Dawn F Ionescu1,2, David A Luckenbaugh3, Mark J Niciu3, Erica M Richards3, Carlos A Zarate3. 1. Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA. 2. Harvard Medical School, Boston, MA, USA. 3. Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Abstract
OBJECTIVE: Patents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressed patients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine's ability to decrease symptoms of depression. METHODS:Thirty-six patients with anxious (n = 21) and non-anxious (n = 15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5 mg/kg) over 40 min. Post-hoc analyses compared changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressed patients with bipolar disorder through 14 days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus a HDRS Anxiety/Somatization Factor score of ≥ 7. RESULTS: A linear mixed model revealed a significant effect of anxiety group on the MADRS (p = 0.04) and HDRS (p = 0.04). Significant drug effects (all p < 0.001) suggested that both anxious and non-anxious groups had an antidepressant response to ketamine. The drug-by-anxiety interactions were not significant (all p > 0.28). CONCLUSIONS: Both anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest a need for further investigations into ketamine's novel role in the treatment of anxious bipolar depression. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
RCT Entities:
OBJECTIVE: Patents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressedpatients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine's ability to decrease symptoms of depression. METHODS: Thirty-six patients with anxious (n = 21) and non-anxious (n = 15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5 mg/kg) over 40 min. Post-hoc analyses compared changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressedpatients with bipolar disorder through 14 days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus a HDRS Anxiety/Somatization Factor score of ≥ 7. RESULTS: A linear mixed model revealed a significant effect of anxiety group on the MADRS (p = 0.04) and HDRS (p = 0.04). Significant drug effects (all p < 0.001) suggested that both anxious and non-anxious groups had an antidepressant response to ketamine. The drug-by-anxiety interactions were not significant (all p > 0.28). CONCLUSIONS: Both anxious and non-anxiouspatients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest a need for further investigations into ketamine's novel role in the treatment of anxious bipolar depression. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Authors: U Feske; E Frank; A G Mallinger; P R Houck; A Fagiolini; M K Shear; V J Grochocinski; D J Kupfer Journal: Am J Psychiatry Date: 2000-06 Impact factor: 18.112
Authors: Nancy Diazgranados; Lobna Ibrahim; Nancy E Brutsche; Andrew Newberg; Phillip Kronstein; Sami Khalife; William A Kammerer; Zenaide Quezado; David A Luckenbaugh; Giacomo Salvadore; Rodrigo Machado-Vieira; Husseini K Manji; Carlos A Zarate Journal: Arch Gen Psychiatry Date: 2010-08
Authors: David V Sheehan; Susan L McElroy; Kathy Harnett-Sheehan; Paul E Keck; Juris Janavs; Jamison Rogers; Robert Gonzalez; Geetha Shivakumar; Trisha Suppes Journal: J Affect Disord Date: 2008-11-29 Impact factor: 4.839
Authors: Mauricio Tohen; Joseph Calabrese; Eduard Vieta; Charles Bowden; Ana Gonzalez-Pinto; Daniel Lin; Wen Xu; Sara Corya Journal: J Affect Disord Date: 2007-05-21 Impact factor: 4.839
Authors: Panos Zanos; Ruin Moaddel; Patrick J Morris; Lace M Riggs; Jaclyn N Highland; Polymnia Georgiou; Edna F R Pereira; Edson X Albuquerque; Craig J Thomas; Carlos A Zarate; Todd D Gould Journal: Pharmacol Rev Date: 2018-07 Impact factor: 25.468
Authors: Andréa T Faccio; Francisco J Ruperez; Nagendra S Singh; Santiago Angulo; Marina F M Tavares; Michel Bernier; Coral Barbas; Irving W Wainer Journal: Biochim Biophys Acta Gen Subj Date: 2018-03-09 Impact factor: 3.770
Authors: Josephine C McGowan; Collin Hill; Alessia Mastrodonato; Christina T LaGamma; Alexander Kitayev; Rebecca A Brachman; Niven R Narain; Michael A Kiebish; Christine A Denny Journal: Neuropsychopharmacology Date: 2018-03-29 Impact factor: 7.853