Adaptation of interpersonal psychotherapy to borderline personality disorder: a comparison of combined therapy and single pharmacotherapy. Pharmacotherapy of impaired affect in recovering schizophrenic patients. Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. Combined treatment of major depression in patients with borderline personality disorder: a comparison with pharmacotherapy. Combined therapy of major depression with concomitant borderline personality disorder: comparison of interpersonal and cognitive psychotherapy. Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. A preliminary study of lamotrigine in the treatment of affective instability in borderline personality disorder.
Combined treatment with interpersonal psychotherapy (IPT) and antidepressants (ADs) has been found more effective than single pharmacotherapy in patients with major depression and concomitant borderline personality disorder (BPD). The aim of our study is to investigate whether combined treatment with a modified version of IPT is still superior to ADs when treating patients with a single diagnosis of BPD.
                Fifty-five consecutive outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnosis of BPD were enrolled. They were randomly assigned to 2 treatment arms for 32 weeks: fluoxetine 20 to 40 mg per day plus clinical management; and fluoxetine 20 to 40 mg per day plus IPT adapted to BPD (IPT-BPD). Eleven patients (20%) discontinued treatment owing to noncompliance. Forty-four patients completed the treatment period. They were assessed at baseline, and at week 16 and 32 with: a semi-structured interview for demographic and clinical variables; Clinical Global Impression Scale (CGI-S); Hamilton Depression Rating Scale (HDRS); Hamilton Anxiety Rating Scale (HARS); Social and Occupational Functioning Assessment Scale (SOFAS); BPD Severity Index (BPD-SI); and a questionnaire for quality of life (Satisfaction Profile [SAT-P]). A univariate general linear model was performed with 2 factors: duration and type of treatment. P values of less than 0.05 were considered significant.
                Remission rates did not differ significantly between subgroups. Duration, but not type of treatment, had a significant effect on CGI-S, HDRS, SOFAS, and total BPD-SI score changes. Combined therapy was more effective on the HARS; the items: interpersonal relationships, affective instability, and impulsivity of BPD-SI; and the factors: psychological functioning and social functioning of SAT-P.
                Combined therapy with adapted IPT was superior to fluoxetine alone in BPD patients, concerning a few core symptoms of the disorder, anxiety, and quality of life. Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken.
                In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks.
                For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.
                Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature. To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP).
                We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures.
                Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone.
                The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted.
                Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au). Combined treatment with psychotherapy and antidepressants is more effective than monotherapies. Recent data show that combined therapy has better results in patients with depression and Axis II codiagnosis. The aim of this study was to compare combined treatment using interpersonal psychotherapy (IPT) with pharmacotherapy alone in patients with depression and borderline personality disorder (BPD).
                There were 39 consecutive outpatients diagnosed with BPD who presented with a major depressive episode enrolled in this study. They were randomly assigned to 1 of 2 treatment groups: fluoxetine 20 mg to 40 mg daily or fluoxetine 20 mg to 40 mg daily plus IPT 1 session weekly. Owing to noncompliance, 7 patients dropped out. We assessed the 32 patients who completed the 24 weeks of treatment at baseline, Week 12, and Week 24, using a semistructured interview for clinical characteristics, the Clinical Global Impression Scale (CGI), the Hamilton Depression Rating Scale (HDRS), and the Hamilton Anxiety Rating Scale (HARS), and 2 self-report questionnaires, that is, the Satisfaction Profile (SAT-P) for quality of life and the 64-item Inventory for Interpersonal Problems (IIP-64). We performed statistical analysis, using univariate general linear models with 2 factors: duration and type of treatment.
                Changes in remission rates, CGI, and HARS score did not differ between treatments. According to changes in the HDRS scores; changes in psychological functioning and social functioning scores on the SAT-P; and changes in vindictive or self-centred, cold or distant, intrusive or needy, and socially inhibited scores on the IIP-64, combined therapy was superior to fluoxetine alone.
                Combined therapy with IPT is more effective than antidepressant therapy alone, both in treating symptoms of major depression and in improving dimensions of quality of life and interpersonal functioning. The combination of antidepressants and brief psychotherapies has been proven more efficacious in treating major depression and is particularly recommended in patients with concomitant personality disorders. We compare the effects of 2 combined therapies, fluoxetine and interpersonal therapy (IPT) or fluoxetine and cognitive therapy (CT), on major depression in patients with borderline personality disorder (BPD).
                Thirty-five consecutive outpatients with a diagnosis of BPD and a major depressive episode (not bipolar and not psychotic) were enrolled. They were randomly assigned to 1 of the 2 combined treatments and treated for 24 weeks. Assessment included a semistructured interview, Clinical Global Impression (CGI) scale, Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Beck Depression Inventory-II (BDI-II), Social and Occupational Functioning Assessment Scale (SOFAS), Satisfaction Profile (SAT-P) for quality of life (QOL), and Inventory of Interpersonal Problems (IIP-64). Statistical analysis was performed using the univariate General Linear Model to calculate the effects of duration and type of treatment.
                No significant differences between treatments were found at CGI, HDRS, BDI-II, and SOFAS score. Combined treatment with CT had greater effects on HARS score and on psychological functioning factor of SAT-P. Combined treatment with IPT was more effective on social functioning factor of SAT-P and on domains domineering or controlling and intrusive or needy of IIP-64.
                Both combined therapies are efficacious in treating major depression in patients with BPD. Differences between CT and IPT concern specific features of subjective QOL and interpersonal problems. These findings lack reliable comparisons and need to be replicated. High cortisol levels are found in severe mood disorders, particularly bipolar disorder. Hypercortisolaemia may cause or exacerbate both neurocognitive impairment and depressive symptoms. We hypothesized that antiglucocorticoid treatments, particularly corticosteroid receptor antagonists, would improve neurocognitive functioning and attenuate depressive symptoms in this disorder. To test this hypothesis, 20 bipolar patients were treated with 600 mg/day of the corticosteroid receptor antagonist mifepristone (RU-486) or placebo for 1 week in a double-blind crossover design. Over the total 6 weeks of the study, neurocognitive and neuroendocrine function were evaluated at baseline, days 21 and 42. Mood symptoms were evaluated weekly. Nineteen subjects completed the protocol; there were no drop-outs due to adverse events. Following treatment with mifepristone, selective improvement in neurocognitive functioning was observed. Spatial working memory performance was significantly improved compared to placebo (19.8% improvement over placebo). Measures of verbal fluency and spatial recognition memory were also improved after mifepristone. Beneficial effects on mood were found; Hamilton Depression Rating Scale scores were significantly reduced compared to baseline (mean reduction of 5.1 points) as were Montgomery-Asberg Depression Rating Scale scores (mean reduction of 6.05 points). No significant change occurred after placebo. These data require replication but provide preliminary evidence that glucocorticoid receptor antagonists may have useful cognitive-enhancing and possibly antidepressant properties in bipolar disorder. The results of pilot trials suggest that omega-3 fatty acids may have efficacy in the treatment of mood symptoms in bipolar disorder.
                We conducted a 4-month, randomized, placebo-controlled, adjunctive trial of ethyl-eicosapentanoate (EPA) 6 g/day in the treatment of bipolar depression and rapid cycling bipolar disorder. Subjects were receiving mood-stabilizing medications at therapeutic doses or plasma concentrations. The measures of efficacy were early study discontinuation, changes from baseline in depressive symptoms (Inventory for Depressive Symptomology total score) and in manic symptoms (Young Mania Rating Scale total score), and manic exacerbations ("switches"). We also measured side effects and bleeding time, a biomarker of drug action.
                Overall, there were no significant differences on any outcome measure between the EPA and placebo groups.
                This study did not find overall evidence of efficacy for adjunctive treatment with EPA 6 g/day in outpatients with bipolar depression or rapid cycling bipolar disorder. This study determined if augmentation of neuroleptics with 3 g/day of ethyl eicosapentaenoic acid (EPA) improves symptoms and cognition in patients with schizophrenia or schizoaffective disorder.
                Eighty-seven patients meeting criteria for schizophrenia or schizoaffective disorder who had residual symptoms despite neuroleptic treatment were randomly assigned to receive either 3 g/day of ethyl EPA (N=43) or placebo (N=44) in a 16-week, double-blind supplementation trial. Assessments were performed at baseline and at weeks 1, 2, 4, 8, 12, and 16; a cognitive battery was administered at baseline and at week 16.
                No differences were found between groups in positive or negative symptoms, mood, cognition, or global impression ratings. Results were similar for the intention-to-treat (N=87) and completer (N=75) groups.
                For schizophrenia patients treated with 3 g/day of ethyl EPA, improvement in residual symptoms and cognitive impairment was no greater than for schizophrenia patients treated with placebo. The objective of this study was to evaluate the effectiveness of lamotrigine in reducing affective instability in borderline personality disorder (BPD). We conducted a 12-week, double-blind, placebo-controlled study of 28 patients who met Revised Diagnostic Interview for Borderlines and Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for BPD. Patients could not meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for bipolar disorder. Patients could be taking one antidepressant during the study. Patients were randomly assigned to treatment with flexible-dose lamotrigine or placebo in a 1 : 1 manner. The primary outcome measures were: (i) the Affective Lability Scale total score; and (ii) the Affective Instability Item of the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). The study randomized 15 patients to receive lamotrigine and 13 patients to receive placebo. Patients in the lamotrigine group had significantly greater reductions in the total Affective Lability Scale scores (P<0.05) and significantly greater reductions in scores on the affective instability item of the ZAN-BPD (P<0.05). A secondary finding was that patients in the lamotrigine group had significantly greater reductions in scores on the ZAN-BPD impulsivity item (P = 0.001). Results from the study suggest that lamotrigine is an effective treatment for affective instability and for the general impulsivity characteristic of BPD.
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).