harvard Bipolar Research Program and Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Christina Demopulos,

    1. Harvard Bipolar Research Program and Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Iftah Yovel,

    1. Harvard Bipolar Research Program and Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Melissa Culhane,

    1. Harvard Bipolar Research Program and Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Jacqueline Ogutha,

    1. Harvard Bipolar Research Program and Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Louisa D Grandin,

    1. Harvard Bipolar Research Program and Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Andrew A Nierenberg,

    1. Harvard Bipolar Research Program and Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • Gary S Sachs

    1. Harvard Bipolar Research Program and Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • This work has been presented in part at the Annual Meeting of the Stanley Medical Research Institute, Washington, DC, November 8–9, 2002; at the 5th International Conference on Bipolar Disorder, Pittsburgh, PA, June 2003; and at the 156th Annual Meeting of the American Psychiatric Association, San Francisco, CA, May 2003.

  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

A Eden Evins, MD, MPH, MGH Schizophrenia Program, 25 Staniford Street, Boston, MA 02114, USA. Fax: +1 617 723 3919;
e-mail: a_eden_evins@hms.harvard.edu

Abstract

Objective:  Despite promising new therapies, bipolar depression remains difficult to treat. Up to half of patients do not respond adequately to currently approved treatments. This study evaluated the efficacy of adjunctive inositol for bipolar depression.

Methods:  Seventeen participants with DSM-IV criteria for bipolar depression and a 17-item Hamilton Rating Scale for Depression (HRSD) ≥15 on proven therapeutic levels of lithium or valproate for >2 weeks were randomized to receive double-blind inositol or placebo for 6 weeks. At the end of double-blind treatment, subjects were eligible for an 8-week open-label trial of inositol.

Results:  Response was defined a priori as >50% reduction in the HRSD and a Clinical Global Impression of 1–2. Four of nine subjects (44%) on inositol and zero of eight subjects on placebo met response criteria (p = 0.053). There was no difference between groups in the average change score for the HRSD or Young Mania Rating Scale (YMRS). Response to inositol was highly variable. Of nine subjects randomized to inositol, two had >50% worsening in HRSD scores at the end of treatment, three had no change and four had >50% improvement. Those who had worsening in depressive symptoms on inositol had significantly higher scores at baseline on the YMRS total score and irritability, disruptive/aggressive behavior and unkempt appearance items.

Conclusions:  There was a trend for more subjects on inositol to show improvement in bipolar depression symptoms, but, on average, inositol was not more effective than placebo as an adjunct for bipolar depression. Baseline levels of anger or hostility may be predictive of clinical response to inositol.

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