HIIT & Severe Mental Illness Meta-analysis

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High Intensity Interval Training (HIIT) for people with Severe Mental
Illness: A systematic review & meta-analysis of intervention studies–
considering diverse approaches for mental and physical recovery

Nicole Korman , Michael Armour , Justin Chapman ,

Simon Rosenbaum , Steve Kisely , Shuichi Suetani , Joseph Firth ,
Dan Siskind

PII: S0165-1781(19)31771-8
DOI: https://doi.org/10.1016/j.psychres.2019.112601
Reference: PSY 112601

To appear in: Psychiatry Research

Received date: 17 August 2019

Revised date: 3 October 2019
Accepted date: 3 October 2019

Please cite this article as: Nicole Korman , Michael Armour , Justin Chapman , Simon Rosenbaum ,
Steve Kisely , Shuichi Suetani , Joseph Firth , Dan Siskind , High Intensity Interval Training (HIIT)
for people with Severe Mental Illness: A systematic review & meta-analysis of intervention studies–
considering diverse approaches for mental and physical recovery, Psychiatry Research (2019), doi:
https://doi.org/10.1016/j.psychres.2019.112601

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Highlights

 High intensity interval training (HIIT) appears as feasible as moderate intensity

continuous training (MCT) for people with severe mental illness (SMI)
 People with SMI may experience promising improvements in cardiorespiratory fitness
(CRF) and depression following HIIT interventions
 HIIT resulted in comparable improvements in CRF as MCT, but a moderate benefit in
depression over MCT
High Intensity Interval Training (HIIT) for people with Severe Mental Illness: A
systematic review & meta-analysis of intervention studies– considering diverse
approaches for mental and physical recovery

Short running title: HIIT & Severe Mental Illness Meta-analysis

*Nicole Kormana,b Michael Armourc Justin Chapmana,f Simon Rosenbaumd Steve

Kiselya,b Shuichi Suetania,f **Joseph Firthd,e **Dan Siskinda,b

Affiliations

a
Addiction and Mental Health Services, Metro South Health Services, Australia
b
School of Medicine, University of Queensland, Brisbane, Australia
c
NICM Health Research Institute, Western Sydney University, Westmead, NSW,
Australia
d
School of Psychiatry, University of New South Wales, Australia
e
Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health,
University of Manchester, Manchester, UK.
f
Queensland Institute of Medical Research, Brisbane, Australia
** Co-senior author

*Corresponding Author
Coorparoo Community Care Unit,
Metro South Addiction and Mental Health Services
6 Baragoola St
Coorparoo
Qld 4005
Australia
P +61 7 37277200
F +61 7 37277250

E n.korman@uq.edu.au
Word count: 4990
References: 61
Tables: 2
Figures: 5
Supplementary Material: 5

Short Running Title: HIIT SMI Meta-analysis

Abstract

There is a mortality gap of 15 to 20 years for people with severe mental illness (SMI -

psychotic spectrum, bipolar, major depressive disorders). Modifiable risk factors

include inactivity and low cardiorespiratory fitness (CRF). Exercise can improve

mental and physical outcomes; optimal type and intensity of exercise for people with

SMI has yet to be determined. High Intensity Interval training (HIIT) is an exercise

with distinct cardio-metabolic advantages in other disease populations compared to

traditional moderate intensity continuous training (MCT). We investigated the

feasibility and efficacy of HIIT for people with SMI.

Major electronic databases were searched, identifying HIIT studies for adults

experiencing SMI. Data on feasibility, safety, study design, sample characteristics,

and physical and psychological outcomes were extracted and systematically

reviewed. Meta-analyses were conducted within group, pre and post HIIT

interventions, and between group, to compare HIIT with control conditions.

Nine articles were identified including three pre/post studies, one non randomised

and five randomised trials, (366 participants, 45.1% female). HIIT appears as

feasible as MCT, with few safety concerns. Following HIIT, there was a moderate

improvement in CRF and depression. There was no difference between HIIT and

MCT for adherence or CRF. HIIT improved depression more than MCT.
 1 Introduction

The mortality gap for people with severe mental illness (SMI) is approximately 15-20

years compared to the general population and the gap is thought to be widening

(Laursen et al., 2019; Tanskanen et al., 2018). The vast majority of this research is

derived from higher income countries; the mortality gap is thought to be even larger

in low income settings (Hjorthøj et al., 2017). Modifiable risk factors such as

inactivity, smoking, poor nutrition and obesity play a significant role, with

cardiovascular and metabolic disease risk in people with SMI estimated as 1.4-2

times the general population (Correll et al., 2017; Osborn et al., 2008).

Cardiorespiratory fitness (CRF) refers to the ability of the circulatory and respiratory

systems to supply oxygen to skeletal muscles during sustained activity (Ross et al.,

2016). Higher CRF levels are associated with improved mortality independent of

obesity, smoking, and substance abuse in the general population (Lee et al., 2010).

People with SMI have low cardiorespiratory fitness (CRF), (Scheewe et al., 2019;

Vancampfort et al., 2017a; Vancampfort et al., 2017b). Exercise interventions are

feasible, can increase CRF in people with SMI (Stubbs et al., 2016; Vancampfort et

al., 2015) and have demonstrated benefits in various mental health outcomes

including cognition, negative and positive symptoms of schizophrenia, depressed

mood (Czosnek et al., 2019; Firth et al., 2019; Stubbs et al., 2018a).

The vast majority of past research into exercise interventions for people with SMI

has investigated continuous aerobic exercise, typically of moderate or moderate to

vigorous intensity in comparison with no activity, (Firth et al., 2015; Vancampfort et

al., 2016a). Additionally, the optimal prescription of exercise with respect to exercise

intensity for people with SMI has yet to be established (Vancampfort et al., 2016a).

High Intensity Interval training (HIIT) is a potent, time efficient type of exercise

training involving repetitive intervals of short bursts of high intensity exercise

(durations between six seconds to four minutes) alternating with periods of rest or

recovery (ten seconds to five minutes), (Batacan et al., 2017). In athletes and the

general population, HIIT is increasingly recognized as an efficacious exercise

modality (Gibala et al., 2012) with demonstrated improvements in CRF, power and

performance, and reductions in fat mass compared to continuous aerobic training

(Gibala et al., 2006; Laursen et al., 2005; Matsuo et al., 2014).

HIIT has also been found to be efficacious in various chronic disease populations

(e.g. heart failure, metabolic syndrome, coronary artery disease) with respect to CRF

and various metabolic risk factors in comparison to continuous training (Weston et

al., 2014; Wisløff et al., 2007).

In a 2017 meta-analysis of exercise interventions for people with SMI, subgroup

analysis revealed interventions involving HIIT were more effective at improving CRF

than low to moderate intensity protocols, indicating intensity may be a factor in the

efficacy of exercise interventions in this population (Vancampfort et al., 2017b).

People with SMI have high cardio-metabolic risks and low CRF, hence HIIT may be

a promising exercise protocol to impact on modifiable risk factors which contribute to

premature mortality.

A 2018 narrative review of exercise interventions in schizophrenia concluded that

HIIT has the potential to reduce metabolic risk factors (Schmitt et al., 2018).

However, this was based on two pre- post studies, a case report and a study on the
effects of a single episode of HIIT, was not systematic, and did not include recently

published randomized controlled trials for people with SMI. In addition, it did not

address possible adverse effects, which is important given the potential risks of

acute exercise in people with significantly low fitness (Thompson et al., 2007b).

Despite the potential benefit, the feasibility and safety of HIIT interventions for people

with SMI remains uncertain. In this systematic review, we aimed to critique the

available evidence for the feasibility and safety and available physical and

psychological outcomes for HITT, for people with SMI.

2 Methods

Protocol and registration

This study was registered with PROSPERO (registration number:

CRD42018104708). The Preferred Reporting Items for Systematic Reviews and

Meta-Analyses (PRISMA) statement recommendations was followed in conducting

this review (Moher et al., 2009).

2.1 Search Strategy

A systematic search of Embase, Pubmed, Cochrane Central trials registry and

PsycINFO was initially conducted from inception to June 2019. The Medical Subject

Heading (MeSH) database was employed to establish all related articles on HIIT and

SMI and related terms, in conjunction with text words. (Search strategy in

Supplementary material 1.)

2.2 Eligibility criteria

Studies involving participants over the age of 18 with a diagnosis of SMI (Johnson,

1997); major depressive disorders, psychotic spectrum disorders and bipolar

disorder were included in the review.

Studies needed to follow a HIIT protocol, defined as intervals of work involving brief

high intensity exercise interspersed by intervals of recovery (at lower intensity or

complete rest), (Batacan et al., 2017). Included studies needed an identified method

of assessing exercise intensity (such as heart rate, rate of perceived exertion or

strength). Studies were excluded if HIIT occurred less than once per week, or less

than 2 weeks duration.

We included all randomized and non-randomised controlled trials and pre/post

studies were considered. Published data in all languages were included and

translated into English where necessary.

2.3 Study Selection

After removal of duplicates, studies meeting inclusion criteria from the search

strategy were identified at title and abstract stage (NK). Studies that met inclusion

criteria at title and abstract stage or that could not be excluded on the basis of

information in the abstract were reviewed at full text level by two independent

authors and assessed according to inclusion criteria (NK and MA). Relevant journals

were hand searched. Snowball searches of key papers and reference lists were

conducted. (Figure 1 for identification of included studies).

2.4 Data Items and Collection process

Data extraction was conducted by NK and MA. Any discrepancies during all stages

of study selection, data extraction and quality assessment were resolved through

discussion with senior authors, DS and JF, and through re-checking original source

papers.

A systematic tool was developed, and quantitative data from each study was

extracted on feasibility (exercise adherence, recruitment, participation), and adverse

events. Secondary data on study design, sample characteristics, exercise protocol

details including details of HIIT intervals and intensity, and physical and

psychological data was collected. Studies were classified based on whether HIIT

was compared with active (exercise) control, inactive (non-exercise) control or no

control group.

Physical and psychological data was categorized into domains:

A) PHYSICAL = physical fitness (VO2max/peak - a measure of an individual’s ability

to absorb and consume oxygen during exercise, resting heart rate, power and

strength)

B) METABOLIC= metabolic health items (Body Mass Index, BMI, body weight,

waist circumference, fasting glucose and lipids, blood pressure, body

composition)

C) PSYCHIATRIC = psychiatric symptoms (positive, negative symptoms,

depressed mood)

D) FUNCTION= quality of life, functioning

Extracted data were validated by MA. Data analysis was conducted by NK, DS and

MA. In cases where data was missing, attempts were made to contact corresponding

authors to obtain this information.

2.5 Study Quality

Two authors (NK and MA) independently assessed all studies using the modified

Physiotherapy Evidence Database (PEDRo) scale, which consists of a checklist of

10 scored yes-or-no items pertaining to the internal validity of studies (Maher et al.,

2003). High quality studies achieved a rating of 7-10; fair; 4-7; poor; 1-3. The

PEDRo scale is included in supplementary material 2.

In addition, two authors (NK and MA) independently assessed RCT’s using the

Cochrane Risk of Bias tool (Higgins et al., 2011), which assesses six domains of

study characteristics that may introduce bias including: random sequence

generation, allocation concealment, blinding of participants, personnel and outcome

assessors, incomplete data, selective reporting or other sources of bias. In both

instances any disagreement in quality assessment rating was resolved by discussion

or if necessary, resolved by a third senior author (DS).

We conducted two types of meta-analyses, 1) within group analyses of pre/post data

following HIIT for all included studies (pre post trials, non-randomised and RCT’s),

and 2) between group analyses for RCT’s utilising endpoint data comparing HIIT with

control conditions, i.e. moderate intensity continuous training (MCT) for all available

physical and psychological outcomes.

All studies provided pre and post means with standard deviation (SD). Two studies

provided means +/- Standard Error (SE) allowing SD to be calculated.

Due to the small size of studies, and variation in exercise conditions and participants,

we used random-effects model for all analyses. Hedges’ g and the 95 % confidence

interval (CI) was calculated as estimates of the effect size. Effect sizes were

categorized as small (0.2–0.4), medium (0.4–0.8), or large (greater than 0.8),

(Cohen, 1988). Where possible, intention-to-treat analyses were sought and

included in the meta-analyses.

Where there were sufficient studies, we conducted a sensitivity analysis to remove

low quality studies (PEDRo ≤ 3).

Heterogeneity (I2) was calculated to assess the risk of bias across studies which was

assessed using the I2 statistic. An I2 of more than 75% was considered to indicate

high level heterogeneity, I2 of 50–75% as indicative of substantial heterogeneity, and

an I2 of less than 40% as low heterogeneity. If there were ten or more studies, we

assessed for publication bias using the Cochrane test for funnel plot asymmetry

(Higgins et al., 2011).

3 Results

The search identified 659 results, providing 525 unique citations after duplicates

were removed (Figure 1). In total, 501 studies were excluded at the title-abstract

stage and 24 records screened. In two cases, authors were contacted regarding

protocols registered as a clinical trial, but no data were available. At the final stage,
21 full text articles were reviewed in full, and nine unique articles met eligibility

criteria and were included in the systematic review and meta-analysis (Abdel-Baki et

al., 2013; Chapman et al., 2017; Gerber et al., 2018; Hanssen et al., 2018;

Heggelund et al., 2011; Minghetti et al., 2018; Romain et al., 2018; Strassnig et al.,

2015; Wu et al., 2015). Additional data were requested for one study (Chapman et

al., 2017).

There were insufficient number of studies to perform subgroup analysis or meta-

regression to evaluate the potential moderating influence of participant and exercise

protocol characteristics.

Publication bias using the Cochrane test for funnel plot asymmetry could not be

evaluated, as fewer than 10 studies were included in each analysis.

3.1 Feasibility and Safety: (Table 1)

Only four out of the nine included studies reported participation, mean 74%, which

ranged between 64 and 85%, (Table 1). Two studies that did not report participation

also excluded participants if they did not attend a minimum number of sessions

(Gerber et al., 2018; Hanssen et al., 2018).

A total of 366/967 participants were recruited into HIIT studies (38%). Approximately

one third (105/366) of HIIT participants (29%) dropped out with no difference

between the HIIT and MCT groups (odds ratio 0.86 (95% CI 0.46 – 1.62); I2 = 0%).
Only one study formally assessed acceptability of HIIT and found similar enjoyment

for both HIIT and MCT groups, although small sample size (n=16), (Chapman et al.,

2017).

One study used a formal adverse events protocol to report adverse events; 4 studies

did not address adverse outcomes. 11 out of 225 participants involved in any HIIT

programs experienced an injury (4.8%) and a further two participants dropped out

due to “physical discomfort”. One HIIT versus MCT study reported adverse events;

the proportion of adverse events was equal in each condition - 2/8 (25%), (Chapman

et al., 2017).

(Insert Table 1)

3.2 Study characteristics: (Table 1)

Of the nine studies meeting criteria, three were pre/post studies involving a single

arm HIIT intervention, two studies compared HIIT against inactive or wait list control,

four studies compared HIIT against a moderate intensity exercise control.

Selected studies included a total of 366 participants, of whom 45% (n = 165) were

females. Of these, 225 participants were in a HIIT program. The mean age was 35.5

years and BMI 28.2kg/m2 (SD 3.7). Three studies included participants with major

depressive disorders, five of schizophrenia and/or bipolar disorders, and one study

included participants with a range of SMI’s (Table 1).

All the included studies employed a training frequency of either 2 or 3 times per

week. Study duration ranged from 4 weeks to 26 weeks but the majority (n=7) were

of short duration, (i.e. 12 weeks or less). An aerobic HIIT exercise protocol (n=8) was
the most commonly employed with one study using a high velocity resistance

protocol.

Mean exercise session duration for HIIT (including rest/recovery), (8 studies) was 31

mins, and MCT (4 studies) was 32.5 minutes; whereas mean exercise minutes per

session (active exercise minus rest) was 17 minutes for HIIT and 22.5 minutes for

MCT. Over half of the HIIT studies (n=6) utilised an interval schedule involving short

(≤ 30 seconds) of exercise “work”; two studies utilised longer work and recovery

periods – (4 minutes work; 3 mins recovery/rest), (Table 1).

Only one study specifically addressed motivation to exercise in the intervention

(Abdel-Baki et al., 2013).

The majority (6/9) of studies involved direct supervision of participants (i.e. personal

trainer, kinesiology or medical students, trained exercise coach), however three

studies did not specifically report on this. Only one study asked participants to

exercise alone without supervision in the last third of the study but did not report

specific adherence to this (Chapman et al., 2017).

Primary outcomes included CRF, (n=3), effects of HIIT on depression (n =3),

feasibility, (n=2), metabolic outcomes, (n=2), effect of HIIT on sports and exercise

motivation (n=1), specific outcome measures are included in Table 2.

(Insert Table 2)
3.3 Quality

Median PEDRo score of 9 included studies was 4. In terms of the PEDRo scale,

three studies were small pre-post studies of low quality and only two studies rated

high quality (Minghetti et al., 2018; Romain et al., 2018), (Supplementary Table 1).

Due to the limited number of randomised trials, all RCT’s were included in our meta-

analysis irrespective of quality, (Supplementary Table 2).

3.4 Physical health

Seven studies measured CRF via VO2max or VO2peak. The majority of studies (5/7)

obtained CRF via direct maximal testing (2 via submaximal tests), (Table1). Pre/post

data was analysed for the seven studies assessing CRF, (two pre/post studies, one

non randomised trial, four RCT’s) and revealed a significant increase in CRF

following HIIT, moderate effect size, high heterogeneity, I2= 75% (Figure 2).

Sensitivity analysis to remove low quality studies revealed a smaller but significant

effect, (hedges g 0.27 (0.123, 0.418, p<0.00), I2=68).

Four of the studies assessing CRF found improvements that were of a magnitude to

be considered clinically significant (Abdel-Baki et al., 2013; Heggelund et al., 2011;

Minghetti et al., 2018; Romain et al., 2018), that is, VO2max or VO2peak increases of

greater than 3.5ml/L/kg), (Kodama et al., 2009).

Individual studies reported small improvements in other physical fitness outcomes

that included net mechanical efficiency of walking (Heggelund et al., 2011), power
and strength (Strassnig et al., 2015) resting heart rate and pulse pressure (Wu et al.,

2015), (Table 2).

Endpoint data in four RCT’s where HIIT was compared with MCT interventions for

CRF, found no significant difference between HIIT and MCT, heterogeneity I 2=0%,

(Figure 3).

3.5 Metabolic Outcomes

Of the nine trials, seven assessed at least one metabolic outcome (Table 2). Few

studies revealed any significant impact following HIIT. We compared pre post data

following HIIT and found no significant effect of HIIT on any anthropometrics

measure; waist circumference (two pre/post, two RCT’s), hedges’ g = -0.16, 95% CI

-0.32, 0.008 p=0.06, I2=0%, BMI (two pre/post, two RCT’s); hedges’ g = -0.039, 95%

CI -0.19, 0.039, p=0.63, I2= 0%, and body weight (two pre/post, two RCT’s and one

nonrandomised trial); hedges’ g = -0.035, 95% CI 0.02, 0.13, p= 0.68, I2 = 0%,

(Supplementary material 3).

Of note, one 14 week pre/post study found a 4.3cm reduction in waist circumference

in an early psychosis population, with greater reductions for participants with high

adherence (>64% of sessions), (Abdel-Baki et al., 2013). Another wait list control

RCT only found significant (3.17cm) change to waist circumference on post hoc

analysis, also in participants with high adherence (>64%) (Romain et al., 2018).
Studies also assessed body composition (n=2), or various components of the

metabolic syndrome such as fasting blood sugar (n=3) and lipids (n=3), however

insufficient number of comparable outcomes for meta-analytic techniques. One 12

week non-randomised controlled trial found HIIT improved high density lipoprotein

(HDL) cholesterol more than control condition involving playing computer games

(Heggelund et al., 2011). No other HIIT study revealed significant changes in fasting

glucose, fasting lipids, blood pressure or body composition. However, the vast

majority of mean baselines values (82%) across all metabolic outcomes were within

normal ranges, except two studies with mildly raised baseline triglycerides (Abdel-

Baki et al., 2013; Romain et al., 2018).

Only one RCT compared HIIT with MCT for metabolic outcomes (weight, waist,

body composition), and found no within or between group changes for any measure,

however this was a very small study (n=16) with high attrition (43.5%), (Chapman et

al., 2017).

3.6 Psychiatric outcomes

3.6.1 Depressed mood

Depression was the most commonly measured mental health outcome (7/9 studies),

(Table 2). We assessed pre/post data following HIIT for depressed mood in seven

studies (two pre/post studies, one non randomised, four RCT’s) and found a

significant improvement in mood, however high heterogeneity, I2=82% (Figure 4). Six

of the seven trials found a significant reduction in depression scores (range 18% to
46% reduction in depression scores). Sensitivity analysis to remove low quality

studies revealed a larger effect on depressed mood (hedges’ g = -0.87, CI; -1.2, -

.048, p=0.00, I2=73.5%).

We assessed endpoint data for depressed mood in four RCT’s comparing HIIT with

MCT as the control condition. We found a moderate improvement in the HIIT group

compared to MCT for depressed mood, heterogeneity I2=0%, (Figure 5).

3.6.2 Positive and negative Symptoms

We were cautious in applying meta-analytic techniques in the presence of high

heterogeneity to a low number of studies, hence systematically reviewed psychiatric

symptoms instead, as there were less studies assessing these outcomes (Seide et

al., 2019).

We found inconsistent findings for positive and negative symptoms pre and post HIIT

studies. Four HIIT studies assessed psychiatric symptoms (via PANSS). There was

no impact of HIIT on positive symptoms for any HIIT trial (Table 2). Two small pre-

post studies revealed significant but small reductions in total psychopathology scores

however another 12 week controlled trial did not find any change in total scores.

In a HIIT versus wait list control study, Romain et al. (2018) found a significant

reduction in negative symptoms (17% reduction from baseline) compared to wait list

control (no change) over 26 weeks, using intention to treat analysis. Wu et al. (2015)

reported a significant but smaller (11%) reduction in a small 8 week pre post study,

both studies found <20% reduction in negative symptoms and hence unlikely to be of
clinical significance (Leucht et al., 2019). Conversely two small pre post studies

found no change to negative symptoms (Heggelund et al., 2011; Strassnig et al.,

2015).

HIIT versus MCT studies did not investigate positive and negative symptoms.

3.6.3 Quality of life and functioning

A small number of HIIT studies investigated quality of life (n=2) and social (Social

and Occupational Functioning scale, SOFAS) and global functioning (Global

Assessment of Functioning, GAF), (n=3), Romain et al found a significant increase in

global functioning compared to wait list control (mean change 4.6 GAF points); likely

to be clinically significant (GAF change >4 points) (Amri et al., 2014; Rickwood et al.,

2015). Two studies found statistically significant improvements in social functioning

following HIIT although unlikely to be of clinical significance (<10 points on the

SOFAS), (Rickwood et al., 2015). Neither of the two HIIT versus inactive control

trials revealed changes to the mental or physical component of quality of life scales,

(Heggelund et al., 2011; Romain et al., 2018). Two small pre post studies found

small increases in clinical global impression of illness severity (CGI), (Abdel-Baki et

al., 2013; Strassnig et al., 2015), but the change was unlikely to be clinically

significant (< 2 CGI points), (Kelly, 2010).

4 Discussion

Based on limited data, HIIT interventions appear to be as feasible as MCT for people

with SMI who are willing to engage in exercise programs. In addition, there may be

improvements to both cardiorespiratory fitness and mood with relatively brief

commitments to active exercise following HIIT.

Participation rates for any HIIT program were high (74%) and comparable with a

meta-analysis of exercise interventions in people with SMI (77- 79%), (Firth et al.,

2015; Vancampfort et al., 2015). Similarly, drop outs from HIIT programs was 29%,

which is comparable with two other recent meta-analysis for other exercise

interventions for people with SMI, (24-32.5%), (Firth et al., 2015; Vancampfort et al.,

2015). HIIT drop out rates were considerably lower than those seen in

antidepressant and antipsychotic medication trials (50%) where side effects of

medication can be a significant barrier to adherence (Lieberman et al., 2010; Martin

et al., 2006). However drop outs from HIIT programs in other disease populations (ie

cardiometabolic) were lower (18%) than our findings (Weston et al., 2014). This

difference may be partially explained by the motivational deficits experienced by

people with SMI (Rabinowitz et al., 2012). Of note, only one HIIT intervention

specifically addressed motivation to exercise (Abdel-Baki et al., 2013). This was

surprising as it is well established that people with SMI experience many physical

and psychological barriers to exercise, including amotivation (Firth et al., 2016;

Soundy et al., 2014) and targeted motivational interventions are a primary

recommendation in the provision of exercise interventions for people with SMI

(Stubbs et al., 2018b; Vancampfort et al., 2015). In future, HIIT study adherence and

participation may be improved with the inclusion of motivational strategies.

Drop-out rates were comparable between HIIT and MCT protocols which has been

similarly reported in HIIT studies in cardiometabolic disease populations (Vella et al.,

2017; Weston et al., 2014). These findings contrast somewhat with the previously

advanced notion that compared to traditional MCT, HIIT may be too psychologically

aversive for people with SMI to adhere to (Biddle et al., 2015; Hardcastle et al.,

2014). Some HIIT studies in other disease populations have found HIIT may be

more enjoyable than MCT as the short recovery periods may provide relief from the

active exercise, contrasting with the experience of continuous exercise (Bartlett et

al., 2011; Tjønna et al., 2008). However the preferences and enjoyment of people

with SMI should be addressed in larger studies, as this is highly relevant when

considering sustainability and effective integration of exercise programs into mental

health settings (Krogh et al., 2014).

The majority of studies were of shorter duration (less than 12 weeks), which may

have been too short to produce maximum benefit. Support for this observation

comes from the finding the longest HIIT study (26 weeks) reported particularly

favourable cardiometabolic benefits in those with high adherence (attended >64%

sessions). Unfortunately, this study also reported high drop out rates (50%), (Romain

et al., 2018). This is reflected in the broader exercise and SMI literature where

benefits only occur in those who adhere for some time to the intervention (Scheewe
et al., 2013; Vancampfort et al., 2016b). Longer term adherence is crucial for

meaningful impact on outcomes, hence the sustainability of longer HIIT programs

requires further research. Additionally, unsupervised HIIT has been successfully

reported in other disease populations (Moholdt et al., 2012; Wisløff et al., 2007). As

only one HIIT and SMI study offered unsupervised HIIT, more investigation of this is

required given the potential impact on resources if supervision is necessary for

adherence in this population.

Whilst CRF reduces cardiovascular events in the general population (Thompson et

al., 2007a), it has been advocated that high intensity exercise may make susceptible

persons at risk of sudden cardiac events. Given people with SMI have low baseline

fitness (Vancampfort et al., 2017b), the safety of any HIIT intervention remains a

primary concern. Based on available data, we found low overall rates of adverse

events in HIIT interventions. Similar findings were reported in a systematic review of

HIIT studies in patients with coronary artery disease and heart failure (Wewege et

al., 2018). Potential HIIT participants should be screened appropriately for

contraindications such as acute or unstable chronic cardiorespiratory conditions or

unstable diabetes (Weston et al., 2014).

We found a moderate overall improvement in CRF following HIIT interventions of a

level shown to reduce mortality in the general population (Kodama et al., 2009),

confirming the efficacy of HIIT found in athletes, sedentary adults, metabolic

populations and people with substance abuse disorders (Batacan et al., 2017;

Flemmen et al., 2014; Weston et al., 2014). This is promising as this occurred with

small time commitments and volumes of active exercise per week. As such, HIIT
may be an attractive prospect for some people with SMI, particularly where the

experience of short bursts of activity is preferable to continuous exercise.

We found that HIIT was comparable to MCT with respect to CRF. Based on available

evidence, adults with SMI may achieve similar improvements in CRF following either

HIIT or MCT protocols and hence choose an exercise protocol that suits both

preference and capabilities – these are important constructs underpinning

autonomous motivation to exercise for people with SMI (Vancampfort et al., 2015).

However, some non-mental health studies in both clinical and non- clinical

populations have found HIIT to be more efficacious than MCT with respect to CRF

(Helgerud et al., 2007; Weston et al., 2014). In a previous meta-analysis of

sedentary adults, improved CRF was associated with a longer duration of study,

more HIIT repetitions, longer active work intervals and longer recovery periods, with

the 4*4 minute interval type being associated with the highest CRF improvements

(Milanović et al., 2015). The majority of our included studies were of shorter duration

(<12 weeks) and employed both shorter work (<60 second) and shorter recovery

intervals, which may offer some explanation for our findings. In this review, there

were insufficient studies to investigate specific properties of the HIIT intervals,

however this should be a focus of future research in people with SMI.

There were insufficient studies to draw conclusions regarding comparison between

HIIT and MCT studies for metabolic outcomes.

For other HIIT studies investigating metabolic outcomes, we found no significant

effect of HIIT on metabolic markers such as fasting glucose, lipids, and blood

pressure. The majority of HIIT participants had normal baseline values for these
outcomes, hence detecting significant change was unlikely. HIIT participants were

overweight (average BMI 28); however, we found no overall effect of HIIT on any

anthropometrics (ie BMI, waist circumference or weight). Previous research in

people with SMI has shown that exercise alone has little impact on anthropometrics,

particularly when dietary interventions are not included (Firth et al., 2015; Pearsall et

al., 2014). However, HIIT studies in cardiometabolic populations have demonstrated

reductions in fat mass, waist circumference, metabolic makers and insulin sensitivity

(Batacan et al., 2017; Weston et al., 2014; Whyte et al., 2010). None of our included

HIIT studies controlled for the dietary intake of participants, which may be a potential

confounding factor. Additionally, people with SMI face unique challenges with their

metabolic health; contributing factors include the obesogenic nature of psychiatric

medications stimulating hunger, cognitive deficits and impaired reward pathways,

which may also explain the lack of impact on metabolic outcomes we found (Alvarez-

Jiménez et al., 2008; Firth et al., 2019; Igor et al., 2006).

We found a significant improvement in depressed mood following any HIIT

intervention, with a sensitivity analysis showing a larger effect size when low quality

studies were removed. These results are in keeping with a substantial body of

evidence regarding the antidepressant effect of exercise (Schuch et al., 2016a). We

also found HIIT interventions for people with SMI had a modest advantage over MCT

for depressed mood. In particular, previous meta-analyses have found that it is

higher level intensity exercise interventions (at least moderate to vigorous) that

resulted in the greatest improvements in mood in both people with schizophrenia and

depression (Firth et al., 2015; Schuch et al., 2016b).

By contrast, HIIT had limited effect on other psychiatric symptoms, quality of life or

functional outcomes. The most promising was seen in negative symptoms in a 26

week RCT with wait list controls although the changes did not reach clinical

significance (Romain et al., 2018). Conversely, two studies showed no impact of

HIIT on negative symptoms at all, although of much shorter study duration (8

weeks), which may explain the differences found, (Heggelund et al., 2011; Strassnig

et al., 2015). Whilst exercise has shown potential to improve negative symptoms

(Firth et al., 2015), the duration and or volume of HIIT employed in included studies

may have been insufficient to produce change or clinically meaningful improvement.

A major limitation to this systematic review was associated with both the limited

number and quality of available studies, (average PEDRo rating was fair, only two

high quality studies), which limits conclusions that can be drawn at this time. Whilst it

is difficult to blind participants in exercise trials, well designed HIIT RCT’s with

adequate concealment and assessor blinding and are required in future. In addition,

HIIT should be compared with control groups that include other types of exercise

protocols and non-exercise interventions.

Whilst participation and adherence rates were high, recruitment was low (38%) and

there may be a selection bias involving only those interested in exercise agreeing to

engage in HIIT. In addition, the majority of analyses were conducted on people who

completed exercise programs, rather than intention to treat, further limiting

generalisability.

Similarly, HIIT protocols were diverse and more research is needed in order to

develop any specific recommendations regarding optimal HIIT prescriptions for

people with SMI. The vast majority of our heterogeneity was low other than for
depression and CRF pre and post HIIT, accordingly those results should be

interpreted with caution.

Further limitations of pre/post meta-analyses were that results were subject to

regression to the mean, non-independence of rating of scores and the placebo effect

given that none of the participants could be blind to intervention group.

Finally, lack of control for dietary intake in HIIT studies could have influenced

metabolic outcomes and should be addressed in future studies.

Based on available evidence, HIIT appears to be feasible and safe for people with

SMI willing to engage in exercise– however more information is needed on the

acceptability of HIIT and whether HIIT protocols can be sustained for longer

durations and without supervision.

HIIT appears to be comparable to MCT for CRF outcomes and may have a

moderate advantage over MCT for depression. Current evidence suggests HIIT may

produce promising improvements in CRF and depression, but little impact on

metabolic outcomes.

Exercise interventions play an important role in improving physical and mental health

outcomes and should be incorporated into the multidisciplinary management offered

to people with SMI. People with SMI should be encouraged to choose an exercise

protocol that suits their preference and capacities; HIIT is a feasible type of exercise

protocol that may be beneficial for those willing to engage in it.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any
commercial or financial relationships that could be construed as a potential conflict of
interest.
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Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) flow diagram.
Fig. 2. Forest plot showing changes in CRF pre and post HIIT. SD, Standard
deviation; IV, inverse variance; CI, confidence interval, df, degrees of freedom.
Fig. 3. Changes in Cardiorespiratory fitness in HIIT and MCT conditions
Fig. 4. Changes in depression, pre and post HIIT
Fig. 5. Changes in depression in HIIT and MCT conditions
Table 1, Study Characteristics and feasibility
Study Exercise Exercise Duration of Mins active Drop Average Details of Motivatio
protocol modality study exercise/ses outs attendance adverse nal
Supervisio Frequency*/w sion HIIT/dro (n/N), % events Strategie
n eek p outs in completers s Y/N
Duration of control
session
Abdel- HIIT: 10 Treadmill, 14 weeks HIIT: 20 HIIT (20/28) No injuries Y
Baki et intervals of aerobic 2*/ week. mins 9/25(36 68.5% stated.
al (2013) 30-second Supervise 30 mins total %) Dropped out
running at d by due to physical
80 to 95% kinesiologi discomfort
of maximal st or (n=2)
heart rate kinesiolog
with 90- y student
second
active
recovery
walks at 50
to 65% of
maximal
heart rate.
CRF via
Submax
test.
Chapma HIIT: 3x4- Stationary 12 weeks HIIT: 21 HIIT 4/8 (total N=36) Exacerbations N
n et al min bouts bike/ duration mins (50%), HIIT 81% of pre-existing
(2017) at 85–95% treadmill, 3*/week MCT 30 MCT 3/8 MCT 86% of conditions:
HRpeak, aerobic HIIT 25 mins mins (37.5%) sessions. HIIT: hip/back
intersperse Supervise MCT 35mins (n=2)
d with 3- d by MCT:
min Personal shin/ankle
recovery trainer-1 (n=2).
bouts 60- session of
70% home-
HRpeak based
MCT 30- unsupervis
min at 65– ed
75% exercise
Hrpeak last 4
CRF via weeks
maximal
test
Gerber HIIT: Cycle 4 weeks HIIT: 12.5 HIIT N/R N/R N
et al Wingate- ergometer, duration mins MCT 10/35
(2018) based aerobic. 3*/week 20 mins (28.5%),
interval Supervise HIIT 35 mins MCT 12
protocol: d by a MCT 30 mins /37
25 trained (32.4%)
repetitions exercise
of 30 coach
seconds of
active work
80% of
VO2max,
30 s
complete
 rest. Both
groups
calorically
equivalent.
CRF via
Maximal
test.

Hanssen HIIT: 25 Cycle 4 weeks HIIT: 12.5 HIIT (total N=12) N/R N
et al mins ergometer, 3*/week mins 6/25, participation
(2018) Wingate- aerobic, HIIT 35 mins MCT 20 (24%) N/R (only
based Supervisio MCT 30 mins mins MCT included if
interval n N/R 7/22, completed
protocol of (31.8%) 11/12
25 sessions)
repetitions
of 30-s
HIIT at
80%
VO2max
followed by
30 s total
rest. (12.5
mins work,
12.5 mins
rest).
MCT - 20
mins, 60%
VO2max.
Both
groups
 were
calorically
equivalent
CRF via
Maximal
test

Heggelu HIIT: 4* 4- Treadmill, 8 weeks HIIT: 28 HIIT (N=24) HIIT- ankle N

nd et al min 85– aerobic 3*/week mins 4/16 HIIT 85% pain (n=1)
(2011) 95% Supervise 36 mins (25%) Control 83%
HRpeak, 3 d by Control -
min of Exercise 2/9
active physiologi (22%)
resting st
periods:
work load
correspond
ing to 70%
HRpeak.
Control: 36
mins
computer
games
CRF via
Maximal
test.
Romain HIIT:10 Treadmill, 26 weeks HIIT: 20 HIIT HIIT (32/52) HIIT- back N
et al intervals of aerobic. duration. mins 19/38 64% pain
(2018) 2 mins: 30 Supervise 2*/ week 50% (n = 2), knee
secs work d by 30 mins Control pain
80% of kinesiologi 3/28, (n = 2), muscle
theoretical st, 11% pain (n = 1),
maximum kinesiolog cramps
HR, y students, (n = 1), minor
increasing medical ankle sprain
to 90% students (n=1)
alternating
with 90
secs active
recovery
(50-65% of
max HR).
Control:
wait list
CRF via
Submax
test
Strassni HIIT: Resistanc 8 weeks N/R HIIT N/R Chest pain N
g et al Maximum e, 11 * 2*/ week 11/23 (n=1)
(2015) power pre upper and Duration of (47%)
tested for lower body HIIT N/R
each computeriz
exercise at ed Keiser
different pneumatic
loads for exercise
1RM - 3 machines,
circuits of Supervisio
10–12 n N/R
 repetitions
on
resistance
machines
with
minimal
recovery
between
reps. 1–2
min rest
between
circuits
Wu et al HIIT: 95% Body 8 weeks HIIT: 9 mins HIIT N/R N/R N
(2015) of max. weight 3*/week 2/20
HR, 5 exercises HIIT 25 mins (10%)
circuits of Supervisio
10 seconds n - N/R
work,
alternating
↑ amounts
of rest (10 -
50
seconds)

HIIT – high intensity interval training, MCT – moderate intensity continuous training, N/R – not reported, HRpeak – peak heart rate, VO2max – a measure of an individual’s ability to absorb and consume oxygen during
exercise s – seconds, mins – minutes, max HR – maximal heart rate, CRF – cardiorespiratory fitness, Submax – submaximal fitness test, Maximal = maximal fitness test.
Table 2, Participants and Outcomes of Studies

Study Primary Outcomes Patient group Mean Duration Study RCT Key findings
age, illness, arms yes/no
years years
Abdel-Baki The feasibility of FEP 26 About HIIT, no No Participants completing the
et al HIIT & effects on 3.6 control program had:
(2013) metabolic and PHYS: HIIT Improved CV
physical/fitness fitness (↑ 38% VO2max*) &
resting heart rate (↓8.6
bpm*) from baseline.
FUNCT: No change in
psychosocial (GAF,
SOFAS) functioning or
illness severity (CGI)
MET: waist circumference
(↓4.3cm*) from baseline. No
other metabolic changes
following HIIT
Chapman, The feasibility & Any SMI: 38 N/R HIIT (n=8) Yes Intention to treat:
et al acceptability of PSYCHOTIC MCT PHYS: Compared to MCT:
(2017) HIIT SPECTRUM (n=8) No difference between HIIT
D/O’s, MDE and MCT group for CV
fitness, no within group
improvement in CV fitness
for either HIIT or MCT.
MET: No impact of HIIT on
any metabolic measures;
No difference between HIIT
& MCT for any metabolic
measure.
PSYCH: HIIT improved
depression (↓35%*DASS-
21SR) from baseline. No
difference between HIIT &
MCT for depression.
Gerber et The effects of HIIT MDD 33 average HIIT Yes PHYS: HIIT Increased CV
al (2018) on exercise and 4 (n=`35) fitness (↑2.4%*VO2max). No
sports motivation in MCT difference between MCT &
hospital (n=37) HIIT for CV fitness. HIIT
increased self-reported
moderate intensity exercise
mins/week (↑17%IPAQ*) &
mod-vig. intensity
mins/week (↑38% IPAQ*)
from baseline. MCT
increased self-reported
moderate (16% v 407 %*),
& mod-vig. mins/week more
than HIIT (38 % v 306 %*)
PSYCH: HIIT reduced
depression (40% ↓*BDI-IISR)
from baseline. No
difference between HIIT &
MCT for depression.
Improvement in intrinsic and
internal motivation for HIIT
(self-determined
motivation*). No difference
between HIIT & MCT for
self-determined motivation.
No difference between HIIT
& MCT in affective valence.
Hanssen Effect of HIIT on MDD 38 N/R HIIT Yes PHYS: Neither HIIT nor
et al depression index (n=25) MCT had a significant within
(2008) severity and MCT group impact on CV fitness
arterial stiffness (n=22) and no difference between
HIIT & MCT. MCT reduced
arterial stiffness significantly
more than HIIT (↓5% HIIT v
↓ 36% MCT* PWR).
MET: No within group or
between group changes in
systolic or diastolic BP.
PSYCH: Compared to MCT,
HIIT significantly improved
depression (↓46% v
33%*BDI-IISR).
Heggelund Effects of HIIT on PSYCHOTIC 34 About HIIT No PHYS: Compared to
et al CV risk and SPECTRUM 8.7 (n=16) computer games; HIIT
(2011) walking ability D/O’s, DD Computer improved CV fitness (↑12%
games v ↓1% VO2peak**), & walking
control efficiency (↑12% v no △ E-
(n=9) net*).
PSYCH: HIIT resulted in no
significant changes in
depression (CDSS), or
psychotic sx severity
(PANSS).
MET: Compared to
computer games: HIIT
significantly improved HDL
(↑4% v ↓ 9%*). No
significant difference in
body weight or BMI.
FUNCT: No significant
changes in QoL (SF-36)
Minghetti The effect of HIIT MDD 36 N./R HIIT Yes PHYS: HIIT Improved CV
et al on depression and (n=35) fitness (↑6.2%*) from
(2018) physical fitness MCT baseline. However, no
(maximal and sub- (n=37) significant difference
maximal fitness) between HIIT & MCT for CV
fitness (6.2% v 6.6% MCT).
PSYCH: HIIT reduced
depression scores
(↓42%*BDISR) for. No
difference between HIIT &
MCT for depression.
Romain et The effects of HIIT BPAD & 31 About HIIT (n= Yes Intention to treat analysis.
al (2018) on PSYCHOTIC 6.5 38) PHYS: HIIT Improved CV
anthropometrics SPECTRUM TAU (n= fitness (↑40%* estimated
(waist D/O’s 28) VO2max) from baseline.
circumference) Wait list control did not
assess CV fitness.
MET: No change in waist
circumference, or other
metabolic markers. Post
hoc analysis on participants
with >64% session
adherence compared to
TAU; 3cm reduction in waist
circumference. (↓3% v no
△*) from baseline. No
within group changes for
TG. No changes to BSL,
Cholesterol, BP - however
all had normal baselines.
PSYCH: Compared to TAU:
HIIT improved negative
symptoms, which worsened
in TAU (HIIT↓ 17%* v
TAU↑7.9%, PANSS). No
changes in HIIT group for
general or positive Sx.
(PANSS)
Strassnig The effects of HIIT PSYCHOTIC 44 About HIIT No PHYS: Improvement in
et al on power, SPECTRUM 12.5 (n=23) power & strength*, across 6
(2015) strength, body D/O’s & BPAD tests of upper and lower
composition, body movements following
physical function HIIT.
MET: HIIT had no impact on
body weight, BMI, body
fat%.
PSYCH: HIIT improved total
psychiatric Sx
(↓7%*PANSS) & reduced
depression (↓33%*CDSSCR)
from baseline.
FUNCT: HIIT Improved
global functioning (↑16%
*CGI) from baseline.
Improvement in cognition:
processing speed (↑23%*),
& verbal memory (↑14%*)
No changes to majority of
other functioning tests
(SPBB) except dryer
loading.
 Wu et al The effects of HIIT SCZ 39 15.3 HIIT No PHYS: Reduction in
(2015) on mental and (n=20) resting heart rate (↓4%*) &
physical health reduction in PP (↓20%*)
outcomes from baseline following HIIT
MET: HIIT reduced body
weight (↓1kg *) & BMI, (↓
0.1%*). Increase in
diastolic BP (↑9%*)
however remained in
normal range and increase
in MAP (↑3.5%*) from
baseline.
PSYCH: HIIT reduced
negative sx (↓9%*PANSS)
& total (↓8%*PANSS) &
general psychopathology
scores (↓13%*PANSS).
Reduction in depressive sx
(↓18%* BDISR) & anxiety
(↓26.4%*BAI). No changes
in positive symptoms.

PSYCHOTIC SPECTRUM D/O’s – psychotic spectrum disorders, BPAD – bipolar disorder, MDD – major depressive disorder, AFF – affective, NON- AFF – non affective psychosis, HIIT – high
intensity interval training, MCT – moderate intensity continuous training, N/R – not reported, VO2max , VO2peak– a measure of an individual’s ability to absorb and consume oxygen during exercise s –
seconds, mins – minutes, Sx – symptoms, PSYCH – Psychiatric, MET – metabolic, PHYS – physical health, FUNCT – functional, E-net – mechanical efficiency of walking, CV – cardiovascular,
PANSS – positive and negative symptoms scale, BAI – Beck Anxiety Inventory, BDI – Beck Depression Inventory, BDI – II – Beck Depression Inventory Version 2, SPBB – moderate-vig. –
moderate to vigorous minutes of exercise, MAP – mean arterial pressure, PP – Pulse pressure, CDSS – Calgary Depression Subscale, DASS- 21 – Depression and Anxiety Subscale 21, TAU –
Treatment As Usual, PWR – Pulse Wave Reflection, BP – blood pressure, CGI – Clinical Global Impression, BSL – fasting blood sugar level, TG – fasting Triglyceride, QoL – quality of life, bpm –
beats per minute, GAF – Global Assessment of Functioning, SOFAS – Social and Occupational Functioning, △ – change, BMI – body mass index, * p< 0.05, ** p< 0.01. SR Self report CRClinician
rated