Paroxetine efficacy in the treatment of generalized anxiety disorder. Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study. [Zotepine versus perazine in patients with paranoid schizophrenia: a double-blind controlled trial of its effectiveness]. Prior benzodiazepine use and buspirone response in the treatment of generalized anxiety disorder. A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms. Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder. Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial. Efficacy and safety of a putative anxiolytic agent: ipsapirone. The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine.
Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD. 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 Four patients in the HAL-D group were withdrawn because of deterioration.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. The dibenzothiepine zotepine is a new potential "atypical" neuroleptic exhibiting powerful antiserotonergic and antidopaminergic properties. The efficacy of zotepine was evaluated in a double-blind controlled trial versus the tricyclic neuroleptic perazine in 41 patients suffering mainly from the paranoid-hallucinatory type of schizophrenia. The key outcome variable was the extent of mental disturbance as defined by the total score of the BPRS. Additional outcome variables were GAS and CGI. In addition, adverse reactions and extrapyramidal side effects were assessed according to the FSUCL scale and the Gerlach and AIMS rating scale, respectively. Additional variables recorded were blood pressure, heart rate and routine laboratory parameters as well as electrocardiogram and electroencephalogram. In the first two days, standard equivalent doses of both drugs were administered. Thereafter, doses were administered as required. The efficacy of both substances was compared after 7, 14 and 28 days of treatment. Both drugs showed a similar antipsychotic efficacy. Under zotepine treatment a 55% improvement of the BPRS total score was observed while perazine led to a 41% BPRS score reduction. After 7 days the zotepine group was significantly more improved than the perazine group, possibly due to a dosing effect in the perazine group. In the zotepine group, fewer adverse reactions and a better benefit/risk index were observed although the differences between the two treatment groups did not reach levels of statistical significance. There were no drug-specific abnormal laboratory findings. Thus, in the present study there was no significant difference between zotepine and perazine with respect to antipsychotic efficacy and side-effect rates. However, zotepine showed a trend to a better benefit/risk index at the end of treatment. An earlier preliminary report suggested that prior treatment with benzodiazepines might predict a reduced response to buspirone in patients diagnosed with generalized anxiety disorder (GAD). To confirm or refute this hypothesis, the present data analysis was conducted.
                One large data set (N = 735) of GAD patients (DSM-III) treated with buspirone, a benzodiazepine, and a placebo was analyzed by dividing all patients into 3 prior benzodiazepine (BZ) treatment groups: no prior BZ treatment, recent (< 1 month) BZ treatment, and remote (> or = 1 month) BZ treatment. Using an intent-to-treat last-observation-carried-forward (LOCF) data set, acute 4-week treatment response was assessed in terms of clinical improvement, attrition, and adverse events as a function of these 3 prior benzodiazepine treatment groups.
                Patient attrition was significantly higher (p < .05) in the recent BZ treatment group than in the remote and no prior BZ treatment groups with lack of efficacy given as the primary reason by patients receiving buspirone but not benzodiazepine or placebo. In the buspirone group, adverse events occurred more frequently in the recent BZ treatment group than in the remote BZ treatment and no prior BZ treatment groups. Finally, clinical improvement with buspirone was similar to benzodiazepine improvement in the no prior BZ treatment and remote BZ treatment groups, but less than benzodiazepine improvement in the recent BZ treatment group, leading to the smallest buspirone/placebo differences in improvement in the recent BZ treatment group.
                These data suggest that the initiation of buspirone therapy in GAD patients who have only recently terminated benzodiazepine treatment should be undertaken cautiously and combined with appropriate patient education. The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms.
                This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF).
                At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight.
                For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients. To compare the relative efficacy and safety of lesopitron 4-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD).
                Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study.
                Outpatient clinic.
                One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup.
                After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12-lead electrocardiograms, laboratory analyses, and adverse event monitoring.
                An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen, with mean changes of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design.
                The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested. Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary. Ipsapirone is an azopirone derivative that selectively interacts with serotonin-1A (5-HT1A) receptors and fails to affect other neurotransmitter receptors. In this study, ipsapirone at 15 mg or 30 mg was compared with diazepam at 15 mg and placebo in a double-blind, random assignment study design in patients with generalized anxiety disorder (GAD). During 4 weeks of treatment, both active drugs were therapeutically superior to placebo, without significant drug vs. drug therapeutic differences. The side-effect profile of ipsapirone at 15 mg was favorable compared to diazepam, but at 30 mg ipsapirone produced significant gastrointestinal disturbances. Cognitive deficits are a core feature of schizophrenia. As a target of intervention, improvements in cognition may lead to improvements in functional outcome.
                The present paper is the first report, to our knowledge, on the neurocognitive effects of aripiprazole. Unlike other second-generation antipsychotics, aripiprazole is a D(2) and D(3) receptor partial agonist. It is unknown what effects this unusual pharmacological profile may yield on neurocognition.
                The present open-label study included data on 169 patients with schizophrenia or schizoaffective disorder who were randomly treated with aripiprazole or olanzapine. Subjects received a neurocognitive battery at baseline, week 8, and 26.
                The aripiprazole group had a significantly greater dropout rate than the olanzapine group. Neurocognitive data were reduced through a principal components analysis that yielded a three-factor solution. The factors were general cognitive functioning, executive functioning, and verbal learning. For general cognitive functioning, both groups improved from baseline and the effects were relatively stable over the 26-week protocol. There were no differential treatment effects. For executive functioning, neither group improved significantly from baseline. For verbal learning, the aripiprazole group improved significantly from baseline to the 8th and 26th week of assessment, and there was a between-group effect favoring aripiprazole over olanzapine that was largely attributable to the differences in performance within the 8th week. Separate analyses were conducted for a measure of sustained attention (Continuous Performance Test-Identical Pairs). There were no differential treatment effects on this measure.
                The findings from this open-label study suggest that the neurocognitive effects of aripiprazole are at least as good as those of olanzapine.
Azapirones appeared to be useful in the treatment of GAD, particularly for those participants who had not been on a benzodiazepine. Azapirones may not be superior to benzodiazepines and do not appear as acceptable as benzodiazepines. Side effects appeared mild and non serious in the azapirone treated group. Longer term studies are needed to show that azapirones are effective in treating GAD, which is a chronic long-term illness.