Psychopharmacology (2012) 224:347348
DOI 10.1007/s00213-012-2880-0
LETTER TO THE EDITOR
Effectiveness and tolerability of long-acting intramuscular
risperidone as adjuvant treatment in refractory borderline
personality disorder
J. L. Carrasco & N. Palomares & M. Daz Mars
Received: 22 August 2012 / Accepted: 6 September 2012 / Published online: 11 October 2012
# Springer-Verlag Berlin Heidelberg 2012
Dear Editor
The lack of effective oral treatments for severely affected
patients with borderline personality disorder (BPD) lead us
to frequently use depot antipsychotic medication in our
personality disorder unit. BPD is characterized by severe
instability of interpersonal relationships, of self-image, and
of affects resulting in marked impulsivity. The importance
of the disorder is reflected in persistent functional impair-
ment and in elevated suicide rates (Cheng et al. 1997; Paris
2005). There is no current consensus on the best treatment
for BPD, and different combinations of oral medications are
being prescribed by physicians (Paris 2011; Silk 2011).
Furthermore low treatment compliance with oral medication
is particularly described in these patients due to their char-
acteristic personal instability which might significantly af-
fect the efficiency of the drugs. For that reason, the
possibility that lack of efficacy of oral treatments in refrac-
tory BPD patients might reflect the lack of compliance
J. L. Carrasco (*) : N. Palomares : M. D. Mars
Institute of Psychiatry and Mental Health,
Hospital Clnico San Carlos,
C/ Martin Lagos s/n,
28040 Madrid, Spain
e-mail: jcarrasco.hcsc@salud.madrid.org
J. L. Carrasco : M. D. Mars
Department of Psychiatry, Medical School,
Universidad Complutense,
Madrid, Spain
J. L. Carrasco : N. Palomares : M. D. Mars
Instituto de Investigacin Sanitaria del Hospital
Clnico San Carlos (IdISSC),
Madrid, Spain
J. L. Carrasco : N. Palomares : M. D. Mars
Centro de Investigacin en Red de Salud Mental (CIBERSAM),
Madrid, Spain
needs to be explored. In that sense, we designed a study to
explore the benefits of using a depot IM medication, long-
acting intramuscular risperidone, in the treatment of BPD
patients refractory to previous oral medication trials.
A total of 49 BPD patients (30 women and 19 men) were
included in the study. Inclusion criteria were the following: (1)
1845 years of age; (2) diagnosis of borderline personality
disorder (BPD) according to DSM IV criteria; (3) score equal
or greater than 16 in the Zanarini Rating Scale for BPD; (4)
severely or very severely ill as defined by a score 5 or
greater in the CGI severity scale; and (5) refractory to a
combination of oral medications commonly used for BPD
treatment. Exclusion criteria were (1) current substance use
dependence disorder; (2) life history of schizophrenia, schiz-
ophreniform disorder, bipolar disorder, or neurological disor-
ders; (3) unstable medical disease or pregnancy; and (4)
demonstrated intolerance to oral risperidone. The sample
mean age was 27 years (SD4.5) and the average duration
of the disease was 7 years (SD3.3). Patients were regularly
treated in the day-care hospital due to severe behavioral dys-
control causing markedly functional impairment. The study
was approved by the Institutional Ethical Committee, and all
patients signed informed consent.
Treatment was started with an initial dose of 37.5 mg IM
injection of LA risperidone repeated every 2 weeks, which
could be raised to 50 mg as to clinical consideration. Patients
were evaluated at months 1, 3, and 6 with clinical scales
including the Zanarini Rating Scale for BPD, the Hamilton
Anxiety Rating Scale, the Brief Psychiatry Rating Scale
(BPRS), the Overt Aggression Scale (OAS), the Clinical
Global Impression scale (CGI), and the Global Assessment
of Functioning (GAF).
Gradual significant improvement of severity ratings was
observed from the first month and during the first 3 months
of treatment (p<0.001), but no significant changes in the
CGI scale were observed between the third and sixth
348 Psychopharmacology (2012) 224:347348

Table 1 Differences between baseline, 3, and 6 months for primary and secondary variables and results

Baseline 3 Months 6 Months Effect sizea pb

MeanSD (n049) MeanSD (n046) MeanSD (n046)

CGI 6.31 (0.62) 3.96 (0.76) 3.82 (0.97) 4.02 <0.001

Zanarini 19.43 (2.52) 14.90 (4.11) 13.13 (4.06) 2.5 <0.001
GAF 52.24 (5.10) 67.04 (7.56) 2.9 <0.001
HARS 22.63 (3.31) 17.45 (3.56) 1.56 <0.001
OAS 16.63 (5.35) 9.80 (4.74) 1.28 <0.001
BPRS
Depression 3.3 (1.3)
Anxiety 5.1 (1)
Psicomotor
Excitation/activation 4.8 (1.1)
Suspiciousness 4.1 (1.3)
Hostility 3.7 (1.4)
Suicidality 4.6 (1.1)
Impulsive behaviors 5.1 (1.0)

Zanarini Rating Scale for BPD, HARS Hamilton Anxiety Rating Scale, BPRS Brief Psychiatry Rating Scale, OAS Overt Aggression Scale, CGI
Clinical Global Impression scale, GAF Global Assessment of Functioning
a
Effect size is estimated as the mean change score (before and after treatment) divided by the standard deviation of the same measure before
treatment
b
Paired Student t test at baseline versus 6 months

months. Symptom reduction was statistically significant for
aggression scores and for anxiety at the end of treatment.
Psychosocial functioning, as scored with the GAF scale,
was significantly increased from the initial visit to the end
of the study. At the last visit, 67 % of patients were consid-
ered responders (CGI change score 1 or 2). Most patients
presented mild adverse events, and only three subjects (6 %)
withdrew the study prematurely.
Qualitative variables were summarized by their frequen-
cy distribution as well as quantitative variables by their
mean and standard deviation (SD). The significances of
within-group changes from baseline to endpoint in the total
scores of the scales were calculated with paired Students t
test (see Table 1). Statistical analyses were performed using
the SPSS 15.0 statistical package.
The observed benefits of IM risperidone on aggression and
anxiety in our study is concordant with previous data reported
for oral risperidone. However, we found significant global
improvement associated to the addition of IM long-acting
risperidone to previous combinations of oral treatments, in-
cluding oral antipsychotics. This does not allow any conclu-
sions on the efficacy of the drug in BPD but raises interesting
issues on the effectiveness of depot medications in BPD.
Thus, improved compliance due to intramuscular administra-
tion might possibly explain the benefits associated to this
treatment option. The present study has several limitations,
particularly the lack of a placebo control group, that need to be
addressed in future efficacy studies. In addition, all patients
included in our study were refractory to previous treatments
and presented severe CGI scores, which suggests that the
sample could not represent the average BPD population.
In sum, we conclude from this preliminary study that
intramuscularly administered depot risperidone might be
an efficient and safe treatment option for refractory BPD
patients probably due to improving patient compliance.
Acknowledgments This research was partially supported by a grant
for research from the Ministry of Science and Innovation FIS 090331.
Conflict of interest None of the authors have any financial interests
or conflicts possibly affecting the objectives or the results of the
present manuscript.
References
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Paris J (2011) Pharmacological treatments for personality disorders. Int Rev
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