Does lithium reduce acute suicidal ideation and behavior? A protocol for a randomized, placebo-controlled multicenter trial of lithium plus Treatment As Usual (TAU) in patients with suicidal major depressive episode

U Lewitzka, B Jabs, M Fülle, V Holthoff, G Juckel, I Uhl, S Kittel-Schneider, A Reif, C Reif-Leonhard, O Gruber, B Djawid, S Goodday, R Haussmann, A Pfennig, P Ritter, J Conell, E Severus, M Bauer, U Lewitzka, B Jabs, M Fülle, V Holthoff, G Juckel, I Uhl, S Kittel-Schneider, A Reif, C Reif-Leonhard, O Gruber, B Djawid, S Goodday, R Haussmann, A Pfennig, P Ritter, J Conell, E Severus, M Bauer

Abstract

Background: Lithium has proven suicide preventing effects in the long-term treatment of patients with affective disorders. Clinical evidence from case reports indicate that this effect may occur early on at the beginning of lithium treatment. The impact of lithium treatment on acute suicidal thoughts and/or behavior has not been systematically studied in a controlled trial. The primary objective of this confirmatory study is to determine the association between lithium therapy and acute suicidal ideation and/or suicidal behavior in inpatients with a major depressive episode (MDE, unipolar and bipolar disorder according to DSM IV criteria). The specific aim is to test the hypothesis that lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a significantly greater decrease in suicidal ideation and/or behavior over 5 weeks in inpatients with MDE.

Methods/design: We initiated a randomized, placebo-controlled multicenter trial. Patients with the diagnosis of a moderate to severe depressive episode and suicidal thoughts and/or suicidal behavior measured with the Sheehan-Suicidality-Tracking Scale (S-STS) will be randomly allocated to add lithium or placebo to their treatment as usual. Change in the clinician administered S-STS from the initial to the final visit will be the primary outcome.

Discussion: There is an urgent need to identify treatments that will acutely decrease suicidal ideation and/or suicidal behavior. The results of this study will demonstrate whether lithium reduces suicidal ideation and behavior within the first 5 weeks of treatment.

Trial registration: ClinicalTrials.gov identifier: NCT02039479.

Figures

Fig. 1
Fig. 1
Trial flow

References

    1. WHO. Preventing suicide: a global imperative. [].
    1. Machado-Vieira R, Manji HK, Zarate CA., Jr The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disorder. 2009;Suppl 2:92–109. doi: 10.1111/j.1399-5618.2009.00714.x.
    1. Quiroz JA, Machado-Vieira R, Zarate CA, Jr, Manji HK. Novel insights into lithium’s mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology. 2010;62:50–60. doi: 10.1159/000314310.
    1. McCarthy MJ, Leckband SG, Kelsoe JR. Pharmacogenetics of lithium in bipolar disorder. Pharmacogenetics. 2010;11:1439–65. doi: 10.2217/pgs.10.127.
    1. Pfennig A, Bauer M. S3guidelines on bipolar disorders are contemporary and important instruments for clinical practice. Nervenarzt. 2013;84:874–5. doi: 10.1007/s00115-013-3796-6.
    1. Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Möller HJ, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the long-term treatment of bipolar disorder. World J Biol Psychiatry. 2013;14:154–219. doi: 10.3109/15622975.2013.770551.
    1. Lam RW, Kennedy SH, Grigoriadis S, McIntyre RS, Milev R, Ramasubbu R, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults III: Pharmacopsychiatry. J Affect Disord. 2009;117:26–43. doi: 10.1016/j.jad.2009.06.041.
    1. Lewitzka U, Severus E, Bauer R, Ritter P, Müller-Oerlinghausen B, Bauer M. The suicide prevention effect of lithium: more than 20 years of evidence. Submitted Int J Bip Disord
    1. Price LH, Charney DS, Delgado PL, Heninger GR. Lithium treatment and serotonergic function. Neuroendocrine and behavioural response to intravenous tryptophan in affective disorder. Arch Gen Psychiatry. 1989;46:13–9. doi: 10.1001/archpsyc.1989.01810010015002.
    1. Ernst CL, Goldberg JF. Antisuicide properties of psychotropic drugs: a critical review. Harv Rev Psychiatry. 2004;12:14–41.
    1. Bschor T, Ritter D, Winkelmann P, Erbe S, Uhr M, Ising M, et al. Lithium monotherapy increases ACTH and cortisol response in the DEX/CRH test in unipolar depressed subjects. A study with 30 treatment-naïve patients. PLoS One. 2011;6 doi: 10.1371/journal.pone.0027613.
    1. Motohashi N. GABA receptor alterations after chronic lithium administration. Comparison with carbamazepine and sodium valproate. Prog Neuropsychopharmacol Biol Psychiatry. 1992;16:571–9. doi: 10.1016/0278-5846(92)90062-J.
    1. Kovacsics CE, Gottesman II, Gould TD. Lithium’s antisuicidal efficacy: elucidation of neurobiological targets using endophenotype strategies. Annu Rev Pharmacol Toxicol. 2009;49:175–98. doi: 10.1146/annurev.pharmtox.011008.145557.
    1. Müller-Oerlinghausen B, Lewitzka U. Lithium reduces pathological aggression and suicidality: a mini-review. Neuropsychobiology. 2010;62:43–9. doi: 10.1159/000314309.
    1. Mühlbauer HD, Müller-Oerlinghausen B. Fenfluramine stimulation of serum cortisol in patients with major affective disorders and healthy controls: further evidence for a central serotonergic action of lithium in man. J Neural Transm. 1985;61:81–94. doi: 10.1007/BF01253053.
    1. Lauterbach E, Felber W, Müller-Oerlinghausen B, Ahrens B, Bronisch T, Meyer T, et al. Adjunctive lithium treatment in the prevention of suicidal behaviour in depressive disorders: a randomised, placebo-controlled, 1-year trial. Acta Psychiatr Scand. 2008;118:469–79. doi: 10.1111/j.1600-0447.2008.01266.x.
    1. Coric V, Stock EG, Pultz J, Marcus R, Sheehan DV. Sheehan Suicidality Tracking Scale (Sheehan-STS): preliminary results from a Multicenter Clinical Trial in Generalized Anxiety Disorder. Psychiatry (Edgmont) 2009;6:26–31.
    1. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168:1266–77. doi: 10.1176/appi.ajp.2011.10111704.
    1. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–9. doi: 10.1192/bjp.134.4.382.
    1. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32:50–5. doi: 10.1111/j.2044-8341.1959.tb00467.x.
    1. National Institute of Mental Health . Clinical Global Impressions. In: Guy W, editor. ECDEU assessment. 1976.
    1. Barratt ES. Factor analysis of some psychometric measures of impulsiveness and anxiety. Psychol Rep. 1965;16:547–54. doi: 10.2466/pr0.1965.16.2.547.
    1. Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity, sensitivity. Br J Psychiatry. 1978;133:429–35. doi: 10.1192/bjp.133.5.429.
    1. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59:22–3.
    1. Spitzer RL, Williams JBW. Structured clinical interview for DSM-III-R personality disorders. New York: Biometrics Research Department. New York State Psychiatric Institute; 1987.
    1. Khan A, Khan SR, Hobus J, Faucett J, Mehra V, Giller EL, et al. Differential pattern of response in mood symptoms and suicide risk measures in severly ill depressed patients assigned to citalopram with placebo or citalopram combined with lithium: role of lithium levels. J Psychiatr Res. 2011;45:1489–96. doi: 10.1016/j.jpsychires.2011.06.016.
    1. Borm GF, Fransen J, Lemmens WA. A simple sample size formula for analysis of covariance in randomized clinical trials. J Clin Epidemiol. 2007;60:1234–8. doi: 10.1016/j.jclinepi.2007.02.006.
    1. Seemüller F, Riedel M, Obermeier M, Bauer M, Adli M, Kronmüller K, et al. Outcomes of 1014 naturalistically treated inpatients wiht major depressive episode. Eur Neuropsychopharmacol. 2010;20:346–55. doi: 10.1016/j.euroneuro.2009.11.011.
    1. Meyer RE, Salzman C, Youngstrom EA, Clayton PJ, Goodwin FK, Mann JJ, et al. Suicidality and risk of suicide-definition, drug safety concerns, and a necessary target for drug development: a consensus statement. J Clin Psychiaty. 2010;71:e1–21. doi: 10.4088/JCP.10cs06070blu.
    1. Bronisch T. Does an attempted suicide actually have a cathartic effect? Acta Psychiatr Scand. 1992;86:228–32. doi: 10.1111/j.1600-0447.1992.tb03257.x.
    1. Davis AT, Schrueder C. The prediction of suicide. Med J Aust. 1990;153:552–4.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다