Paola Bozzatello

Paliperidone ER in the Treatment of Borderline Personality Disorder: A Pilot Study of Efficacy and Tolerability.

Antipsychotics are recommended for the treatment of impulsive dyscontrol and cognitive perceptual symptoms of borderline personality disorder (BPD). Three reports supported the efficacy of oral risperidone on BPD psychopathology. Paliperidone ER is the metabolite of risperidone with a similar mechanism of action, and its osmotic release reduces plasmatic fluctuations and antidopaminergic effects. The aim of this study is to evaluate efficacy and safety of paliperidone ER in BPD patients. 18 outpatients with a DSM-IV-TR diagnosis of BPD were treated for 12 weeks with paliperidone ER (3–6 mg/day). They were assessed at baseline, week 4, and week 12, using the CGI-Severity item, the BPRS, the HDRS, the HARS, the SOFAS, the BPD Severity Index (BPDSI), and the Barratt Impulsiveness Scale (BIS-11). Adverse events were evaluated with the DOTES. Paliperidone ER was shown to be effective and well tolerated in reducing severity of global symptomatology and specific BPD symptoms, such as impulsive dyscontrol, anger, and cognitive-perceptual disturbances. Results need to be replicated in controlled trials.

Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data

A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day.

Efficacy of omega-3 fatty acids in the treatment of borderline personality disorder: a study of the association with valproic acid.

Omega-3 fatty acids have received increasing interest due to their effects in stabilizing plasmatic membranes and regulating cell signaling. The efficacy of omega-3 fatty acids in psychiatric disorders, in particular mood disorders, has been studied. There have been two trials on eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) in the treatment of borderline personality disorder (BPD). The present 12-week controlled trial aimed to assess the efficacy of the association of EPA and DHA with valproic acid, compared to single valproic acid, in 43 consecutive BPD outpatients. Participants were evaluated at baseline and after 12 weeks with: Clinical Global Impression – Severity (CGI-S), Hamilton Scales for depression and anxiety (HAM-D, HAM-A), Social and Occupational Functioning Assessment Scale (SOFAS), borderline personality disorder severity index (BPDSI), Barratt Impulsiveness Scale – version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self-Harm Inventory (SHI) and Dosage Record Treatment Emergent Symptom Scale (DOTES).

Efficacy and tolerability of duloxetine in the treatment of patients with borderline personality disorder: a pilot study

Guidelines of the American Psychiatric Association for borderline personality disorder (BPD) indicate selective serotonin reuptake inhibitors and the serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine for treating affective dysregulation and impulsive behavioural dyscontrol symptoms. The SNRI duloxetine has been studied in patients with major depression, generalized anxiety disorder and fibromyalgia, showing particular efficacy on somatic complaints. This study investigates duloxetine in the treatment of patients with BPD. Eighteen outpatients with a DSM-IV-TR diagnosis of BPD were treated with open-label duloxetine, 60 mg/day, for 12 weeks. Patients were assessed at baseline, week 4 and 12 with the CGI Severity item, the BPRS, the HAM-D, the HAM-A, the SOFAS, the BPD Severity Index (BPDSI) and the HSCL-90-Somatization Subscale (HSCL-90 SOM). Adverse effects were evaluated using the Dosage Record Treatment Emergent Symptom Scale. Statistics were performed with the analysis of variance. Significant P values were ≤0.05. Fourteen patients completed the study. Four patients (22.2%) discontinued treatment in the first 4 weeks because of non-compliance. A significant change was found for: BPRS, HAM-D, SOFAS, BPDSI total score and items ‘impulsivity’, ‘outbursts of anger’ and ‘affective instability’ and HSCL-90 SOM. Adverse effects were mild headache and nausea. Initial results suggest that duloxetine is an effective and well-tolerated treatment for BPD, with positive effects on somatic symptoms.

No effect of serotoninergic gene variants on response to interpersonal counseling and antidepressants in major depression.

Objective Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. Methods One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). Results IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. Conclusion Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.

Combined therapy with interpersonal psychotherapy adapted for borderline personality disorder: A two-years follow-up.

Few investigations evaluated the long-term effects of psychotherapies in borderline personality disorder (BPD). In a previous study, we compared efficacy of combination of fluoxetine and interpersonal psychotherapy adapted to BPD (IPT-BPD) versus single fluoxetine administered for 32 weeks. This study is aimed to investigate whether the results obtained with the addition of IPT-BPD persist during a follow-up period. Forty-four patients who completed the 32 weeks trial underwent 24 months of follow-up receiving fluoxetine 20-40 mg/day. Clinical Global Impression Severity (CGI-S), Hamilton Rating Scales for Depression and Anxiety (HDRS, HARS), Social and Occupational Functioning Assessment Scale (SOFAS), Satisfaction Profile (SAT-P), and Borderline Personality Disorder Severity Index (BPDSI) were repeated at 6, 12, and 24 months. Statistical analysis was performed with the general linear model. Results showed that most of the differences between combined therapy and single pharmacotherapy at the end of the 32 weeks trial were maintained after 24 months follow-up. The addition of IPT-BPD to medication produced greater effects on BPD symptoms (impulsivity and interpersonal relationships) and quality of life (perception of psychological and social functioning) that endured after termination of psychotherapy. On the contrary, different effects on anxiety symptoms and affective instability were lost after 6 months.

Combined treatment of borderline personality disorder with interpersonal psychotherapy and pharmacotherapy: Predictors of response

Borderline personality disorder (BPD) is characterized by affective instability, impulsive behaviors, and disturbed interpersonal relationships. A previous study of our group found that combined therapy with interpersonal psychotherapy adapted to BPD (IPT-BPD) and fluoxetine was superior to single pharmacotherapy in BPD patients. The aim of the present study was to examine what clinical factors predicted response to combined therapy in patients evaluated in the previous efficacy study. The subgroup of 27 patients allocated to combined therapy was analyzed. Patients were treated for 32 weeks with fluoxetine 20-40 mg/day plus IPT-BPD. Patients were assessed at baseline and week 32 with an interview for demographic and clinical variables, CGI-S, HDRS, HARS, SOFAS, BPDSI, and SAT-P. Statistical analysis was performed with multiple regression. The difference of CGI-S score between baseline and week 32 (∆CGI-S) was the dependent variable. Factors significantly and independently related to ∆CGI-S were the BPDSI total score and the items abandonment, affective instability, and identity. Patients with more severe BPD psychopathology and with a higher degree of core symptoms such as fear of abandonment, affective instability, and identity disturbance have a better chance to improve with combined therapy with fluoxetine and IPT-BPD.

Interpersonal Psychotherapy Adapted for Borderline Personality Disorder(IPT-BPD): A Review of Available Data and a Proposal of Revision

Interpersonal psychotherapy (IPT) was developed by Klerman in 1984 for patients with major depression. IPT is aimed to the resolution of interpersonal difficulties, improving both social functioning and psychiatric symptoms. The promising results that this model of psychotherapy has obtained in unipolar depression have led investigators to enlarge the application of IPT beyond this clinical population. Specific adaptations of IPT have been required to address the different psychopathological and clinical characteristics of each disorder. IPT has been proposed to treat borderline personality disorder because of the frequent comorbidity with mood disorders and the serious relational problems. Markowitz and colleagues in 2006 proposed an adaptation for this severe personality disorder, IPT-BPD, including a specific conceptualization of BPD, a prolonged length of treatment to 34 sessions, and a more flexible setting. Clinical efficacy of this adaptation of IPT was investigated in a few clinical trials during the last decade. Our research group conducted three randomized controlled trials. Our findings suggested that combined treatment with IPT-BPD and antidepressants (fluoxetine) can be considered a useful treatment option in treating BPD patients. The efficacy of this combined therapy was superior to single pharmacotherapy in improving core BPD symptom clusters, including disturbed interpersonal relationships, inadequate control of impulsive behaviors, and affective instability. The main effects of IPT-BPD registered after 32 weeks of treatment were maintained during a follow-up of two years. In particular, the superior effects of the addition of IPT-BPD on impulsive behavioral dyscontrol and interpersonal relationships instability were maintained. More severe BPD symptoms and higher degree of fear of abandonment, affective instability, and impaired identity were identified as predictors of response to combined therapy. On the basis of our experience, we present a proposal of revision of IPT-BPD (IPT-BPD-R) with the aim to deal with problems emerged from patients’ treatment.

Effectiveness of psychosocial treatments on symptoms and functional domains in schizophrenia spectrum disorders: a prospective study in a real-world setting

Abstract Purpose: Data of investigations suggested that psychosocial interventions are required to provide a more complete and effective treatment of schizophrenia spectrum disorders. In particular, art therapy was found an effective psychosocial intervention in SSD. Moreover, some authors reported that Befriending was as effective as cognitive behavior therapy in the treatment of schizophrenic patients. The aim of this study is to test Befriending in comparison with Group Art Therapy in patients with SSD, in order to identify differences of effects between treatments. Materials and methods: All subjects were evaluated at baseline and after six months with the Clinical Global-Impression-Severity Scale; the 18-item Italian version of the Brief Psychiatric Rating Scale; the Coping Inventory for Stressful Situations; the Rosenberg Self-Esteem Scale; the Global Assessment of Functioning scale; and the Personal and Social Performance scale. Statistical analysis was performed with chi-square tests for categorical variables and analyses of variance for continuous variables to compare the two groups at baseline. A two-way analysis of variance for repeated measures was performed for clinical and psychosocial variables. Results: A significant improvement over trial duration (within-group effect) was observed for both treatments in psychosocial functioning, self-esteem, and thought disturbance. Befriending was found superior to Art therapy (between-group effect) in improving psychosocial functioning. Both interventions were found efficacious in improving emotion-oriented coping strategies (within group effect), with a significant difference (between group effect) favoring Befriending. Conclusions: Both interventions, in spite of some differences of efficacy, can be considered an important contribution to improve the patients’ real-world functioning. Implications for rehabilitation Our study confirmed the need to include a set of psychosocial interventions for patients with schizophrenia spectrum disorders among usual treatment modalities. Techniques such as Befriending and Art therapy can be considered an important contribution to the treatment instruments required by the new community model for mental health. Befriending was found superior to Art therapy (between group effect) in improving psychosocial functioning. Both interventions were found efficacious in improving emotion-oriented coping strategies (within group effect), with a significant difference (between group effect) favoring Befriending.

Combination of Omega-3 Fatty Acids and Valproic Acid in Treatment of Borderline Personality Disorder: A Follow-Up Study

Background and ObjectivesSome evidence of efficacy has been found for omega-3 fatty acids in patients with borderline personality disorder (BPD). In a previous 12-week randomized trial we assessed the efficacy of the combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with valproic acid, in comparison with valproic acid monotherapy, in 43 BPD outpatients. Combined therapy was superior to valproic acid monotherapy (the control group) in the treatment of some BPD symptoms: impulsive–behavioral dyscontrol, outbursts of anger, and self-harm. The present study is a 24-week follow-up aimed at evaluating whether the differences in efficacy between the two subgroups were maintained after discontinuation of omega-3 fatty acids.MethodsThirty-four patients who completed the 12-week trial entered the follow-up study. Participants were evaluated at the beginning and at the end of the follow-up period using the rating scales that showed a significant difference between the groups after the 12-week trial with fatty acids supplementation: the Borderline Personality Disorder Severity Index (BPDSI) (items ‘impulsivity’ and ‘outbursts of anger’), Barratt Impulsiveness Scale–Version 11 (BIS-11), and Self Harm Inventory (SHI). Statistical analysis was performed with analysis of variance (ANOVA) for repeated measures.ResultsAt the end of the follow-up a significant difference within groups was maintained for all four variables examined, while a significant difference between groups was maintained for outbursts of anger. Concerning tolerability, no clinically significant adverse effects were registered during the follow-up period.ConclusionsCombined therapy with omega-3 fatty acids showed long-lasting effects after discontinuation in terms of anger control.Trial registrationThe trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) and allocated the code: ACTRN12612001150831.