679547

research-article2016
APY0010.1177/1039856216679547Australasian PsychiatryLenardon et al.

Australasian
Regular Article Psychiatry
Australasian Psychiatry

The successful concurrent  ­–5

1
© The Royal Australian and
New Zealand College of Psychiatrists 2016

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DOI: 10.1177/1039856216679547
antipsychotics in a patient with apy.sagepub.com

treatment-resistant schizophrenia
and history of serious violence:
a case report
Anna Lenardon  Specialist Registrar, Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
Mona Ahmed  Specialist Registrar, Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
Katie-Lynn Harfield  Mental Health Nurse (Team Leader), Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
Mrigendra Das  Consultant Forensic Psychiatrist, Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK and;
College Tutor, Oxford School of Psychiatry, Oxford, UK, and; Consultant Forensic Psychiatrist, Top End Mental Health Service,
Parap, NT, Australia

Abstract
Objective: This case report describes a forensic psychiatric patient presenting with treatment-resistant schizophre-
nia and serious interpersonal violence complicated by poor adherence to oral medication who was treated success-
fully with two concurrent long-acting depot antipsychotics.
Method: Treatment response was measured for a 6-month period at 6-weekly intervals, post-initiation using the
Positive and Negative Symptoms of Schizophrenia with Excited Component score (PANSS-EC), Brief Psychiatric Rat-
ing Scale (BPRS) and Clinical Global Impression Scale (CGI).
Results: At 6 months, the presentation was found to have markedly improved. The overall PANSS-EC score was
reduced by 43.9%, with reductions in Positive Symptom and Excited Component subscales most evident. BPRS
Score was reduced from 81 at baseline to 47 at 18 weeks. There was improvement in the patient’s level of coopera-
tiveness, aggression and engagement in ward therapeutic activities.
Conclusion: Although concurrent use of two depot antipsychotics requires further exploration, there is potential ben-
efit for patient groups presenting with treatment-resistant schizophrenia and poor compliance. Due to risk of serious
adverse effects which are difficult to reverse with long-acting formulations, we recommend this option be reserved for
this complex patient population and exclusively in care settings allowing close physical health monitoring.

Keywords:  combination antipsychotics, depot antipsychotics, long-acting antipsychotics, treatment-resistant

schizophrenia

A
considerable proportion of patients with schizo-
phrenia are treatment resistant, and despite the
increased variety of antipsychotic medications
available the recommended treatment option remains
Clozapine. In cases particularly when Clozapine is not
tolerated, a combination of antipsychotics can be used.1
The use of concurrent antipsychotics in treatment-resist-
ant illness has also been explored in the literature;2,3
however, this is predominantly with oral formulations.
Within the forensic psychiatric population the clinical
picture may be complicated by the presence of co-morbid
illness (personality disorder, developmental disorder and
substance misuse) and challenging violent behaviours.
As a result, poor treatment compliance is often a key con-
cern not only in acute settings, but also in longer-term
maintenance treatment.4 In such cases depot antipsy-
chotics may be indicated.
Corresponding author:
Mrigendra Das, Top End Mental Health Service, PO Box 140,
Parap, NT 0804, Australia.
Email mrigen.das@btinternet.com

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We report the case of a forensic psychiatric patient diag-
nosed with treatment-resistant schizophrenia detained
in a United Kingdom High Secure psychiatric hospital
due to significant history of violence. His presentation is
complicated by poor adherence to oral treatment
whereby he had successfully sabotaged progress on mul-
tiple occasions by discontinuing medication. He was
therefore trialled on two concurrent depot antipsychotic
medications and demonstrated a good response. To our
knowledge, the concurrent use of two depot antipsy-
chotics as maintenance treatment has not been reported
in the literature.
Method
The patient’s therapeutic response to two concurrent
long-acting depot antipsychotics was monitored for 6
months at 6-weekly intervals using the Positive and
Negative Symptoms of Schizophrenia with Excited
Component score5 (PANSS-EC), the Brief Psychiatric rat-
ing Scale6 (BPRS) and the Clinical Global Impression
Scale7 (CGI).
Case history
Mr A is a 52-year-old man with treatment-resistant
schizophrenia diagnosed at the age of 24. His illness was
characterised initially by two to three hospitalisations
annually within the context of poor medication compli-
ance and poly-substance misuse. In addition he has an
extensive forensic history of acquisitive crimes and
spent prolonged periods in prison. Since 2010, his pres-
entation deteriorated requiring continuous detention in
secure hospital.
In 2012, due to increased levels of interpersonal violence
and challenging behaviour, he was transferred to one of
the three high-security hospitals in England where he
remains detained under the Mental Health Act 1983
(amended 2007).
Mr A has previously presented with persistent highly
disturbed behaviours requiring frequent periods in seclu-
sion. This is characterised by poor self-care, poor dietary
intake, faecal smearing and interpersonal aggression,
which has all limited his ability to engage in ward-based
therapeutic activities.
Mr A’s past treatment has included various high-dose
oral and depot antipsychotics as well as Clozapine and a
course of electro-convulsive therapy treatment in
February 2015. A key concern has been his poor compli-
ance with oral medications, which has been a persistent
problem even during periods of relative stability. This
has meant an adequate trial to assess response to
Clozapine has not been practicable as he discontinued
this within days of commencing titration.
From July 2015, Mr A was treated with high-dose
Olanzapine depot and oral Aripiprazole with a degree of
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Australasian Psychiatry 
improvement noted: behaviour was less challenging,
necessitating fewer periods in seclusion. Consequently,
he was able to socialise more, engage in activities and
personal hygiene and dietary intake improved.
However, shortly after this improvement was noted, he
began refusing oral Aripiprazole. This is part of a previ-
ously well-observed pattern of poor treatment compli-
ance with deliberate sabotaging of progress. To
circumvent this and ensure compliance, a decision was
taken for Mr A to be commenced on Aripiprazole depot
(400 mg monthly) concurrently with Olanzapine depot
(405 mg every 10 days). Due to Mr A’s incapacity to con-
sent, treatment was authorised by a Second Opinion
Appointed Doctor (an independent consultant psychia-
trist) prior to treatment in October 2015.
The rationale for combining Olanzapine and Aripiprazole
was twofold. Firstly, the favourable side-effect profile of
Aripiprazole makes it an option to ameliorate the
increased risk of the metabolic syndrome8 and weight
gain associated with Olanzapine. Secondly, the novel
activity of Aripiprazole as a partial dopaminergic (D2)
agonist ensures more varied receptor activity.
Mr A’s mental state and progress were monitored with
the BPRS, PANSS-EC and CGI for a period of 6 months.
Periods of seclusion and incident reporting (including
incidents of deliberate self-harm, verbal and physical
aggression and behavioural disturbances such as faecal
smearing) were also measured.
Mr A’s physical health was monitored; baseline blood
tests (full blood count, liver, renal, lipids, bone profile,
random glucose, body mass index and prolactin) and
vital signs were within normal range and remained so at
6 months. He complied with full physical examination,
but refused ECG. There was no evidence of extra-pyram-
idal side effects.
Treatment outcomes
Mr A commenced treatment with two concurrent depot
antipsychotics, a medication regimen constituting three
injections monthly. Over a 6-month period on this regi-
men clinical outcomes were measured at 6-weekly inter-
vals using the BPRS and PANSS. The PANSS Excited
Component subscale scores were used as a measure of
agitation and behavioural disturbance.
The clinical presentation improved overall, with a reduc-
tion in episodes of behavioural disturbance requiring
periods in seclusion. Prior to commencing treatment, Mr
A had required long-term segregation (LTS); however,
this was discontinued in December 2015, soon after ini-
tiation of combination of Olanzapine depot and oral
Aripiprazole. Since then he has, by and large, required
only very short-term intermittent periods in seclusion
and not required any periods in LTS.
As illustrated below, symptom severity reduced, which
was associated with improved quality of life, sleep
Lenardon et al.

Figure 1.  (a) PANSS positive scale ratings. (b) PANSS negative scale ratings. (c) PANSS excited component score.
(d) General psychopathology.
PANSS: Positive and Negative Symptoms of Schizophrenia.

­ atterns, dietary intake, behavioural disturbance and

p 6 and 12 weeks, respectively). The CGI Illness Severity
personal hygiene. There was a 43.9% reduction in over- Score also reduced from 7 at baseline to 3 and CGI Global
all PANSS-EC score from 102 to 73 (reductions in the Improvement from 7 to 2 (see Table 1).
individual scales and overall score) (see Figure 1 (a)–(d)).
There were also striking reductions in the overall score of Mr A has been engaging in more meaningful social inter-
the BPRS, with the overall score reduced from 81 at base- actions and occupational activities. Since December
line to 47 at 18 weeks (with overall scores of 72 and 59 at 2015, there have been no incidents of violence or

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Table 1.  Clinical global impression scale
Baseline 2 months 4 months
Illness severity 7 5 3
Global improvement 7 3 2
Illness severity
0 = Not assessed; 1 = Normal – not at all ill; 2 = Border­
line mentally ill; 3 = Mildly ill; 4 = Moderately ill;
5 = Markedly ill; 6 = Severely ill; 7 = Among the most
extremely ill patients.
Global improvement.
0 = Not assessed; 1 = Very much improved; 2 = Much
improved; 3 = Minimally improved; 4 = No change; 5 =
Minimally worse; 6 = Much worse; 7 = Very much worse.
assaultive behaviours, including cessation of faecal
smearing which has been a concerning behaviour in the
past. Whilst there have been intermittent fluctuations
requiring brief periods in seclusion this, has not pro-
gressed to LTS in the last 3 months.
Physical health monitoring continues to be carried out
regularly as outlined above, with no untoward physical
health complications or adverse side effects reported. At
the time of reporting he has remained on Aripiprazole
depot (400 mg monthly IM) concurrently with Olanzapine
depot (405 mg every 10 days IM).
Discussion
Treatment resistance and unsatisfactory functional out-
comes in patients with schizophrenia remain a signifi-
cant clinical and public health problem. We report on
the successful management of a patient with chronic
treatment-resistant schizophrenia in a forensic high-
security hospital using two concurrent depot antipsy-
chotics. Over the 6-month treatment period the patient
showed global improvements in symptoms, behavioural
disturbance and interpersonal violence.
Improvements in symptoms and aggression within the
forensic population9 have been reported with Olanzapine
IM depot alone. However, Mr A had been treated with
Olanzapine depot for a number of months; the marked
improvements in July 2015 were noted after addition of
oral Aripiprazole, forming the basis to convert to intra-
muscular long-acting Aripiprazole.
Despite evidence-based guidance recommending that
antipsychotic co-treatment be reserved only for cases
where multiple mono-therapies (including Clozapine)
are unsuccessful, surveys worldwide note combination
antipsychotic use is common practice.10 In addition to
there being little rationale for combining antipsychotics
with the same putative dopamine D2 receptor blockade
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Australasian Psychiatry 
activity, ‘poly-pharmacy’ is already an intrinsic charac-
teristic of most antipsychotics due to their multiple
pharmaco-dynamic neurotransmitter effects. Moreover,
the concurrent use of antipsychotic depot medication is
a practice that has not been explored in the literature.
Nevertheless, for patients with treatment-resistant ill-
ness which is also complicated by persistently poor
adherence to oral treatment (making Clozapine a less
viable option) there could be a role for concurrent depot
antipsychotics. In this case, treatment with concurrent
Olanzapine (equivalent to oral dose of 40 mg daily) and
Aripiprazole depot (equivalent to 30 mg daily) medica-
tion was found to be beneficial. The patient, who had
presented with severe treatment-refractory psychosis
and extreme behavioural disturbances for several years,
is continuing to demonstrate considerable improve-
ments in presentation after 6 months of treatment.
Crucially, he has also tolerated the treatment well, with-
out physical health complications or adverse side effects
observed, and compliance has been assured with use of
concurrent depot antipsychotics.
A key concern in such instances is the potential for
serious adverse side effects (including Neuroleptic
­
Malignant Syndrome) which would be difficult to
reverse given the preparation and mode of administra-
tion of depot treatment. As such, we would recommend
that whilst a concurrent depot antipsychotic regime
appears a safe and effective option in this case, it should
be reserved for use only where treatment-resistant psy-
chosis is coupled with poor adherence with oral treat-
ment and exclusively in care settings that allow for
close physical health monitoring.
Whilst we acknowledge difficulties in generalising from
a single case study to broader clinical practice, concur-
rent antipsychotic depot medication could prove to be
an effective treatment option in this rare patient popula-
tion, and further work is necessary to examine this.
Disclosure
The authors report no conflict of interest. The authors alone are responsible for the content
and writing of the paper.
Funding
The authors received no financial support for the research, authorship, and/or publication of
this article.
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