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. Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study. Improving treatment of late life depression in primary care: a randomized clinical trial. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Sustained efficacy of dialectical behaviour therapy for borderline personality disorder. Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program. London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. I: effects of the treatment phase. A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed adolescents receiving antidepressant medication. Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Clinical, EEG mapping and psychometric studies in negative schizophrenia: comparative trials with amisulpride and fluphenazine. A double-blind comparison of valproate and lithium in the treatment of acute mania. Omega-3 fatty acids in bipolar disorder: clinical and research considerations. A double-blind controlled study of clinical efficacy of maprotiline and amitriptyline in depression. A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia. Cognitive therapy and pharmacotherapy. Singly and together in the treatment of depression.
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. Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals. Facilitate primary care physicians' compliance with recommended standards of care for late life depression by reducing barriers to recognition and treatment.
                Randomized controlled clinical trial of physician-targeted interventions.
                Academic primary care group practice caring for an urban, medically indigent patient population.
                Patients aged 60 and older who exceeded the threshold on the Centers for Epidemiologic Studies Depression Scale (CES-D) and the Hamilton Depression Rating Scale (HAM-D) and their primary care physicians.
                Physicians of intervention patients were provided with patient-specific treatment recommendations during 3 special visits scheduled specifically to address the patient's symptoms of depression. In general, physicians were encouraged to establish a diagnosis of depression and educate their patient about the diagnosis, discontinue medications that can cause or exacerbate depressive symptoms, initiate antidepressants when appropriate, and consider referral to psychiatry. Guidelines for prescribing antidepressants were provided. Control physicians received no intervention, and control patients received usual care.
                Frequency of recording a depression diagnosis, stopping medications associated with depression, initiating antidepressant medication, and psychiatry referral; mean changes in HAM-D and Sickness Impact Profile (SIP) scores.
                One hundred three physicians and 175 patients were involved in the clinical trial. Physicians of intervention patients were more likely to diagnose depression and prescribe antidepressants (P < 0.01). There were no differences between the groups in the frequency of stopping medications associated with depression or referrals to psychiatry. Medications with the strongest cause and effect relationship to depression were infrequently used in this cohort of patients. Although both groups showed improvement in HAM-D and SIP scores, we were unable to demonstrate significant differences in HAM-D or SIP scores between the 2 groups.
                Intensive screening and feedback of patient-specific treatment recommendations increased the recognition and treatment of late life depression by primary care physicians. However, we were unable to demonstrate significant improvement in depression or disability severity among intervention patients despite the informational support provided to their physicians. Efforts to improve the functional status of these patients may require more integrated interventions and more aggressive attempts to target psychosocial stressors traditionally outside the purview of primary care. Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder.
                A 4-month, double-blind, placebo-controlled study, comparing omega3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder.
                A Kaplan-Meier survival analysis of the cohort found that the omega3 fatty acid patient group had a significantly longer period of remission than the placebo group (P = .002; Mantel-Cox). In addition, for nearly every other outcome measure, the omega3 fatty acid group performed better than the placebo group.
                Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder. Dialectical Behaviour Therapy (DBT) is considered one of the most promising treatments for borderline personality disorder (BPD). Recently, we reported significantly positive effects of 12 months DBT on parasuicidal behaviour and impulsivity in a mixed group of female BPD patients with and without substance abuse. Fifty-eight women with BPD were randomly assigned to either 52 weeks of DBT or treatment as usual (TAU). Follow-up assessment took place at 78 weeks, i.e., 6 months after discontinuation of DBT. Participants were clinical referrals from addiction treatment and psychiatric services. Outcome measures included parasuicidal behaviour, impulsivity and substance abuse. Six months after treatment discontinuation, the benefits of DBT over TAU in terms of lower levels of parasuicidal and impulsive behaviours, and in alcohol use, sustained. No differences between the treatment conditions were found for drug abuse. In conclusion, DBT seems to have a sustained effect on some of the core symptoms of BPD and on alcohol problems in a mixed population of female borderline patients with and without substance abuse problems. Little information has been published on the impact of antihypertensive medications on quality of life in older persons. Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition, mood, or leisure activities.
                A multicenter double-blind randomized controlled trial was conducted over an average of 5 years' followup involving 16 academic clinical trial clinics. Participants consisted of 4736 persons (1.06%) selected from 447,921 screenees aged 60 years and older. Systolic blood pressure at baseline ranged from 160 to 219 mm Hg, while diastolic blood pressure was less than 90 mm Hg. Participants were randomized to active antihypertensive drug therapy or matching placebo. Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1, while step 2 consisted of 25 to 50 mg of atenolol. If atenolol was contraindicated, 0.05 to 0.10 mg of reserpine could be used for the second-step drug. The impact of drug treatment on measures of cognitive, emotional, and physical function and leisure activities was assessed.
                Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and, for some measures, a slight positive effect on cognitive, physical, and leisure function. The positive findings in favor of the treatment group were small. There was no effect on measures related to emotional state. Measures of cognitive and emotional function were stable in both groups for the duration of the study. Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period.
                The overall study cohort exhibited decline over time in activities of daily living, particularly the more strenuous ones, and some decline in certain leisure activities. However, mood, cognitive function, basic self-care, and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study. Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition, emotional state, physical function, or leisure activities. A series of small, mainly uncontrolled, studies have suggested that techniques adapted from cognitive-behavioural therapy (CBT) for depression can improve outcome in psychosis, but no large randomised controlled trial of intensive treatment for medication-resistant symptoms of psychosis has previously been published.
                Sixty participants who each had at least one positive and distressing symptom of psychosis that was medication-resistant were randomly allocated between a CBT and standard care condition (n = 28) and a standard care only control condition (n = 32). Therapy was individualised, and lasted for nine months. Multiple assessments of outcome were used.
                Over nine months, improvement was significant only in the treatment group, who showed a 25% reduction on the BPRS. No other clinical, symptomatic or functioning measure changed significantly. Participants had a low drop-out rate from therapy (11%), and expressed high levels of satisfaction with treatment (80%). Fifty per cent of the CBT group were treatment responders (one person became worse), compared with 31% of the control group (three people became worse and another committed suicide).
                CBT for psychosis can improve overall symptomatology. The findings provide evidence that even a refractory group of clients with a long history of psychosis can engage in talking about psychotic symptoms and their meaning, and this can improve outcome. To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care.
                A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the experimental protocol (n = 75) versus TAU SSRI plus brief CBT (n = 77). Participants were identified by a recent dispense of SSRI medication followed by telephone screening. Adolescents with a diagnosis of major depressive disorder (n = 152) were enrolled. The CBT program employed cognitive restructuring and/or behavioral activation training. Therapists consulted with prescribing pediatricians to improve medication adherence.
                Through 1-year follow-up, the authors found CBT advantages on the Short Form-12 Mental Component Scale (p = .04), reductions in TAU outpatient visits (p = .02), and days' supply of all medications (p = .01). No effects were detected for major depressive disorder episodes; a nonsignificant trend favoring CBT was detected on the Center for Epidemiology Depression Scale (p = .07).
                The authors detected a weak CBT effect, possibly rendered less significant by the small sample and likely attenuated by the unexpected reduction in SSRI pharmacotherapy in the CBT condition. Small, incremental improvements over monotherapy, such as observed in this study, most likely represent the new norm in adolescent depression treatment research. 5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5'-MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12-23 at the Mini Mental State Examination (MMSE) and > or = 18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5'-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey's Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23 +/- 5 to 20 +/- 6 in the 5'-MTHF (p < 0.05 vs baseline), and from 23 +/- 3 to 21 +/- 4 in the TRZ group (p < 0.05 vs baseline). A further significant decrease to 18 +/- 6 and 19 +/- 5 respectively was obtained at the end of the treatment period (p < 0.05 vs week 4) with 5'-MTHF and TRZ.(ABSTRACT TRUNCATED AT 250 WORDS) Based on recent quantitative EEG findings of increased slow activity in negative schizophrenia indicating organicity, it was hypothesized that neuroleptics decreasing delta/theta activity should be beneficial for schizophrenics with predominantly negative symptoms. Thus, a double-blind, clinical, psychometric and neurophysiological study was carried out in 40 hospitalized patients with unproductive schizophrenia (mean age: 31 years; ICD diagnoses: 295.0, 295.1 and 295.6) who were treated randomly either with the benzamide amisulpride (AMI; n = 19) or low doses of fluphenazine (FLU; n = 21). In the first 2 weeks the daily doses were 50 mg AMI or 2 mg FLU, respectively, from the third week on up to the sixth week 100 mg AMI and 4 mg FLU. Clinical evaluations, psychometry and EEG mapping were performed on day 1 (hours 0 and 4--acute effect), on day 14 (hour 0--subacute effect) and on day 42 (hours 0 and 4--chronic and superimposed effects). Three AMI patients discontinued therapy prematurely because of productive symptoms (days 14, 28 and 35), while in the FLU group 2 patients dropped out due to depressive symptoms (days 21, 28), 1 due to productive symptoms (day 35), 1 due to ineffectiveness (day 28), and 1 because of an akinetic crisis (day 6). Statistical evaluation demonstrated a significant improvement in the AMDP apathy and Andreasen SANS score in both groups with the patients remaining severely ill as rated by the CGI. FLU-treated patients needed significantly more anticholinergic medication than the AMI-treated group. Psychometric evaluation showed in regard to the noopsyche significant improvement after subacute, chronic and superimposed AMI, while FLU-treated patients showed significant improvement only after subacute treatment. AMI was significantly superior to FLU at the hours 0 and 4 of day 42. The thymopsyche improved after subacute, chronic and superimposed administration of both compounds with a significant superiority of AMI on days 14 and 42 (4 h postdrug). EEG mapping showed a decrease of delta/theta and increase of beta activity as well as an acceleration of the centroid after acute and superimposed AMI on day 42 as compared with baseline; FLU patients exhibited a decrease of delta/theta activity and an acceleration of the total centroid too, while alpha activity was augmented and beta activity tended to be reduced. Our study demonstrated that, in addition to the new benzamide AMI, FLU in low doses may also be regarded as a neuroleptic with activating properties and may be utilized in the treatment of schizophrenics with predominantly negative symptoms. This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics, such as the presence of a mixed affective state, might predict a differential response to the two drugs.
                Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week, randomized, double-blind, parallel-groups trial of treatment with lithium carbonate or valproate. Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia, change version (SADS-C), the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS). Drug effects were compared by using repeated measures analysis of variance (ANOVA).
                At the end of the study, nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably, as measured by changes in the SADS-C mania, BPRS, and GAS scores. Elevated pretreatment SADS-C depression scores were associated with good response to valproate. ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response.
                Lithium and valproate were both effective in improving manic symptoms, and lithium was slightly more efficacious overall. Unlike the case with lithium, favorable response to valproate was associated with high pretreatment depression scores. Therefore, treatment with valproate alone may be particularly effective in manic patients with mixed affective states. Several lines of evidence suggest that omega-3 fatty acids may be important in the pathophysiology, treatment or prevention of bipolar disorder (BD). Electronic and manual searches were conducted in order to review the literature relevant to the etiology and treatment of BDs with omega-3 fatty acids. We also present data from a randomized, double-blind, placebo-controlled pilot study conducted at three sites (N = 10) comparing an omega-3 fatty acid (docosahexaenoic acid, DHA) versus placebo, added to psychosocial treatment for women with BD who chose to discontinue standard pharmacologic treatment while attempting to conceive. While some epidemiologic and preclinical data support the role of omega-3 fatty acids in BD, clinical trials to date have yielded conflicting results. In our pilot study of 10 Caucasian women taking DHA while attempting to conceive (BP1 = 9, BPII = 1), age 27-42 years, DHA was well tolerated and suggests that a larger study would be feasible. The elucidation of the potential role of omega-3 fatty acids as a treatment for BD requires further study. The current data are not sufficient to support a recommendation of monotherapy treatment as a substitute for standard pharmacologic treatments. However, judicious monotherapy in selected clinical situations, or adjunctive use, may be warranted pending further data from adequately powered controlled clinical trials. Our pilot trial of DHA in women who plan to stop conventional psychotropics in order to conceive suggests that such trials are feasible. A multiclinic double-blind controlled study was performed on the effects of MAP in both inpatients and outpatients with AMT as control drug. 1. Subjects consisted of 41 male and 45 female patients suffering from various types of depression. MAP was assigned to 42 cases and AMT to 44 cases. Of these patients, 14 MAP cases and 10 AMT cases were subsequently dropped for a variety of reasons to obtain 28 MAP cases and 34 AMT cases as evaluable. 2. The global improvement ratings were compared and found not significantly different for any week between the two treatments. 3. The global improvement ratings by the characteristic features of patients did not show any significant difference in any items studied between the two treatments. 4. The symptomatic improvement ratings (on the Hamilton R.S. for assessment by the physician) indicated that AMT was more effective on "anxiety (psychic)." 5. The symptomatic improvement ratings (on the Beck self-assessment scale by the patient) indicated that MAP was more effective on "work" and AMT on "pathos", "feeling of satisfaction", "withdrawal" and "loss of libido." 6. During the treament period, 74.3 percent of the MAP group and 76.9 percent of the AMT group of patients showed some side effects of accompanying symptoms, with no significant difference recognized between the two treatments. Itemwise, however, the incidence of tremor was significantly lower (p-=0.06) in the MAP group. Moreover, the MAP group tended to be less liable to such anticholinergic side effects as dry mouth, constipation, trouble of accomodation, urinary disturbance and palpitation. 7. On the basis of the above findings, it is concluded that MAP is as effective against depression as AMT and less liable to the anticholinergic side effects. It is, therefore, a very useful antidepressant. This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response.
                Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study.
                The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group.
                Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone. Eight-seven moderately to severely depressed psychiatric outpatients were randomly assigned to 12 weeks of cognitive therapy (CT) (n = 24), pharmacotherapy (n = 24), CT plus pharmacotherapy (n = 22), or CT plus active placebo (n = 17). Seventy patients completed the treatment protocol. Seventeen dropped out before the end of the treatment period. Patients who completed treatment showed significant improvement in mean scores on two common measures of severity of depression (the Beck Depression Inventory and the Hamilton Rating Scale for Depression) between evaluation and termination. Improvement did not differ as a function of the different treatment modalities. Inclusion of dropout patients' end-point scores did not alter these results. Treatment gains in all groups were maintained at one-month follow-up assessment. A portion of this study replicated an earlier study. While the results were not identical, they indicated that either CT or antidepressant drug treatment can be effective in treating outpatients with primary, nonbipolar depression of moderate or greater severity. Combining treatments did not lead either to additive effects or negative interactions.
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).