Effectiveness of Pharmacotherapy for Severe Personality Disorders: Meta-Analyses of Randomized Controlled Trials

Treatment Center for Personality Disorders, Symfora Group, Centers for Mental Healthcare, Amersfoort, The Netherlands.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 09/2009; 71(1):14-25. DOI: 10.4088/JCP.08r04526gre
Source: PubMed


There has been little systematic attempt to validate current pharmacologic treatment algorithms and guidelines for severe personality disorder.
We evaluated studies on the effectiveness of psychoactive drugs on specific symptom domains for borderline and/or schizotypal personality disorder.
The literature was searched for placebo-controlled randomized clinical trials (PC-RCTs) on the effectiveness of psychopharmacologic drugs in personality disorder patients. The PubMed, PsychINFO, PiCarta, Cochrane, and Web of Science databases were searched using the search terms borderline personality, schizotypal personality, personality disorder, cluster A, cluster B, treatment, drug, pharmacotherapy, antipsychotic, antidepressant, mood stabilizer, effect, outcome, review, and meta-analysis for studies published between 1980 and December 2007, and references were identified from bibliographies from articles and books.
Placebo-controlled randomized clinical trials on the efficacy of antipsychotics, antidepressants, and mood stabilizers regarding cognitive-perceptual symptoms, impulsive-behavioral dyscontrol, and affective dysregulation (with subdomains depressed mood, anxiety, anger, and mood lability) were selected in patients with well defined borderline and/or schizotypal personality disorder. Studies whose primary emphasis was on the treatment of Axis I disorders were excluded. Meta-analyses were conducted using 21 retrieved studies.
Antipsychotics have a moderate effect on cognitive-perceptual symptoms (5 PC-RCTs; standardized mean difference [SMD]=0.56) and a moderate to large effect on anger (4 PC-RCTs; SMD=0.69). Antidepressants have no significant effect on impulsive-behavioral dyscontrol and depressed mood. They have a small but significant effect on anxiety (5 PC-RCTs; SMD=0.30) and anger (4 PC-RCTs; SMD=0.34). Mood stabilizers have a very large effect on impulsive-behavioral dyscontrol (6 PC-RCTs; SMD=1.51) and anger (7 PC-RCTs; SMD=1.33), a large effect on anxiety (3 PC-RCTs; SMD=0.80), but a moderate effect on depressed mood (5 PC-RCTs; SMD=0.55). Mood lability as an outcome measure was seldomly assessed. Mood stabilizers have a more pronounced effect on global functioning (3 PC-RCTs; SMD=0.79) than have antipsychotics (5 PC-RCTs; SMD=0.37). The effect of antidepressants on global functioning is negligible.
Drug therapy tailored to well-defined symptom domains can have a beneficial effect on patients with severe personality disorder. The findings from this study raise questions on current pharmacologic algorithms.

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    • "First of all, they may support the opinion expressed by some authors (Saddichha and Schuetz, 2014) that non-planning impulsivity needs to be taken into account when planning for treatment, as it leads to poor problem solving and low resilience, and to a lack of sense of future. As regards drug treatment, we found only one randomized controlled trial dealing with impulsivity in bipolar disorders, which showed an improvement of nonplanning impulsivity with lithium (Hollander et al., 2005), although there is some evidence for efficacy of other mood stabilizers , antipsychotics and antidepressants on impulsive behavior (Ingenhoven et al., 2010; Singh and Zarate, 2006). Our finding may explain why there are contradictory data regarding better adherence with lithium as compared to other mood stabilizers in bipolar patients (Sajatovic et al., 2007). "
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    ABSTRACT: Adherence to medication is a major issue in bipolar disorder. Non-planning impulsivity, defined as a lack of future orientation, has been demonstrated to be the main impulsivity domain altered during euthymia in bipolar disorder patients. It was associated with comorbidities. To investigate relationship between adherence to medication and non-planning impulsivity, we included 260 euthymic bipolar patients. Adherence to medication was evaluated by Medication Adherence Rating Scale and non-planning impulsivity by Barrat Impulsiveness Scale. Univariate analyses and linear regression were used. We conducted also a path analysis to examine whether non-planning impulsivity had direct or indirect effect on adherence, mediated by comorbidities. Adherence to medication was correlated with non-planning impulsivity, even after controlling for potential confounding factors in linear regression analysis (Beta standardized coefficient=0.156; p=0.015). Path analysis demonstrated only a direct effect of non-planning impulsivity on adherence to medication, and none indirect effect via substance use disorders and anxiety disorders. Our study is limited by its cross-sectional design and adherence to medication was assessed only by self-questionnaire. Higher non-planning impulsivity is associated with low medication adherence, without an indirect effect via comorbidities. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 05/2015; 184:60-66. DOI:10.1016/j.jad.2015.05.041 · 3.38 Impact Factor
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    • "Pharmacological treatment is used as a complement to psychotherapy as it partially targets only some of the dimensions of the disorder, such as impulsive behavioural dyscontrol and affective dysregulation (Ingenhoven et al. 2010). In the complex pharmacological treatment algorithm of BPD (Ingenhoven et al. 2010), related comorbidities should be included and targeted (American Psychiatric Association 2001). Among the comorbidities frequently encountered in BPD sufferers, the adult attention deficit hyperactivity disorder (ADHD) is of particular interest, because of its comorbidity rate of about 16 % on the one hand (Philipsen et al. 2008), and because it appears to share some core features with BPD, such as impulsiveness, emotional dysregulation , anger and stress management issues (Philipsen et al. 2009; van Dijk et al. 2012) on the other. "
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    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is frequently comorbid with borderline personality disorder (BPD). However, few studies have examined how comorbid BPD-ADHD patients, treated or not with methylphenidate (MPH), respond to psychotherapy compared to non-comorbid BPD patients. In this perspective, we used a naturalistic study to compare, during a month-long intensive dialectical behaviour therapy (DBT), the clinical course of BPD patients and comorbid BPD-ADHD patients who were treated or untreated with MPH. Out of the 158 BPD patients recruited, 59 had adult ADHD as a comorbidity; among these, 29 underwent a treatment with MPH or des-methylphenidate, while the 30 others did not. MPH treatment was given non-randomly and only when ADHD was considered to be hampering the capacity of the subjects to follow the therapy. Patients completed the following forms upon admission and after 1 month of treatment: the adult ADHD Self-Report Scale (ASRS v.1.1), the Barratt Impulsiveness Scale (BIS-10), the State-Trait Anger Expression (STAXI), the Beck Depression Inventory II (BDI-II), and the Beck Hopelessness Scale. At baseline, comorbid BPD-ADHD patients showed significantly higher impulsiveness than BPD patients. In the entire sample, there was a significant decrease in all dimensions ranging from small to large effect sizes during the 4-week intensive DBT. BPD-ADHD patients who were undergoing MPH treatment showed a significantly improved response to DBT treatment for Trait-State Anger scores, motor impulsiveness, depression severity, and ADHD severity, when compared to those without stimulant medication. This study outlines the importance of systematically screening BPD patients for ADHD, since a MPH-based treatment will improve the symptoms of patients who are comorbid for BPD and ADHD. Due to the non-random allocation of subjects, more severely affected patients were more readily placed on MPH; this suggests that the more severe the ADHD symptoms, the greater the chance for the patient of being treated.
    ADHD Attention Deficit and Hyperactivity Disorders 01/2015; 7(3). DOI:10.1007/s12402-015-0165-2
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    • "Valproate, lamotrigine, and topiramate offer greater therapeutic benefits in treating affective instability and impulsivity in BPD.22,29 As a class, anticonvulsant medications offer moderate-to-large effects on impulsive aggression, affective instability, and overall functioning, with potentially greater effect size than associated with atypical antipsychotic treatment.25,27 Trials with topiramate suggest a broad spectrum of therapeutic benefit, particularly in anger and interpersonal functioning.106-110 "
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    ABSTRACT: The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning.
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