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Psychopharmacology (2012) 224:347348

DOI 10.1007/s00213-012-2880-0


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 needs to be explored. In that sense, we designed a study to

The lack of effective oral treatments for severely affected explore the benefits of using a depot IM medication, long-
patients with borderline personality disorder (BPD) lead us acting intramuscular risperidone, in the treatment of BPD
to frequently use depot antipsychotic medication in our patients refractory to previous oral medication trials.
personality disorder unit. BPD is characterized by severe A total of 49 BPD patients (30 women and 19 men) were
instability of interpersonal relationships, of self-image, and included in the study. Inclusion criteria were the following: (1)
of affects resulting in marked impulsivity. The importance 1845 years of age; (2) diagnosis of borderline personality
of the disorder is reflected in persistent functional impair- disorder (BPD) according to DSM IV criteria; (3) score equal
ment and in elevated suicide rates (Cheng et al. 1997; Paris or greater than 16 in the Zanarini Rating Scale for BPD; (4)
2005). There is no current consensus on the best treatment severely or very severely ill as defined by a score 5 or
for BPD, and different combinations of oral medications are greater in the CGI severity scale; and (5) refractory to a
being prescribed by physicians (Paris 2011; Silk 2011). combination of oral medications commonly used for BPD
Furthermore low treatment compliance with oral medication treatment. Exclusion criteria were (1) current substance use
is particularly described in these patients due to their char- dependence disorder; (2) life history of schizophrenia, schiz-
acteristic personal instability which might significantly af- ophreniform disorder, bipolar disorder, or neurological disor-
fect the efficiency of the drugs. For that reason, the ders; (3) unstable medical disease or pregnancy; and (4)
possibility that lack of efficacy of oral treatments in refrac- demonstrated intolerance to oral risperidone. The sample
tory BPD patients might reflect the lack of compliance 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-
J. L. Carrasco (*) : N. Palomares : M. D. Mars control causing markedly functional impairment. The study
Institute of Psychiatry and Mental Health,
was approved by the Institutional Ethical Committee, and all
Hospital Clnico San Carlos,
C/ Martin Lagos s/n, patients signed informed consent.
28040 Madrid, Spain Treatment was started with an initial dose of 37.5 mg IM
e-mail: jcarrasco.hcsc@salud.madrid.org injection of LA risperidone repeated every 2 weeks, which
J. L. Carrasco : M. D. Mars
could be raised to 50 mg as to clinical consideration. Patients
Department of Psychiatry, Medical School, were evaluated at months 1, 3, and 6 with clinical scales
Universidad Complutense, including the Zanarini Rating Scale for BPD, the Hamilton
Madrid, Spain Anxiety Rating Scale, the Brief Psychiatry Rating Scale
(BPRS), the Overt Aggression Scale (OAS), the Clinical
J. L. Carrasco : N. Palomares : M. D. Mars
Instituto de Investigacin Sanitaria del Hospital Global Impression scale (CGI), and the Global Assessment
Clnico San Carlos (IdISSC), of Functioning (GAF).
Madrid, Spain Gradual significant improvement of severity ratings was
J. L. Carrasco : N. Palomares : M. D. Mars
observed from the first month and during the first 3 months
Centro de Investigacin en Red de Salud Mental (CIBERSAM), of treatment (p<0.001), but no significant changes in the
Madrid, Spain 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
Depression 3.3 (1.3)
Anxiety 5.1 (1)
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
Effect size is estimated as the mean change score (before and after treatment) divided by the standard deviation of the same measure before
Paired Student t test at baseline versus 6 months

months. Symptom reduction was statistically significant for particularly the lack of a placebo control group, that need to be
aggression scores and for anxiety at the end of treatment. addressed in future efficacy studies. In addition, all patients
Psychosocial functioning, as scored with the GAF scale, included in our study were refractory to previous treatments
was significantly increased from the initial visit to the end and presented severe CGI scores, which suggests that the
of the study. At the last visit, 67 % of patients were consid- sample could not represent the average BPD population.
ered responders (CGI change score 1 or 2). Most patients In sum, we conclude from this preliminary study that
presented mild adverse events, and only three subjects (6 %) intramuscularly administered depot risperidone might be
withdrew the study prematurely. an efficient and safe treatment option for refractory BPD
Qualitative variables were summarized by their frequen- patients probably due to improving patient compliance.
cy distribution as well as quantitative variables by their
mean and standard deviation (SD). The significances of Acknowledgments This research was partially supported by a grant
within-group changes from baseline to endpoint in the total for research from the Ministry of Science and Innovation FIS 090331.
scores of the scales were calculated with paired Students t
Conflict of interest None of the authors have any financial interests
test (see Table 1). Statistical analyses were performed using or conflicts possibly affecting the objectives or the results of the
the SPSS 15.0 statistical package. present manuscript.
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 References
improvement associated to the addition of IM long-acting
risperidone to previous combinations of oral treatments, in-
Cheng AT, Mann AH, Chan KA (1997) Personality disorder and
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sions on the efficacy of the drug in BPD but raises interesting Paris J (2005) Recent advances in the treatment of borderline personality
issues on the effectiveness of depot medications in BPD. disorder. Can J Psychiatry 50(8):435441
Paris J (2011) Pharmacological treatments for personality disorders. Int Rev
Thus, improved compliance due to intramuscular administra-
Psychiatry 23(3):303309. doi:10.3109/09540261.2011.586993
tion might possibly explain the benefits associated to this Silk KR (2011) The process of managing medications in patients with
treatment option. The present study has several limitations, borderline personality disorder. J Psychiatr Pract 17(5):311319