Inositol augmentation of lithium or valproate for bipolar depression
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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Inositol produced no significant improvements in depression scores between control and bipolar groups.
“No significant improvements in depression scores between control and bipolar groups were found (Eden Evins et al. 2006).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Eden Evins et al. 2006
Cites
Kessler, R. C. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950010008002 · Cited by 12,370 · see citing works
The Brief Psychiatric Rating Scale.
Overall, J. E., & Gorham, D. R. (1962) · Psychological Reports · doi:10.2466/pr0.1962.10.3.799 · Cited by 11,090 · see citing works
A Rating Scale for Mania: Reliability, Validity and Sensitivity
Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978) · British Journal of Psychiatry · doi:10.1192/bjp.133.5.429 · Cited by 8,744 · see citing works
Development of a Rating Scale for Primary Depressive Illness
Hamilton, M. (1967) · British Journal of Social and Clinical Psychology · doi:10.1111/j.2044-8260.1967.tb00530.x · Cited by 8,410 · see citing works
Relapse and impairment in bipolar disorder
(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.11.1635 · Cited by 762 · see citing works
Affective disorders in five United States communities
Weissman, M. M., Leaf, P. J., Tischler, G. L., Blazer, D. G., Karno, M., BRUCE, M. L., & Florio, L. P. (1988) · Psychological Medicine · doi:10.1017/s0033291700001975 · Cited by 625 · see citing works
A common mechanism of action for three mood-stabilizing drugs
Williams, R. S. B., Cheng, L., Mudge, A. W., & Harwood, A. J. (2002) · Nature · doi:10.1038/417292a · Cited by 617 · see citing works
Leung, C. M., Wing, Y. K., Kwong, P. K., & Shum, A. L. K. (1999) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1999.tb10897.x · Cited by 407 · see citing works
SAFTEE: a technique for the systematic assessment of side effects in clinical trials.
Levine, J., & Schooler, N. (1986) · PubMed · Cited by 329 · see citing works
Goldstein, D. J., Lu, Y., Detke, M. J., Wiltse, C., Mallinckrodt, C., & Demitrack, M. A. (2004) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000132448.65972.d9 · Cited by 314 · see citing works
Clozapine for treatment-refractory mania
Calabrese, J. R., Kimmel, S. E., Woyshville, M. J., RAPPORT, D. J., Faust, C. J., Thompson, P. A., & Meltzer, H. Y. (1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.6.759 · Cited by 266 · see citing works
Double-blind, controlled trial of inositol treatment of depression
Levine, J., Barak, Y., Gonzalves, M., Szor, H., Elizur, A., Kofman, O., & Belmaker, R. H. (1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.5.792 · Cited by 230 · see citing works
Inositol treatment of obsessive-compulsive disorder
Fux, M., Levine, J., Aviv, A., & Belmaker, R. H. (1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.9.1219 · Cited by 209 · see citing works
Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder
Benjamin, J., Levine, J., Fux, M., Aviv, A., Levy, D., & Belmaker, R. H. (1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.7.1084 · Cited by 177 · see citing works
Decreased Prefrontal Myo-Inositol in Major Depressive Disorder
Coupland, N. J., Ogilvie, C. J., Hegadoren, K., Seres, P., Hanstock, C. C., & Allen, P. S. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.02.027 · Cited by 174 · see citing works
Shimon, H., Agam, G., Belmaker, R. H., Hyde, T. M., & Kleinman, J. E. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.8.1148 · Cited by 157 · see citing works
Baraban, J. M., Worley, P. F., & Snyder, S. H. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.10.1251 · Cited by 141 · see citing works
Clozapine in the Treatment of Refractory Psychotic Mania
Green, A. I., Tohen, M., Patel, J. K., Banov, M. D., DuRand, C. J., Berman, I., Chang, H., Zarate, C. A., Posener, J. A., Lee, H., et al. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.6.982 · Cited by 134 · see citing works
Clozapine in the treatment of dysphoric mania
Suppes, T. M., McElroy, S. L., Gilbert, J. M., Dessain, E. C., & Cole, J. O. (1992) · Biological Psychiatry · doi:10.1016/0006-3223(92)90108-c · Cited by 123 · see citing works
Reduced myo-inositol levels in cerebrospinal fluid from patients with affective disorder.
Barkai, A. I., Dl, D., Gross, H. A., et al. (1978) · PubMed · Cited by 107 · see citing works
Palatnik, A., Frolov, K., Fux, M., & Benjamin, J. (2001) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200106000-00014 · Cited by 107 · see citing works
TREATMENT-RESISTANT BIPOLAR DEPRESSION
Sachs, G. S. (1996) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70285-9 · Cited by 107 · see citing works
Self-citationInositol as an add‐on treatment for bipolar depression
Chengappa, K. R., Levine, J., Gershon, S., Mallinger, A. G., Hardan, A. Y., Vagnucci, A. H., Pollock, B. G., Luther, J. F., Buttenfield, J., Verfaille, S., et al. (2000) · Bipolar Disorders · doi:10.1034/j.1399-5618.2000.020107.x · Cited by 102 · see citing works
Inositol treatment raises CSF inositol levels
Levine, J., Rapaport, A., Lev, L., et al. (1993) · Brain Research · doi:10.1016/0006-8993(93)90761-b · Cited by 65 · see citing works
Yohannes, A. M., Baldwin, R. C., & Connolly, M. J. (2000) · International Journal of Geriatric Psychiatry · doi:10.1002/1099-1166(200012)15:12 · Cited by 58 · see citing works
How can the mood stabilizer VPA limit both mania and depression?
Cheng, L., Lumb, M., Polgár, L., et al. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.12.003 · Cited by 56 · see citing works
Onset of action for duloxetine 60 mg once daily: double-blind, placebo-controlled studies
Brannan, S. K., Mallinckrodt, C. H., Detke, M. J., Watkin, J. G., & Tollefson, G. D. (2004) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2004.05.005 · Cited by 53 · see citing works
Wolfson, M., Bersudsky, Y., Zinger, E., Simkin, M., Belmaker, R. H., & Hertz, L. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02371-9 · Cited by 42 · see citing works
Long-term lithium and mortality
Coppen, A. J., Standish‐Barry, H. M. A. S., Bailey, J., Houston, G., Silcocks, P. B. S., & Hermon, C. (1990) · The Lancet · doi:10.1016/0140-6736(90)91232-y · Cited by 41 · see citing works
Inositol for depressive disorders
Taylor, M. J., Wilder, H., Bhagwagar, Z., & Geddes, J. R. (2004) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004049.pub2 · Cited by 32 · see citing works
CSF inositol does not predict antidepressant response to inositol
Levine, J., Kurtzman, L., Rapoport, A., Zimmerman, J., Bersudsky, Y., Shapiro, J., Belmaker, R. H., & Agam, G. (1996) · Journal of Neural Transmission · doi:10.1007/bf01271260 · Cited by 25 · see citing works
Comparison of therapeutic modalities for mania.
Small, J. G., Klapper, M. H., Milstein, V., Marhenke, J. D., & Small, I. F. (1996) · PubMed · Cited by 25 · see citing works
Atack, J. R., Levine, J. S., & Belmaker, R. H. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00065-1 · Cited by 15 · see citing works
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Grunze, H., Vieta, E., Goodwin, G. M., Bowden, C., Licht, R. W., Möller, H.-J., Kasper, S., & WFSBP Task Force On Treatment Guidelines For Bipolar Disorders (2010) · The World Journal of Biological Psychiatry · doi:10.3109/15622970903555881 · Cited by 399 · see citing works
Johannessen Landmark, C. (2008) · CNS Drugs · doi:10.2165/00023210-200822010-00003 · Cited by 316 · see citing works
Antioxidants as potential therapeutics for neuropsychiatric disorders
Pandya, C. D., Howell, K. R., & Pillai, A. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.10.017 · Cited by 222 · see citing works
Fountoulakis, K. N., Tohen, M., & Zarate, C. A. (2022) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2021.10.003 · Cited by 146 · see citing works
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- Authors
- A E, E., Demopulos, C., Yovel, I., Culhane, M., Ogutha, J., Grandin, L. D., Nierenberg, A. A., & Sachs, G. S.
- Affiliations
- Harvard University (US)
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2006-03-15
- Volume
- 8
- Issue
- 2
- Pages
- 168-174
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- OpenAlex
- W2107762716
- Cited by
- 77
- References
- 33
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 7 · 2012: 8
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Stanley Medical Research Institute
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- myo-inositol, bipolar depression, lithium, valproic acid, adjunctive therapy, treatment-resistant depression, irritability, anger, hostility, treatment response prediction, mood stabilizers
- MeSH terms
- Adult, Antidepressive Agents, Bipolar Disorder, Double-Blind Method, Female, Humans, Inositol, Male, Middle Aged, Brief Psychiatric Rating Scale, Surveys and Questionnaires, Sensitivity and Specificity, Severity of Illness Index, Antipsychotic Agents, Valproic Acid, Lithium Carbonate, Diagnostic and Statistical Manual of Mental Disorders
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