Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial

BMC Psychiatry

Tomohito Hamazaki¹  Kenji Hashimoto³  Hiroko Noguchi²  Kenta Matsumura²  Kei Hamazaki⁴  Naohiro Yonemoto²  Daisuke Nishi²  Yutaka Matsuoka² 

[1] Department of Clinical Sciences, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Toyama, Japan;CREST, Japan Science and Technology Agency, 3256 Midoricho, 190-0014, Tachikawa, Tokyo, Japan;Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, 260-8670, Chuo-ku, Chiba, Japan;Department of Public Health, Faculty of Medicine, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Toyama, Japan

关键词: Prevention;    Accidental injury;    Posttraumatic stress disorder;    Eicosapentaenoic acid;    Docosahexaenoic acid;    Omega-3 fatty acid;    Fish oil;   

Others  :  1124185
DOI  :  10.1186/1471-244X-13-8

 received in 2012-07-27, accepted in 2013-01-03,  发布年份 2013

【 摘 要 】

Background

Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial.

Methods/design

The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012.

Discussion

This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people.

Trial registration

ClinicalTrials.gov Identifier NCT00671099

【 授权许可】

   
2013 Matsuoka et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Krug EG, Sharma GK, Lozano R: The global burden of injuries. Am J Public Health 2000, 90(4):523-526.
• [2]MacKenzie EJ, Rivara FP, Jurkovich GJ, Nathens AB, Frey KP, Egleston BL, Salkever DS, Scharfstein DO: A national evaluation of the effect of trauma-center care on mortality. N Engl J Med 2006, 354(4):366-378.
• [3]Verger P, Dab W, Lamping DL, Loze J-Y, Deschaseaux-Voinet C, Abenhaim L, Rouillon F: The psychological impact of terrorism: an epidemiologic study of posttraumatic stress disorder and associated factors in victims of the 1995–1996 bombings in France. Am J Psychiatry 2004, 161(8):1384-1389.
• [4]Shalev AY, Freedman S, Peri T, Brandes D, Sahar T, Orr SP, Pitman RK: Prospective study of posttraumatic stress disorder and depression following trauma. Am J Psychiatry 1998, 155(5):630-637.
• [5]Schnyder U, Moergeli H, Klaghofer R, Buddeberg C: Incidence and prediction of posttraumatic stress disorder symptoms in severely injured accident victims. Am J Psychiatry 2001, 158(4):594-599.
• [6]O'Donnell ML, Creamer M, Pattison P, Atkin C: Psychiatric morbidity following injury. Am J Psychiatry 2004, 161(3):507-514.
• [7]Hamanaka S, Asukai N, Kamijo Y, Hatta K, Kishimoto J, Miyaoka H: Acute stress disorder and posttraumatic stress disorder symptoms among patients severely injured in motor vehicle accidents in Japan. Gen Hosp Psychiatry 2006, 28(3):234-241.
• [8]Hepp U, Moergeli H, Buchi S, Bruchhaus-Steinert H, Kraemer B, Sensky T, Schnyder U: Post-traumatic stress disorder in serious accidental injury: 3-year follow-up study. Br J Psychiatry 2008, 192(5):376-383.
• [9]Matsuoka Y, Nishi D, Nakajima S, Kim Y, Homma M, Otomo Y: Incidence and prediction of psychiatric morbidity after a motor vehicle accident in japan: the tachikawa cohort of motor vehicle accident study. Crit Care Med 2008, 36(1):74-80.
• [10]Bryant RA, O'Donnell ML, Creamer M, McFarlane AC, Clark CR, Silove D: The psychiatric sequelae of traumatic injury. Am J Psychiatry 2010, 167(3):312-320.
• [11]Schnyder U, Wittmann L, Friedrich-Perez J, Hepp U, Moergeli H: Posttraumatic stress disorder following accidental injury: rule or exception in Switzerland? Psychother Psychosom 2008, 77(2):111-118.
• [12]Matsuoka Y, Nishi D, Yonemoto N, Nakajima S, Kim Y: Towards an explanation of inconsistent rates of posttraumatic stress disorder across different countries: infant mortality rate as a marker of social circumstances and basic population health. Psychother Psychosom 2010, 79(1):56-57.
• [13]Schnyder U, Moergeli H, Trentz O, Klaghofer R, Buddeberg C: Prediction of psychiatric morbidity in severely injured accident victims at one-year follow-up. Am J Respir Crit Care Med 2001, 164(4):653-656.
• [14]Ehlers A, Clark DM, Hackmann A, McManus F, Fennell M, Herbert C, Mayou R: A randomized controlled trial of cognitive therapy, a self-help booklet, and repeated assessments as early interventions for posttraumatic stress disorder. Arch Gen Psychiatry 2003, 60(10):1024-1032.
• [15]Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR: Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol Psychiatry 2003, 54(9):947-949.
• [16]Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, Cahill L, Orr SP: Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry 2002, 51(2):189-192.
• [17]Nishi D, Matsuoka Y, Kawase E, Nakajima S, Kim Y: Mental health service requirements in a Japanese medical centre emergency department. Emerg Med J 2006, 23(6):468-469.
• [18]Hibbeln JR: Fish consumption and major depression. Lancet 1998, 351(9110):1213.
• [19]Hibbeln JR: Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 2002, 69(1–3):15-29.
• [20]Noaghiul S, Hibbeln JR: Cross-national comparisons of seafood consumption and rates of bipolar disorders. Am J Psychiatry 2003, 160(12):2222-2227.
• [21]Suzuki S, Akechi T, Kobayashi M, Taniguchi K, Goto K, Sasaki S, Tsugane S, Nishiwaki Y, Miyaoka H, Uchitomi Y: Daily omega-3 fatty acid intake and depression in Japanese patients with newly diagnosed lung cancer. Br J Cancer 2004, 90(4):787-793.
• [22]Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J: Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry 2006, 67(12):1954-1967.
• [23]Ross BM, Seguin J, Sieswerda LE: Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids Health Dis 2007, 6:21. BioMed Central Full Text
• [24]Lin PY, Su KP: A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 2007, 68(7):1056-1061.
• [25]Martins JG: EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr 2009, 28(5):525-542.
• [26]Sublette ME, Ellis SP, Geant AL, Mann JJ: Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry 2011, 72(12):1577-1584.
• [27]Martins JG, Bentsen H, Puri BK: Eicosapentaenoic acid appears to be the key omega-3 fatty acid component associated with efficacy in major depressive disorder: a critique of bloch and hannestad and updated meta-analysis. Mol Psychiatry 2012, 17(12):1144-1149.
• [28]Beltz BS, Tlusty MF, Benton JL, Sandeman DC: Omega-3 fatty acids upregulate adult neurogenesis. Neurosci Lett 2007, 415(2):154-158.
• [29]Wu A, Ying Z, Gomez-Pinilla F: Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma 2004, 21(10):1457-1467.
• [30]Calderon F, Kim HY: Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem 2004, 90(4):979-988.
• [31]Kawakita E, Hashimoto M, Shido O: Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience 2006, 139(3):991-997.
• [32]Venna VR, Deplanque D, Allet C, Belarbi K, Hamdane M, Bordet R: PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus. Psychoneuroendocrinology 2009, 34(2):199-211.
• [33]Squire LR: Memory and Brain. Oxford: Oxford University Press; 1987.
• [34]Feng R, Rampon C, Tang YP, Shrom D, Jin J, Kyin M, Sopher B, Miller MW, Ware CB, Martin GM: Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron 2001, 32(5):911-926.
• [35]Ressler KJ, Mayberg HS: Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci 2007, 10(9):1116-1124.
• [36]Kitamura T, Saitoh Y, Takashima N, Murayama A, Niibori Y, Ageta H, Sekiguchi M, Sugiyama H, Inokuchi K: Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell 2009, 139(4):814-827.
• [37]Matsuoka Y: Clearance of fear memory from the hippocampus through neurogenesis by omega-3 fatty acids: a novel preventive strategy for posttraumatic stress disorder? Biopsychosoc Med 2011, 5:3. BioMed Central Full Text
• [38]Matsuoka Y, Nishi D, Yonemoto N, Hamazaki K, Hashimoto K, Hamazaki T: Omega-3 fatty acids for secondary prevention of posttraumatic stress disorder after accidental injury: an open-label pilot study. J Clin Psychopharmacol 2010, 30(2):217-219.
• [39]Matsuoka Y, Nishi D, Yonemoto N, Hamazaki K, Hamazaki T, Hashimoto K: Potential role of brain-derived neurotrophic factor in omega-3 fatty acid supplementation to prevent posttraumatic distress after accidental injury: an open-label pilot study. Psychother Psychosom 2011, 80(5):310-312.
• [40]Folstein MF, Folstein SE, McHugh PR: "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975, 12(3):189-198.
• [41]Hamazaki T, Sawazaki S, Itomura M, Asaoka E, Nagao Y, Nishimura N, Yazawa K, Kuwamori T, Kobayashi M: The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study. J Clin Invest 1996, 97(4):1129-1133.
• [42]Sawazaki S, Hamazaki T, Yazawa K, Kobayashi M: The effect of docosahexaenoic acid on plasma catecholamine concentrations and glucose tolerance during long-lasting psychological stress: a double-blind placebo-controlled study. J Nutr Sci Vitaminol 1999, 45(5):655-665.
• [43]Brewin CR, Andrews B, Valentine JD: Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. J Consult Clin Psychol 2000, 68(5):748-766.
• [44]Ozer EJ, Best SR, Lipsey TL, Weiss DS: Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. Psychol Bull 2003, 129(1):52-73.
• [45]Itomura M, Fujioka S, Hamazaki K, Kobayashi K, Nagasawa T, Sawazaki S, Kirihara Y, Hamazaki T: Factors influencing EPA+DHA levels in red blood cells in Japan. In Vivo 2008, 22(1):131-135.
• [46]Baker SP, O'Neill B: The injury severity score: an update. J Trauma 1976, 16(11):882-885.
• [47]Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 1974, 2(7872):81-84.
• [48]Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA: Mild traumatic brain injury in U.S. soldiers returning from iraq. N Engl J Med 2008, 358(5):453-463.
• [49]Gil S, Caspi Y, Ben-Ari IZ, Koren D, Klein E: Does memory of a traumatic event increase the risk for posttraumatic stress disorder in patients with traumatic brain injury? a prospective study. Am J Psychiatry 2005, 162(5):963-969.
• [50]Scott J, Huskisson EC: Graphic representation of pain. Pain 1976, 2(2):175-184.
• [51]Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982, 5(6):649-655.
• [52]Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM: The development of a clinician-administered PTSD scale. J Trauma Stress 1995, 8(1):75-90.
• [53]Asukai N, Hirohata S, Kato H, Konishi T: Psychometric properties of the japanese-language version of the clinician-administered PTSD scale for DSM-IV (in japanese). Jpn J Traumatic Stress 2003, 1(1):47-53.
• [54]Brunet A, Weiss DS, Metzler TJ, Best SR, Neylan TC, Rogers C, Fagan J, Marmar CR: The peritraumatic distress inventory: a proposed measure of PTSD criterion A2. Am J Psychiatry 2001, 158(9):1480-1485.
• [55]Nishi D, Matsuoka Y, Noguchi H, Sakuma K, Yonemoto N, Yanagita T, Homma M, Kanba S, Kim Y: Reliability and validity of the japanese version of the peritraumatic distress inventory. Gen Hosp Psychiatry 2009, 31(1):75-79.
• [56]Connor KM, Davidson JR: Development of a new resilience scale: the connor-davidson resilience scale (CD-RISC). Depress Anxiety 2003, 18(2):76-82.
• [57]Buss AH, Perry M: The aggression questionnaire. J Pers Soc Psychol 1992, 63(3):452-459.
• [58]Tsubono Y, Takamori S, Kobayashi M, Takahashi T, Iwase Y, Iitoi Y, Akabane M, Yamaguchi M, Tsugane S: A data-based approach for designing a semiquantitative food frequency questionnaire for a population-based prospective study in Japan. J Epidemiol 1996, 6(1):45-53.
• [59]Tsugane S, Sasaki S, Kobayashi M, Tsubono Y, Akabane M: Validity and reproducibility of the self-administered food frequency questionnaire in the JPHC study cohort I: study design, conduct and participant profiles. J Epidemiol 2003, 13(1 Suppl):S2-S12.
• [60]Kobayashi M, Sasaki S, Kawabata T, Hasegawa K, Tsugane S: Validity of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC study cohort I to assess fatty acid intake: comparison with dietary records and serum phospholipid level. J Epidemiol 2003, 13(1 Suppl):S64-S81.
• [61]Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959, 37(8):911-917.
• [62]O'Donnell ML, Creamer M, Bryant RA, Schnyder U, Shalev A: Posttraumatic disorders following injury: an empirical and methodological review. Clin Psychol Rev 2003, 23(4):587-603.
• [63]Montgomery SA, Asberg M: A new depression scale designed to be sensitive to change. Br J Psychiatry 1979, 134:382-389.
• [64]Takahashi N, Tomita K, Higuchi T, Inada T: The inter-rater reliability of the japanese version of the montgomery-asberg depression rating scale (MADRS) using a structured interview guide for MADRS (SIGMA). Hum Psychopharmacol 2004, 19(3):187-192.
• [65]Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC: 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(20):22-33. quiz 34–57
• [66]Otsubo T, Tanaka K, Koda R, Shinoda J, Sano N, Tanaka S, Aoyama H, Mimura M, Kamijima K: Reliability and validity of japanese version of the mini-international neuropsychiatric interview. Psychiatry Clin Neurosci 2005, 59(5):517-526.
• [67]Matsuoka Y, Nishi D, Nakajima S, Yonemoto N, Hashimoto K, Noguchi H, Homma M, Otomo Y, Kim Y: The Tachikawa cohort of motor vehicle accident study investigating psychological distress: design, methods and cohort profiles. Soc Psychiatry Psychiatr Epidemiol 2009, 44(4):341.
• [68]Weiss DS, Marmar CR: The Impact of Event Scale Revised. In Assessing psychological trauma and PTSD. Edited by Wilson JP, Keane TM. New York: The Guilford Press; 1997:399-411.
• [69]Asukai N, Kato H, Kawamura N, Kim Y, Yamamoto K, Kishimoto J, Miyake Y, Nishizono-Maher A: Reliability and validity of the Japanese-language version of the impact of event scale-revised (IES-R-J): four studies of different traumatic events. J Nerv Ment Dis 2002, 190(3):175-182.
• [70]Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 1983, 67(6):361-370.
• [71]Kugaya A, Akechi T, Okuyama T, Okamura H, Uchitomi Y: Screening for psychological distress in japanese cancer patients. Jpn J Clin Oncol 1998, 28(5):333-338.
• [72]McHorney CA, Ware JE Jr, Raczek AE: The MOS 36-item short-form health survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 1993, 31(3):247-263.
• [73]Ware JE, Snow KK, Kosinski M, Gandek B: SF-36 health survey manual and interpretation guide. Boston: New England Medical Center; 1993.
• [74]Fukuhara S, Bito S, Green J, Hsiao A, Kurokawa K: Translation, adaptation, and validation of the SF-36 Health Survey for use in Japan. J Clin Epidemiol 1998, 51(11):1037-1044.
• [75]Ando A, Soga S, Yamasaki K, Shimai S, Shimada H, Utsuki N, Oashi O, Sakai A: Development of the japanese version of the buss-perry aggression questionnaire (BAQ). Shinrigaku kenkyu: The Japanese journal of psychology 1999, 70(5):384-392.
• [76]Tucker PM, Pfefferbaum B, North CS, Kent A, Burgin CE, Parker DE, Hossain A, Jeon-Slaughter H, Trautman RP: Physiologic reactivity despite emotional resilience several years after direct exposure to terrorism. Am J Psychiatry 2007, 164(2):230-235.
• [77]Orr SP, Lasko NB, Shalev AY, Pitman RK: Physiologic responses to loud tones in Vietnam veterans with posttraumatic stress disorder. J Abnorm Psychol 1995, 104(1):75-82.
• [78]Pitman RK, Orr SP, Forgue DF, de Jong JB, Claiborn JM: Psychophysiologic assessment of posttraumatic stress disorder imagery in Vietnam combat veterans. Arch Gen Psychiatry 1987, 44(11):970-975.
• [79]Matsumura K, Noguchi H, Nishi D, Matsuoka Y: Effects of omega-3 fatty acids on the psychophysiologoical assessment for secondary prevention of posttraumatic stress disorder: and open-label pilot study. Global Journal of Health Science 2012, 4(1):3-9.