Diet and Aggression: Reducing Aggression Among Chronic Psychiatric Inpatients Through Dietary Supplementation

Diet and Aggression: Reducing Aggression Among Chronic Psychiatric Inpatients Through Supplementation of Multivitamins, Minerals and n-3 Fatty Acids

The overall goal of this study is to investigate whether the daily administration of multivitamins, minerals and n-3 fatty acids will reduce aggression in long-term psychiatric inpatients and will thereby reduce costs of care.

Study Overview

• Status: Completed
• Conditions: Psychiatric Hospitalization
• Intervention / Treatment: Dietary supplement: Orthica Soft Multi Mini and Orthica Fish EPA Mini

Detailed Description

Aggressive incidents are highly prevalent among chronic psychiatric inpatients. Previous studies have demonstrated the potential of multivitamin-, mineral-, and n-3 fatty acids (n-3FA) supplementation to reduce aggression in adolescent and forensic populations. To test the hypothesis that multivitamin-, mineral-, and n-3FA supplementation reduces aggression among chronic psychiatric inpatients, we designed a pragmatic, randomised, double-blind, placebo controlled, multicentre intervention study among psychiatric inpatients residing in long-stay psychiatric wards. During 6 months, one group receives 2 supplements daily from Orthica: one containing vitamins and minerals (vitamins [B1, B2, B3, B5, B6, B11, B12, C, D, E, Beta Carotene; Calcium, Iodine, Copper, Magnesium, Selenium, Iron, Zinc, Potassium, Chrome, Manganese]) and one containing fish fatty acids (n-3FA: eicosapentaenic acid [EPA] and docosahexaenic acid [DHA]) and the other group receives 2 placebo capsules.

The main study parameter is the number of aggressive incidents from baseline (t0) to endpoint (six months post baseline, t3). Patients who wish to participate enter a 2-week run-in phase in which they take 2 placebo capsules daily. After positive evaluation of this run-in phase patients are randomized to the active or the control condition. Participants will then start the daily use of 2 supplement capsules or 2 placebo capsules, which will continue for 6 months. At 3 time points (at baseline [t0] and at 2 and 6 months post-baseline [t2 and t3]), three questionnaires measuring feelings of aggression, quality of life, and psychiatric symptoms will be administered. Also, at t0 and t3 (micro)nutrient status will be determined. Finally, at 4 time points (t0, 2 weeks post baseline [t1], t2 and t3), nursing staff will report on observed levels of aggression and social dysfunction.

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Oegstgeest, Netherlands, 2342 EB
    • Rivierduinen
  • The Hague, Netherlands, 2512 HN
    • Parnassia
  • Gelderland
    • Ermelo, Gelderland, Netherlands, 3853 LC
      • GGZ Centraal
  • Noord-Braband
    • Eindhoven, Noord-Braband, Netherlands, 5626 ND
      • GGZ Eindhoven
  • Utrecht
    • Den Dolder, Utrecht, Netherlands, 3734 AC
      • Fivoor
  • Zuid-Holland
    • Delft, Zuid-Holland, Netherlands
      • GGZ Delfland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• residing at a facility for long-term psychiatric inpatient care
• age 18 or over

Exclusion Criteria:

• pregnancy
• breastfeeding
• known contra-indication for using the supplements used in this study
• expected discharge or transfer within the next 8 weeks
• current use of dietary supplements and refusal to stop using these for the duration of the study
• failure to complete run-in phase
• contra-indication for the use of pork-gelatin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: nutritional supplement; 2 Orthica Soft Multi Mini capsules and 1 Orthica Fish EPA Mini capsule per day; duration: 6 months	Dietary supplement: Orthica Soft Multi Mini and Orthica Fish EPA Mini; daily intake of 2 Orthica Soft Multi Mini capsules (containing vitamins [B1, B2, B3, B5, B6, B11, B12, C, D, E, Beta Carotene] and minerals [Iodine, Copper, Selenium, Iron, Zinc, Chrome, Manganese]) and 1 Orthica Fish EPA Mini capsule (containing n-3FA: eicosapentaenic acid [EPA] and docosahexaenic acid [DHA])
Placebo Comparator: placebo; During 6 months one group receives 3 placebo supplements daily with identical look and feel to Orthica Soft Multi Mini and Orthica Fish EPA Mini	Dietary supplement: Orthica Soft Multi Mini and Orthica Fish EPA Mini; daily intake of 2 Orthica Soft Multi Mini capsules (containing vitamins [B1, B2, B3, B5, B6, B11, B12, C, D, E, Beta Carotene] and minerals [Iodine, Copper, Selenium, Iron, Zinc, Chrome, Manganese]) and 1 Orthica Fish EPA Mini capsule (containing n-3FA: eicosapentaenic acid [EPA] and docosahexaenic acid [DHA])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of aggressive incidents	The main study parameter is the number of aggressive incidents from baseline (t0) to endpoint (six months post baseline, t3), as registered daily on the ward by nurses using the Dutch version of the Staff Observation Aggression Scale- Revised version (SOAS-R)	daily for the total duration of the (six-month) intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient feelings of aggression	the Aangepaste Versie van de Agressievragenlijst (AVL-AV, 1), a 12 item self-report questionnaire about feelings of aggression.	At 3 points (baseline [t0], 2 months post baseline [t2] and six months post baseline[ t3])
Patient quality of life	the World Health Organization Quality of Life Questionnaire (WHO-QL-bref 5), a 26-item observer rated quality of life instrument.	At 3 points (baseline [t0], 2 months post baseline [t2] and six months post baseline[ t3])
Patient psychiatric symptoms	The verkorte Comprehensive Psychopathological Rating Scale (vCPRS), a 25-item observer rated instrument on affective symptoms, which includes the Montgomery-Åsberg Depression Rating Scale (MADRS).	At 3 points (baseline [t0], 2 months post baseline [t2] and six months post baseline[ t3])
Observed patient social dysfunction	Nursing staff will fill in the Social Dysfunction Aggression Scale (SDAS), measuring observed levels of aggression and social dysfunction.	At 4 points (baseline [t0], 2 weeks post baseline [t1], 2 months post baseline[t2] and six months post baseline [t3])

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient micronutrient status	Blood samples (50cc) will be taken to determine micronutrient status, including Vitamins A, E, B1, B6, B12, D, and folate, total iron, magnesium, and the fatty acid spectrum.	At 2 points (baseline [t0] and six months post baseline [t3])

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Atrium Innovations
• Investigators: Principal Investigator: Erik J. Giltay, MD PhD, Leiden University Medical Center

Publications and helpful links

General Publications

• Hornsveld RH, Muris P, Kraaimaat FW, Meesters C. Psychometric properties of the aggression questionnaire in Dutch violent forensic psychiatric patients and secondary vocational students. Assessment. 2009 Jun;16(2):181-92. doi: 10.1177/1073191108325894. Epub 2008 Oct 13.
• Nijman H, Palmstierna T. Measuring aggression with the staff observation aggression scale--revised. Acta Psychiatr Scand Suppl. 2002;(412):101-2. doi: 10.1034/j.1600-0447.106.s412.21.x.
• Asberg M, Schalling D. Construction of a new psychiatric rating instrument, the Comprehensive Psychopathological Rating Scale (CPRS). Prog Neuropsychopharmacol. 1979;3(4):405-12. doi: 10.1016/0364-7722(79)90055-9.
• Skevington SM, Lotfy M, O'Connell KA; WHOQOL Group. The World Health Organization's WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial. A report from the WHOQOL group. Qual Life Res. 2004 Mar;13(2):299-310. doi: 10.1023/B:QURE.0000018486.91360.00.
• Schoenthaler SJ, Bier ID. The effect of vitamin-mineral supplementation on juvenile delinquency among American schoolchildren: a randomized, double-blind placebo-controlled trial. J Altern Complement Med. 2000 Feb;6(1):7-17. doi: 10.1089/acm.2000.6.7.
• Gesch CB, Hammond SM, Hampson SE, Eves A, Crowder MJ. Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Randomised, placebo-controlled trial. Br J Psychiatry. 2002 Jul;181:22-8. doi: 10.1192/bjp.181.1.22.
• Zaalberg A, Nijman H, Bulten E, Stroosma L, van der Staak C. Effects of nutritional supplements on aggression, rule-breaking, and psychopathology among young adult prisoners. Aggress Behav. 2010 Mar-Apr;36(2):117-26. doi: 10.1002/ab.20335.
• Legare N, Brosseau E, Joyal CC. Omega-3 and violence in schizophrenia. Schizophr Res. 2007 Nov;96(1-3):269. doi: 10.1016/j.schres.2007.05.023. Epub 2007 Jul 16. No abstract available.
• Benton D. The impact of diet on anti-social, violent and criminal behaviour. Neurosci Biobehav Rev. 2007;31(5):752-74. doi: 10.1016/j.neubiorev.2007.02.002. Epub 2007 Mar 4.
• de Bles NJ, Gast DAA, van der Slot AJC, Didden R, van Hemert AM, Rius-Ottenheim N, Giltay EJ. Lessons learned from two clinical trials on nutritional supplements to reduce aggressive behaviour. J Eval Clin Pract. 2022 Aug;28(4):607-614. doi: 10.1111/jep.13653. Epub 2022 Jan 17.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: July 9, 2015
• First Submitted That Met QC Criteria: July 14, 2015
• First Posted (Estimate): July 15, 2015

Study Record Updates

• Last Update Posted (Actual): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: nutrition; n-3 fatty acids; aggression; psychiatry; inpatients admitted >2 years
• Additional Relevant MeSH Terms: Behavioral Symptoms; Aggression
• Other Study ID Numbers: P14.332; 836031016 (Other Grant/Funding Number: ZonMW); NL51850.058.14 (Registry Identifier: Toetsing online); 5176 (NTR)