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P.3.c.005 Paliperidone in the treatment of borderline personality disorder: a pilot study of efficacy and tolerability
P.3.c Psychotic disorders and antipsychotics - Antipsychotics (clinical) and significance was defined as an alpha < 0.05. This study was approved by the Institutional Review Board of Inje University. Results: 37 patients were randomly assigned to olanzapine 1M (n = 12), haloperidol 1M (n = 10), haloperidol+lorazepam 1M (n = 15). No significant differences in demographics and clinical characteristics at the baseline were found among three groups. The proportion of patient with a clinical diagnosis of acute agitation in association with schizophrenia was 60%, with bipolar disorder with psychotic features was 30%, and brief psychotic disorder was 10%. All three groups showed significantly decrease PANSS EC scores at 2 hours compared to baseline (within group effect) (P < 0.0001), however, no significant difference in PANSS EC scores was found among groups. BARS score was also significantly decreased in within all three groups(p < 0.001), but was not different among groups. Dizziness (1 in haloperidol group), dry mouth (1 in haloperidol+lorazepam), and blurred vision (1 in olanzapine group) were reported, however, no serious adverse event was found in all three groups. Conclusions: Olanzapine 1M was effective in treating acutely agitated psychotic patients without serious treatment-emergent adverse events. However, no significant advantage of olanzapine 1M was found over haloperidol 1M alone or haloperidol+lorazepam 1M. Small sample size, non-blinded study design may be limitations of our study. Well designed further study will be needed to confirm our finding. This study was supported by grants from the Inje University and Dongseo Hospital, Republic of Korea. No authors received any financial support from the pharmaceutical industry for this study. References
[1] Stephen R. Marder. A review of agitation in mental illness: Treatment guidelines and current therapies. J clin Psychiatry 2006;67 (suppl 10) 13-21 [2] Wright P, Birkett M, David SR, Meehan K, Ferchland I, Alaka KJ, Saunders Je, Krueger J, Bradley P, San L, Bernardo M, Reinstein M, Breier A. Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Am J Psychiatry 2001;158:1149-1151 [3] Centorrino F, Meyers AL, Ah1 J, Cincotta SL, Zun L, Gulliver AH, Kinon BJ, Houston JP. An observational study of the effectiveness and safety of intramuscular olanzapine in the treatment of acute agitation in patients with bipolar mania or schizophrenialschizoaffective disorder. Hum Psychopharmacol. 2007 Oct;22(7):455-62
1p.3.c.oo51 Paliperidone
in the treatment of borderline personality disorder: a pilot study of efficacy and tolerability
P. Bozzatello1 ., S. Bellino 1, C. Rinaldi 1 , F. Bogett02 . 1Service for Personality Disorders Unit of Psychiatry 1, Department of Neurosciences University of Turin, Turin, Italy; 2 Unit of Psychiatry 1, Department of Neurosciences University of TUrin, Turin, Italy Antipsychotics are widely used in clinical practice for treating borderline personality disorder (BPD) related symptoms. Although this use has not been approved by the FDA, APA guidelines [1] recommend the use of atypical antipsychotics, primarily for their effects on cognitive perceptual disturbances, such as transient psychotic or dissociative symptoms, but also for their efficacy in reducing affective symptoms (mood instability, anxiety, anger). Atypical antipsychotics promise to be superior to traditional neuroleptics, probably due to their dual mechanism of action,
S513
involving both serotonergic and dopaminergic dysfunctions that have been related to borderline phenomena. Newer antipsychotics are also associated with fewer extrapyramidal side effects and with a lower risk of tardive dyskinesia than traditional neuroleptics. Two preliminary studies [2,3] supported a good efficacy of risperidone on a large spectrum of BPD psychopathology, particularly on affective instability, aggressiveness and hostility, and psychotic-like symptoms. Paliperidone is the active metabolite of risperidone (9-hydroxyrisperidone) and has a similar profile of action (a greater affinity for 5-HT2A blockade relative to D2 blockade and a low affinity for muscarinic receptors resulting in absence of anticholinergic side effects). Paliperidone ER is the first atypical antipsychotic with an extended release, which is achieved by the osmotic-controlled release oral delivery system. This mechanism offers several advantages: a stable plasmatic level allows to avoid initial dosage adjustment and reduces antidopaminergic effects. The aim of the present study is to investigate efficacy and safety of paliperidone in patients with BPD. Eight consecutive outpatients with a DSM-IV-TR diagnosis of BPD were treated for 12 weeks with paliperidone ER 3-6 mg/die. Patients fulfilled a series of exclusion criteria. Criteria for exclusion were lifetime diagnosis of dementia or other cognitive disorders, schizophrenia or other psychotic disorders, and/or bipolar disorders; a co-occurring major depressive episode and/or substance abuse disorder in the last six months. Current use of psychotropic medications, and/or psychotherapy in the three months before recruitment were also excluded. Female patients in childbearing use were excluded if they were not using adequate birth control methods. Assessments were done at baseline, week 4 and week 12, using the Clinical Global Impression-Severity (CGI-S), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Scales for Depression and Anxiety (HDR-S, HAR-S), the Social Occupational Functioning Assessment Scales (SOFAS), and the BPD Severity Index (BPDSI). Adverse events were evaluated with the Dosage Record and Treatment Emergent Symptom Scale. Statistical analysis was performed with the ANOVA for repeated measures. Significant level was p=0.05. Two patients droppedout: one for non-compliance, one for gastrointestinal adverse effects. Others mild adverse effects were EPS, insomnia and agitation. Significant changes were found for: CGI-S (p = 0.003), BPRS (p=0.002), BPDSI total scores (p=0.001) and items "outbursts of anger" (p=0.0005), "impulsivity" (p=0.021) and "dissociative symptoms and paranoid ideation" (p=O.OOI). Initial results indicate that paliperidone is efficacious in reducing global symptoms and a few core symptoms of BPD and is well tolerated. Further controlled studies on larger samples are required to verify these findings. References
[1] Oldham J.M., 2001 Practice guidelines for the treatment of borderline personality disorder. American Psychiatric Association, Arlington, VA. [2] Rocca P., Marchiaro L., Cocuzza E., Bogetto E, 2002 Treatment of borderline personality disorder with risperidone. J. Clin. Psychiatry 63, 241-244. [3] Friedel R.O., Jackson W.T., Huston C.S., May R.S., Kirby N.L., Stoves A., 2008 Risperidone treatment of borderline personality disorder assessed by a borderline personality disorder-specific outcome measure: a pilot study. J. Clin. Psychopharmacol. 28, 345-347.
[1] Stephen R. Marder. A review of agitation in mental illness: Treatment guidelines and current therapies. J clin Psychiatry 2006;67 (suppl 10) 13-21 [2] Wright P, Birkett M, David SR, Meehan K, Ferchland I, Alaka KJ, Saunders Je, Krueger J, Bradley P, San L, Bernardo M, Reinstein M, Breier A. Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Am J Psychiatry 2001;158:1149-1151 [3] Centorrino F, Meyers AL, Ah1 J, Cincotta SL, Zun L, Gulliver AH, Kinon BJ, Houston JP. An observational study of the effectiveness and safety of intramuscular olanzapine in the treatment of acute agitation in patients with bipolar mania or schizophrenialschizoaffective disorder. Hum Psychopharmacol. 2007 Oct;22(7):455-62
1p.3.c.oo51 Paliperidone
in the treatment of borderline personality disorder: a pilot study of efficacy and tolerability
P. Bozzatello1 ., S. Bellino 1, C. Rinaldi 1 , F. Bogett02 . 1Service for Personality Disorders Unit of Psychiatry 1, Department of Neurosciences University of Turin, Turin, Italy; 2 Unit of Psychiatry 1, Department of Neurosciences University of TUrin, Turin, Italy Antipsychotics are widely used in clinical practice for treating borderline personality disorder (BPD) related symptoms. Although this use has not been approved by the FDA, APA guidelines [1] recommend the use of atypical antipsychotics, primarily for their effects on cognitive perceptual disturbances, such as transient psychotic or dissociative symptoms, but also for their efficacy in reducing affective symptoms (mood instability, anxiety, anger). Atypical antipsychotics promise to be superior to traditional neuroleptics, probably due to their dual mechanism of action,
S513
involving both serotonergic and dopaminergic dysfunctions that have been related to borderline phenomena. Newer antipsychotics are also associated with fewer extrapyramidal side effects and with a lower risk of tardive dyskinesia than traditional neuroleptics. Two preliminary studies [2,3] supported a good efficacy of risperidone on a large spectrum of BPD psychopathology, particularly on affective instability, aggressiveness and hostility, and psychotic-like symptoms. Paliperidone is the active metabolite of risperidone (9-hydroxyrisperidone) and has a similar profile of action (a greater affinity for 5-HT2A blockade relative to D2 blockade and a low affinity for muscarinic receptors resulting in absence of anticholinergic side effects). Paliperidone ER is the first atypical antipsychotic with an extended release, which is achieved by the osmotic-controlled release oral delivery system. This mechanism offers several advantages: a stable plasmatic level allows to avoid initial dosage adjustment and reduces antidopaminergic effects. The aim of the present study is to investigate efficacy and safety of paliperidone in patients with BPD. Eight consecutive outpatients with a DSM-IV-TR diagnosis of BPD were treated for 12 weeks with paliperidone ER 3-6 mg/die. Patients fulfilled a series of exclusion criteria. Criteria for exclusion were lifetime diagnosis of dementia or other cognitive disorders, schizophrenia or other psychotic disorders, and/or bipolar disorders; a co-occurring major depressive episode and/or substance abuse disorder in the last six months. Current use of psychotropic medications, and/or psychotherapy in the three months before recruitment were also excluded. Female patients in childbearing use were excluded if they were not using adequate birth control methods. Assessments were done at baseline, week 4 and week 12, using the Clinical Global Impression-Severity (CGI-S), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Scales for Depression and Anxiety (HDR-S, HAR-S), the Social Occupational Functioning Assessment Scales (SOFAS), and the BPD Severity Index (BPDSI). Adverse events were evaluated with the Dosage Record and Treatment Emergent Symptom Scale. Statistical analysis was performed with the ANOVA for repeated measures. Significant level was p=0.05. Two patients droppedout: one for non-compliance, one for gastrointestinal adverse effects. Others mild adverse effects were EPS, insomnia and agitation. Significant changes were found for: CGI-S (p = 0.003), BPRS (p=0.002), BPDSI total scores (p=0.001) and items "outbursts of anger" (p=0.0005), "impulsivity" (p=0.021) and "dissociative symptoms and paranoid ideation" (p=O.OOI). Initial results indicate that paliperidone is efficacious in reducing global symptoms and a few core symptoms of BPD and is well tolerated. Further controlled studies on larger samples are required to verify these findings. References
[1] Oldham J.M., 2001 Practice guidelines for the treatment of borderline personality disorder. American Psychiatric Association, Arlington, VA. [2] Rocca P., Marchiaro L., Cocuzza E., Bogetto E, 2002 Treatment of borderline personality disorder with risperidone. J. Clin. Psychiatry 63, 241-244. [3] Friedel R.O., Jackson W.T., Huston C.S., May R.S., Kirby N.L., Stoves A., 2008 Risperidone treatment of borderline personality disorder assessed by a borderline personality disorder-specific outcome measure: a pilot study. J. Clin. Psychopharmacol. 28, 345-347.