Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures. A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test. Low dose beta blockade in acute stroke ("BEST" trial): an evaluation. Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients. Adjunctive imipramine in the treatment of postpsychotic depression. A controlled trial. Clinical, EEG mapping and psychometric studies in negative schizophrenia: comparative trials with amisulpride and fluphenazine. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Behavioral and physiological effects of a beta blocker and relaxation therapy on mild hypertensives.
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). To evaluate the efficacy and tolerability of levetiracetam (LEV) as adjunctive therapy in children (4 to 16 years) with treatment-resistant partial-onset seizures.
                This multicenter, randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 14-week double-blind treatment period. During the treatment period, patients received either placebo or LEV add-on therapy and were up-titrated to a target dose of 60 mg/kg/day.
                One hundred ninety-eight patients (intent-to-treat population) provided evaluable data. The reduction in partial-onset seizure frequency per week for LEV adjunctive therapy over placebo adjunctive therapy was significant (26.8%; p = 0.0002; 95% CI 14.0% to 37.6%). A 50% or greater reduction of partial seizure frequency per week was attained in 44.6% of the LEV group (45/101 patients), compared with 19.6% (19/97 patients) receiving placebo (p = 0.0002). Seven (6.9%) LEV-treated patients were seizure-free during the entire double-blind treatment period, compared with one (1.0%) placebo-treated patient. One or more adverse events were reported by 88.1% of LEV-treated patients and 91.8% of placebo patients. The most common treatment-emergent adverse events were somnolence, accidental injury, vomiting, anorexia, hostility, nervousness, rhinitis, cough, and pharyngitis. A similar number of patients in each group required a dose reduction or withdrew from the study as a result of an adverse event.
                Levetiracetam adjunctive therapy administered at 60 mg/kg/day is efficacious and well tolerated in children with treatment-resistant partial seizures. The aim of this study was to assess the efficacy of lipophilic beta-blockers in preventing recurrent neurocardiogenic syncope and the value of head-up tilt test (HUT) in predicting response to therapy. The efficacy of beta-blockers in recurrent syncope is controversial. The value of HUT in predicting efficacy of therapy has not been investigated. Fifty-six patients (44+/-18 years, 36 women) with recurrent syncope (> 1 event in the last 6 months) of suspected neurocardiogenic origin were included in the study. Independent of the response to HUT, patients were randomized to receive metoprolol or propanolol at the maximal tolerated dose (28 patients, group A, 86+/-23 vs 98+/-29 mg/d) or no pharmacological therapy (28 patients, group B). The primary endpoint was the first recurrence of syncope. During the 1-year of follow-up, 20 patients of group A and 8 of group B had no recurrence. In group A, of 20 patients without recurrences 12 had a positive and 8 a negative HUT result while of 8 patients with recurrences 5 had a positive and 3 a negative response to HUT. In the group B, of 20 patients with recurrences 10 had a positive and 10 a negative HUT result while of 8 patients without recurrences 4 had a positive and 4 a negative response to HUT. In a multivariate Cox-regression analysis, medical therapy was the only independent factor for predicting recurrence of syncope (P = 0.004); HUT had no influence in this regard (P = 0.773). In conclusion, lipophilic beta-blockers appear efficacious in preventing recurrent syncope of suspected neurocardiogenic origin. The efficacy of therapy seems to be not predicted by HUT. The beta blocker stroke ("BEST") trial was designed to see if the apparent protective effect of propranolol on cerebral function in patients with subarachnoid haemorrhage applied also to patients suffering from acute stroke. Three hundred and two conscious patients with clinically diagnosed hemispheric strokes sustained within the past 48 hours were randomly assigned to receive atenolol, propranolol, or matching placebo capsules for three weeks. More early deaths occurred among the patients allocated to receive beta blockers, but this was largely explained by differences in the initial characteristics of the patients among the different treatment groups. By contrast, the outcome in a further 60 patients, who had been taking beta blockers at the time of their stroke but were otherwise similar to the patients in the trial, was considerably better, suggesting that prior treatment with beta blockers might be protective. The search for an effective medical treatment for acute stroke must continue. The approach used here, in which neurological outcome was assessed in a modest number of patients with a view to proceeding subsequently to a full scale trial of functional outcome, allows practical benefits of a treatment to be evaluated under realistic conditions and an ineffective treatment to be eliminated without undue cost. Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study.
                Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study.
                Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium.
                Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation. The efficacy of adjunctive imipramine hydrochloride treatment for syndromally defined postpsychotic depression was assessed in a six-week, double-blind, placebo-controlled study. All patients had been diagnosed as having schizophrenia or schizoaffective disorder, all were receiving stable doses of fluphenazine decanoate, and all had received benztropine mesylate in an attempt to rule out neuroleptic-induced akinesia. Patients randomized to imipramine therapy fared significantly better in terms of their global improvement and in terms of individual symptoms that are components of the depression syndrome. There were no significant differences in outcome psychosis ratings or side effects. This study indicates the existence of an identifiable syndrome of secondary depression in this patient group that is likely to respond favorably to treatment with adjunctive imipramine. 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. Switching patients from one antipsychotic to another can lead to tolerability problems or transient symptom exacerbations. It is important to compare switching strategies to determine which methods produce the best possible patient outcomes.
                To investigate the efficacy, safety and tolerability of three dosing strategies for switching chronic, stable patients with schizophrenia from current oral antipsychotic monotherapy to once-daily oral aripiprazole monotherapy.
                Patients in this 8-week, open-label, outpatient study were randomized to: 1). immediate initiation of 30 mg/day aripiprazole with simultaneous immediate discontinuation of current antipsychotic; 2). immediate initiation of 30 mg/day aripiprazole while tapering off current antipsychotic over 2 weeks; or 3). up-titrating aripiprazole to 30 mg/day over 2 weeks, while simultaneously tapering off current antipsychotic. Efficacy assessments included PANSS, CGI-S, and CGI-I scores. Safety assessments included: adverse events (AEs) recording, evaluation of extrapyramidal symptoms (EPS), vital signs, ECG, and clinical laboratory tests.
                Efficacy with aripiprazole was maintained during the study with numerical improvements compared with baseline in all three groups. The overall incidence of AEs was broadly comparable across all groups, and AEs were generally mild to moderate in severity and time-limited. Discontinuations due to AEs were comparable across the groups. No deterioration in EPS occurred in any group. The reduction in body weight and plasma prolactin levels following switch to aripiprazole were comparable across the three groups.
                Any of the three strategies evaluated can be used safely for switching patients to aripiprazole from antipsychotic monotherapy. Furthermore, patients' symptoms may continue to improve after switching to aripiprazole. In this industrial-based study we compared the blood pressure (BP)-lowering effectiveness of relaxation, a beta blocker, and the combined use of these two treatments in 47 untreated, mildly hypertensive blue collar steel workers. Using a randomized two by two factorial design, patients received either nadolol or placebo drug daily, and either a relaxation training or an education program, each lasting 8 weeks. A pre-intervention and post-intervention stress test measured response of heart rate and BP to mental and physical tasks. BP assessments were done at baseline, post-intervention, 1 month, and 3 month follow-up. Change in several self-report measures was determined. Results showed that beta blocker was more effective in lowering BP than placebo, but relaxation was not more effective in lowering BP than health education. The combined effect of beta blocker and relaxation was not superior to beta blocker alone. Compliance with relaxation practice was not superior to compliance with medication. We conclude that pharmacologic treatment is superior to the relaxation therapy tested.
Existing evidence is limited and dated. Any possible benefit of adjunctive beta-blocker therapy is obscured by poor reporting within the studies. Important data on quality of life, satisfaction, healthy days, and cost are not available. Considering the number of people whose symptoms are only partially responsive to antipsychotic medication, well conducted and reported trials in this area could be justified.