Metacognitive interpersonal therapy in borderline personality disorder: Clinical and neuroimaging outcomes from the CLIMAMITHE study-A randomized clinical trial.

Different psychotherapeutic approaches demonstrated their efficacy but the possible neurobiological mechanism underlying the effect of psychotherapy in borderline personality disorder (BPD) patients is poorly investigated. We assessed the effects of metacognitive interpersonal therapy (MIT) on BPD features and other dimensions compared to structured clinical management (SCM). We also assessed changes in amygdala activation by viewing emotional pictures after psychotherapy. One hundred forty-one patients were referred and 78 BPD outpatients were included and randomized to MIT or SCM. Primary outcome was emotional dysregulation assessed with the Difficulties in Emotion Regulation Scale (DERS). We also assessed BPD symptomatology, number of PD criteria, metacognitive abilities, state-psychopathology, depression, impulsiveness, interpersonal functioning, and alexithymia. A subset of 60 patients underwent functional magnetic resonance imaging before and after 1 year of psychotherapy to assess amygdala activation by viewing standardized emotional pictures (secondary outcome). DERS scores decreased in both groups (time effect p < .001). The Cohen's d effect size for change (baseline posttreatment) on DERS was very large (d = 0.84) in MIT, and large (d = 0.76) in SCM. Both groups significantly improved in depressive symptoms, state-psychopathology, alexithymia, and interpersonal functioning. MIT showed larger effect on metacognitive functions than SCM (Time × Group p < .001). Both interventions showed a significant effect on BPD symptomatology although SCM group showed a larger decrease. On the contrary, MIT group showed larger decrease in impulsivity and number of PD criteria. Interestingly, both MIT and SCM modulated amygdala activation in BPD patients. MIT is a valid and effective psychotherapy for BPD with an impact on amygdala activation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Symptomatic Disorders in Adults and Adolescents With Borderline Personality Disorder.

Symptomatic disorders often co-occur with borderline personality disorder (BPD). This study's purpose was to compare the rates of comorbidity reported by adult and adolescent inpatients with BPD, including complex comorbidity (i.e., a combination of disorders of affect and impulsivity). One hundred four adolescents (aged 13-17) and 290 adults (aged 18-35) with BPD were interviewed using an age-appropriate semistructured interview for the assessment of symptomatic disorders. Lifetime rates of mood disorders and ADHD were quite similar for the two study groups. However, rates of anxiety disorders, including PTSD, substance use disorders, eating disorders, and complex comorbidity were significantly higher among adults than adolescents. Taken together, the results of this study suggest that broadly defined disorders of both affect and impulsivity are more common among adults than adolescents with BPD. They also suggest that a pattern of complex comorbidity is even more distinguishing for these two groups of borderline patients.

Affective and Behavioral Characteristics of Adolescent and Adult Borderline Personality Disorder.

Adults with borderline personality disorder (BPD) report greater affective lability, impulsivity, and aggression compared to same-age peers, but no studies have examined whether these findings are replicable among adolescents with BPD and their peers, or whether adolescents and adults with BPD report symptoms of comparable severity. One hundred and one adolescent (age 13-17) BPD inpatients and 60 age-matched, psychiatrically healthy adolescents completed self-report measures for affective lability, impulsivity, and aggression. Comparison samples included 29 and 41 adult outpatients with BPD and 127 community adults with BPD. Adolescents with BPD reported greater severity of all symptoms except nonplanning impulsiveness compared to peers. They reported similar symptom severity to adults but reported less severe verbal aggression and anger. Adolescents with BPD are distinguishable from typically developing adolescents on self-reported, dimensional affective and behavioral symptom measures, and may experience these symptoms at comparable severity to adult counterparts.

Sexual Orientation and Gender of Intimate Relationship Partners Among Adolescents With BPD and Psychiatrically Healthy Adolescents.

The first aim of this study was to describe reported sexual orientation in a group of adolescents diagnosed with borderline personality disorder compared to a group of psychiatrically healthy adolescents. The second purpose was to compare data on dating and gender of dating partners in the same two groups. Two semistructured interviews, which assessed sexual orientation, dating history, and gender of dating partners, were administered to 104 borderline adolescents and 60 psychiatrically healthy comparison subjects. Borderline adolescents were significantly more likely than comparison subjects to report having a gay/lesbian/bisexual orientation. They also were significantly more likely to date and to report dating a same-gender partner or same- and other-gender partners than comparison subjects. The results of this study suggest that same-gender attraction and/or intimate relationships may be an important interpersonal issue for approximately one-third of adolescents with BPD.

Parameters of reported childhood sexual abuse and assault in adolescents and adults with borderline personality disorder.

OBJECTIVE: Prior research has demonstrated a link between childhood sexual abuse and borderline personality disorder (BPD) in adolescents and adults and has indicated that more severe abuse is related to poorer psychosocial functioning. The present study describes the overall severity of sexual abuse/assault in adolescents and adults with BPD and compares both groups on specific parameters of abusive and assaultive experiences. METHODS: Participants included 104 adolescent (aged 13-17 years) inpatients with BPD and 290 adult inpatients with BPD. All participants completed two interviews that assessed the presence and severity of sexual abuse/assault. RESULTS: Of the studied patients with BPD, 26.0% of adolescents and 62.4% of adults reported a childhood history of sexual abuse/assault before the age of 18. Adults had higher scores on an index of sexual abuse severity than adolescents, and a higher proportion of adults reported scores in the severe range. Adults with BPD were also more likely than adolescents to report having experienced sexual abuse/assault that occurred at multiple developmental stages, was frequent (i.e. weekly basis or more), was longer in duration (i.e. a year or more) and was perpetrated by a parent. The groups did not differ on other parameters. CONCLUSIONS: Taken together, these results suggest that adults with BPD are more likely to report childhood sexual abuse/assault than adolescents with BPD. Additionally, adults report histories of sexual abuse/assault that are more severe than adolescents with BPD, with specific differences observed in timing, frequency, duration and perpetrator. © 2020 John Wiley & Sons, Ltd.

Risk Factors for Borderline Personality Disorder in Adolescents.

The objective of this study was to assess the association between variables reflecting childhood adversity, protective childhood experiences, and the five-factor model of personality and BPD in adolescents. Two groups of adolescents were studied: 104 met criteria for BPD and 60 were psychiatrically healthy. Adverse and protective childhood experiences were assessed using a semistructured interview. The five-factor model of personality was assessed using the NEO-FFI. Eight of nine variables indicating severity of abuse and neglect, positive childhood relationships, childhood competence, and the personality factors studied were found to be significant bivariate risk factors for adolescent BPD. However, in a multivariate model, severity of neglect, higher levels of neuroticism, and lower levels of childhood competence were found to be the best risk factor model. Taken together, the results of this study suggest that all three types of risk factors studied are significantly associated with BPD in adolescents.

Whole-brain microstructural white matter alterations in borderline personality disorder patients.

BACKGROUND: Borderline personality disorder (BPD) is a psychiatric condition associated with the impairment of the frontolimbic network. However, a growing body of studies suggests that brain dysfunction underling BPD could involve other brain areas. We explored the whole-brain white matter (WM) organization in BPD patients to clarify the structural pattern underlying the disease and its relationship with clinical features. METHODS: Fourteen BPD patients and 14 healthy controls underwent a multidimensional clinical assessment and diffusion tensor imaging acquisition. Measures of fractional anisotropy (FA) and mean, axial and radial (RD) diffusivity were collected, and alterations in the WM were assessed using the voxelwise approach, including substance and alcohol abuse as covariates. Voxelwise regression analysis was performed to identify associations between microstructural changes and clinical feature in BPD. RESULTS: Group comparisons showed alterations only for FA and RD: FA decreased in the right posterior hemisphere, while RD increased bilaterally and widespread in anterior and posterior areas (p < 0.05, threshold-free cluster enhancement corrected). Moreover, WM alterations of the corpus callosum were related to anxiety in BPD group. DISCUSSION: Our data support the idea that structural alterations underling BPD also involve cortico-cortical pathways, corticothalamic and corticostriatal tracts, suggesting that the frontolimbic model should be reinterpreted. © 2019 John Wiley & Sons, Ltd.

Abnormalities in functional connectivity in borderline personality disorder: Correlations with metacognition and emotion dysregulation.

A few studies reported functional abnormalities at rest in borderline personality disorder (BPD), but their relationship with clinical aspect is unclear. We aimed to assess functional connectivity (FC) in BPD patients and its association with BPD clinical features. Twenty-one BPD patients and 14 healthy controls (HC) underwent a multidimensional assessment and resting-state fMRI. Independent component analysis was performed to identify three resting-state networks: default mode network (DMN), salience network (SN), and executive control network (ECN). FC differences between BPD and HC were assessed with voxel-wise two-sample t-tests. Additionally, we investigated the mean FC within each network and the relationship between connectivity measures and BPD clinical features. Patients showed significant lower mean FC in the DMN and SN, while, at the local level, a cluster of lower functional connectivity emerged in the posterior cingulate cortex of the DMN. The DMN connectivity was positively correlated with the anger-state intensity and expression, while the SN connectivity was positively correlated with metacognitive abilities and a negative correlation emerged with the interpersonal aggression. The dysfunctional connectivity within these networks might explain clinical features of BPD patients.

Superwellness Program: a cognitive-behavioral therapy-based group intervention to reduce weight gain in patients treated with antipsychotic drugs

Objective: To assess the effectiveness of a cognitive-behavioral therapy-based intervention (Superwellness Program) on weight gain compared with a treatment-as-usual (TAU) approach in patients treated with antipsychotics, and to evaluate the relationship between body mass index (BMI) variation and clinical variables. Method: Eighty-five patients treated with antipsychotics were allocated across two groups, experimental (n=59) and control (n=26). The Superwellness Program (experimental group) consisted of 32 twice-weekly 1-hour sessions, conducted by a psychologist and a nutritionist/nurse, concurrently with moderate food intake and moderate physical activity plans. Sociodemographic, clinical, and biological variables were collected at baseline, at the end of intervention (16 weeks), and after 6 months. Results: BMI change from baseline differed significantly between the experimental and control groups, with a larger decrease in the experimental group (F = 5.5, p = 0.021). Duration of illness moderated the effect of treatment on BMI (p = 0.026). No significant (p = 0.499) effect of intervention during the follow-up period was found. Interestingly, the intervention indirectly induced a significant (p = 0.024) reduction in metabolic risk by reducing BMI. Conclusion: A cognitive-behavioral therapy-based intervention could be useful in reducing weight in a clinical population taking antipsychotics, with consequent benefit to physical and mental health.

Prevalence and severity of childhood adversity in adolescents with BPD, psychiatrically healthy adolescents, and adults with BPD.

OBJECTIVE: Existing research has demonstrated that both adolescents and adults with borderline personality disorder (BPD) report higher rates of childhood adversity than their same-age peers; no studies have examined if adolescents and adults with BPD differ based on the extent of these experiences. In the present study, we compared the prevalence rates and severity of multiple forms of abuse and neglect in adolescents and adults with BPD and in psychiatrically healthy adolescents. METHODS: Participants included 104 adolescent (aged 13-17 years) inpatients with BPD, 60 age-matched, psychiatrically healthy adolescents, and 290 adult inpatients with BPD. All participants completed an interview that assessed the presence and severity of multiple forms of childhood abuse and neglect. RESULTS: A significantly higher percentage of adolescents with BPD reported 5 of 12 pathological childhood experiences and described more severe abusive experiences than their psychiatrically healthy peers. In comparison with adolescents with BPD, a significantly higher percentage of adults with BPD reported nearly all forms of childhood adversity and rated these experiences as more severe. CONCLUSIONS: Taken together, these results suggest that adults with BPD report more severe profiles of abuse and neglect than adolescents with the disorder, even though adolescents with BPD differ from healthy peers. Copyright © 2017 John Wiley & Sons, Ltd.

Psychosocial functioning in adolescents with and without borderline personality disorder.

OBJECTIVE: Little is known about the psychosocial functioning of adolescents with borderline personality disorder (BPD). The main objective of this paper is to compare the psychosocial functioning of a group of adolescents with BPD to a group of psychiatrically healthy adolescents. METHODS: The present cross-sectional study included 104 adolescent inpatients with BPD, compared with 60 age-matched psychiatrically healthy comparison subjects. All participants were rigorously diagnosed using three semi-structured interviews: the Structured Clinical Interview for DSM-IV Childhood Diagnoses, the Revised Diagnostic Interview for Borderlines and the Childhood Interview for DSM-IV Borderline Personality. All subjects were also interviewed using the adolescent version of the Background Information Schedule to assess multiple facets of psychosocial functioning. RESULTS: Adolescents with BPD rated their relationships with their parents as significantly less positive, were more likely to date, but spent more time alone than their healthy counterparts. In addition, adolescents with BPD reported significantly more problems at work and school (i.e. lower frequency of having a good work or school history, higher frequency of being suspended or expelled from school) and significantly lower rates of participation in extra-curricular activities than their healthy counterparts. CONCLUSIONS: Taken together, the results of this study suggest that adolescents with BPD are more impaired in both the social and vocational areas of functioning than psychiatrically healthy comparison subjects. They might also suggest that an overlooked area of strength concerns their relationships with peers. Copyright © 2017 John Wiley & Sons, Ltd.

Prevalence rates of borderline symptoms reported by adolescent inpatients with BPD, psychiatrically healthy adolescents and adult inpatients with BPD.

OBJECTIVE: The validity of borderline personality disorder (BPD) in children and adolescents has not been studied in a rigorous manner reflecting the criteria of Robins and Guze first detailed in 1970. This paper and the others in this series address some aspects of this multifaceted validation paradigm, which requires that a disorder has a known clinical presentation, can be delimited from other disorders, 'runs' in families, and something of its aetiology, treatment response and course is known. METHODS: Three groups of subjects were studied: 104 adolescent inpatients meeting the Revised Diagnostic Interview for Borderlines and DSM-IV criteria for BPD, 60 psychiatrically healthy adolescents and 290 adult inpatients meeting the Revised Diagnostic Interview for Borderlines and DSM-III-R criteria for BPD. RESULTS: Adolescents with BPD had significantly higher prevalence rates of 22 of the 24 symptoms studied than psychiatrically healthy adolescents. Only rates of serious treatment regressions and countertransference problems failed to reach the Bonferroni-corrected level of 0.002. Adolescents and adults with BPD had only four symptomatic differences that reached this level of significance, with adolescents with BPD reporting significantly lower levels of quasi-psychotic thought, dependency/masochism, devaluation/manipulation/sadism and countertransference problems than adults with BPD. CONCLUSIONS: Taken together, the results of this study suggest that adolescents report BPD as severe as that reported by adults. They also suggest that BPD in adolescents is not a tumultuous phase of normal adolescence. Copyright © 2017 John Wiley & Sons, Ltd.

Prevalence rates of childhood protective factors in adolescents with BPD, psychiatrically healthy adolescents and adults with BPD.

OBJECTIVE: Existing literature on the aetiology of borderline personality disorder (BPD) has primarily focused on pathological childhood experiences, while little to no research has been conducted on protective factors that may serve to ameliorate these symptoms. The current study attempts to fill this gap in the literature by comparing the rates of childhood protective factors among adolescents with BPD, psychiatrically healthy adolescents and adults with BPD. METHODS: One hundred and four subjects were adolescent inpatients between the ages of 13 and 17 who met Revised Diagnostic Interview for Borderlines and Diagnostic and Statistical Manual of Mental Disorders Fourth Edition criteria for BPD. Sixty were age-matched psychiatrically healthy comparison subjects. Two hundred and ninety subjects were adult inpatients between the ages of 18 and 35 who met Revised Diagnostic Interview for Borderlines and Revised Diagnostic and Statistical Manual of Mental Disorders Third Edition criteria for BPD. All three groups were interviewed by using the Revised Childhood Experiences Questionnaire, a semi-structured interview that assesses pathological and protective childhood experiences. RESULTS: Psychiatrically healthy adolescents reported significantly higher rates of 4 out of 18 protective factors than adolescents with BPD. Adolescents with BPD reported significantly higher rates of 5 of these 18 protective factors than adults with BPD. Adults with BPD were significantly more likely to endorse having a steady after school or weekend work record than adolescents with BPD. CONCLUSIONS: Taken together, the results of this study suggest that adolescents meeting criteria for BPD report lower rates of some protective factors than psychiatrically healthy adolescents. They also suggest that they have higher rates of some protective factors than adults with BPD. Copyright © 2017 John Wiley & Sons, Ltd.

Superwellness Program: a cognitive-behavioral therapy-based group intervention to reduce weight gain in patients treated with antipsychotic drugs.

OBJECTIVE:: To assess the effectiveness of a cognitive-behavioral therapy-based intervention (Superwellness Program) on weight gain compared with a treatment-as-usual (TAU) approach in patients treated with antipsychotics, and to evaluate the relationship between body mass index (BMI) variation and clinical variables. METHOD:: Eighty-five patients treated with antipsychotics were allocated across two groups, experimental (n=59) and control (n=26). The Superwellness Program (experimental group) consisted of 32 twice-weekly 1-hour sessions, conducted by a psychologist and a nutritionist/nurse, concurrently with moderate food intake and moderate physical activity plans. Sociodemographic, clinical, and biological variables were collected at baseline, at the end of intervention (16 weeks), and after 6 months. RESULTS:: BMI change from baseline differed significantly between the experimental and control groups, with a larger decrease in the experimental group (F = 5.5, p = 0.021). Duration of illness moderated the effect of treatment on BMI (p = 0.026). No significant (p = 0.499) effect of intervention during the follow-up period was found. Interestingly, the intervention indirectly induced a significant (p = 0.024) reduction in metabolic risk by reducing BMI. CONCLUSION:: A cognitive-behavioral therapy-based intervention could be useful in reducing weight in a clinical population taking antipsychotics, with consequent benefit to physical and mental health.

Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials.

BACKGROUND: Dose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the present study is to examine dose equivalence of antidepressants by a less arbitrary and more systematic method. METHODS: We used data from all randomized, double-blind, flexible-dose trials comparing fluoxetine or paroxetine as standard drugs with any other active antidepressants as monotherapy in the acute phase treatment of unipolar depression. We calculated the ratio of the mean doses for each study and weighted it by the total sample size to find the weighted mean ratio for each drug, which was then used to define the drug׳s dosage equivalent to fluoxetine 40mg/d. RESULTS: We included 83 studies (14 131 participants). In the primary analysis, fluoxetine 40mg/day was equivalent to paroxetine dosage of 34.0mg/day, agomelatine 53.2mg/day, amitriptyline, 122.3mg/day, bupropion 348.5mg/day, clomipramine 116.1mg/day, desipramine 196.3mg/day, dothiepin 154.8mg/day, doxepin 140.1mg/day, escitalopram 18.0mg/day, fluvoxamine 143.3mg/day, imipramine 137.2mg/day, lofepramine 250.2mg/day, maprotiline 118.0mg/day, mianserin, 101.1mg/day, mirtazapine 50.9mg/day, moclobemide 575.2mg/day, nefazodone 535.2mg/day, nortriptyline 100.9mg/day, reboxetine 11.5mg/day, sertraline 98.5mg/day, trazodone 401.4mg/day, and venlafaxine 149.4mg/day. Sensitivity analyses corroborated the results except for doxepin. LIMITATIONS: The number of studies for some drugs was small. The current method assumes dose response relationship of antidepressants. CONCLUSIONS: Our findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research.

Paroxetine versus other anti-depressive agents for depression.

BACKGROUND: Paroxetine is the most potent inhibitor of the reuptake of serotonin of all selective serotonin reuptake inhibitors (SSRIs) and has been studied in many randomised controlled trials (RCTs). However, these comparative studies provided contrasting findings and systematic reviews of RCTs have always considered the SSRIs as a group, and evidence applicable to this group of drugs might not be applicable to paroxetine alone. The present systematic review assessed the efficacy and tolerability profile of paroxetine in comparison with tricyclics (TCAs), SSRIs and newer or non-conventional agents. OBJECTIVES: 1. To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of Major Depressive Disorder.2. To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.3. To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialized Register (CCDANCTR, to 30 September 2012), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). Reference lists of relevant papers and previous systematic reviews were handsearched. Pharmaceutical companies marketing paroxetine and experts in this field were contacted for supplemental data. SELECTION CRITERIA: All randomised controlled trials allocating participants with major depression to paroxetine versus any other antidepressants (ADs), both conventional (such as TCAs, SSRIs) and newer or non-conventional (such as hypericum). For trials which had a cross-over design, only results from the first randomisation period were considered. DATA COLLECTION AND ANALYSIS: Two review authors independently checked eligibility and extracted data using a standard form. Data were then entered in RevMan 5.2 with a double-entry procedure. Information extracted included study and participant characteristics, intervention details, settings and efficacy, acceptability and tolerability measures. MAIN RESULTS: A total of 115 randomised controlled trials (26,134 participants) were included. In 54 studies paroxetine was compared with older ADs, in 21 studies with another SSRI, and in 40 studies with a newer or non-conventional antidepressant other than SSRIs. For the primary outcome (patients who responded to treatment), paroxetine was more effective than reboxetine at increasing patients who responded early to treatment (Odds Ratio (OR): 0.66, 95% Confidence Interval (CI) 0.50 to 0.87, number needed to treat to provide benefit (NNTb) = 16, 95% CI 10 to 50, at one to four weeks, 3 RCTs, 1375 participants, moderate quality of evidence), and less effective than mirtazapine (OR: 2.39, 95% CI 1.42 to 4.02, NNTb = 8, 95% CI 5 to 14, at one to four weeks, 3 RCTs, 726 participants, moderate quality of evidence). Paroxetine was less effective than citalopram in improving response to treatment (OR: 1.54, 95% CI 1.04 to 2.28, NNTb = 9, 95% CI 5 to 102, at six to 12 weeks, 1 RCT, 406 participants, moderate quality of evidence). We found no clear evidence that paroxetine was more or less effective compared with other antidepressants at increasing response to treatment at acute (six to 12 weeks), early (one to four weeks), or longer term follow-up (four to six months). Paroxetine was associated with a lower rate of adverse events than amitriptyline, imipramine and older ADs as a class, but was less well tolerated than agomelatine and hypericum. Included studies were generally at unclear or high risk of bias due to poor reporting of allocation concealment and blinding of outcome assessment, and incomplete reporting of outcomes. AUTHORS' CONCLUSIONS: Some possibly clinically meaningful differences between paroxetine and other ADs exist, but no definitive conclusions can be drawn from these findings. In terms of response, there was a moderate quality of evidence that citalopram was better than paroxetine in the acute phase (six to 12 weeks), although only one study contributed data. In terms of early response to treatment (one to four weeks) there was moderate quality of evidence that mirtazapine was better than paroxetine and that paroxetine was better than reboxetine. However there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any time point. Even if some differences were identified, the findings from this review are better thought as hypothesis forming rather than hypothesis testing and it would be reassuring to see the conclusions replicated in future trials. Finally, most of included studies were at unclear or high risk of bias, and were sponsored by the drug industry. The potential for overestimation of treatment effect due to sponsorship bias should be borne in mind.

Fluoxetine versus other types of pharmacotherapy for depression.

BACKGROUND: Depression is common in primary care and is associated with marked personal, social and economic morbidity, thus creating significant demands on service providers. The antidepressant fluoxetine has been studied in many randomised controlled trials (RCTs) in comparison with other conventional and unconventional antidepressants. However, these studies have produced conflicting findings.Other systematic reviews have considered selective serotonin reuptake inhibitor (SSRIs) as a group which limits the applicability of the indings for fluoxetine alone. Therefore, this review intends to provide specific and clinically useful information regarding the effects of fluoxetine for depression compared with tricyclics (TCAs), SSRIs, serotonin-noradrenaline reuptake inhibitors (SNRIs), monoamineoxidase inhibitors (MAOIs) and newer agents, and other conventional and unconventional agents. OBJECTIVES: To assess the effects of fluoxetine in comparison with all other antidepressive agents for depression in adult individuals with unipolar major depressive disorder. SEARCH METHODS: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Review Group Controlled Trials Register (CCDANCTR)to 11May 2012. This register includes relevant RCTs from the Cochrane Central Register of Controlled Trials (CENTRAL) (all years),MEDLINE (1950 to date), EMBASE (1974 to date) and PsycINFO (1967 to date). No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were handsearched. The pharmaceutical company marketing fluoxetine and experts in this field were contacted for supplemental data. SELECTION CRITERIA: All RCTs comparing fluoxetine with any other AD (including non-conventional agents such as hypericum) for patients with unipolar major depressive disorder (regardless of the diagnostic criteria used) were included. For trials that had a cross-over design only results from the first randomisation period were considered. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two review authors using a standard form. Responders to treatment were calculated on an intention-to-treat basis: dropouts were always included in this analysis. When data on dropouts were carried forward and included in the efficacy evaluation, they were analysed according to the primary studies; when dropouts were excluded from any assessment in the primary studies, they were considered as treatment failures. Scores from continuous outcomes were analysed by including patients with a final assessment or with the last observation carried forward. Tolerability data were analysed by calculating the proportion of patients who failed to complete the study due to any causes and due to side effects or inefficacy. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI) using the random-effects model. Continuous data were analysed using standardised mean differences (SMD) with 95% CI. MAIN RESULTS: A total of 171 studies were included in the analysis (24,868 participants). The included studies were undertaken between 1984 and 2012. Studies had homogenous characteristics in terms of design, intervention and outcome measures. The assessment of quality with the risk of bias tool revealed that the great majority of them failed to report methodological details, like the method of random sequence generation, the allocation concealment and blinding. Moreover, most of the included studies were sponsored by drug companies, so the potential for overestimation of treatment effect due to sponsorship bias should be considered in interpreting the results. Fluoxetine was as effective as the TCAs when considered as a group both on a dichotomous outcome (reduction of at least 50% on the Hamilton Depression Scale) (OR 0.97, 95% CI 0.77 to 1.22, 24 RCTs, 2124 participants) and a continuous outcome (mean scores at the end of the trial or change score on depression measures) (SMD 0.03, 95% CI -0.07 to 0.14, 50 RCTs, 3393 participants). On a dichotomousoutcome, fluoxetine was less effective than dothiepin or dosulepin (OR 2.13, 95% CI 1.08 to 4.20; number needed to treat (NNT) =6, 95% CI 3 to 50, 2 RCTs, 144 participants), sertraline (OR 1.37, 95% CI 1.08 to 1.74; NNT = 13, 95% CI 7 to 58, 6 RCTs, 1188 participants), mirtazapine (OR 1.46, 95% CI 1.04 to 2.04; NNT = 12, 95% CI 6 to 134, 4 RCTs, 600 participants) and venlafaxine(OR 1.29, 95% CI 1.10 to 1.51; NNT = 11, 95% CI 8 to 16, 12 RCTs, 3387 participants). On a continuous outcome, fluoxetine was more effective than ABT-200 (SMD -1.85, 95% CI -2.25 to -1.45, 1 RCT, 141 participants) and milnacipran (SMD -0.36, 95% CI-0.63 to -0.08, 2 RCTs, 213 participants); conversely, it was less effective than venlafaxine (SMD 0.10, 95% CI 0 to 0.19, 13 RCTs,3097 participants). Fluoxetine was better tolerated than TCAs considered as a group (total dropout OR 0.79, 95% CI 0.65 to 0.96;NNT = 20, 95% CI 13 to 48, 49 RCTs, 4194 participants) and was better tolerated in comparison with individual ADs, in particular amitriptyline (total dropout OR 0.62, 95% CI 0.46 to 0.85; NNT = 13, 95% CI 8 to 39, 18 RCTs, 1089 participants), and among the newer ADs ABT-200 (total dropout OR 0.18, 95% CI 0.08 to 0.39; NNT = 3, 95% CI 2 to 5, 1 RCT, 144 participants), pramipexole(total dropout OR 0.12, 95% CI 0.03 to 0.42, NNT = 3, 95% CI 2 to 5, 1 RCT, 105 participants), and reboxetine (total dropout OR0.60, 95% CI 0.44 to 0.82, NNT = 9, 95% CI 6 to 24, 4 RCTs, 764 participants). AUTHORS' CONCLUSIONS: The present study detected differences in terms of efficacy and tolerability between fluoxetine and certain ADs, but the clinical meaning of these differences is uncertain.Moreover, the assessment of quality with the risk of bias tool showed that the great majority of included studies failed to report details on methodological procedures. Of consequence, no definitive implications can be drawn from the studies' results. The better efficacy profile of sertraline and venlafaxine (and possibly other ADs) over fluoxetine may be clinically meaningful,as already suggested by other systematic reviews. In addition to efficacy data, treatment decisions should also be based on considerations of drug toxicity, patient acceptability and cost.

Structural brain features of borderline personality and bipolar disorders.

A potential overlap between bipolar disorder (BD) and borderline personality disorder (BPD) has been recently proposed. We aimed to assess similarities and differences of brain structural features in BD and BPD. Structural magnetic resonance imaging (MRI) was performed in 26 inpatients with BPD, 14 with BD, and 40 age-and sex-matched healthycontrols (HC). Voxel-based morphometry analysis with Statistical Parametric Mapping (SPM) was used to localize and quantify gray (GM) and white matter (WM) abnormalities in BD and BPD compared to HC and to identify those specifically affected in each patient group. Region of interest (ROI)-based analyses were also performed for confirmation. GM density changes in BD are significantly more diffuse and severe than in BPD, as demonstrated in both SPM- and ROI-based analyses. The topography of GM alterations showed some regions of overlap, but each disorder had specific regions of abnormality (involving both cortical and subcortical structures in BD, confined mainly to fronto-limbic regions in BPD). WM density changes were less pronounced in both conditions and involved completely different regions. Although BPD and BD show a considerable overlap of GM changes, the topography of alterations is more consistent with the separate conditions hypothesis and with the vulnerability of separate neural systems.