Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce.

OBJECTIVES: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. METHODS: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. RESULTS: Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support (recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/-), folic acid (-), vitamin C (-), tryptophan (+/-), creatine (+/-), inositol (-), magnesium (-), and n-acetyl cysteine (NAC) (+/-) and SAMe (+/-) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/-). NAC was weakly recommended (+) in the treatment of OCD-related disorders; however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/-) and omega-9 fatty acids (-), acetyl L carnitine (-), and zinc (+/-) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John's wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (-) and chamomile (+/-) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/-). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy. CONCLUSIONS: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Plasma estradiol levels and antidepressant effects of omega-3 fatty acids in pregnant women.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) reduce depressive symptoms through an anti-inflammatory effect, and injection of both omega-3 PUFAs and estradiol (E2) induces antidepressant-like effects in rats by regulating the expression of inflammatory cytokines. The aims of this study were to examine the association of increased E2 during pregnancy with depressive symptoms and with inflammatory cytokines in women who were and were not supplemented with omega-3 PUFAs. METHODS: Pregnant women with Edinburgh Postnatal Depression Scale scores ≥9 were recruited at 12-24 weeks of gestation. The participants were randomly assigned to receive 1800 mg omega-3 fatty acids (containing 1206 mg eicosapentaenoic acid [EPA]) or placebo for 12 weeks. E2, omega-3 PUFAs, high-sensitivity C-reactive protein, interleukin-6, and adiponectin were measured at baseline and at the 12-week follow-up. Multivariable regression analyses were conducted to examine the association of the changes of E2 and omega-3 PUFAs with the changes in depressive symptoms and with the changes of inflammatory cytokines at follow-up by intervention group. RESULTS: Of the 108 participants in the trial, 100 (92.6%) completed the follow-up assessment including blood sampling. Multivariable regression analyses revealed that the increase of EPA and E2 was significantly associated with a decrease in depressive symptoms among the participants assigned to the omega-3 group, but not among those assigned to the placebo group. Neither E2 nor any PUFAs were associated with a change in inflammatory cytokines. CONCLUSION: Supplementation with EPA and increased levels of E2 during pregnancy might function together to alleviate antenatal depression through a mechanism other than anti-inflammation.

Differences between Japan and Taiwan in the treatment of pregnant women with depressive symptoms by omega-3 fatty acids: An open-label pilot study.

OBJECTIVES: Although safe approaches for improving depression in pregnancy are required and the efficacy of omega-3 polyunsaturated fatty acids (PUFAs) has been suggested, the amount of supplemental omega-3 PUFAs has varied among previous studies and adequate amount might be different among countries. The aim of this pilot study is to explore the feasibility of using 1800 mg of omega-3 PUFAs supplementation for our future double-blind, placebo-control trial, and to clarify the clinical difference and the similarity between two sites of Japan and Taiwan. METHODS: Pregnant women between 12 and 24 weeks' gestation with depressive symptoms were recruited. Participants were supplemented daily with omega-3 PUFAs capsules containing 1206 mg eicosapentaenoic acid and 609 mg docosahexaenoic acid for 12 weeks. The primary outcome was change in total score on the 17-item Hamilton Rating Scale for Depression (HAMD) at 12 weeks after supplementation. RESULTS: Eight pregnant women in Japan and five in Taiwan participated in the study. A substantial proportion of pregnant women reported high consumption of omega-3 supplements and dietary fish were excluded in Taiwan rather than in Japan sites. The decrease in HAMD score from baseline to 12 weeks after the start of the intervention was significantly larger in Japanese participants than in Taiwanese participants (Wilcoxon rank sum test; P = 0.045). DISCUSSION: The improvement of depressive symptoms was smaller at the Taiwan site than at the Japan site. Differences in psychopathology of recruited participants identified by self-rating scales might affect the degree of population heterogeneity and the treatment efficacy. A randomized-controlled trial is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01948596.

Limited effect of omega-3 fatty acids on the quality of life in survivors of traumatic injury: A randomized, placebo-controlled trial.

Empirical evidence is divided on whether n-3 polyunsaturated fatty acid levels are associated with quality of life (QOL). This study investigated the effects of docosahexaenoic acid (DHA) supplementation on QOL in survivors of traumatic injury. In this secondary analysis of a double-blind, randomized controlled trial, we recruited 110 trauma patients (82% men; mean age, 39.6 years) in an intensive care unit. Fifty-three received DHA-rich supplements and 57 received placebo for 12 weeks. We used the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) to assess QOL at the end of intervention. DHA did not significantly affect any QOL domain on the SF-36 after 12 weeks. In the DHA group, changes in the erythrocyte levels of eicosapentaenoic acid (EPA) + DHA and EPA were positively correlated with the SF-36 mental component. DHA did not influence QOL of trauma patients, but increased EPA levels during the trial were associated with better QOL in patients receiving omega-3.

Serum polyunsaturated fatty acids and risk of psychiatric disorder after acute coronary syndrome: A prospective cohort study.

BACKGROUND: Around 20% of patients with acute coronary syndrome (ACS) develop depression. Furthermore, some observational studies revealed baseline polyunsaturated fatty acids (PUFAs) may affect the prognosis of depression after ACS. This prospective cohort study examined the association between psychiatric disorder and PUFAs after ACS. METHODS: Subjects were ACS patients admitted to a Tokyo teaching hospital. Psychiatric morbidity as a primary endpoint was measured using structured interview 3 months after admission. At admission, serum n-3 and n-6 PUFAs were measured by gas chromatography and patients were interviewed to evaluate medical information. Multiple logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals to examine the association between PUFAs at baseline and psychiatric disorder after ACS. RESULTS: Between March 2014 and August 2016, 100 patients completed the follow-up assessment. Eleven patients (11%) showed some form of new-onset psychiatric disorder at 3 months, mainly depressive episode (major, 5; minor, 1) and PTSD (full, 1; partial, 2). Psychiatric disorder was predicted by serum linoleic acid level (OR=3.96) and Hospital Anxiety and Depression Scale total score (OR=1.34) at baseline. No significant associations were seen with other PUFAs. LIMITATIONS: The results were obtained from a single hospital and based on a small number of participants. There might be some patients with new-onset psychiatric disorder among the refused patients. CONCLUSIONS: Psychiatric disorder incidence in ACS patients might be lower in Japan than in Western countries. Reduced intake of linoleic acid-containing foods might prevent depression or PTSD after ACS.

Effects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Psychophysiological symptoms (e.g., pounding heart) are known to be a prominent feature of post-traumatic stress disorder (PTSD). Although omega-3 polyunsaturated fatty acids (PUFAs) have a beneficial potential pharmacological effect of preventing these psychophysiological symptoms, no clinical data is yet available. Therefore, we conducted a randomized, double-blind, placebo-controlled trial of Japanese accident survivors. METHODS: A total of 83 participants received either omega-3 PUFAs (1470mg docosahexaenoic acid and 147mg eicosapentaenoic acid per day) or placebo within 10 days of the accidental injury. After 12-week supplementation, participants performed script-driven imagery of their traumatic event during monitoring of their heart rate and skin conductance. RESULTS: Analysis revealed that heart rate during both rest and script-driven imagery was significantly lower in the omega-3 group than the placebo group, whereas baseline heart rate was comparable between the two groups. LIMITATIONS: The present trial was conducted at a single-center in Japan and psychophysiological symptoms of PTSD in most participants were not serious. CONCLUSION: These findings suggest that post-trauma supplementation of omega-3 PUFAs might be effective for the secondary prevention of psychophysiological symptoms of PTSD.

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

BACKGROUND: Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. METHODS: The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. DISCUSSION: The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02166424 . Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.

Association between frequency of fried food consumption and resilience to depression in Japanese company workers: a cross-sectional study.

BACKGROUND: Long-chain n-3 and n-6 polyunsaturated fatty acids (LC n-3/n-6 PUFA) play important roles in emotional regulation. We previously reported an association between fish consumption, which is major source of LC n-3 PUFA, and resilience to depression, where resilience is the ability to cope with stress in the face of adversity. Although the traditional Japanese dietary pattern of high fish consumption is associated with low depressive symptoms, the current Japanese diet pattern has become westernized. Westernized diets contain excessive amounts of LC n-6 PUFA due to high intake of vegetable oils commonly used in fried food and are associated with risk of depression. The aim of this study was to examine the association between frequency of fried food consumption and resilience to depression. METHODS: Participants were 715 Japanese company workers. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms, and the 14-item Resilience Scale (RS-14) was used to measure resilience. Frequency of fish and fried food consumption was assessed using a self-report questionnaire based on the Food Frequency Questionnaire. Regression analyses using Preacher and Hayes' bootstrap script were used to adjust for demographic factors, frequency of physical exercise, and fish consumption. RESULTS: Significant associations were identified between frequency of fried food consumption and total CES-D score (path c, B = 0.72; P < 0.01), between frequency of fried food consumption and total RS-14 score (path a, B = -1.73, P < 0.01), and between total RS-14 score and CES-D score (path b, B = -0.35; P < 0.01). The association between fried food consumption and total CES-D score was not significant when we controlled for RS-14 score. Bootstrapping results showed that there was a significant positive indirect association between frequency of fried food and CESD score through RS-14 (95 % bias-corrected and accelerated confidence interval = 0.34 to 0.92). CONCLUSION: Frequency of fried food consumption was associated with lower resilience to depression. Further nutritional interventional studies to increase resilience and prevent depression are warranted.

Change in blood levels of eicosapentaenoic acid and posttraumatic stress symptom: A secondary analysis of data from a placebo-controlled trial of omega3 supplements.

BACKGROUND: Eicosapentaenoic acid (EPA) is suggested to be protective against posttraumatic stress disorder (PTSD) from two observational studies. We previously conducted a randomized controlled trial and found no effect of docosahexaenoic acid (DHA) for prevention of PTSD. This secondary analysis aimed to determine whether change in blood levels of EPA is associated with PTSD symptoms. METHODS: The percentages of EPA, DHA, and arachidonic acid (AA) were measured in erythrocyte membranes at baseline and posttreatment in 110 participants with severe physical injury who were randomly assigned to receive either a daily dose of 1,470mg DHA and 147mg EPA or of placebo for 12 weeks. Associations between change in erythrocyte fatty acid levels during the trial controlling for each baseline level and PTSD severity at 12 weeks were analyzed by treatment arm. RESULTS: In the omega3 supplements arm, changes in EPA+DHA (p=.023) and EPA (p=.001) as well as the EPA:AA ratio (p=.000) and EPA: DHA ratio (p=.013) were inversely correlated with PTSD severity. Change in AA was positively correlated with PTSD severity (p=.001). LIMITATION: This trial was conducted at a single-center in Japan and PTSD symptoms in most participants were not serious. CONCLUSIONS: Increased erythrocyte level of EPA during the trial was associated with low severity of PTSD symptoms in patients receiving omega3 supplements.

Docosahexaenoic acid for selective prevention of posttraumatic stress disorder among severely injured patients: a randomized, placebo-controlled trial.

OBJECTIVE: Docosahexaenoic acid (DHA) might help prevent or attenuate posttraumatic stress disorder (PTSD) symptoms. We examined the efficacy and safety of DHA for preventing PTSD (DSM-IV) after severe accidental injury. METHOD: From December 2008 to August 2013, we conducted a randomized, double-blind, placebo-controlled trial of 110 accident-injured patients consecutively admitted to an intensive care unit of the National Disaster Medical Center in Tokyo, Japan. All patients were taught about their psychological reactions to accidental injury for 20 minutes and were randomly assigned to receive 1,470 mg/d of DHA plus 147 mg/d of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. The primary outcome was total score on the Clinician-Administered PTSD Scale (CAPS) at 3-month follow-up. Secondary outcomes included PTSD diagnosis (full-blown or partial PTSD). Adherence to the interventions was assessed by erythrocyte fatty acid composition. RESULTS: At 3 months, the CAPS total score revealed no differences between the 2 groups (10.78 in the DHA group vs 9.22 in the placebo group; n = 100; P = .572). We found that 11.1% of the DHA group and 5.5% of the placebo group developed PTSD. The erythrocyte level of DHA and EPA in the DHA group was significantly elevated compared to the placebo group (P < .01). CONCLUSIONS: Docosahexaenoic acid supplementation was not superior to placebo for the secondary prevention of PTSD symptoms at 3 months after severe accidental injury. The efficacy of a different ratio of DHA and EPA and higher doses of omega-3 fatty acids as secondary prevention of PTSD remains to be determined. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00671099.

Implementation of psychiatric-focused lifestyle medicine programs in Asia.

Lifestyle-focused health programs are growing in interest throughout Western society, and a range of lifestyle factors are known to enhance both physical and mental health. However, it remains largely unknown as to whether this approach is salient for the Asian context. The major components of integrative lifestyle-focused health programs to enhance mental and physical health are considered to include the evidence-based adoption of physical activity and exercise, dietary modification, general psychoeducation, adequate relaxation/sleep and social interaction, use of mindfulness techniques, the reduction of substance use, attention of intersecting environmental factors, and the potential use of motivation and goal-setting techniques. This paper outlines an overview of the evidence underpinning these elements, and discusses potential barriers and challenges, and what logistical considerations may need to be addressed in the implementation of such programs within the context of Asian cultures.

Hypnosis for induction of labour.

BACKGROUND: Induction of labour using pharmacological and mechanical methods can increase complications. Complementary and alternative medicine methods including hypnosis may have the potential to provide a safe alternative option for the induction of labour. However, the effectiveness of hypnosis for inducing labour has not yet been fully evaluated. OBJECTIVES: To assess the effect of hypnosis for induction of labour compared with no intervention or any other interventions. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014), handsearched relevant conference proceedings, contacted key personnel and organisations in the field for published and unpublished references. SELECTION CRITERIA: All published and unpublished randomised controlled trials (RCTs) and cluster-RCTs of acceptable quality comparing hypnosis with no intervention or any other interventions, in which the primary outcome is to assess whether labour was induced. DATA COLLECTION AND ANALYSIS: Two review authors assessed the one trial report that was identified (but was subsequently excluded). MAIN RESULTS: No RCTs or cluster-RCTs were identified from the search strategy. AUTHORS' CONCLUSIONS: There was no evidence available from RCTs to assess the effect of hypnosis for induction of labour. Evidence from RCTs is required to evaluate the effectiveness and safety of this intervention for labour induction. As hypnosis may delay standard care (in case standard care is withheld during hypnosis), its use in induction of labour should be considered on a case-by-case basis.Future RCTs are required to examine the effectiveness and safety of hypnotic relaxation for induction of labour among pregnant women who have anxiety above a certain level. The length and timing of the intervention, as well as the staff training required, should be taken into consideration. Moreover, the views and experiences of women and staff should also be included in future RCTs.

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

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.

Attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among disaster medical assistance team members after the Great East Japan Earthquake: the APOP randomized controlled trial.

BACKGROUND: On March 11, 2011, a magnitude 9.0 earthquake, the most powerful ever recorded in Japan, and a massive tsunami struck off the coast of the Sanriku region. A Disaster Medical Assistance Team, a mobile medical team with specialized training that is deployed during the acute phase of a disaster, was dispatched to areas with large-scale destruction and multiple injured and sick casualties. Previous studies have reported critical incident stress (i.e. posttraumatic stress disorder symptoms and depressive symptoms) among rescue workers as well as the need for screening and prevention for posttraumatic stress disorder. So far we have shown in an open trial that posttraumatic stress disorder symptoms in critically injured patients can be reduced by taking omega-3 fatty acids intended to stimulate hippocampal neurogenesis. METHOD/DESIGN: This study is designed to determine the effectiveness of attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among Disaster Medical Assistance Team members after the Great East Japan Earthquake, and is named the APOP randomized controlled trial which is currently ongoing. First, we will provide psycho-education on posttraumatic distress, which is common in responders to the Disaster Medical Assistance Team members deployed to the disaster area. Second, observational research will be conducted to evaluate critical incident stress following the completion of medical activities. Third, team members who provide consent to participate in the intervention research will be randomly divided into a group given an omega-3 fatty acid supplement and a group not given the supplements. Outcome will be evaluated at 12 weeks after the supplements are shipped to the team members. DISCUSSION: Measures that address critical incident stress in disaster responders are important, but there is no substantial evidence that links such measures with prevention of posttraumatic stress disorder. Thus, any confirmation through this study that the intake of omega-3 fatty acid supplements serves as a simple preventative measure for critical incident stress will be of great significance. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000005367.