TYPE Clinical Trial

PUBLISHED 23 June 2023

DOI 10.3389/fpsyt.2023.1171661

Family psychoeducation to
OPEN ACCESS improve outcome in caregivers
and patients with schizophrenia: a
EDITED BY
Yann Hode,
Association Psychoeducation Profamille,
France

REVIEWED BY
randomized clinical trial
Mario Luciano,
University of Campania Luigi Vanvitelli, Italy
Massimo Casacchia,
Arnaud Tessier 1,2,3*, Karine Roger 1, Alexandra Gregoire 1,
University of L’Aquila, Italy Pauline Desnavailles 1 and David Misdrahi 1,2,3
*CORRESPONDENCE
Department of Adult Psychiatry, Charles Perrens Hospital, Bordeaux, France, 2 Aquitaine Institute for
1
Arnaud Tessier
Cognitive and Integrative Neuroscience, Bordeaux, France, 3 Fondation Fondamental, Créteil, France
[email protected]

RECEIVED 22 February 2023

ACCEPTED 06 June 2023
PUBLISHED 23 June 2023
Introduction: Schizophrenia is recognized for its severe impact on both patients
CITATION
and caregivers. In a 12-month follow-up randomized clinical trial, we aimed
Tessier A, Roger K, Gregoire A,
Desnavailles P and Misdrahi D (2023) Family to measure the efficacy of a brief family psychoeducation program in terms of
psychoeducation to improve outcome in reducing relapse risk and improving medication adherence in patients, as well as
caregivers and patients with schizophrenia: a
reducing caregiver burden, depression and increasing knowledge of the illness.
randomized clinical trial.
Front. Psychiatry 14:1171661. Methods: A total of 25 days of patients with schizophrenia (DSM-IV-TR) and family
doi: 10.3389/fpsyt.2023.1171661
primary caregivers were recruited in a single regional psychiatric outpatient facility
COPYRIGHT located in Bordeaux. In the active group, caregivers received a psychoeducational
© 2023 Tessier, Roger, Gregoire, Desnavailles
and Misdrahi. This is an open-access article
intervention consisting of six sessions spread over 1.5 months, while the control
distributed under the terms of the Creative group was placed on a waiting list. Sociodemographic, symptom severity (PANSS)
Commons Attribution License (CC BY). The and medication adherence (MARS) from patients were assessed at baseline and
use, distribution or reproduction in other
forums is permitted, provided the original
relapse rates was recorded during the 12months follow-up period. Caregivers’
author(s) and the copyright owner(s) are burden (ZBI), depression (CES-D), quality of life (S-CGQoL), knowledge of the
credited and that the original publication in this disease (KAST) and therapeutic alliance (4PAS-C) were assessed at baseline, three
journal is cited, in accordance with accepted
academic practice. No use, distribution or
and 6months.
reproduction is permitted which does not Results: On the 25 patients included, the mean age was 33.3years (SD=9.7)
comply with these terms.
with a mean duration of disease of 7.48years (SD=7.1). On the 25 caregivers
included, the mean age was 50.6years (SD=14.0). Twenty-one were female
(84.0%), 12 were married (48.0%) and 11 lived alone (44.0%). For patients, the
family psychoeducation intervention significantly reduced the risk of relapse
with a significant effect found at 12months follow-up (p=0.014). No change was
observed on medication adherence. For caregivers, the intervention reduced
the burden (p=0.031), decreased the depression (p=0.019), and increased the
knowledge on schizophrenia (p=0.024). Analyzes for repeated measures showed
a statistically significant difference in therapeutic alliance (p=0.035).
Conclusion: As confirmed by previous studies, the brief multifamily program
(consisting of six sessions over a period of 1.5months) was found to be effective
in improving outcomes for caregivers (e.g., burden, depression, knowledge)
and patients (e.g., preventing relapse) in the context of routine care. Given its
short duration, this program is expected to be easily implementable within the
community.
Clinical trial registration: https://clinicaltrials.gov/, NCT03000985.

KEYWORDS

psychoeducation, caregivers, schizophrenia, relapse, burden, depression, therapeutic

alliance, quality of life

Frontiers in Psychiatry 01 frontiersin.org

Tessier et al. 10.3389/fpsyt.2023.1171661

Introduction Methods
Schizophrenia is a chronic and severe mental disorder which Study site and participants
has serious consequences for both the patient and caregivers. The
burden of schizophrenia on caregivers had been demonstrated (1–4) This randomized single-blind controlled trial adopted a two arms
and justify that family have to be included in the care plan with parallel groups design. The controlled trial was conducted at a single
adequate information and support (5). Therefore, family regional psychiatric outpatient facility located in Bordeaux, France,
intervention should be developed to reduce the burden of caregivers registered in ClinicalTrials.gov (Ref.: NCT03000985). A total of
and enhance patients’ prognosis. For patients, family 25 dyads of patients and family primary caregivers were recruited
psychoeducation has been effective in improving outcomes in between December 2014 and December 2019. The inclusion criteria
schizophrenia with a better level of global functioning, medication for patients were (i) a diagnosis of schizophrenia or schizoaffective
adherence, and a reduction in the use of healthcare resources and disorder according to DSM-IV-TR criteria (20), (ii) age of at least
the frequency of relapse (6–8). A recent systematic review including 18 years, and (iii) being in a stable phase and receiving outpatients’
11 studies demonstrates consistent improvement in many outcome routine care. Exclusion criteria consisted of a history of traumatic head
measures of patients, such as relapse rates and medication injury, any current or past major medical or neurological illness, and
adherence, but heterogeneity in symptoms reliefs (9). Its mental retardation. The inclusion criteria for caregivers were males or
effectiveness has also been demonstrated for individuals at clinical females aged 18 years or older who were currently caring for a relative
high risk for psychosis although rigorous further studies are diagnosed with schizophrenia or schizoaffective disorder and
required (10). Through psychoeducation, a better understanding of receiving appropriate outpatient clinical care. Caregivers who had
the illness was associated with a better insight and medication previously received a standardized psychoeducational intervention or
adherence (11). For caregivers, increased knowledge of the disease had intellectual disability, dementia or any other psychiatric condition
reduces aspects related to stigma, stress and burden which were excluded from the study. Participants were assigned to one of the
contributes to a supportive social environment to increase the two study groups through a computer-generated random process. On
patient’s awareness of the disease and adapted care (12, 13). the 25 caregivers 11 were the mother, 7 the father, 2 the sister, 1 the
It has been demonstrated that family psychoeducation is brother, 1 spouse/husband, 1 the aunt and finally 2 were the child of
effective and is considered part of the guideline recommendations patient. In the active group, caregivers received a psychoeducational
in the treatment of schizophrenia (5, 14, 15). A Cochrane review intervention consisting of six sessions spread over 1.5 months, while
confirmed a 20% reduction in relapse rates compared with usual the control group, which received treatment as usual (TAU), was
care (7). Caregivers’ outcomes from family psychoeducation are placed on a waiting list without any additional strategies. All
less commonly studied. The only meta-analysis of family outcomes participants including patients and caregivers signed an informed
found considerable positive effects on relatives’ burden and consent form prior to randomization and trial inclusion. The study
psychological distress, the relationship between relatives and the protocol involving human participant was reviewed and approved by
patient, and family functioning (16). A review of family the local human subject research ethics committee.
psychoeducation programs suggested that it was more likely to
be effective in families if knowledge of the disease and other
outcomes such as burden, family functioning, emotional response Intervention
etc. were systematically assessed to reflect the specific goals of the
intervention (8). Despite recommendations and significant results, The Schiz’Aides program is a multifamily psychoeducational
family psychoeducation is not a widely accessible option in mental program, which was built for caregivers of patients with schizophrenia,
health services, often due to limitations including a lack of interest consisting of six sessions over a 1.5 months period. Each session lasted
from families, limited availability of care staff, or a shortage of an average of 1 h and 30 min and was delivered in a group format led
trained professionals in these programs (5, 17, 18). A review of by a nurse and a psychologist who were trained to provide
more than 30 randomized clinical trials (RCTs) pointed out that psychoeducation. One specific session of the program included the
application of family psychoeducation in routine settings remains participation of a psychiatrist and a social worker. The program
limited, reflecting attitudinal, knowledge, practice and systemic follows international guidelines concerning these interventions (5).
barriers to implementation (19). The first session focuses on the presentation of each family and the
The objective of this study was to compare the efficacy of a experience of their relative’s illness. It also provides an opportunity to
new brief family psychoeducation program (consisting of 6 gather families’ expectations and to present the program’s themes. The
sessions over 1.5 months) to treatment as usual (TAU) in a single second session is dedicated in understanding the disease. The objective
center randomized clinical trial. Our aim was to measure the is to give caregivers the criteria to identify symptoms, as well as
impact of the intervention on both caregivers and patients over a etiological factors (multifactorial hypothesis). The third session
12-month follow-up period, in comparison to usual care. focuses on drug treatments (role, forms, efficacy, side effects),
We hypothesized that the psychoeducation program would reduce non-drug treatments (mainly psychotherapies such as cognitive
the risk of relapse and improve medication adherence in patients remediation) and finally forms/modes of hospitalization. The fourth
with schizophrenia, while also enhancing the quality of life, session allows the caregiver to better manage their patients’ crisis
reducing caregiver burden, improving the therapeutic alliance, states. The objective is to identify the warning signs and the adaptive
increasing knowledge of the illness, and reducing depression reaction to adopt. The sharing of experiences between the different
in caregivers. families is strongly encouraged. The fifth session focuses on the

Frontiers in Psychiatry 02 frontiersin.org

Tessier et al. 10.3389/fpsyt.2023.1171661

patient’s daily life, i.e., the psychosocial and cognitive consequences, Alliance Scale – Caregiver (4PAS-C) is an 11-item questionnaire (e.g.,
as well as negative symptoms hindering a good rehabilitation. “I believe my doctor is helping us”; “I have a better understanding of
Solutions for care, networks and associations are presented. The sixth the symptoms of my relative’s illness.”) scored using a Likert-type
session focuses on the caregivers’ experiences: the weight of the format. Responses range from 1 (“strongly disagree”) to 4 (“strongly
disease, verbalization of feelings. Afterward, a review of the program agree”) and scores range from 11 to 44, with higher scores indicating
is made and answers to the last questions are given. A booster session of a more positive alliance (Cronbach’s alpha: 0.91). The questionnaire
is conducted six months after the initial phase. This session allows to yields two subscores (Empathy and Psychoeducation) and a Visual
improve the program’s efficacy and to monitor the implementation of Analog Scale score (0 to 100) (30); the Compliance Rating Scale
daily effective strategies. The Schiz’Aides program has a complete (CRS), a seven-point rating scale, score ranging from 1 (complete
manual with a session guide, which can be provided upon request. refusal) to 7 (active participation) (31).

Data collection Statistical analysis

Patient’s assessment Analyzes were conducted based on the “intention-to-treat”

Patients were assessed once at inclusion. Sociodemographic principle; patients and caregivers were analyzed according to the
information (gender, age, marital status, level of education, living randomization group they were allocated to and regardless of the
situation) and illness history (duration of illness, lifetime suicide intervention they followed. Baseline characteristics of patients and
attempt, history of treatments, BMI) were collected. Symptom severity caregivers were compared between intervention and control groups
was assessed using the Positive And Negative Syndrome Scale using appropriate tests. They were no dropout at follow-up visits.
(PANSS) (21) and medication adherence was evaluated with the When normality assumption was not rejected, an independent
Medication Adherence Rating Scale (MARS) (Kuder–Richardson-20: t-test was used for continuous variables. Otherwise, the Mann–
0.60) (22). With the agreement of the authors (23), our team translated Whitney U test was performed. Categorical data were compared
the scale into French, then validated it by reverse translation into using a chi-squared test or a Fisher’s exact test if necessary.
English with the author. The scale was then used and validated in a Longitudinal repeated measures (baseline, 3 and 6 months) of
large national cohort of 319 patients suffering from schizophrenia (24, caregivers’ scales were analyzed in each randomized group using
25). Relapses, defined as new psychiatric hospitalization, were whether repeated measures ANOVA (for normal distributed data)
recorded by reviewing the computerized medical records at 3, 6, and or Friedman test (for non-normal distributed data), followed by a
12 months from baseline. post-hoc analysis using the Wilcoxon signed-rank test with
Benjamini-Hochberg correction.
Caregivers’ assessment All p values were two-sided, and the level of statistical significance
Caregivers were assessed at baseline, and at 3 and 6 months after was set to 5%. Statistical analyzes were performed with IBM SPSS
the completion of the psychoeducational program. Self-administered statistics, version 26.0. Complete test statistics are displayed in the
questionnaires were used to assess the different dimensions: the respective tables and Supplementary data.
knowledge of the disease using the Knowledge About Schizophrenia
Test (KAST). The KAST is an 18-item multiple-choice questionnaire
(e.g., “Medicines that are used for hearing voices are called …”; “A Results
person strongly believes that the FBI has put a computer chip in his/
her body. This symptom is called a …”) with five response options and Sample characteristics at baseline
the score ranges from 0 to a maximum possible score of 21 (indicating
good knowledge) (Kuder–Richardson-20: 0.82) (26); the Quality of On the 25 patients included, the mean age was 33.3 years
Life with Schizophrenia-Caregiver Quality of Life questionnaire (SD = 9.7). They were 6 females (24.0%) with a mean duration of
(S-CGQoL) contains 25 items scored with a six-point Likert scale and disease of 7.48 years (SD = 7.1). The majority were single (n = 24, 96%),
describing seven dimensions, with 100 indicating the best possible lived alone (n = 15, 60%) and were unemployed (n = 22, 88%).
level of QoL and 0 the worst (27); the burden of disease was assessed Regarding the clinical variables, patients had a mean duration of
with the Zarit Burden Interview (ZBI). The ZBI includes 22 statements illness of 7.5 years (SD = 7.1), a mean number of antipsychotics of 1.20
(e.g., “Do you feel that because of the time you spend with your (SD = 0.5) and a mean antipsychotic dose of 4.55 mg (SD = 4.2)
relative that you do not have enough time for yourself?”; “Do you feel chlorpromazine equivalent. All patients were treated with a second-
your health has suffered because of your involvement with your generation antipsychotic. The mean total PANSS score was 70.76
relative?”) recorded in a 0–4 Likert scale (total score range 0 to 88), (SD = 11.8) and the mean score on the MARS scale was 6.52 (SD = 1.9)
that rates the subjective component of burden (Cronbach’s alpha: 0.92) (moderate compliance). At baseline the two study groups were
(28); the Center for Epidemiologic Studies – Depression Scale significant different on PANSS scores, antipsychotic dose, and
(CES-D) is a 20-item questionnaire that measures depressive BMI. The sociodemographic and clinical characteristics of the sample
symptoms and related behaviors experienced over the past week, with are presented in Table 1.
each item rated on a 0–3 Likert scale. Possible scores range from 0 to On the 25 caregivers included, the mean age was 50.6 years
60, with higher scores indicating more severe depressive symptoms. A (SD = 14.0). Twenty-one were female (84.0%), 12 were married
cutoff score of 16 or greater is indicative of individuals at risk for (48.0%) and 11 lived alone (44.0%). Twenty-two had a level of
clinical depression (Cronbach’s alpha: 0.90) (29); the 4-Point ordinal education higher than the high school (88%). The mean quality of life

Frontiers in Psychiatry 03 frontiersin.org

Tessier et al. 10.3389/fpsyt.2023.1171661

TABLE 1 Demographic and clinical characteristics of patients and caregivers included in the study.

Patients Caregivers
Fisher’s exact test Fisher’s exact test
Active (PsyEduc) Control (TAU) Active (PsyEduc) Control (TAU)
(N=12) (N=13) (N=12) (N=13)
VARIABLES n (%) n (%) p n (%) n (%) p

Gender, male 8 (66.7) 11 (84.6) 0.561 3 (25.0) 1 (7.7) 0.603

Marital status, married 0 (0.0) 1 (7.7) 1.000 8 (66.7) 4 (30.8) 0.567

Housing, alone (vs. 8 (66.7) 7 (53.8) 0.806 8 (66.7) 3 (23.1) 0.284

accompanied)

Level of education, high 9 (75.0) 7 (53.8) 0.494 1 (8.3) 2 (15.4) 0.838

school or lower

Employment status, work 1 (8.3) 2 (15.4) 1.000

(vs. unemployed)

Second generation of 11 (91.7) 10 (76.9) 0.593

antipsychotics (vs. first)

Mann–Whitney U-test Mann–Whitney U-test

for independent samples for independent samples

Mean (SD) Mean (SD) p Mean (SD) Mean (SD) p

Age (years) 36.17 (11.3) 30.62 (7.7) 0.161 45.92 (15.7) 56.89 (8.5) 0.055

BMI (kg/m2) 27.06 (5.0) 24.06 (3.5) 0.034*

Number of children 0.17 (0.4) 0.00 (0.0) 0.148

Duration of illness (years) 7.83 (6.2) 7.15 (8.0) 0.298

Number of suicide 0.08 (0.3) 0.15 (0.4) 0.629

attempts (lifetime)

Average number of 1.25 (0.6) 1.15 (0.4) 0.898

antipsychotics

Antipsychotic dose (1 mg 3.54 (4.0) 5.48 (4.3) 0.043*

chlorpromazine
equivalent)

PANSS 64.58 (10.2) 76.46 (10.5) 0.009*

Positive symptoms 13.50 (3.6) 18.77 (4.3) 0.003*

Negative symptoms 17.50 (4.9) 19.31 (6.7) 0.453

General psychopathology 33.58 (4.5) 38.38 (4.0) 0.010*

MARS 6.78 (1.7) 6.33 (2.0) 0.601

Medication adherence 2.67 (0.9) 2.67 (1.1) 0.969

behavior

Attitude to taking 3.11 (0.6) 2.83 (1.3) 0.970

medication

Negative side-effects 1.00 (1.0) 0.83 (0.9) 0.726

Mean (SD): mean +/− standard deviation.
BMI, Body Mass Index; PANSS, Positive and Negative Syndrome Scale; MARS, Medication Adherence Rating Scale. *Significant difference with p < 0.05 are in bold text.

was 70.80 (SD = 16.5). Burden was scored as medium with a mean of (ZBI) and the level of depression (CES-D) [β = 0.78, CI = (0.06, 1.50),
37.75 (SD = 7.9). Knowledge of the disease was rated as “moderate” p = 0.036].
with a mean score of 13.1 (SD = 2.3) and therapeutic alliance was
rated as “good” with a mean sore of 30.94 (SD = 7.4). Depression was
rated as “moderate” with a mean score on CES-D of 20.37 (SD = 11.4). Patient’s outcome
No significant difference was found between groups for
sociodemographic and psychometrics scores of caregivers at baseline. A lower rate of relapse was observed at 3, 6 and 12 months for
A positive significant association was found, between the burden patients whose caregivers participated in the intervention group. The

Frontiers in Psychiatry 04 frontiersin.org

Tessier et al. 10.3389/fpsyt.2023.1171661

TABLE 2 Comparison of patients’ outcomes (cumulative relapse (re-hospitalization) rates and perceived medication adherence) following time.

M3 M6 M12
Active Control Active Control Active Control
(PsyEduc) (TAU) (PsyEduc) (TAU) (PsyEduc) (TAU)
(N=12) (N=13) (N=12) (N=13) (N=12) (N=13)
n (%) n (%) p n (%) n (%) p n (%) n (%) p
Cumulative 0 (0.0) 3 (37.5) 0.058 0 (0.0) 3 (37,5) 0.082 0 (0.0) 4 (50.0) 0.014*
relapses

Mean (SD) Mean (SD) p Mean (SD) Mean (SD) p Mean (SD) Mean (SD) p

CRS 6.22 (1.4) 5.88 (1.6) 0.778 5.82 (1.7) 6.13 (1.5) 0.747 5.80 (2.2) 6.75 (0.5) 0.661
SD, Standard Deviation; CRS, Compliance Rating Scale.
Percentages are adjusted for lost and missing data. *Significant difference with p < 0.05 are in bold text.

difference was significant at 12 months (p = 0.014). Medication The efficacy of family psychoeducation in patient with
adherence assessed by CRS estimated by caregivers was not modified schizophrenia has been well established in previous studies (9, 19). A
by the intervention (see details in Table 2). review of the literature showed that family intervention can improve
relapse and hospital admission rates in early psychosis (32).
Additionally, studies conducted in chronic schizophrenia found that
Caregiver’s outcome family psychoeducation can reduce the risk of relapse (25, 26, 33, 34).
These interventions have also been shown to be cost saving and are
The results indicated a significant difference in the total score of included in international treatment guidelines (14, 15). These findings
the KAST at 1.5 months (p = 0.024). Caregivers who received highlight the importance of incorporating family psychoeducation as
psychoeducation had higher scores (mean: 15.45; SD: 1.4) than a part of the comprehensive treatment plan for patients
caregivers in the control group (mean: 12.38; SD: 3.4). This difference with schizophrenia.
was not observed at 6 months (p = 0.098). Two significant results were Despite expectations, we did not show any impact of the family
found at 6 months: first, the ZBI score (burden) (p = 0.031), showed a psychoeducation on medication adherence. This result is consistent
significant reduction for caregivers in the active group (mean: 20.17; with a previous study where carers’ knowledge about schizophrenia
SD: 8.0) compared to the control group (mean: 35.60; SD: 12.1); appeared to be not related to compliance (35). Medication adherence
secondly, the CES-D score (depression) showed a significant reduction which is recognized as complex and multi-determined phenomenon
(p = 0.019), for caregivers in the active group (mean: 6.20; SD: 4.9) cannot be resolved by a single, non-specific intervention. Moreover,
compared to the control group (mean: 14.20; SD: 3.6). No significant the caregiver’s judgment of their relative’s medication intake may
differences were found for quality of life and therapeutic alliance, be influenced by factors such as the amount of time spent together and
regardless of the visit. Additional details are provided in Table 3. the patient’s regimen (oral or injectable antipsychotic). This presents
Analyzes for repeated measures showed a statistically significant a limitation for the interpretation of scores on the CRS and highlights
difference in therapeutic alliance (4PAS-C total score) (p = 0.035) and the need for a combination of objective measures (e.g., pill counts,
two sub-scores: Visual Analogic Scale (p = 0.015), and Psychoeducation serum levels) and validated self-report scales to accurately assess
(p = 0.036). There was also a significant improvement in the burden, medication adherence (25, 36). Nevertheless, the level of caregiver
as evaluated by ZBI (p = 0.040; see Table 4 for details). Post hoc burden may also have an impact on medication adherence, as
analysis did not yield any significant results, despite an overall demonstrated by recent studies, which underscore the importance of
perceived improvement of therapeutic alliance between caregiver and supportive programs for caregivers (9, 37).
the healthcare team and a reduction in the burden In caregivers we found at baseline a significant association
(Supplementary data). between the level of depression and the burden estimated with the
Zarit Burden Interview. This association is confirmed by the study
from Mittendorfer-Rutz (4) in a nationwide comparative study of
Discussion parents of offspring with schizophrenia, rheumatoid arthritis, multiple
sclerosis, epilepsy, and healthy controls. The results of this study
The efficacy of a family psychoeducational program was assessed showed that the parents of a patient with schizophrenia were at a
through a randomized clinical trial (RCT) on a community dwelling higher risk for burden and had a 2.7 times higher risk of needing
patient with schizophrenia and their caregivers. Principal findings specialized psychiatric health care. We found a significant effect in
should be summarized as follows: (i) For patients, the family caregiver’s burden at 6 months follow-up, suggesting a temporal
psychoeducation intervention reduced the risk of relapse with a learning effect with a gradual reduction in burden over time attributed
significant effect found at 12 months follow-up. However, no change to the family psychoeducation program. The impact of schizophrenia
was observed on medication adherence; (ii) For caregivers, the on caregivers can result in a significant burden including emotional,
intervention reduced the burden, decreased the depression, increased psychological, physical and financial strain associated with feelings of
the knowledge on schizophrenia, and strengthened the shame, embarrassment, guilt and blame (16, 37). Reducing caregiver
therapeutic alliance. burden is crucial for patient management, and for the caregiver

Frontiers in Psychiatry 05 frontiersin.org

Tessier et al. 10.3389/fpsyt.2023.1171661

TABLE 3 Comparisons of caregiver’s outcomes (scores on psychometric scales) at each visit.

Mann–Whitney U-test for independent samples

M0 M3 M6
Active Control Active Control Active Control
(PsyEduc) (TAU) (PsyEduc) (TAU) (PsyEduc) (TAU)
(N=12) (N=13) (N=12) (N=13) (N=12) (N=13)
VARIABLES Mean (SD) Mean (SD) p Mean (SD) Mean (SD) p Mean (SD) Mean (SD) p

S-CGQoL 73.17 (20.5) 67.25 (7.4) 0.376 79.64 (20.3) 74.62 (6.6) 0.458 87.83 (14.8) 70.60 (14.0) 0.080

Psychological and
15.00 (4.6) 12.00 (3.3) 0.128 15.55 (4.3) 14.00 (4.4) 0.452 19.17 (2.6) 13.60 (6.1) 0.073
physical well-being

Psychological
burden and daily 21.25 (7.5) 20.38 (6.8) 0.794 23.45 (6.2) 23.25 (6.6) 0.946 24.83 (3.5) 20.00 (8.2) 0.221
life

Relationships with
8.25 (5.6) 5.75 (5.8) 0.415 8.18 (5.3) 6.00 (5.6) 0.405 10.33 (4.1) 6.00 (5.0) 0.149
spouse

Relationships with
8.00 (4.9) 9.88 (3.6) 0.367 10.45 (3.6) 9.00 (3.9) 0.415 11.00 (4.3) 10.80 (4.0) 0.939
psychiatric team

Relationships with
6.50 (2.6) 4.63 (3.8) 0.204 6.36 (2.8) 6.50 (2.8) 1.000 7.83 (2.0) 5.60 (3.2) 0.194
family

Relationships with
5.67 (3.3) 5.25 (3.2) 0.783 7.44 (2.4) 6.25 (2.9) 0.375 6.67 (2.1) 5.40 (3.4) 0.468
friends

Material burden 8.50 (6.3) 9.38 (2.3) 0.666 8.18 (6.1) 9.63 (2.9) 0.867 8.00 (6.8) 9.20 (1.8) 0.692

ZBI 37.67 (17.3) 37.88 (19.9) 0.980 30.45 (16.9) 35.38 (21.4) 0.582 20.17 (8.0) 35.60 (12.1) 0.031*

KAST 13.67 (1.6) 12.25 (3.1) 0.192 15.45 (1.4) 12.38 (3.4) 0.024* 15.33 (1.9) 12.80 (2.7) 0.098

4PAS-C 30.30 (7.8) 31.75 (7.1) 0.691 36.67 (7.8) 35.50 (6.8) 0.749 36.40 (10.7) 32.50 (9.9) 0.593

Visual analogic
50.50 (34.3) 49.38 (30.5) 0.943 71.11 (25.0) 67.50 (26.3) 0.776 71.00 (34.0) 49.50 (46.2) 0.321
scale

Empathy 14.20 (3.4) 15.50 (3.4) 0.435 17.11 (3.3) 16.63 (3.1) 0.626 17.00 (5.2) 15.00 (4.2) 0.521

Psychoeducation 16.10 (4.6) 16.25 (3.9) 0.942 19.56 (4.5) 18.88 (3.9) 0.745 19.40 (5.7) 17.50 (5.9) 0.641

CES-D 20.27 (13.3) 20.50 (8.9) 0.967 14.91 (10.0) 23.54 (11.3) 0.118 6.20 (4.9) 14.20 (3.6) 0.019*
SD, Standard Deviation; S-CGQoL, Schizophrenia Caregiver Quality of Life questionnaire; ZBI, Zarit Burden Interview; KAST, Knowledge About Schizophrenia Test; 4PAS-C, 4-Point ordinal
Alliance Scale–Caregiver; CES-D, Center for Epidemiologic Studies–Depression scale.*Significant difference with p < 0.05 are in bold text.

himself, as it can help to reduce depression, burden-related care and caregivers in the intervention group. This demonstrates the relevance
associated costs (38). of the information delivered during psychoeducation and its directly
At baseline, the level of depression is evaluated as “moderate” in measurable effect (33). However, at 6 months, the difference between
both groups, with a score above the threshold fixed at 16 on CES-D the two groups was no longer significant. There was a spontaneous
scale. Previous studies had shown that caregivers of patients with improvement in the score in the control group, which may be related
schizophrenia are at higher risk for developing depression (4, 38). In to the caregivers’ self-training by different resources (books, internet,
a large survey, Gupta et al. found a 10% increased of depression in meeting with the treating psychiatrist...). Knowledge of the disease
caregivers of patients with schizophrenia compared to non-caregivers have been found to be associated with a better medication adherence
and caregivers of adults with other conditions (38). At 6 months, in in patients (11). The Cochrane review highlights the benefits of patient
comparison with TAU, the intervention was found to significantly psychoeducation in reducing relapse and readmission rates,
reduce depression. Depressive symptoms can have a negative impact promoting medication adherence, and shortening hospital stays.
on family interactions and lead to maladaptive behaviors toward the These findings suggest that psychoeducation not only has a positive
patient. Our findings is consistent with a previous RCT showed the impact on patients, but also on their family caregivers, making it a
usefulness of a family intervention in reducing caregiver’s depressive clinically effective and cost-beneficial intervention (39). The central
symptoms as measured by the CES-D, and a moderate effect in role of family support in care was recently coroborated in an Italian
reducing the subjective burden as assessed by the ZBI over an multicenter study of 136 caregivers, where caregivers’ personal growth
8 months follow-up period (2). was associated with good family functioning and adequate professional
The purpose of family psychoeducation is to increase caregiver’s support (40). Another study focused on the functioning pointed out
knowledge and understanding of illness and treatment. A significant that interpersonal relationships and work skills are the impaired
improvement in the knowledge of the disease (KAST) was found in functional areas in both patients and caregivers (41).

Frontiers in Psychiatry 06 frontiersin.org

Tessier et al. 10.3389/fpsyt.2023.1171661

Therapeutic alliance has been found to be enhanced by the family

S-CGQoL–PsPhW, Psychological and Physical Well-being; PsBDL, Psychological Burden and Daily Life; RS, Relationships with Spouse; RPT, Relationships with Psychiatric Team; RFa: Relationships with Family; RFr: Relationships with Friends; MB: Material Burden;
Total
CRS

0.545

0.761

2.000

0.368
psychoeducation intervention. To our best knowledge, the
therapeutic alliance between caregivers and healthcare staff has never
been investigated in cohorts of patients with schizophrenia.
CES-D

Total Interactions with the health care staff during the family

1.852

0.236

1.476

0.291
psychoeducation group strengthened the relationship and
understanding with the caregiver. This was explored in other
0.036* pathologies such as cancer (42).
5.167

1.588

0.297
PE

In contrast to the study by Savanaud et al., we did not find any

impact of the intervention on quality of life (38, 43). Quality of life
may be influenced by the heterogeneous relational degree of the
2.000

0.368

5.167

0.755
Em

caregiver (parents, partner, child…). Indeed, it has been shown that

4PAS-C

parents of a patient have a lower quality of life than the patient’s

0.015*

siblings as demonstrated in a recent Croatian study (44). Although

VAS

7.354

0.594

0.497

72% of the included caregivers in our sample were the ill loved one,
no significant results emerged regarding their quality of life. Most
Total

0.035*

studies with similar design have focused on the patient’s quality of life
5.218

0.743

0.515

rather than the caregiver’s (45, 46). We found one recent Indian RCT,
that showed a significant improvement in overall quality of life scores
KAST

in the experimental group caregivers compared to control group at the

Total

3.756

0.061

0.762

0.498

end of the program, after 6 months (47).

Thus, our study provides evidence of the efficacy of a short
multifamily program (six sessions over 1.5 months) for caregivers
ZARIT

Total

0.040*
4.507

0.460

0.647

(depression, knowledge) and patients (preventing relapse) in the

context of routine care. This program can be repeated multiple times
during the year. Previous RCTs and Evidence-Based Medicine (EBM)
0.545

0.761

1.000

0.410
MB

have considered the same primary evidence (9); however, the

implementation of this evidence in routine care is limited (19).
Moreover, To the best of our knowledge, and within the context of
0.900

0.638

2.308

0.200
RFr

French mental health, psychoeducational programs for patients have

TABLE 4 Evolutions in psychometric scales’ scores by group: Friedman’s ANOVA for repeated measures.

been more extensively developed than those for caregivers. The brevity
4-PAS-C–VAS, Visual Analogic Scale; Em, Empathy; PE, Psychoeducation. *Significant difference with p < 0.05 are in bold text.
RFa

0.556

0.590

3.797

0.069

of this program should facilitate its implementation in the community.

RPT

1.433

0.284

0.615

0.564

Limitations
S-CGSQoL

Although our study has several strengths, there are some

0.231

0.798

0.054

0.948
RS

limitations that must be acknowledged. Our limited sample size could

limit the reliability of our results. Additionally, the single-center
PsBDL

design of our study may introduce a selection bias, which may affect
0.290

0.754

0.498

0.626

the representativeness of our sample. To fully understand the effects

of the intervention and to confirm our encouraging results, a larger,
multi-center study should be done. However, in the context of the
PsPhW

French mental health psychiatric service, the regional psychiatric

1.634

0.243

0.161

0.854

outpatient facility should be considering as a good representation of

the population of a community dwelling patient suffering of
Index, global S-CGQoL score. S-CGQoL scores, ranging.

schizophrenia. Although patients were considered to be in a stable

from 0 to 100 (with 100 indicating best quality of life).
Total

0.785

0.482

1.071

0.387

phase with only minor modifications to their prescribed medication

during follow-up, this issue was not controlled and should
be considered as a limitation in assessing the effectiveness of the
Friedman’s

psychoeducational program in preventing relapse.

Khi-square

Khi-square

In conclusion, as confirmed by previous studies, the brief

ANOVA

multifamily program (consisting of six sessions over a period of

1.5 months) was found to be effective in improving outcomes for
p

caregivers (e.g., burden, depression, knowledge) and patients (e.g.,

(PsyEduc)

preventing relapse) in the context of routine care. Given its short

Control
(TAU)
Active

duration, this program is expected to be easily implementable within

the community.

Frontiers in Psychiatry 07 frontiersin.org

Tessier et al. 10.3389/fpsyt.2023.1171661

Data availability statement Health (PHRIP “2013–0017–PsyEduc”). The funding source had no
role in the conduct or publication of the study.
The raw data supporting the conclusions of this article will
be made available by the authors, without undue reservation.
Acknowledgments
Ethics statement The authors thank the team of the CMP de Talence (Pôle PGU of
the CH Charles Perrens) in the elaboration and the conduction of the
The studies involving human participants were reviewed and program, particularly: the psychiatrist M. Lescarret, J. Libert, and M-C
approved by Committee for the Protection of Persons–South West and Levassor; the nurses I. Tanguy, M-L Bamas, and F. Campedel; the
Overseas 3 (CPP-SOOM3) Study folder: 2014/58. Department of psychologists A. Rebollo and H. Tastet; the social worker A. Bonnat.
Clinical Pharmacology, Bordeaux Hospital, Place Amélie Raba Léon
33076 BORDEAUX Cedex FRANCE Tel: +33 (0)5 57 81 76 07 Email:
[email protected] Web: http://www.cpp-soom3.u-bordeaux2. Conflict of interest
fr/. The patients/participants provided their written informed consent
to participate in this study. 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.
Author contributions
KR and DM were involved in generating hypotheses, the Publisher’s note
management of the study and the development of the
psychoeducational program. KR, AG, and DM were involved in the All claims expressed in this article are solely those of the authors
conduction of the psychoeducational program (Schiz’Aides). AT and and do not necessarily represent those of their affiliated organizations,
PD conducted statistical analyzes. AT, PD, and DM wrote the first or those of the publisher, the editors and the reviewers. Any product
complete manuscript. All authors were involved in the patients’ that may be evaluated in this article, or claim that may be made by its
recruitment, the clinical evaluation, acquisition of the clinical data, manufacturer, is not guaranteed or endorsed by the publisher.
modified the manuscript and approved the final version.

Supplementary material
Funding
The Supplementary material for this article can be found online
This work was supported by a grant from the Nurses and at: https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1171661/
Paramedics Research Hospital Program from the French Ministry of full#supplementary-material

References
1. Addington J, McCleery A, Addington D. Three-year outcome of family work in an 9. Alhadidi MM, Lim Abdullah K, Yoong TL, Al Hadid L, Danaee M. A systematic
early psychosis program. Schizophr Res. (2005) 79:107–16. doi: 10.1016/j. review of randomized controlled trials of psychoeducation interventions for patients
schres.2005.03.019 diagnosed with schizophrenia. Int J Soc Psychiatry. (2020) 66:542–52. doi:
10.1177/0020764020919475
2. Martín-Carrasco M, Fernández-Catalina P, Domínguez-Panchón AI, Gonçalves-
Pereira M, González-Fraile E, Muñoz-Hermoso P, et al. A randomized trial to assess the 10. Herrera SN, Sarac C, Phili A, Gorman J, Martin L, Lyallpuri R, et al.
efficacy of a psychoeducational intervention on caregiver burden in schizophrenia. Eur Psychoeducation for individuals at clinical high risk for psychosis: a scoping review.
Psychiatry. (2016) 33:9–17. doi: 10.1016/j.eurpsy.2016.01.003 Schizophr Res. (2023) 252:148–58. doi: 10.1016/j.schres.2023.01.008
3. Sari A, Duman ZÇ. Effects of the family support and psychoeducation program 11. Chan KWS, Hui LMC, Wong HYG, Lee HME, Chang WC, Chen YHE. Medication
based on the Calgary family intervention model on the coping, psychological distress adherence, knowledge about psychosis, and insight among patients with a schizophrenia-
and psychological resilience levels of the family caregivers of chronic psychiatric spectrum disorder. J Nerv Ment Dis. (2014) 202:25–9. doi: 10.1097/NMD.0000000000000068
patients. Arch Psychiatr Nurs. (2022) 41:1–10. doi: 10.1016/j.apnu.2022.07.014
12. Bilgin A, Ozdemir L. Interventions to improve the preparedness to Care for Family
4. Mittendorfer-Rutz E, Rahman S, Tanskanen A, Majak M, Mehtälä J, Hoti F, et al. Caregivers of Cancer patients: a systematic review and Meta-analysis. Cancer Nurs.
Burden for parents of patients with schizophrenia-a Nationwide comparative study of (2022) 45:E689–705. doi: 10.1097/NCC.0000000000001014
parents of offspring with rheumatoid arthritis, multiple sclerosis, epilepsy, and healthy
controls. Schizophr Bull. (2019) 45:794–803. doi: 10.1093/schbul/sby130 13. Brent BK, Giuliano AJ, Zimmet SV, Keshavan MS, Seidman LJ. Insight into illness
in patients and caregivers during early psychosis: a pilot study. Schizophr Res. (2011)
5. Harvey C. Family psychoeducation for people living with schizophrenia and their 127:100–6. doi: 10.1016/j.schres.2010.12.024
families. BJPsych Advances. (2018) 24:9–19. doi: 10.1192/bja.2017.4
14. Canadian Psychiatric Association. Clinical practice guidelines. Treatment of
6. Zhang M, Wang M, Li J, Phillips MR. Randomised-control trial of family schizophrenia. Can J Psychiatr. (2005) 50:7S–57S.
intervention for 78 first-episode male schizophrenic patients. An 18-month study in
Suzhou, Jiangsu. Br J Psychiatry Suppl. (1994) 24:96–102. 15. NICE. Psychosis and schizophrenia in adults: prevention and management guidance.
(2014). Available at: https://www.nice.org.uk/guidance/cg178 (Accessed February 9,
7. Pharoah F, Mari J, Rathbone J, Wong W. Family intervention for schizophrenia. 2023).
Cochrane Database Syst Rev. (2006) 2006:CD000088. doi: 10.1002/14651858.CD000088.
pub2 16. Cuijpers P. The effects of family interventions on relatives’ burden: a meta- analysis.
United Kingdom: Centre for Reviews and Dissemination (1999).
8. Lobban F, Postlethwaite A, Glentworth D, Pinfold V, Wainwright L, Dunn G, et al.
A systematic review of randomised controlled trials of interventions reporting outcomes 17. Harvey C, O’Hanlon B. Family psycho-education for people with schizophrenia
for relatives of people with psychosis. Clin Psychol Rev. (2013) 33:372–82. doi: 10.1016/j. and other psychotic disorders and their families. Aust N Z J Psychiatry. (2013) 47:516–20.
cpr.2012.12.004 doi: 10.1177/0004867413476754

Frontiers in Psychiatry 08 frontiersin.org

Tessier et al. 10.3389/fpsyt.2023.1171661

18. Casacchia M, Roncone R. Italian families and family interventions. J Nerv Ment 34. Mayoral F, Berrozpe A, de la Higuera J, Martinez-Jambrina JJ, de Dios LJ, Torres-
Dis. (2014) 202:487–97. doi: 10.1097/NMD.0000000000000149 Gonzalez F. Efficacy of a family intervention program for prevention of hospitalization
in patients with schizophrenia. A naturalistic multicenter controlled and randomized
19. McFarlane WR, Dixon L, Lukens E, Lucksted A. Family psychoeducation and
study in Spain. Rev Psiquiatr. Salud Ment. (2015) 8:83–91. doi: 10.1016/j.
schizophrenia: a review of the literature. J Marital Fam Ther. (2003) 29:223–45. doi:
rpsm.2013.11.001
10.1111/j.1752-0606.2003.tb01202.x
35. Sellwood W, Tarrier N, Quinn J, Barrowclough C. The family and compliance in
20. American Psychiatric Association. Diagnostic and statistical manual of mental
schizophrenia: the influence of clinical variables, relatives’ knowledge and expressed
disorders: DSM-IV-TR. New Delhi: Jaypee Brothers Medical Publishers (2000). 943 p.
emotion. Psychol Med. (2003) 33:91–6. doi: 10.1017/s0033291702006888
21. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS)
36. Velligan DI, Weiden PJ, Sajatovic M, Scott J, Carpenter D, Ross R, et al. Expert
for schizophrenia. Schizophr Bull. (1987) 13:261–76. doi: 10.1093/schbul/13.2.261
consensus panel on adherence problems in serious and persistent mental illness. The
22. Thompson K, Kulkarni J, Sergejew AA. Reliability and validity of a new medication expert consensus guideline series: adherence problems in patients with serious and
adherence rating scale (MARS) for the psychoses k. Schizophr Res. (2000) 42:241–7. doi: persistent mental illness. J Clin Psychiatry. (2009) 70:1–46.
10.1016/S0920-9964(99)00130-9
37. Kretchy IA, Osafo J, Agyemang SA, Appiah B, Nonvignon J. Psychological burden
23. Misdrahi D, Verdoux H, Llorca P-M, Baylé F-J. Therapeutic adherence and and caregiver-reported non-adherence to psychotropic medications among patients with
schizophrenia: the interest of the validation of the French translation of medication schizophrenia. Psychiatry Res. (2018) 259:289–94. doi: 10.1016/j.psychres.2017.10.034
adherence rating scale (MARS). Encéphale. (2004) 30:409–10.
38. Gupta S, Isherwood G, Jones K, Van Impe K. Assessing health status in informal
24. Fond G, Boyer L, Boucekine M, Aden LA, Schürhoff F, Tessier A, et al. Validation schizophrenia caregivers compared with health status in non-caregivers and caregivers
study of the medication adherence rating scale. Results from the FACE-SZ national of other conditions. BMC Psychiatry. (2015) 15:162. doi: 10.1186/s12888-015-0547-1
dataset. Schizophr Res. (2017) 182:84–9. doi: 10.1016/j.schres.2016.10.023
39. Xia J, Merinder LB, Belgamwar MR. Psychoeducation for schizophrenia. Cochrane
25. Misdrahi D, Tessier A, Swendsen J, Berna F, Brunel L, Capdevielle D, et al. Database Syst Rev. (2011) 2011):CD002831. doi: 10.1002/14651858.CD002831.pub2
Determination of adherence profiles in schizophrenia using self-reported adherence:
40. Roncone R, Giusti L, Bianchini V, Casacchia M, Carpiniello B, Aguglia E, et al.
results from the FACE-SZ dataset. J Clin Psychiatry. (2016) 77:e1130–6. doi: 10.4088/
Family functioning and personal growth in Italian caregivers living with a family
JCP.15m10115
member affected by schizophrenia: results of an add-on study of the Italian network
26. Compton MT, Quintero L, Esterberg ML. Assessing knowledge of schizophrenia: for research on psychoses. Front Psych. (2022) 13:1042657. doi: 10.3389/
development and psychometric properties of a brief, multiple-choice knowledge test for use fpsyt.2022.1042657
across various samples. Psychiatry Res. (2007) 151:87–95. doi: 10.1016/j.psychres.2006.05.019
41. Galderisi S, Rossi A, Rocca P, Bertolino A, Mucci A, Bucci P, et al. Pathways to
27. Richieri R, Boyer L, Reine G, Loundou A, Auquier P, Lançon C, et al. The functional outcome in subjects with schizophrenia living in the community and their
schizophrenia caregiver quality of life questionnaire (S-CGQoL): development and unaffected first-degree relatives. Schizophr Res. (2016) 175:154–60. doi: 10.1016/j.
validation of an instrument to measure quality of life of caregivers of individuals with schres.2016.04.043
schizophrenia. Schizophr Res. (2011) 126:192–201. doi: 10.1016/j.schres.2010.08.037
42. Dionne-Odom JN, Bakitas MA, Ferrell B. Psychoeducational interventions for
28. Zarit SH, Todd PA, Zarit JM. Subjective burden of husbands and wives as caregivers: cancer family caregivers In: . Cancer caregivers. New York: Oxford University Press
a longitudinal study. Gerontologist. (1986) 26:260–6. doi: 10.1093/geront/26.3.260 (2019). 105–29.
29. Morin AJS, Moullec G, Maïano C, Layet L, Just J-L, Ninot G. Psychometric 43. Sauvanaud F, Kebir O, Vlasie M, Doste V, Amado I, Krebs M-O. Therapeutic
properties of the Center for Epidemiologic Studies Depression Scale (CES-D) in French benefit of a registered psychoeducation program on treatment adherence, objective and
clinical and nonclinical adults. Rev Epidemiol Sante Publique. (2011) 59:327–40. doi: subjective quality of life: French pilot study for schizophrenia. Encéphale. (2017)
10.1016/j.respe.2011.03.061 43:235–40. doi: 10.1016/j.encep.2015.12.028
30. Misdrahi D, Verdoux H, Lançon C, Bayle F. The 4-point ordinal Alliance self- 44. Margetić M, Jakovljević J, Furjan Z, Margetić B, Marsanić V. Quality of life of key
report: a self-report questionnaire for assessing therapeutic relationships in routine caregivers of schizophrenia patients and association with kinship. Cent Eur J Public
mental health. Compr Psychiatry. (2009) 50:181–5. doi: 10.1016/j.comppsych.2008.06.010 Health. (2013) 21:220–3. doi: 10.21101/cejph.a3918
31. Kemp R, Kirov G, Everitt B, Hayward P, David A. Randomised controlled trial of 45. Greenberg JS, Knudsen KJ, Aschbrenner KA. Prosocial family processes and the
compliance therapy. 18-month follow-up. Br J Psychiatry. (1998) 172:413–9. doi: quality of life of persons with schizophrenia. Psychiatr Serv. (2006) 57:1771–7. doi:
10.1192/bjp.172.5.413 10.1176/ps.2006.57.12.1771
32. Bird V, Premkumar P, Kendall T, Whittington C, Mitchell J, Kuipers E. Early 46. Khalil AH, ELNahas G, Ramy H, Abdel Aziz K, Elkholy H, El-Ghamry R. Impact
intervention services, cognitive-behavioural therapy and family intervention in early of a culturally adapted behavioural family psychoeducational programme in patients
psychosis: systematic review. Br J Psychiatry. (2010) 197:350–6. doi: 10.1192/bjp. with schizophrenia in Egypt. Int J Psychiatry Clin Pract. (2019) 23:62–71. doi:
bp.109.074526 10.1080/13651501.2018.1480786
33. Cassidy E, Hill S, O’Callaghan E. Efficacy of a psychoeducational intervention in 47. Verma PK, Walia TS, Chaudhury S, Srivastava S. Family psychoeducation with
improving relatives’ knowledge about schizophrenia and reducing rehospitalisation. Eur caregivers of schizophrenia patients: impact on perceived quality of life. Ind Psychiatry
Psychiatry. (2001) 16:446–50. doi: 10.1016/s0924-9338(01)00605-8 J. (2019) 28:19–23. doi: 10.4103/ipj.ipj_2_19

Frontiers in Psychiatry 09 frontiersin.org