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European Psychiatry 37 (2016) 3542

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European Psychiatry
journal homepage: http://www.europsy-journal.com

Original article

LAI versus oral: A case-control study on subjective experience of


antipsychotic maintenance treatment
F. Pietrini a,*, M. Spadafora a, L. Tatini a, G.A. Talamba a, C. Andrisano b, G. Boncompagni c,
M. Manetti d, V. Ricca a, A. Ballerini a
a

Psychiatric unit, department of neuroscience, psychology, drug research and child health, section of neuroscience, university of Florence, Via delle Gore 2H,
50134 Florence, Italy
Department of biomedical and neuromotor sciences, university of Bologna, Bologna, Italy
c
Department of mental health and substance abuse, local health trust of Bologna, Bologna, Italy
d
Therapeutic psychiatric community, Campo del Vescovo Union, La Spezia, Italy
b

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 12 January 2016
Received in revised form 5 April 2016
Accepted 13 May 2016
Available online

Background: To present real-world evidence on the differences between long-acting injectable (LAI) and
oral antipsychotic maintenance treatment (AMT) in terms of subjective well-being, attitudes towards
drug and quality of life in a sample of remitted schizophrenic subjects.
Methods: Twenty outpatients with remitted schizophrenia treated with either olanzapine or
paliperidone and switching from the oral to the LAI formulation of their maintenance treatment were
recruited before the switch (LAI-AMT group). A group of 20 remitted schizophrenic subjects with oral
AMT and matching main sociodemographic, clinical and treatment variables made up the control group
(oral-AMT group). All participants were assessed in terms of objective (PANSS, YMRS, MADRS) and
subjective (SWN-K, DAI-10, SF-36) treatment outcomes at baseline (T0) and after 6 months (T1).
Results: Between T0 and T1, general psychopathology of the PANSS, DAI-10, and all but one of the SWN-K
dimensions (except for social integration), showed signicantly higher percentages of improvement in
the LAI-AMT group compared to the oral-AMT group. A generalized expansion of health-related quality
of life, with better functioning in almost all areas of daily living, was reported by the LAI-AMT group after
the 6-month period. In contrast, the oral-AMT group reported a signicant worsening of health-related
quality of life in the areas of emotional role and social functioning in the same period.
Conclusions: Our study indicates possible advantages of LAI over oral antipsychotic formulation in terms
of subjective experience of maintenance treatment in remitted schizophrenic patients. Size and duration
of this study need to be expanded in order to produce more solid and generalizable results.
2016 Elsevier Masson SAS. All rights reserved.

Keywords:
Schizophrenia and psychosis
Antipsychotics
Quality of life
Quality of care

1. Introduction
Relapse and rehospitalisation lead to proven negative consequences in terms of course, treatment, prognosis and impact on the
healthcare system of schizophrenia [1,2]. For this reason, clinical
remission and relapse prevention are considered main goals in the
long-term management of this condition [3] and antipsychotic
maintenance treatment (AMT) is recommended to minimize the
relapse and readmission risk [4,5].
Unfortunately, adherence to antipsychotic treatment is often
compromised in schizophrenia [1,2]. The problem of poor

* Corresponding author. Tel.: +39 055 794 7487; fax: +39 055 794 7531.
E-mail address: francesco.pietrini@uni.it (F. Pietrini).
http://dx.doi.org/10.1016/j.eurpsy.2016.05.008
0924-9338/ 2016 Elsevier Masson SAS. All rights reserved.

compliance is a central issue in the treatment of this disorder,


and may hamper the achievement of the patients optimal
functioning and quality of life even in the ones who are considered
clinically stable [4,6].
Although adherence to an antipsychotic prescription is a
complex and multifactorial phenomenon, patients attitude
towards treatment seems to represent one of its most important
components, with compliance being strongly inuenced by the
patients perception of treatment benets and costs [711]. In
particular, empirical evidence suggests that adherence of stable
patients with schizophrenia is strongly related to the recognition
of the positive effects of the pharmacological treatment on daily
life [1214]. Specically, during long-term therapy, subjective
perception of general wellness and quality of life clearly inuences
and maintains adherence to treatment [15]. As a consequence,

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F. Pietrini et al. / European Psychiatry 37 (2016) 3542

a signicant role has been recently assigned to the notion of


subjective well-being and quality of life in patients undergoing
AMT [1618].
LAI antipsychotics requiring monthly or biweekly injections
were developed to reduce problems with treatment non-compliance [14,19]. They have shown signicant advantages over oral
antipsychotics, including a less burdensome dosing schedule, more
consistent drug plasma levels, and the requirement of regular visits
with a health-care professional [14]. Not surprisingly, LAI-AMT
have been shown to reduce relapse and hospitalization rates,
compared with oral-AMT [5,2022]. However, although a growing
interest in subjective recovery from schizophrenia is developing in
the scientic community, only a few studies have been devoted to
the differences between LAI and oral AMT in terms of patients
subjective experience of treatment [14,18,2328]. Moreover, the
fact that the pre-post or mirror image design of the available
real-world studies on this topic implies the lack of a control group
may represent a serious methodological limitation of this source of
evidence [2931]. To our knowledge, no study has yet compared
LAI and oral AMT in terms of subjective experience of treatment in
a case-control study. For this reason, in this observational, casecontrol study, we aimed at evaluating the differences between LAI
and oral AMT in terms of subjective well-being, attitudes towards
drug, and quality of life in a sample of remitted schizophrenic
subjects.
2. Methods
2.1. Study design
This 6-month, prospective, longitudinal, open-label, nonrandomised, case-control, observational study is part of the
Long-acting injectable antipsychotics on functioning and experience (LAI-FE) project, a wide observational program currently
ongoing at the LAI clinic of the Psychiatric unit of the department of
neuroscience, psychology, drug research and child health of the
university of Florence (Italy). The present work introduces
preliminary results, and comprised two parts: a baseline visit
(T0) and a prospective follow-up visit at month 6 (T1). It was purely
observational and in no way inuenced the intervention that
patients would have received otherwise. The whole project was
conducted in accordance with the current International conference
on harmonisation of technical requirements for good clinical
practice guidelines, as contained in the Declaration of Helsinki. The
study protocol and consent were approved by the independent
ethics committee of the study centre. All of the diagnostic
procedures and psychometric tests are part of the routine clinical
assessment performed at our clinic. The project protocol was fully
explained, and all subjects provided written consent to the
collection and analysis of their data. Patient condentiality was
ensured at all times.
2.2. Participants
All adult outpatients with schizophrenia [32] attending our LAI
clinic between April 2015 and November 2015 and requiring an
antipsychotic maintenance treatment were consecutively enrolled
in the study, provided they met the following inclusion criteria:
 age between 18 and 65 years;
 outpatients status;
 complete clinical remission, as assessed by means of the Positive
and negative syndrome scale (PANSS) [33], the MontgomeryAsberg depression rating scale (MADRS) [34], and the Young
mania rating scale (YMRS) [35], and dened as satisfying all of
the following cut-off scores at the same time:

 PANSS total score  58 [36] and a score of  3 on each of the


following PANSS items: delusions (P1), conceptual disorganization (P2), hallucinatory behaviour (P3), blunted affect (N1),
passive/apathetic social withdrawal (N4), lack of spontaneity
and ow of conversation (N6), mannerism and posturing (G5)
and unusual thought content (G9) [37],
 MADRS total score  10,
 YMRS total score  12;
 had been on a stabilized single antipsychotic treatment with
either oral olanzapine or paliperidone for more than 4 weeks;
 were about to be switched to the equivalent maintenance
regimen with the LAI formulation of the same antipsychotic
(olanzapine pamoate [38] or paliperidone palmitate [39]).
The decision to change treatment strategy was made according
to current clinical guidelines for the use and management of LAI
antipsychotics [40], suggesting that they should be considered and
systematically proposed as a treatment option to any patient for
whom maintenance antipsychotic treatment is indicated.
Patients were excluded if: they were receiving antipsychotic
treatment for the rst time, were treated with clozapine during the
previous 3 months, had participated in a clinical trial during the
previous month, or had previously demonstrated poor response or
tolerability to any antipsychotic. Patients were also excluded if
they had any of the following: current diagnosis of other
psychiatric disorders, substance abuse and/or addiction, serious
and unstable medical condition, neurological and/or cognitive
impairment or illiteracy, history or current symptoms of tardive
dyskinesia, history of severe drug allergy or hypersensitivity,
history of neuroleptic malignant syndrome. Female patients who
were pregnant, breastfeeding or without adequate contraception
were also excluded.
After applying the mentioned inclusion and exclusion criteria,
21 subjects with remitted schizophrenia switching from oral- to
LAI-AMT were enrolled. One patient failed to complete the study
protocol because he decided to continue his LAI treatment program
in a different outpatient facility of the National Health Service. The
LAI-AMT group therefore consisted of 20 adult subjects with
remitted schizophrenia (7 males and 13 females).
A group of 20 remitted schizophrenic subjects undergoing a
maintenance treatment with a single oral antipsychotic drawn
from the general psychiatry outpatient service of our clinic and
satisfying the same inclusion and exclusion criteria (except for the
last of the mentioned inclusion criteria) made up the control group.
The 20 oral-AMT control subjects were selected by means of an
individual matching to cases for the main sociodemographic,
clinical and treatment variables.
In the clinicians judgment, enrolled patients were expected to
follow the treatment plan and not to need other changes in
concomitant pharmacological or non-pharmacological treatments.
They were also expected to regularly attend the follow-up
psychiatric consultations, that were coordinated with the dates
of the injections in the case of the LAI-AMT subjects.
Both groups received monthly psychiatric consultations for the
whole duration of the study. Moreover, since the outpatient
services of our clinic belong to the National Health System and
guarantee full accessibility to the general population, needed
treatments were provided at no cost for patients. The study sample
therefore consisted of 40 adult subjects with remitted schizophrenia (14 males and 26 females), comprised of a LAI- and of an oralAMT group of 20 subjects each.
2.3. Assessment
Subjects of both groups were assessed at enrolment (baseline
visit before the switch for the LAI-AMT group), and after 6 months

F. Pietrini et al. / European Psychiatry 37 (2016) 3542

of AMT (follow-up visit). Sociodemographic, clinical and treatment


data were collected at each visit by two expert psychiatrists
who were blind to the clinical and treatment status of the
subjects they assessed and with whom they had no therapeutic
relationship.
The diagnosis of schizophrenia was made according to the
Diagnostic and statistical manual of mental disorders, fth edition
(DSM-5) [32] as assessed by the Structured clinical interview for
DSM-IV axis i disorders patient edition (SCID-I/P) [41], and
conrmed by treating clinician for compatibility between old
DSM-IV-TR [42] and new DSM-5 diagnostic criteria.
Symptomatic improvement of enrolled subjects was measured
by evaluating the mean percent absolute change of the PANSS,
MADRS and YMRS scores between the baseline visit (T0) and the 6month follow-up visit (T1).
2.4. Outcome measures
Together with the mentioned psychometric assessment of
current psychopathology, the following patient-reported outcomes were assessed at T0 and T1 in both AMT groups:
 subjective experience of treatment, as measured by the
Subjective Well-being under Neuroleptics scale short form
(SWN-K) [8];
 attitudes towards drug as measured by the Drug Attitude
Inventory short version (DAI-10) [43];
 health-related quality of life as measured by the Short Form-36
health survey (SF-36) [44].
The SWN-K [8] is a 20-item self-rating scale, developed to
measure the subjective experience of psychotic patients associated
with the use of antipsychotics. It contains ve subscales consisting
of four items each: mental functioning, self-control, emotional
regulation, social integration, and physical functioning. The total
score ranges from a minimum of 20 (poor subjective experience) to
a maximum of 120 (excellent subjective experience).
The DAI-10 [43] is a 10-item self-rating scale, developed to
assess how the attitude, experience and beliefs of patients about
antipsychotics may affect compliance. Scores range from 10 (very
poor attitude) to +10 (best possible attitude).
The SF-36 [44,45] is a 36-question, self-reported measure of
quality of life, generating scores for eight domains: general health,
vitality, role emotional (ability to perform life role tasks based on
emotional functioning), mental health (depression and anxiety),
physical functioning (ability to perform physical tasks), role
physical (ability to perform life role, i.e. work based on physical
functioning), bodily pain and social functioning (ability to perform
social tasks). Each scale is linearly transformed into a 0to100
scale with higher scores representing better health status and
functioning.
Changes in subjective experience of treatment of enrolled
subjects were measured by evaluating the mean percent absolute
variation of the SWN-K and DAI-10 scores between the baseline
visit (T0) and the 6-month follow-up visit (T1). Changes in healthrelated quality of life of enrolled subjects were also assessed by
comparing the SF-36 mean scores of the two evaluations.
2.5. Statistical analysis
For discrete variables, absolute and relative frequencies were
calculated. For continuous variables, descriptive statistics
(mean  standard deviation [SD], mean  standard error [SE], median, range) were calculated. Paired and independent samples students
t-test, and Pearsons Chi2 test (x2) were performed when appropriate.
In particular, independent samples students t-test was used for

37

between-group analysis and paired samples students t-test was used


for repeated measures analysis. For the independent samples t-test,
Cohens d was used as a measure of effect size. Statistical analysis was
performed by means of the Statistical package for social sciences
(SPSS) for Windows (release 20.0, IBM, 2011).
3. Results
3.1. Patients and treatment
A total of 41 subjects with remitted schizophrenia were
enrolled in the study (all patients were Caucasian), with
40 completing the 6-month period (97.6% of the total sample).
One patient discontinued the study because he chose to carry on
the LAI treatment program in a different outpatient service.
Baseline sociodemographic, clinical and treatment characteristics
of the sample are summarized in Table 1. As expected, no
statistically signicant difference in the main sociodemographic,
clinical and treatment variables was found between the oral- and
LAI-AMT groups. The LAI-AMT group included 15 patients treated
with oral olanzapine (1015 mg/day) and ve with oral paliperidone (912 mg/day), who were switched to the equivalent
regimen with LAI olanzapine pamoate (300405 mg/month) and
LAI paliperidone palmitate (100150 mg/month) respectively. No
clinically signicant treatment-associated adverse events (TAEs),
post-injection syndrome (PIS) reactions, side effects or local
complications in the site of injections occurred. Patients of both
groups regularly attended the monthly follow-up psychiatric
consultations, which were coordinated with the dates of the
injections in the case of the LAI-AMT group. Concomitant
medications were recorded throughout the study. However, no
change in concomitant treatments at entry was needed for the
whole duration of the study.
3.2. Efcacy measures
All of the 40 schizophrenic patients included in the study
maintained complete clinical remission during the 6-month period
(data not shown). Repeated measures analysis on the LAI-AMT
group (Fig. 1) showed an overall improvement of psychopathological measures over the 6-month period (T0 vs. T1), not reaching
statistical signicance only in the case of the negative aspects of
the syndrome (as measured by the negative scale of the PANSS).
More in details, signicant reductions in mean PANSS positive
(t[19] = 2.655,
P = 0.016)
and
general
psychopathology
(t[19] = 4.610, P = 0.000), YMRS (t[19] = 2.642, P = 0.016) and MDRS
(t[19] = 3.749, P = 0.001) scores were found in this group.
Differently from that of the LAI-AMT group, repeated measures
analysis of the oral-AMT group only showed non-signicant
changes in psychopathology during the same period (Fig. 1). In
particular, between T0 and T1, the oral-AMT group showed nonsignicant reductions of the mean MDRS, YMRS, PANSS positive
and general psychopathology scores, together with a nonsignicant increase of mean PANSS negative psychopathology
score.
In regards to between-group analysis, the comparison between
the LAI- and the oral-AMT groups showed greater reductions in
symptom severity between T0 and T1 in the former, although such
difference was statistically signicant only in terms of mean
percent decrease of the PANSS general psychopathology score
(t[38] = 2.842, P = 0.007) (Fig. 1).
3.3. Patient-reported outcomes
Changes in patients subjective experience of treatment and
attitudes towards drug during the 6-month period in both study

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F. Pietrini et al. / European Psychiatry 37 (2016) 3542

Table 1
Baseline characteristics of the sample.
Characteristic

Sociodemographic variables
Gender (M)
Age (years)
Education (years)
Marital status (single)
Clinical history
Illness duration (years)
Episodes of illness
Hospitalizations
Number of different antipsychotics received in the past
Psychopathology
PANSS
General
Positive
Negative
YMRS
MDRS
Antipsychotic treatment
Olanzapine
10 mg/day or 300 mg/month
Olanzapine
15 mg/day or 405 mg/month
Paliperidone
9 mg/day or 100 mg/month
Paliperidone
12 mg/day or 150 mg/month
Adherence to treatment
DAI-10
Concomitant treatments
None
Antidepressants
Mood stabilizers
Anxiolytics
Concomitant treatment for adverse effects of antipsychotics

AMT

x2

LAI
n = 20

Oral
n = 20

7 (35.0)
40.55  11.00
12.20  3.42
12 (60.0)

7 (35.0)
45.10  10.68
11.60  4.40
12 (60.0)

0.000

0.000

1.327
0.481

1.000
0.192
0.633
1.000

20.20  10.08
3.70  1.45
2.80  1.00
2.70  1.12

21.85  12.83
3.50  1.70
2.80  1.76
3.10  1.25

0.452
0.400
0.000
1.061

0.654
0.692
1.000
0.295

46.65  8.98
26.90  6.33
10.80  4.07
8.95  2.93
4.75  4.13
6.10  2.43

45.70  8.00
26.55  4.98
9.20  1.99
9.90  3.59
3.65  3.03
6.61  2.35

0.353
0.194
1.579
0.916
0.961
0.662

0.726
0.847
0.126
0.365
0.343
0.512

4 (20.0)

4 (20.0)

0.000

1.000

11 (55.0)

11 (55.0)

0.000

1.000

2 (10.0)

2 (10.0)

0.000

1.000

3 (15.0)

3 (15.0)

0.000

1.000

3.10  4.61

4.75  3.85

1.228

0.227

8
8
7
0
0

6
8
9
1
0

0.440
0.000
0.417
1.026
0.000

0.507
1.000
0.519
0.311
1.000

(40.0)
(40.0)
(35.0)
(0.0)
(0.0)

(30.0)
(40.0)
(45.0)
(5.0)
(0.0)

Statistics: discrete variables are reported as number (within-group percentage); Continuous variables are reported as mean  standard deviation. AMT: antipsychotic
maintenance treatment; LAI: long-acting injectable; N: number; M: male; single: single or not in a stable relationship; PANSS: Positive and negative syndrome scale total score;
general: general psychopathology subscale of the PANSS; positive: positive subscale of the PANSS; negative: negative subscale of the PANSS; YMRS: Young mania rating scale;
MDRS: Montgomery-Asberg depression rating scale; DAI-10: drug attitude inventory short version.

groups are depicted in Fig. 2. As evidenced by repeated measures


analysis, the LAI-AMT group reported a highly signicant progress
in the experience of treatment between T0 and T1, with a
remarkable increase of the mean DAI-10 score (t[19] = 3.590,
P = 0.002) and a generalized improvement of the ve SWN-K
subscales mean scores (emotional regulation: t[19] = 2.680,
P = 0.015; self-control: t[19] = 3.155, P = 0.005; mental functioning: t[19] = 4.310, P = 0.000; physical functioning: t[19] = 3.719,
P = 0.001; social integration: t[19] = 4.059, P = 0.001) (Fig. 2).
On the other side, repeated measures analysis showed no
signicant changes in attitudes towards drug and subjective
experience of treatment in the oral-AMT group during the same
period (Fig. 2). Moreover, compared to the oral-AMT group in the
between-group analysis, the LAI-AMT group reported signicantly
better changes in the DAI-10 mean percent score (t[38] = 3.266,
P = 0.003, Cohens d = 1.03), as well as in the SWN-K emotional
regulation (t[38] = 2.964, P = 0.007, Cohens d = 0.94), self-control
(t[38] = 3.530, P = 0.002, Cohens d = 1.12), mental functioning
(t[38] = 4.619, P = 0.000, Cohens d = 1.46), and physical functioning (t[38] = 3.535, P = 0.001, Cohens d = 1.12) mean percent scores
between T0 and T1 (Fig. 2).
Changes in patients health-related quality of life (as measured
by the SF-36) between T0 and T1, as derived by repeated measure
analysis, are reported in Fig. 3. A generalized expansion of healthrelated quality of life, with better functioning in all areas of daily
living, was reported by the LAI-AMT group (Fig. 3). Such
improvement did not reach statistical signicance only in the

case of perceived physical functioning and bodily pain (general


health: t[19] = 4.187, P = 0.000; vitality: t[19] = 3.199, P = 0.005;
role emotional: t[19] = 2.900, P = 0.009; mental health:
t[19] = 2.969, P = 0.008; role physical: t[19] = 2.854, P = 0.010;
social functioning: t[19] = 3.687, P = 0.002). In contrast, the oralAMT group reported a sensible worsening of health-related quality
of life between T0 and T1, as underlined by statistically signicant
reductions in emotional role (t[19] = 2.697, P = 0.014) and social
functioning (t[19] = 2.651, P = 0.016) mean scores (Fig. 3).
4. Discussion
4.1. LAI versus oral from the outside
Since prevention plays a major role in the treatment of any
chronic condition, it is important to notice that none of the subjects
included in the study showed illness relapse or needed hospitalization during the 6-month period. This result seems to conrm the
importance of a stable AMT in order to minimize the risk of relapse
and readmission in schizophrenia, independently from the
treatment formulation [4,5].
In regards to efcacy, in this study, changes in patients
psychopathology were evaluated both from a quantitative
(psychometric measures) and a qualitative (clinical remission)
point of view, in an effort to create an objective reference
background to specically address the effects of subjective
experience of treatment on patient-reported functional outcomes.

F. Pietrini et al. / European Psychiatry 37 (2016) 3542

39

Fig. 1. Changes in psychopathology after 6 months of antipsychotic maintenance treatment.

Nonetheless, we observed an appreciable symptomatic improvement of the LAI-AMT group 6 months after the switch to the LAI
regimen, with no signicant treatment-associated side effects or
adverse events (Fig. 1). These results are consistent with previous
reports indicating the switch from oral to LAI antipsychotic
treatment as a safe and effective intervention in clinically stable
schizophrenic patients [14,19,21,22,46]. It is noteworthy that the
small but generalized improvement in psychometric scores
(between 0.56% and 6.19%) of the LAI-AMT group between T0
and T1 is particularly valuable in clinical practice, since it may
suggest the switch to LAI-AMT as a possible optimization strategy
for schizophrenic patients who already achieved clinical remission
with oral antipsychotics [18,23,24,27,28].
Differently from the LAI-AMT group, the oral-AMT group only
showed non-signicant changes in psychopathology during the
study period. When compared to this group, the LAI-AMT group
showed additional recovery in the general aspects of the
schizophrenic syndrome (PANSS general psychopathology subscale) (Fig. 1). Interestingly enough, among clinical features
evaluated by the PANSS, those addressed by the general
psychopathology subscale seem to be the most inuenced by
subjective treatment-related factors, such as subjective side
effects and attitudes towards drug (i.e. somatic concern,

tension, depression, motor retardation, uncooperativeness,


disorientation, poor attention, lack of judgment and insight,
disturbance of volition, preoccupation, active social avoidance,
etc.) [33,36].
Taken together, these data seem to conrm the possible
superiority of LAI-AMT over oral-AMT in the achievement of
optimal clinical efcacy, even in those patients who are considered
clinically remitted [18,23,24,27]. This is likely due to the LAI
antipsychotics ability to control titration to effective doses, to
steady plasma drug levels, to avoid rst-pass metabolism, and to
guarantee delivery of medication [14,19,21,22].
4.2. LAI versus oral from the inside
The shift from objectivity to subjectivity has led to well-being,
adherence and quality of life becoming key concepts in the
treatment of psychotic disorders [47]. The importance of those
aspects is supported by the increasing evidence on the strong
relation between positive attitudes towards treatment, subjective
well-being, and the improved functioning and life satisfaction; as
well, their protective value against relapse and readmission risk is
also signicant [25,79,11,47]. For these reasons, in this study, we
aimed at evaluating the differences between LAI- and oral-AMT in

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F. Pietrini et al. / European Psychiatry 37 (2016) 3542

Fig. 2. Changes in subjective experience of treatment after 6 months of antipsychotic maintenance treatment.

terms of subjective experience of treatment, attitudes towards


drug and quality of life in a sample of remitted schizophrenic
subjects.
Subjects from the LAI-AMT group reported a signicant
progress in their attitudes towards drug 6 months after being
switched to the LAI formulation of their AMT (Fig. 2). The fact that a
signicant improvement of patients perception and beliefs about
treatment (mean percent absolute change of DAI-10
score = +12,25%) was found in a group of remitted patients
suggests that LAI treatment may improve patients attitude
towards (and therefore adherence to) AMT independently from

the positive effect on compliance due to its efcacy on symptoms


[14,18,25,26,48].
As already stated, subjective well-being is a central component
of recovery from psychotic disorders, as well as a fundamental
determinant of patients compliance and quality of life [25,7
9,11,47]. In this study, we found a signicant and generalized
improvement of the subjective experience of treatment associated
with the 6-month LAI-AMT administration (Fig. 2). Meaningfully,
such improvements in subjective experience of treatment seem to
be reected in an enrichment of the LAI-AMT groups healthrelated quality of life in the corresponding areas of daily living

Fig. 3. Health-related quality of life at baseline and after 6 months of antipsychotic maintenance treatment.

F. Pietrini et al. / European Psychiatry 37 (2016) 3542

(emotional role, mental health, role physical, vitality, general


health, social functioning) (Fig. 3). Better health-related quality of
life and treatment satisfaction are also likely to positively affect
patient attitudes towards long-term therapy, and may contribute
to improve compliance.
In contrast, no signicant changes in attitudes towards drug
and in subjective experience of treatment were found in the oralAMT group during the study period (Fig. 2). On the contrary, this
group reported a worsening of health-related quality of life
between T0 and T1, especially in the area of emotional role and
social functioning (Fig. 3). Consequently, compared to the oralAMT group, the LAI-AMT group preformed signicantly better in
terms of attitudes towards treatment and subjective well-being in
the areas of emotional regulation, self-control, mental functioning,
and physical functioning (Fig. 2). The lower propensity of LAI
antipsychotic formulations to cause adverse subjective experiences and, in turn, to impair patients quality of life, may account for
these differences and could be due to the peculiar pharmacokinetic
and pharmacodynamic characteristics of LAI antipsychotics
[14,19], as well as to other individual and environmental
treatment-related factors (i.e. not having to take pills may increase
social adaptation, autonomy, and may reduce stigma; periodic
treatment monitoring may improve therapeutic alliance, etc.)
[2]. The parallel improvement of subjective experience of
treatment and health-related quality of life in the LAI-AMT group
found in this study seems to suggest, one more time, the switch to
LAI antipsychotic treatment as a possible strategy to address the
subjective core of an optimal and satisfying recovery. This result,
together with the reported superiority of LAI-AMT over oral-AMT
in reducing rehospitalization rates [20,49], could lead to consider
LAI antipsychotic treatment as a rst-line treatment of early
episodes of psychotic disorders, rather than reserved for the last
stages [5055].
4.3. Strengths and limitations
Size and duration represent major limitations of the present
study. In fact, both of these factors are essential in order to produce
solid and generalizable results. However, the ndings of this study
may be of some clinical interest since, to our knowledge, this is the
rst case-control study comparing LAI to oral antipsychotic
maintenance treatment in remitted schizophrenic subjects by
presenting real-world clinical experience and focusing on patients
perspective.
Objective measurement of oral-AMT group adherence to
treatment (i.e. plasma drug levels) was not possible in this study.
Although this represents a limitation of the present study, the
positive clinicians preliminary judgment on the adherence of
enrolled subjects together with the good baseline attitude
towards treatment of the oral-AMT group (as indicated by high
baseline DAI-10 scores of this group) (Table 1) support the
adequate compliance to antipsychotic treatment of the control
group.
The interpretation of our data is limited by factors inherent to
open-label studies [31]. In fact, the open-label design may imply
the risks of bias for internal and external validity. For example, the
patients knowledge of his/her actual treatment and the introduction of a new treatment formulation may bias subjective outcomes
due to expectancy bias and changes in service provision and
utilization. However, the design of this observational study was
tailored to reduce both inter-subject variability (multidimensional
matching, presence of complete remission) and intra-subject
variability (patients clinical and treatment stability, single
antipsychotic treatment, xed antipsychotic drug and regimen,
no change in concomitant treatments, analysis of percent
variations).

41

The analytic approach of this study was intentionally not


focused on factors such as disorder subtypes, indications to LAI
treatment, and efcacy of different molecules, in an effort to
produce an inclusive and trans-nosographic frame in which to
interpret the subjective (rather than the objective) effects of being
switched from an oral to a LAI antipsychotic maintenance
treatment on patients experience.
4.4. Conclusions
The study indicates possible advantages of LAI over oral
antipsychotic administration in terms of subjective experience
of maintenance treatment of remitted schizophrenic patients.
Larger improvements of subjective well-being, attitudes towards
drug and health-related quality of life in subjects switched to LAI
antipsychotic administration suggest this option as a safe and
effective strategy to address the subjective core of an optimal and
satisfying recovery from schizophrenia.
Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgements
None.
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