Pharmacological interventions for people with borderline personality disorder.

BACKGROUND: Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods. OBJECTIVES: To assess the effects of pharmacological treatment for people with BPD. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication. SELECTION CRITERIA: Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis. MAIN RESULTS: We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty-nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD -0.18, 95% confidence interval (CI) -0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD -0.27, 95% CI -0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD -0.07, 95% CI -0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self-harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale-Modified-Self-Injury item (0-5 points), 95% CI -10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide-related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI -0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD -0.26, 95% CI -1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD -0.36, 95% CI -1.96 to 1.25; 2 trials, 44 participants). Very low-certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD -0.16, 95% CI -0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD -0.25, 95% CI -0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD -0.01, 95% CI -0.28 to 0.26; 2 trials, 214 participants). Low-certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD -0.21, 95% CI -0.34 to -0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD -0.58, 95% CI -1.14 to -0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD -0.07, 95% CI -0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low-certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non-standardised. The available evidence on non-serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified. AUTHORS' CONCLUSIONS: This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.

Psychotherapies for borderline personality disorder: a focused systematic review and meta-analysis.

BACKGROUND: A recently updated Cochrane review supports the efficacy of psychotherapy for borderline personality disorder (BPD). AIMS: To evaluate the effects of standalone and add-on psychotherapeutic treatments more concisely. METHOD: We applied the same methods as the 2020 Cochrane review, but focused on adult samples and comparisons of active treatments and unspecific control conditions. Standalone treatments (i.e. necessarily including individual psychotherapy as either the sole or one of several treatment components) and add-on interventions (i.e. complementing any ongoing individual BPD treatment) were analysed separately. Primary outcomes were BPD severity, self-harm, suicide-related outcomes and psychosocial functioning. Secondary outcomes were remaining BPD diagnostic criteria, depression and attrition. RESULTS: Thirty-one randomised controlled trials totalling 1870 participants were identified. Among standalone treatments, statistically significant effects of low overall certainty were observed for dialectical behaviour therapy (self-harm: standardised mean difference (SMD) -0.54, P = 0.006; psychosocial functioning: SMD -0.51, P = 0.01) and mentalisation-based treatment (self-harm: risk ratio 0.51, P < 0.0007; suicide-related outcomes: risk ratio 0.10, P < 0.0001). For adjunctive interventions, moderate-quality evidence of beneficial effects was observed for DBT skills training (BPD severity: SMD -0.66, P = 0.002; psychosocial functioning: SMD -0.45, P = 0.002), and statistically significant low-certainty evidence was observed for the emotion regulation group (BPD severity: mean difference -8.49, P < 0.00001), manual-assisted cognitive therapy (self-harm: mean difference -3.03, P = 0.03; suicide-related outcomes: SMD -0.96, P = 0.005) and the systems training for emotional predictability and problem-solving (BPD severity: SMD -0.48, P = 0.002). CONCLUSIONS: There is reasonable evidence to conclude that psychotherapeutic interventions are helpful for individuals with BPD. Replication studies are needed to enhance the certainty of findings.

Psychological interventions for antisocial personality disorder.

BACKGROUND: Antisocial personality disorder (AsPD) is associated with poor mental health, criminality, substance use and relationship difficulties. This review updates Gibbon 2010 (previous version of the review). OBJECTIVES: To evaluate the potential benefits and adverse effects of psychological interventions for adults with AsPD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also searched reference lists and contacted study authors to identify studies. SELECTION CRITERIA: Randomised controlled trials of adults, where participants with an AsPD or dissocial personality disorder diagnosis comprised at least 75% of the sample randomly allocated to receive a psychological intervention, treatment-as-usual (TAU), waiting list or no treatment. The primary outcomes were aggression, reconviction, global state/functioning, social functioning and adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: This review includes 19 studies (eight new to this update), comparing a psychological intervention against TAU (also called 'standard Maintenance'(SM) in some studies). Eight of the 18 psychological interventions reported data on our primary outcomes. Four studies focussed exclusively on participants with AsPD, and 15 on subgroups of participants with AsPD. Data were available from only 10 studies involving 605 participants. Eight studies were conducted in the UK and North America, and one each in Iran, Denmark and the Netherlands. Study duration ranged from 4 to 156 weeks (median = 26 weeks). Most participants (75%) were male; the mean age was 35.5 years. Eleven studies (58%) were funded by research councils. Risk of bias was high for 13% of criteria, unclear for 54% and low for 33%. Cognitive behaviour therapy (CBT) + TAU versus TAU One study (52 participants) found no evidence of a difference between CBT + TAU and TAU for physical aggression (odds ratio (OR) 0.92, 95% CI 0.28 to 3.07; low-certainty evidence) for outpatients at 12 months post-intervention. One study (39 participants) found no evidence of a difference between CBT + TAU and TAU for social functioning (mean difference (MD) -1.60 points, 95% CI -5.21 to 2.01; very low-certainty evidence), measured by the Social Functioning Questionnaire (SFQ; range = 0-24), for outpatients at 12 months post-intervention. Impulsive lifestyle counselling (ILC) + TAU versus TAU One study (118 participants) found no evidence of a difference between ILC + TAU and TAU for trait aggression (assessed with Buss-Perry Aggression Questionnaire-Short Form) for outpatients at nine months (MD 0.07, CI -0.35 to 0.49; very low-certainty evidence). One study (142 participants) found no evidence of a difference between ILC + TAU and TAU alone for the adverse event of death (OR 0.40, 95% CI 0.04 to 4.54; very low-certainty evidence) or incarceration (OR 0.70, 95% CI 0.27 to 1.86; very low-certainty evidence) for outpatients between three and nine months follow-up. Contingency management (CM) + SM versus SM One study (83 participants) found evidence that, compared to SM alone, CM + SM may improve social functioning measured by family/social scores on the Addiction Severity Index (ASI; range = 0 (no problems) to 1 (severe problems); MD -0.08, 95% CI -0.14 to -0.02; low-certainty evidence) for outpatients at six months. 'Driving whilst intoxicated' programme (DWI) + incarceration versus incarceration One study (52 participants) found no evidence of a difference between DWI + incarceration and incarceration alone on reconviction rates (hazard ratio 0.56, CI -0.19 to 1.31; very low-certainty evidence) for prisoner participants at 24 months. Schema therapy (ST) versus TAU One study (30 participants in a secure psychiatric hospital, 87% had AsPD diagnosis) found no evidence of a difference between ST and TAU for the number of participants who were reconvicted (OR 2.81, 95% CI 0.11 to 74.56, P = 0.54) at three years. The same study found that ST may be more likely to improve social functioning (assessed by the mean number of days until patients gain unsupervised leave (MD -137.33, 95% CI -271.31 to -3.35) compared to TAU, and no evidence of a difference between the groups for overall adverse events, classified as the number of people experiencing a global negative outcome over a three-year period (OR 0.42, 95% CI 0.08 to 2.19). The certainty of the evidence for all outcomes was very low. Social problem-solving (SPS) + psychoeducation (PE) versus TAU One study (17 participants) found no evidence of a difference between SPS + PE and TAU for participants' level of social functioning (MD -1.60 points, 95% CI -5.43 to 2.23; very low-certainty evidence) assessed with the SFQ at six months post-intervention. Dialectical behaviour therapy versus TAU One study (skewed data, 14 participants) provided very low-certainty, narrative evidence that DBT may reduce the number of self-harm days for outpatients at two months post-intervention compared to TAU. Psychosocial risk management (PSRM; 'Resettle') versus TAU One study (skewed data, 35 participants) found no evidence of a difference between PSRM and TAU for a number of officially recorded offences at one year after release from prison. It also found no evidence of difference between the PSRM and TAU for the adverse event of death during the study period (OR 0.89, 95% CI 0.05 to 14.83, P = 0.94, 72 participants (90% had AsPD), 1 study, very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence available on psychological interventions for adults with AsPD. Few interventions addressed the primary outcomes of this review and, of the eight that did, only three (CM + SM, ST and DBT) showed evidence that the intervention may be more effective than the control condition. No intervention reported compelling evidence of change in antisocial behaviour. Overall, the certainty of the evidence was low or very low, meaning that we have little confidence in the effect estimates reported. The conclusions of this update have not changed from those of the original review, despite the addition of eight new studies. This highlights the ongoing need for further methodologically rigorous studies to yield further data to guide the development and application of psychological interventions for AsPD and may suggest that a new approach is required.

Pharmacological interventions for antisocial personality disorder.

BACKGROUND: Antisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death. Certain types of medication (drugs) may help people with AsPD. This review updates a previous Cochrane review, published in 2010. OBJECTIVES: To assess the benefits and adverse effects of pharmacological interventions for adults with AsPD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also checked reference lists and contacted study authors to identify studies. SELECTION CRITERIA: Randomised controlled trials in which adults (age 18 years and over) with a diagnosis of AsPD or dissocial personality disorder were allocated to a pharmacological intervention or placebo control condition. DATA COLLECTION AND ANALYSIS: Four authors independently selected studies and extracted data. We assessed risk of bias and created 'Summary of findings tables' and assessed the certainty of the evidence using the GRADE framework. The primary outcomes were: aggression; reconviction; global state/global functioning; social functioning; and adverse events. MAIN RESULTS: We included 11 studies (three new to this update), involving 416 participants with AsPD. Most studies (10/11) were conducted in North America. Seven studies were conducted exclusively in an outpatient setting, one in an inpatient setting, and one in prison; two studies used multiple settings. The average age of participants ranged from 28.6 years to 45.1 years (overall mean age 39.6 years). Participants were predominantly (90%) male. Study duration ranged from 6 to 24 weeks, with no follow-up period. Data were available from only four studies involving 274 participants with AsPD. All the available data came from unreplicated, single reports, and did not allow independent statistical analysis to be conducted. Many review findings were limited to descriptive summaries based on analyses carried out and reported by the trial investigators. No study set out to recruit participants on the basis of having AsPD; many participants presented primarily with substance abuse problems. The studies reported on four primary outcomes and six secondary outcomes. Primary outcomes were aggression (six studies) global/state functioning (three studies), social functioning (one study), and adverse events (seven studies). Secondary outcomes were leaving the study early (eight studies), substance misuse (five studies), employment status (one study), impulsivity (one study), anger (three studies), and mental state (three studies). No study reported data on the primary outcome of reconviction or the secondary outcomes of quality of life, engagement with services, satisfaction with treatment, housing/accommodation status, economic outcomes or prison/service outcomes.   Eleven different drugs were compared with placebo, but data for AsPD participants were only available for five comparisons. Three classes of drug were represented: antiepileptic; antidepressant; and dopamine agonist (anti-Parkinsonian) drugs. We considered selection bias to be unclear in 8/11 studies, attrition bias to be high in 7/11 studies, and performance bias to be low in 7/11 studies. Using GRADE, we rated the certainty of evidence for each outcome in this review as very low, meaning that we have very little confidence in the effect estimates reported. Phenytoin (antiepileptic) versus placebo One study (60 participants) reported very low-certainty evidence that phenytoin (300 mg/day), compared to placebo, may reduce the mean frequency of aggressive acts per week (phenytoin mean = 0.33, no standard deviation (SD) reported; placebo mean = 0.51, no SD reported) in male prisoners with aggression (skewed data) at endpoint (six weeks). The same study (60 participants) reported no evidence of difference between phenytoin and placebo in the number of participants reporting the adverse event of nausea during week one (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.06 to 16.76; very low-certainty evidence). The study authors also reported that no important side effects were detectable via blood cell counts or liver enzyme tests (very low-certainty evidence). The study did not measure reconviction, global/state functioning or social functioning. Desipramine (antidepressant) versus placebo One study (29 participants) reported no evidence of a difference between desipramine (250 to 300 mg/day) and placebo on mean social functioning scores (desipramine = 0.19; placebo = 0.21), assessed with the family-social domain of the Addiction Severity Index (scores range from zero to one, with higher values indicating worse social functioning), at endpoint (12 weeks) (very low-certainty evidence). Neither of the studies included in this comparison measured the other primary outcomes: aggression; reconviction; global/state functioning; or adverse events. Nortriptyline (antidepressant) versus placebo One study (20 participants) reported no evidence of a difference between nortriptyline (25 to 75 mg/day) and placebo on mean global state/functioning scores (nortriptyline = 0.3; placebo = 0.7), assessed with the Symptom Check List-90 (SCL-90) Global Severity Index (GSI; mean of subscale scores, ranging from zero to four, with higher scores indicating greater severity of symptoms), at endpoint (six months) in men with alcohol dependency (very low-certainty evidence). The study measured side effects but did not report data on adverse events for the AsPD subgroup. The study did not measure aggression, reconviction or social functioning. Bromocriptine (dopamine agonist) versus placebo One study (18 participants) reported no evidence of difference between bromocriptine (15 mg/day) and placebo on mean global state/functioning scores (bromocriptine = 0.4; placebo = 0.7), measured with the GSI of the SCL-90 at endpoint (six months) (very low-certainty evidence). The study did not provide data on adverse effects, but reported that 12 patients randomised to the bromocriptine group experienced severe side effects, five of whom dropped out of the study in the first two days due to nausea and severe flu-like symptoms (very low-certainty evidence). The study did not measure aggression, reconviction and social functioning. Amantadine (dopamine agonist) versus placebo The study in this comparison did not measure any of the primary outcomes. AUTHORS' CONCLUSIONS: The evidence summarised in this review is insufficient to draw any conclusion about the use of pharmacological interventions in the treatment of antisocial personality disorder. The evidence comes from single, unreplicated studies of mostly older medications. The studies also have methodological issues that severely limit the confidence we can draw from their results. Future studies should recruit participants on the basis of having AsPD, and use relevant outcome measures, including reconviction.

Psychological therapies for people with borderline personality disorder.

BACKGROUND: Over the decades, a variety of psychological interventions for borderline personality disorder (BPD) have been developed. This review updates and replaces an earlier review (Stoffers-Winterling 2012). OBJECTIVES: To assess the beneficial and harmful effects of psychological therapies for people with BPD. SEARCH METHODS: In March 2019, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication. SELECTION CRITERIA: Randomised controlled trials comparing different psychotherapeutic interventions with treatment-as-usual (TAU; which included various kinds of psychotherapy), waiting list, no treatment or active treatments in samples of all ages, in any setting, with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. There were 11 secondary outcomes, including individual BPD symptoms, as well as attrition and adverse effects. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's 'Risk of bias' tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis. MAIN RESULTS: We included 75 randomised controlled trials (4507 participants), predominantly involving females with mean ages ranging from 14.8 to 45.7 years. More than 16 different kinds of psychotherapy were included, mostly dialectical behaviour therapy (DBT) and mentalisation-based treatment (MBT). The comparator interventions included treatment-as-usual (TAU), waiting list, and other active treatments. Treatment duration ranged from one to 36 months. Psychotherapy versus TAU Psychotherapy reduced BPD symptom severity, compared to TAU; standardised mean difference (SMD) -0.52, 95% confidence interval (CI) -0.70 to -0.33; 22 trials, 1244 participants; moderate-quality evidence. This corresponds to a mean difference (MD) of -3.6 (95% CI -4.4 to -2.08) on the Zanarini Rating Scale for BPD (range 0 to 36), a clinically relevant reduction in BPD symptom severity (minimal clinical relevant difference (MIREDIF) on this scale is -3.0 points). Psychotherapy may be more effective at reducing self-harm compared to TAU (SMD -0.32, 95% CI -0.49 to -0.14; 13 trials, 616 participants; low-quality evidence), corresponding to a MD of -0.82 (95% CI -1.25 to 0.35) on the Deliberate Self-Harm Inventory Scale (range 0 to 34). The MIREDIF of -1.25 points was not reached. Suicide-related outcomes improved compared to TAU (SMD -0.34, 95% CI -0.57 to -0.11; 13 trials, 666 participants; low-quality evidence), corresponding to a MD of -0.11 (95% CI -0.19 to -0.034) on the Suicidal Attempt Self Injury Interview. The MIREDIF of -0.17 points was not reached. Compared to TAU, psychotherapy may result in an improvement in psychosocial functioning (SMD -0.45, 95% CI -0.68 to -0.22; 22 trials, 1314 participants; low-quality evidence), corresponding to a MD of -2.8 (95% CI -4.25 to -1.38), on the Global Assessment of Functioning Scale (range 0 to 100). The MIREDIF of -4.0 points was not reached. Our additional Trial Sequential Analysis on all primary outcomes reaching significance found that the required information size was reached in all cases. A subgroup analysis comparing the different types of psychotherapy compared to TAU showed no clear evidence of a difference for BPD severity and psychosocial functioning. Psychotherapy may reduce depressive symptoms compared to TAU but the evidence is very uncertain (SMD -0.39, 95% CI -0.61 to -0.17; 22 trials, 1568 participants; very low-quality evidence), corresponding to a MD of -2.45 points on the Hamilton Depression Scale (range 0 to 50). The MIREDIF of -3.0 points was not reached. BPD-specific psychotherapy did not reduce attrition compared with TAU. Adverse effects were unclear due to too few data. Psychotherapy versus waiting list or no treatment Greater improvements in BPD symptom severity (SMD -0.49, 95% CI -0.93 to -0.05; 3 trials, 161 participants), psychosocial functioning (SMD -0.56, 95% CI -1.01 to -0.11; 5 trials, 219 participants), and depression (SMD -1.28, 95% CI -2.21 to -0.34, 6 trials, 239 participants) were observed in participants receiving psychotherapy versus waiting list or no treatment (all low-quality evidence). No evidence of a difference was found for self-harm and suicide-related outcomes. Individual treatment approaches DBT and MBT have the highest numbers of primary trials, with DBT as subject of one-third of all included trials, followed by MBT with seven RCTs. Compared to TAU, DBT was more effective at reducing BPD severity (SMD -0.60, 95% CI -1.05 to -0.14; 3 trials, 149 participants), self-harm (SMD -0.28, 95% CI -0.48 to -0.07; 7 trials, 376 participants) and improving psychosocial functioning (SMD -0.36, 95% CI -0.69 to -0.03; 6 trials, 225 participants). MBT appears to be more effective than TAU at reducing self-harm (RR 0.62, 95% CI 0.49 to 0.80; 3 trials, 252 participants), suicidality (RR 0.10, 95% CI 0.04, 0.30, 3 trials, 218 participants) and depression (SMD -0.58, 95% CI -1.22 to 0.05, 4 trials, 333 participants). All findings are based on low-quality evidence. For secondary outcomes see review text. AUTHORS' CONCLUSIONS: Our assessments showed beneficial effects on all primary outcomes in favour of BPD-tailored psychotherapy compared with TAU. However, only the outcome of BPD severity reached the MIREDIF-defined cut-off for a clinically meaningful improvement. Subgroup analyses found no evidence of a difference in effect estimates between the different types of therapies (compared to TAU) . The pooled analysis of psychotherapy versus waiting list or no treatment found significant improvement on BPD severity, psychosocial functioning and depression at end of treatment, but these findings were based on low-quality evidence, and the true magnitude of these effects is uncertain. No clear evidence of difference was found for self-harm and suicide-related outcomes. However, compared to TAU, we observed effects in favour of DBT for BPD severity, self-harm and psychosocial functioning and, for MBT, on self-harm and suicidality at end of treatment, but these were all based on low-quality evidence. Therefore, we are unsure whether these effects would alter with the addition of more data.

Oxytocin modulates the effective connectivity between the precuneus and the dorsolateral prefrontal cortex.

Our social activity is heavily influenced by the process of introspection, with emerging research suggesting a role for the Default Mode Network (DMN) in social cognition. We hypothesize that oxytocin, a neuropeptide with an important role in social behaviour, can effectively alter the connectivity of the DMN. We test this hypothesis using a randomized, double-blind, crossover, placebo-controlled trial where 15 healthy male participants received 24 IU oxytocin or placebo prior to a resting-state functional MRI scan. We used Granger Causality Analysis for the first time to probe the role of oxytocin on brain networks and found that oxytocin reverses the pattern of effective connectivity between the bilateral precuneus and the left dorsolateral prefrontal cortex (dlPFC), a key central executive network (CEN) region. Under placebo, the bilateral precuneus exerted a significant negative causal influence on the left dlPFC and the left dlPFC exerted a significant positive causal influence on the bilateral precuneus. However, under oxytocin, these patterns were reversed, i.e. positive causal influence from the bilateral precuneus to the left dlPFC and negative causal influence from the left dlPFC to the bilateral precuneus (with statistically significant effects for the right precuneus). We propose that these oxytocin-induced effects could be a mechanistic process by which it modulates social cognition. These results provide a measurable target for the physiological effects of oxytocin in the brain and offer oxytocin as a potential agent to enhance the cooperative role of the predominantly 'task-inactive' 'default mode' brain regions in both healthy and patient populations.

Characteristics and Pathways of Long-Stay Patients in High and Medium Secure Settings in England; A Secondary Publication From a Large Mixed-Methods Study.

Background: Many patients experience extended stays within forensic care, but the characteristics of long-stay patients are poorly understood. Aims: To describe the characteristics of long-stay patients in high and medium secure settings in England. Method: Detailed file reviews provided clinical, offending and risk data for a large representative sample of 401 forensic patients from 2 of the 3 high secure settings and from 23 of the 57 medium secure settings in England on 1 April 2013. The threshold for long-stay status was defined as 5 years in medium secure care or 10 years in high secure care, or 15 years in a combination of high and medium secure settings. Results: 22% of patients in high security and 18% in medium security met the definition for "long-stay," with 20% staying longer than 20 years. Of the long-stay sample, 58% were violent offenders (22% both sexual and violent), 27% had been convicted for violent or sexual offences whilst in an institutional setting, and 26% had committed a serious assault on staff in the last 5 years. The most prevalent diagnosis was schizophrenia (60%) followed by personality disorder (47%, predominantly antisocial and borderline types); 16% were categorised as having an intellectual disability. Overall, 7% of the long-stay sample had never been convicted of any offence, and 16.5% had no index offence prompting admission. Although some significant differences were found between the high and medium secure samples, there were more similarities than contrasts between these two levels of security. The treatment pathways of these long-stay patients involved multiple moves between settings. An unsuccessful referral to a setting of lower security was recorded over the last 5 years for 33% of the sample. Conclusions: Long-stay patients accounted for one fifth of the forensic inpatient population in England in this representative sample. A significant proportion of this group remain unsettled. High levels of personality pathology and the risk of assaults on staff and others within the care setting are likely to impact on treatment and management. Further research into the treatment pathways of longer stay patients is warranted to understand the complex trajectories of this group.

European Psychiatric Association (EPA) guidance on forensic psychiatry: Evidence based assessment and treatment of mentally disordered offenders.

Forensic psychiatry in Europe is a specialty primarily concerned with individuals who have either offended or present a risk of doing so, and who also suffer from a psychiatric condition. These mentally disordered offenders (MDOs) are often cared for in secure psychiatric environments or prisons. In this guidance paper we first present an overview of the field of forensic psychiatry from a European perspective. We then present a review of the literature summarising the evidence on the assessment and treatment of MDOs under the following headings: The forensic psychiatrist as expert witness, risk, treatment settings for mentally disordered offenders, and what works for MDOs. We undertook a rapid review of the literature with search terms related to: forensic psychiatry, review articles, randomised controlled trials and best practice. We searched the Medline, Embase, PsycINFO, and Cochrane library databases from 2000 onwards for adult groups only. We scrutinised publications for additional relevant literature, and searched the websites of relevant professional organisations for policies, statements or guidance of interest. We present the findings of the scientific literature as well as recommendations for best practice drawing additionally from the guidance documents identified. We found that the evidence base for forensic-psychiatric practice is weak though there is some evidence to suggest that psychiatric care produces better outcomes than criminal justice detention only. Practitioners need to follow general psychiatric guidance as well as that for offenders, adapted for the complex needs of this patient group, paying particular attention to long-term detention and ethical issues.

Clozapine dose for schizophrenia.

BACKGROUND: Schizophrenia and related disorders such as schizophreniform and schizoaffective disorder are serious mental illnesses characterised by profound disruptions in thinking and speech, emotional processes, behaviour and sense of self. Clozapine is useful in the treatment of schizophrenia and related disorders, particularly when other antipsychotic medications have failed. It improves positive symptoms (such as delusions and hallucinations) and negative symptoms (such as withdrawal and poverty of speech). However, it is unclear what dose of clozapine is most effective with the least side effects. OBJECTIVES: To compare the efficacy and tolerability of clozapine at different doses and to identify the optimal dose of clozapine in the treatment of schizophrenia, schizophreniform and schizoaffective disorders. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (August 2011 and 8 December 2016). SELECTION CRITERIA: All relevant randomised controlled trials (RCTs), irrespective of blinding status or language, that compared the effects of clozapine at different doses in people with schizophrenia and related disorders, diagnosed by any criteria. DATA COLLECTION AND ANALYSIS: We independently inspected citations from the searches, identified relevant abstracts, obtained full articles of relevant abstracts, and classified trials as included or excluded. We included trials that met our inclusion criteria and reported useable data. For dichotomous data, we calculated the relative risk (RR) and the 95% confidence interval (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD) again based on a random-effects model. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. MAIN RESULTS: We identified five studies that could be included. Each compared the effects of clozapine at very low dose (up to 149 mg/day), low dose (150 mg/day to 300 mg/day) and standard dose (301 mg/day to 600 mg/day). Four of the five included studies were based on a small number of participants. We rated all the evidence reported for the main outcomes of interest as low or very low quality. No data were available for the main outcomes of global state, service use or quality of life. Very low dose compared to low doseWe found no evidence of effect on mental state between low and very low doses of clozapine in terms of average Brief Psychiatric Rating Scale-Anchored (BPRS-A) endpoint score (1 RCT, n = 31, MD 3.55, 95% CI -4.50 to 11.60, very low quality evidence). One study found no difference between groups in body mass index (BMI) in the short term (1 RCT, n = 59, MD -0.10, 95% CI -0.95 to 0.75, low-quality evidence). Very low dose compared to standard doseWe found no evidence of effect on mental state between very low doses and standard doses of clozapine in terms of average BPRS-A endpoint score (1 RCT, n = 31, MD 6.67, 95% CI -2.09 to 15.43, very low quality evidence). One study found no difference between groups in BMI in the short term (1 RCT, n = 58, MD 0.10, 95% CI -0.76 to 0.96, low-quality evidence) Low dose compared to standard doseWe found no evidence of effect on mental state between low doses and standard doses of clozapine in terms of both clinician-assessed clinical improvement (2 RCTs, n = 141, RR 0.76, 95% CI 0.36 to 1.61, medium-quality evidence) and clinically important response as more than 30% change in BPRS score (1 RCT, n = 176, RR 0.93, 95% CI 0.78 to 1.10, medium-quality evidence). One study found no difference between groups in BMI in the short term (1 RCT, n = 57, MD 0.20, 95% CI -0.84 to 1.24, low-quality evidence).We found some evidence of effect for other adverse effect outcomes; however, the data were again limited. Very low dose compared to low doseThere was limited evidence that serum triglycerides were lower at low-dose clozapine compared to very low dose in the short term (1 RCT, n = 59, MD 1.00, 95% CI 0.51 to 1.49). Low dose compared to standard doseWeight gain was lower at very low dose compared to standard dose (1 RCT, n = 27, MD -2.70, 95% CI -5.38 to -0.02). Glucose level one hour after meal was also lower at very lose dose (1 RCT, n = 58, MD -1.60, 95% CI -2.90 to -0.30). Total cholesterol levels were higher at very low compared to standard dose (1 RCT, n = 58, n = 58, MD 1.00, 95% CI 0.20 to 1.80). Low dose compared to standard doseThere was evidence of fewer adverse effects, measured as lower TESS scores, in the low-dose group in the short term (2 RCTs, n = 266, MD -3.99, 95% CI -5.75 to -2.24); and in one study there was evidence that the incidence of lethargy (RR 0.77, 95% CI 0.60 to 0.97), hypersalivation (RR 0.70, 95% CI 0.57 to 0.84), dizziness (RR 0.56, 95% CI 0.39 to 0.81) and tachycardia (RR 0.57, 95% CI 0.45 to 0.71) was less at low dose compared to standard dose. AUTHORS' CONCLUSIONS: We found no evidence of effect on mental state between standard, low and very low dose regimes, but we did not identify any trials on high or very high doses of clozapine. BMI measurements were similar between groups in the short term, although weight gain was less at very low dose compared to standard dose in one study. There was limited evidence that the incidence of some adverse effects was greater at standard dose compared to lower dose regimes. We found very little useful data and the evidence available is generally of low or very low quality. More studies are needed to validate our findings and report on outcomes such as relapse, remission, social functioning, service utilisation, cost-effectiveness, satisfaction with care, and quality of life. There is a particular lack of medium- or long-term outcome data, and on dose regimes above the standard rate.

Empathy, ToM, and self-other differentiation: an fMRI study of internal states.

This study used functional magnetic resonance imaging to examine the neural substrates of empathy, Theory of Mind (ToM), and self-other differentiation involved in the adaptive understanding of people's internal states. Three conditions were distinguished in both sad and neutral (no obvious emotion) contexts. The empathy condition involved imagining what another person is feeling while the more cognitively loaded ToM condition involved imagining what would make another person feel better. The self-reference condition required participants to imagine how they would feel in someone else's situation. Areas previously implicated in empathy, ToM, and self-other differentiation were identified within the different conditions, regardless of emotional context. Specifically, the frontal and temporal poles responded more strongly for ToM than for empathy. The self-reference condition was associated with stronger dorsolateral prefrontal response than the empathy condition, while the reverse comparison revealed a stronger role for right frontal pole. Activations in frontal pole and orbitofrontal cortex were shared between the three conditions. Contrasts of parameter estimates demonstrated modulation by emotional context. The findings of common and differential patterns of responding observed in prefrontal and temporal regions suggest that within the social cognition network empathy, ToM and self-other differentiation have distinct roles that are responsive to context.

Psychological therapies for people with borderline personality disorder.

BACKGROUND: Psychotherapy is regarded as the first-line treatment for people with borderline personality disorder. In recent years, several disorder-specific interventions have been developed. This is an update of a review published in the Cochrane Database of Systematic Reviews in 2006. OBJECTIVES: To assess the effects of psychological interventions for borderline personality disorder (BPD). SEARCH METHODS: We searched the following databases: CENTRAL 2010(3), MEDLINE (1950 to October 2010), EMBASE (1980 to 2010, week 39), ASSIA (1987 to November 2010), BIOSIS (1985 to October 2010), CINAHL (1982 to October 2010), Dissertation Abstracts International (31 January 2011), National Criminal Justice Reference Service Abstracts (15 October 2010), PsycINFO (1872 to October Week 1 2010), Science Citation Index (1970 to 10 October 2010), Social Science Citation Index (1970 to 10 October 2010), Sociological Abstracts (1963 to October 2010), ZETOC (15 October 2010) and the metaRegister of Controlled Trials (15 October 2010). In addition, we searched Dissertation Abstracts International in January 2011 and ICTRP in August 2011. SELECTION CRITERIA: Randomised studies with samples of patients with BPD comparing a specific psychotherapeutic intervention against a control intervention without any specific mode of action or against a comparative specific psychotherapeutic intervention. Outcomes included overall BPD severity, BPD symptoms (DSM-IV criteria), psychopathology associated with but not specific to BPD, attrition and adverse effects. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed the risk of bias in the studies and extracted data. MAIN RESULTS: Twenty-eight studies involving a total of 1804 participants with BPD were included. Interventions were classified as comprehensive psychotherapies if they included individual psychotherapy as a substantial part of the treatment programme, or as non-comprehensive if they did not.Among comprehensive psychotherapies, dialectical behaviour therapy (DBT), mentalisation-based treatment in a partial hospitalisation setting (MBT-PH), outpatient MBT (MBT-out), transference-focused therapy (TFP), cognitive behavioural therapy (CBT), dynamic deconstructive psychotherapy (DDP), interpersonal psychotherapy (IPT) and interpersonal therapy for BPD (IPT-BPD) were tested against a control condition. Direct comparisons of comprehensive psychotherapies included DBT versus client-centered therapy (CCT); schema-focused therapy (SFT) versus TFP; SFT versus SFT plus telephone availability of therapist in case of crisis (SFT+TA); cognitive therapy (CT) versus CCT, and CT versus IPT.Non-comprehensive psychotherapeutic interventions comprised DBT-group skills training only (DBT-ST), emotion regulation group therapy (ERG), schema-focused group therapy (SFT-G), systems training for emotional predictability and problem solving for borderline personality disorder (STEPPS), STEPPS plus individual therapy (STEPPS+IT), manual-assisted cognitive treatment (MACT) and psychoeducation (PE). The only direct comparison of an non-comprehensive psychotherapeutic intervention against another was MACT versus MACT plus therapeutic assessment (MACT+). Inpatient treatment was examined in one study where DBT for PTSD (DBT-PTSD) was compared with a waiting list control. No trials were identified for cognitive analytical therapy (CAT).Data were sparse for individual interventions, and allowed for meta-analytic pooling only for DBT compared with treatment as usual (TAU) for four outcomes. There were moderate to large statistically significant effects indicating a beneficial effect of DBT over TAU for anger (n = 46, two RCTs; standardised mean difference (SMD) -0.83, 95% confidence interval (CI) -1.43 to -0.22; I(2) = 0%), parasuicidality (n = 110, three RCTs; SMD -0.54, 95% CI -0.92 to -0.16; I(2) = 0%) and mental health (n = 74, two RCTs; SMD 0.65, 95% CI 0.07 to 1.24 I(2) = 30%). There was no indication of statistical superiority of DBT over TAU in terms of keeping participants in treatment (n = 252, five RCTs; risk ratio 1.25, 95% CI 0.54 to 2.92).All remaining findings were based on single study estimates of effect. Statistically significant between-group differences for comparisons of psychotherapies against controls were observed for BPD core pathology and associated psychopathology for the following interventions: DBT, DBT-PTSD, MBT-PH, MBT-out, TFP and IPT-BPD. IPT was only indicated as being effective in the treatment of associated depression. No statistically significant effects were found for CBT and DDP interventions on either outcome, with the effect sizes moderate for DDP and small for CBT. For comparisons between different comprehensive psychotherapies, statistically significant superiority was demonstrated for DBT over CCT (core and associated pathology) and SFT over TFP (BPD severity and treatment retention). There were also encouraging results for each of the non-comprehensive psychotherapeutic interventions investigated in terms of both core and associated pathology.No data were available for adverse effects of any psychotherapy. AUTHORS' CONCLUSIONS: There are indications of beneficial effects for both comprehensive psychotherapies as well as non-comprehensive psychotherapeutic interventions for BPD core pathology and associated general psychopathology. DBT has been studied most intensely, followed by MBT, TFP, SFT and STEPPS. However, none of the treatments has a very robust evidence base, and there are some concerns regarding the quality of individual studies. Overall, the findings support a substantial role for psychotherapy in the treatment of people with BPD but clearly indicate a need for replicatory studies.

Moral decision-making, ToM, empathy and the default mode network.

Automatic intuitions and deliberate reasoning, sourcing internal representations of our personal norms and values, contribute to our beliefs of what is right and wrong. We used fMRI to directly compare moral (M) and non-moral (NM) decision-making processes using scenarios requiring conscious deliberation, whereby the main character declared an intention to take a course of action. Furthermore, we examined the relationship between BOLD signal, associated with M>NM decision-making, and moral judgment competence, psychopathy, and empathy. We observed greater activity in various parts of Theory of Mind, empathy and default mode networks during M>NM decision-making. There was a trend for high scores on primary psychopathy to correlate with decreased M>NM BOLD activation in an area extending from dorsolateral prefrontal cortex to medial prefrontal cortex. We suggest that moral decision-making entails a greater degree of internally directed processing, such as self-referential mental processing and the representation of intentions and feelings, than non-moral decision-making.

Mirtazapine antagonises the subjective, hormonal and neuronal effects of m-chlorophenylpiperazine (mCPP) infusion: a pharmacological-challenge fMRI (phMRI) study.

Aberrant signalling through central 5-HT(2C) receptor pathways has been implicated in various psychiatric disorders but this has not been amenable to experimental investigation in the absence of a valid in-vivo biomarker of functional 5-HT(2C) neurotransmission. One approach is drug-challenge pharmaco-magnetic resonance imaging (phMRI). We have previously shown that intravenous administration of the 5-HT(2C) agonist m-chlorophenylpiperazine (mCPP) elicits increases in blood oxygenation dependent signal (BOLD) in regions consistent with the distribution of 5-HT(2C) receptors. In the current study we determined whether BOLD signal responses to mCPP could be blocked by pre-treatment with a 5-HT(2C) antagonist. Healthy male volunteers received oral mirtazapine, 5-HT(2)/5-HT(3) receptor antagonist, or placebo 90min prior to intravenous mCPP challenge phMRI. BOLD signal increases following mCPP infusion occurred in areas known to be rich in 5-HT(2C) receptors such as the substantia nigra, hypothalamus, pallidum and amygdala. These responses were attenuated by mirtazapine pre-treatment. The results suggest that mCPP-challenge phMRI produces reliable patterns of response that are mediated by 5-HT(2C) receptors; these responses may therefore be useful in-vivo measures of 5-HT(2C) function in psychiatric disorders.

The QCAE: a Questionnaire of Cognitive and Affective Empathy.

Empathy has been inconsistently defined and inadequately measured. This research aimed to produce a new and rigorously developed questionnaire. Exploratory (n1 = 640) and confirmatory (n2 = 318) factor analyses were employed to develop the Questionnaire of Cognitive and Affective Empathy (QCAE). Principal components analysis revealed 5 factors (31 items). Confirmatory factor analysis confirmed this structure in an independent sample. The hypothesized 2-factor structure (cognitive and affective empathy) was tested and provided the best and most parsimonious fit to the data. Gender differences, convergent validity, and construct validity were examined. The QCAE is a valid tool for assessing cognitive and affective empathy.

Pharmacological interventions for schizotypal personality disorder.

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effects of pharmacological interventions for people with Schizotypal Personality Disorder (SzPD).

Pharmacological interventions for paranoid personality disorder.

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effects of pharmacological interventions for people with paranoid personality disorder (PPD).

Pharmacological interventions for antisocial personality disorder.

BACKGROUND: Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance misuse, unemployment, homelessness and relationship difficulties. OBJECTIVES: To evaluate the potential beneficial and adverse effects of pharmacological interventions for people with AsPD. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1950 to September 2009), EMBASE (1980 to 2009, week 37), CINAHL (1982 to September 2009), PsycINFO (1872 to September 2009) , ASSIA (1987 to September 2009) , BIOSIS (1985 to September 2009), COPAC (September 2009), National Criminal Justice Reference Service Abstracts (1970 to July 2008), Sociological Abstracts (1963 to September 2009), ISI-Proceedings (1981 to September 2009), Science Citation Index (1981 to September 2009), Social Science Citation Index (1981 to September 2009), SIGLE (1980 to April 2006), Dissertation Abstracts (September 2009), ZETOC (September 2009) and the metaRegister of Controlled Trials (September 2009). SELECTION CRITERIA: Controlled trials in which participants with AsPD were randomly allocated to a pharmacological intervention and a placebo control condition. Two trials comparing one drug against another without a placebo control are reported separately. DATA COLLECTION AND ANALYSIS: Three review authors independently selected studies. Two review authors independently extracted data. We calculated mean differences, with odds ratios for dichotomous data. MAIN RESULTS: Eight studies met the inclusion criteria involving 394 participants with AsPD. Data were available from four studies involving 274 participants with AsPD. No study set out to recruit participants solely on the basis of having AsPD, and in only one study was the sample entirely of AsPD participants. Eight different drugs were examined in eight studies. Study quality was relatively poor. Inadequate reporting meant the data available were generally insufficient to allow any independent statistical analysis. The findings are limited to descriptive summaries based on analyses carried out and reported by the trial investigators. All the available data were derived from unreplicated single reports. Only three drugs (nortriptyline, bromocriptine, phenytoin) were effective compared to placebo in terms of improvement in at least one outcome. Nortriptyline was reported in one study as superior for men with alcohol dependency on mean number of drinking days and on alcohol dependence, but not for severity of alcohol misuse or on the patient's or clinician's rating of drinking. In the same study, both nortriptyline and bromocriptine were reported as superior to placebo on anxiety on one scale but not on another. In one study, phenytoin was reported as superior to placebo on the frequency and intensity of aggressive acts in male prisoners with impulsive (but not premeditated) aggression. In the remaining two studies, both amantadine and desipramine were not superior to placebo for adults with opioid and cocaine dependence, and desipramine was not superior to placebo for men with cocaine dependence. AUTHORS' CONCLUSIONS: The body of evidence summarised in this review is insufficient to allow any conclusion to be drawn about the use of pharmacological interventions in the treatment of antisocial personality disorder.

Pharmacological interventions for borderline personality disorder.

BACKGROUND: Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off-label use"), mostly targeting affective or impulsive symptom clusters. OBJECTIVES: To assess the effects of drug treatment in BPD patients. SEARCH STRATEGY: We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field. SELECTION CRITERIA: Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects. DATA COLLECTION AND ANALYSIS: Two authors selected trials, assessed quality and extracted data, independently. MAIN RESULTS: Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants.The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed.Adverse event data were scarce, except for olanzapine. There was a possible increase in self-harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition.Direct drug comparisons comprised two first-generation antipsychotics (loxapine versus chlorpromazine), first-generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second-generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes. AUTHORS' CONCLUSIONS: The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Psychological interventions for antisocial personality disorder.

BACKGROUND: Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance use, unemployment, homelessness and relationship difficulties. OBJECTIVES: To evaluate the potential beneficial and adverse effects of psychological interventions for people with AsPD. SEARCH STRATEGY: Our search included CENTRAL Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO, ASSIA, BIOSIS and COPAC. SELECTION CRITERIA: Prospective, controlled trials in which participants with AsPD were randomly allocated to a psychological intervention and a control condition (either treatment as usual, waiting list or no treatment). DATA COLLECTION AND ANALYSIS: Three authors independently selected studies. Two authors independently extracted data. We calculated mean differences, with odds ratios for dichotomous data. MAIN RESULTS: Eleven studies involving 471 participants with AsPD met the inclusion criteria, although data were available from only five studies involving 276 participants with AsPD. Only two studies focused solely on an AsPD sample. Eleven different psychological interventions were examined. Only two studies reported on reconviction, and only one on aggression. Compared to the control condition, cognitive behaviour therapy (CBT) plus standard maintenance was superior for outpatients with cocaine dependence in one study, but CBT plus treatment as usual was not superior for male outpatients with recent verbal/physical violence in another. Contingency management plus standard maintenance was superior for drug misuse for outpatients with cocaine dependence in one study but not in another, possibly because of differences in the behavioural intervention. However, contingency management was superior in social functioning and counselling session attendance in the latter. A multi-component intervention utilising motivational interviewing principles, the 'Driving Whilst Intoxicated program', plus incarceration was superior to incarceration alone for imprisoned drink-driving offenders. AUTHORS' CONCLUSIONS: Results suggest that there is insufficient trial evidence to justify using any psychological intervention for adults with AsPD. Disappointingly few of the included studies addressed the primary outcomes defined in this review (aggression, reconviction, global functioning, social functioning, adverse effects). Three interventions (contingency management with standard maintenance; CBT with standard maintenance; 'Driving Whilst Intoxicated program' with incarceration) appeared effective, compared to the control condition, in terms of improvement in at least one outcome in at least one study. Each of these interventions had been originally developed for people with substance misuse problems. Significant improvements were mainly confined to outcomes related to substance misuse. No study reported significant change in any specific antisocial behaviour. Further research is urgently needed for this prevalent and costly condition.

Pharmacological interventions for obsessive-compulsive personality disorder.

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the potential beneficial and adverse effects of pharmacological interventions for people with obsessive-compulsive personality disorder and to make recommendations for future areas of research.