Diet and Aggression: Reducing aggression among chronic psychiatric inpatients through supplementation of multivitamins, minerals and n-3 fatty acids

Aggressive incidents frequently occur among long-term psychiatric inpatients
(n=12.201 in The Netherlands Knispel et al., 2013). Incidents, such as verbal
aggression towards persons, aggression towards objects, threats, non-compliance
with hospital rules, disinhibited (sexual) behaviour, fighting, assault on
patients or staff, self-harm and suicide attempt; follow from a wide range of
causes such as psychosocial stressors, patient history, psychopathology,
resistance to treatment, and being institutionalized. The magnitude of the
aggression problem becomes evident in a review of 122 studies conducted in
various psychiatric settings, showing that severe aggressive incidents occurred
on average 5.8 times per 100 occupied bed days, amounting to 21 (standard
deviation [SD]=42) serious events per bed per year (Bowers et al., 2011). The
large SD indicates extreme variability across studies. A pilot study in 3
chronic inpatient wards (in Oegstgeest, The Hague, and Amsterdam) within the
present study demonstrated an incidence rate of 112 aggression incidents per
patient per year. This number can be divided in 35 major incidents (severe
threats, fighting, assault on patients or staff, self-harm, suicide attempt),
and 77 minor incidents (verbal aggression, threats, non-compliance with
hospital rules, aggression towards objects, disinhibited [sexual] behaviour)
(Hazewinkel et al., in preparation). Aggression has serious consequences;
incidents can have physical consequences, may cause stress, and can be
traumatic for patients as well as staff (Nijman et al., 2005; Bowers et al.,
2011; Arnetz et al., 1997). Consequences of aggression can also be expressed
in terms of financial costs. Finally, aggression is one of the reasons
long-term psychiatric inpatients remain admitted involuntarily. Policymakers
prioritize aggression reduction in (mental) health care. Containment of
aggression and its consequences is achieved through (coerced) medication,
observation, show of force, restraint, seclusion, time-out, and security
policies like locking ward doors, but also through aggression-anticipation and
environment- and client-focused approaches (Bowers et al., 2011). However,
further reduction of aggressive incidents remains necessary as becomes evident
from initiatives like the petition *handen af van ggz
verpleegkundigen* (www.handenafvanggzverpleegkundigen.nl), and the action plan
against aggression in care
(http://www.rijksoverheid.nl/nieuws/2012/03/22/ministers-presenteren-gezamenlijk
-actieplan-tegen-agressie-in-de-zorg%5B2%5D.html), an initiative of the
ministries of *Volksgezondheid, Welzijn en Sport* (VWS), *Binnenlandse Zaken en
Koninkrijksrelaties* (BZK), *Veiligheid & Justitie* (VJ), and social parties.
The need for aggression reduction is also felt strongly among nursing staff, as
is reflected in responses to a short anonymous online survey we conducted among
psychiatric nurses (n=19), who unanimously endorsed the need for new methods
for reducing aggression.
A number of randomised controlled trials (RCTs) demonstrated anti-aggressive
effects of multi-ingredient formulae, including multiple vitamins, minerals,
and n-3FA (i.e., omega-3 fatty acids), see figure 1. An RCT of vitamins and
minerals in 62 juvenile delinquents showed a 28% (95%CI: 18-45%) decrease in
violent and nonviolent offences over a 13-week period (Schoenthaler et al.,
1997). A subsequent RCT of vitamins and minerals in 80 frequently disciplined
schoolchildren showed a 47% (95%CI: 29-65%) reduction in the number of violent
and nonviolent delinquent acts during a 4-month period (Schoenthaler et al.,
2000). An RCT of vitamins, minerals, and n-3FA in 231 prisoners showed a 26%
(95%CI: 8-44%) reduction in the number of offences and antisocial behaviour
during a 2-39 week period (Gesch et al., 2002). Another vitamin, mineral, and
n-3FA-RCT in 221 young adult prisoners demonstrated an incidence rate ratio of
0.60 (95%CI: 0.37-0.96) during a 1-3 month period (Zaalberg et al., 2010).
Finally, a pilot study with 12 treatment resistant schizophrenia patients
demonstrated reduced agitation and psychopathology and increased functioning
upon n-3FA supplementation (Legare et al., 2007).
Chronic psychiatric inpatients are known to have poor nutritional status
(Francis et al., 2010; Grol et al., 2005). This is the result of energy-dense
and nutrient-poor diets, low appetite, and insufficient outdoor activities but
also of the detrimental effect of psychotropics on appetite and
gastrointestinal function, and possible interactions with food and nutrients
(Gray et al., 1989). Based on the high prevalence of aggression and the poor
nutritional status of this patient group, we hypothesize that the aggression
reducing effect of vitamin-, micronutrient-, and n-3FA-supplementation in this
group may be substantial. Providing nutritional supplements to this patient
group may result in reduction of aggression, decrease of costs related to
aggression, and increase in patients* quality of life.

The main objective in this study is to test the hypothesis that suppletion with
vitamins, minerals and n-3 fatty acids in long-term psychiatric inpatients will
reduce the number of aggressive incidents.

The proposed study is a pragmatic multicentre randomised double-blind placebo
controlled intervention trial with an intervention period of 6 months. As the
wash-out period of nutritional supplements is in some cases unknown, we propose
a parallel design.

During six months, one group will receive three capsules daily: 1 Orthica Fish
EPA Mini en 2 Orthica Multi Energie, the other group will receive three placebo
capsules daily.

Patients who agree to participate will enter a two-week run-in phase in which
they will take three placebo capsules daily. After this run-in phase the use of
three capsules per day will be evaluated, if this evaluation is positive
participants will be randomised (baseline) to active or control condition.
Participants will then start the daily use of three nutritional supplement
capsules daily or three placebo capsules daily which will continue for six
months.
At three moments (baseline, two months post baseline and six months post
baseline) three questionnaires will be administered: the Aangepaste Versie van
de Agressievragenlijst (AVL-AV, Hornsveld et al., 2009), a 12 item self report
questionnaire about feelings of aggression; the Dutch version of the World
Health Organization Quality of Life Questionnaire (WHO-QL-bref, De Vries & van
Heck, 1996), a 26-item observer rated quality of life instrument; the verkorte
Comprehensive Psychopathological Rating Scale (vCPRS, Montgomery et al., 1979),
a 25-item observer rated questionnaire measuring affective symptoms. Also, at
baseline and at six months post baseline two bloodsamples (25cc each) will be
taken to determine nutrient status and patient background information (BMI,
bloodpressure, drug use, information regarding diagnosis and treatment from the
medical file, and social demographic information) will be collected . All
data-collection will take place at the department where the patient resides.
Within the study aggression incidents will be registered by nursing staff in
the department using the Staff Observation Aggression Scale-revised (SOAS-R,
Nijman et al., 1999). As registration of severe incidents is already part of
standard care, this registration will not form any burden for the patient.
Also, at 4 time points (baseline, two weeks post baseline, two months post
baseline and six months post baseline), nursing staff will fill in the Social
Dysfunction Aggression Scale (SDAS, Wistedt et al., 1990), measuring the
observed level of aggression and social dysfunction.
The risks of participating in this study are minimal, the risk of blood
collection is that of a small local hematoma, feeling light headed, fainting or
local infection. The use of the supplements Orthica Soft Multi and Orthica Fish
EPA MAX has not been associated with any significant risks. Burden associated
with participation is also minimal with questionnaires at three time points and
blood sample collection at two points. Participants will be compensated for
their time. Potential benefits of participating in this study are a direct and
indirect increase in quality of life through improved nutrition as well as
reduction of aggressive incidents.