Lithium and Valproate Levels Do Not Correlate with Ketamine’s Antidepressant Efficacy in Treatment-Resistant Bipolar Depression
Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine’s antidepressant effects would be improved by therapeutic doses of lithium versus...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2015/858251 |
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| author | Annie J. Xu Mark J. Niciu Nancy B. Lundin David A. Luckenbaugh Dawn F. Ionescu Erica M. Richards Jennifer L. Vande Voort Elizabeth D. Ballard Nancy E. Brutsche Rodrigo Machado-Vieira Carlos A. Zarate |
| author_facet | Annie J. Xu Mark J. Niciu Nancy B. Lundin David A. Luckenbaugh Dawn F. Ionescu Erica M. Richards Jennifer L. Vande Voort Elizabeth D. Ballard Nancy E. Brutsche Rodrigo Machado-Vieira Carlos A. Zarate |
| author_sort | Annie J. Xu |
| collection | DOAJ |
| description | Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine’s antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine’s antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n=23, 0.79 ± 0.15 mEq/L) or valproate (n=13, 79.6 ± 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure—the Montgomery-Åsberg Depression Rating Scale (MADRS)—was assessed before infusion and at numerous postinfusion time points. Both lithium (F1,118 = 152.08, p<0.001, and d=2.27) and valproate (F1,128 = 20.12, p<0.001, and d=0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F1,28 = 2.51, p=0.12, and d=0.60). Serum lithium and valproate levels did not correlate with ketamine’s antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithium may not potentiate ketamine’s antidepressant efficacy in treatment-resistant bipolar depression. |
| format | Article |
| id | doaj-art-f5c2b1156ceb4665afe4763b0eb1e260 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-f5c2b1156ceb4665afe4763b0eb1e2602025-02-03T05:52:55ZengWileyNeural Plasticity2090-59041687-54432015-01-01201510.1155/2015/858251858251Lithium and Valproate Levels Do Not Correlate with Ketamine’s Antidepressant Efficacy in Treatment-Resistant Bipolar DepressionAnnie J. Xu0Mark J. Niciu1Nancy B. Lundin2David A. Luckenbaugh3Dawn F. Ionescu4Erica M. Richards5Jennifer L. Vande Voort6Elizabeth D. Ballard7Nancy E. Brutsche8Rodrigo Machado-Vieira9Carlos A. Zarate10New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY 10595, USANational Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USANational Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USANational Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USAMassachusetts General Hospital, Depression Clinical & Research Program, 1 Bowdoin Square, 6th Floor, Boston, MA 02114, USANational Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USADepartment of Psychiatry & Psychological Services, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USANational Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USANational Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USANational Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USANational Institute of Mental Health, National Institutes of Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Drive, Building 10/CRC, Bethesda, MD 20892, USAKetamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine’s antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine’s antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n=23, 0.79 ± 0.15 mEq/L) or valproate (n=13, 79.6 ± 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure—the Montgomery-Åsberg Depression Rating Scale (MADRS)—was assessed before infusion and at numerous postinfusion time points. Both lithium (F1,118 = 152.08, p<0.001, and d=2.27) and valproate (F1,128 = 20.12, p<0.001, and d=0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F1,28 = 2.51, p=0.12, and d=0.60). Serum lithium and valproate levels did not correlate with ketamine’s antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithium may not potentiate ketamine’s antidepressant efficacy in treatment-resistant bipolar depression.http://dx.doi.org/10.1155/2015/858251 |
| spellingShingle | Annie J. Xu Mark J. Niciu Nancy B. Lundin David A. Luckenbaugh Dawn F. Ionescu Erica M. Richards Jennifer L. Vande Voort Elizabeth D. Ballard Nancy E. Brutsche Rodrigo Machado-Vieira Carlos A. Zarate Lithium and Valproate Levels Do Not Correlate with Ketamine’s Antidepressant Efficacy in Treatment-Resistant Bipolar Depression Neural Plasticity |
| title | Lithium and Valproate Levels Do Not Correlate with Ketamine’s Antidepressant Efficacy in Treatment-Resistant Bipolar Depression |
| title_full | Lithium and Valproate Levels Do Not Correlate with Ketamine’s Antidepressant Efficacy in Treatment-Resistant Bipolar Depression |
| title_fullStr | Lithium and Valproate Levels Do Not Correlate with Ketamine’s Antidepressant Efficacy in Treatment-Resistant Bipolar Depression |
| title_full_unstemmed | Lithium and Valproate Levels Do Not Correlate with Ketamine’s Antidepressant Efficacy in Treatment-Resistant Bipolar Depression |
| title_short | Lithium and Valproate Levels Do Not Correlate with Ketamine’s Antidepressant Efficacy in Treatment-Resistant Bipolar Depression |
| title_sort | lithium and valproate levels do not correlate with ketamine s antidepressant efficacy in treatment resistant bipolar depression |
| url | http://dx.doi.org/10.1155/2015/858251 |
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