Propranolol in schizophrenia: a double blind, placebo controlled trial of propranolol as an adjunct to neuroleptic medication. A double-blind, placebo-controlled study of adjunctive nadolol in the management of violent psychiatric patients. Oxprenolol in schizophrenic patients with tardive dyskinesia: a double-blind placebo-controlled, crossover study. Propranolol as an adjunct to the treatment of schizophrenia. Adjunctive nadolol in the treatment of acutely aggressive schizophrenic patients. Low-dose mirtazapine: a new option in the treatment of antipsychotic-induced akathisia. A randomized, double-blind, placebo- and propranolol-controlled trial. A trial of propranolol in chronic schizophrenia. Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study. A placebo-controlled trial of nadolol in the treatment of neuroleptic-induced akathisia.
A double blind, placebo controlled trial was carried out to examine the contribution of propranolol as an adjunct to neuroleptic medication in the treatment of chronic schizophrenic patients whose florid symptoms had not remitted with neuroleptic medication alone. Propranolol was shown to have a more beneficial effect than placebo, but the results were much less dramatic than those which have been described in previous studies. Recent work has shown that there may be a pharmacokinetic interaction between propranolol and neuroleptics, and this should be considered as one possible explanation of our findings. We report a controlled 3-week study (n = 30) of adjunctive use of nadolol, 80 to 120 mg per day, vs. placebo for the management of violent psychiatric patients. There were no remarkable adverse cardiac effects at this dose. The active treatment group showed lower total Brief Psychiatric Rating Scale (BPRS) scores after the first week of treatment (analysis of covariance [ANCOVA], p less than .08) and similar trends for the activation factor and the hostility scale. There were parallel findings for measures of extrapyramidal symptoms (EPS) (Simpson-Angus Neurological Rating Scale), which were reliable after the second week (ANCOVA, p less than .02). A significant association between changes in EPS and BPRS scores was found by regression analysis, after the effects of baseline measures were removed. Given that nadolol does not penetrate the central nervous system well, the antiaggressive effects may be associated with sympathetic nervous system feedback mechanisms. Tardive dyskinesia is a syndrome of involuntary movements that develops during or following long-term neuroleptic treatment. Current treatment of tardive dyskinesia is unsatisfactory. Neuroleptics can reduce the syndrome, but the underlying pathogenetic process is probably aggravated during treatment. The use of these drugs is necessary, however, when the patient simultaneously exhibits intense psychotic and dyskinetic symptoms. In this controlled study, 8 patients were treated with a beta-blocker drug, oxprenolol, as a slow-release preparation that was administered in increasing doses up to 640 mg per day for one month. We conclude that this drug can ameliorate both the psychotic features of schizophrenics and their tardive dyskinetic movements without producing significant side-effects. Propranolol contributed usefully to the practical management of patients with chronic schizophrenia whose florid symptoms had not remitted with major tranquillisers. 14 patients who had received an average equivalent of 954 mg per day of chlorpromazine for 10 years were given, in addition, either propranolol or a placebo for 12 weeks. Both groups had improved by the twelfth week, but the propranolol group had improved significantly more. This study assessed the safety and efficacy of nadolol 120 mg/day compared with placebo, when administered adjunctively to neuroleptic in a group of acutely aggressive schizophrenic patients.
                Thirty-four male patients enrolled in this double-blind, placebo-controlled trial. The subjects were evaluated with the Brief Psychiatric Rating Scale (BPRS) and the Simpson Angus Neurologic Rating Scale for extrapyramidal effects. The total BPRS score as well as three factors, thought disturbance, hostility, and activation, was analyzed.
                Compared with those who received placebo, the patients taking nadolol showed significant improvement on total BPRS score, particularly on the thought disturbance and activation factors, after the first treatment week (p = .05). By the end of the second treatment week, the patients taking placebo also began to show improvement, and the group differences were no longer significant. The patients treated with nadolol showed significantly more improvement on Simpson-Angus scores than those who received placebo (p = .03). However, there was no significant correlation between BPRS and Simpson-Angus changes. In the nadolol group, patients with and without akathisia showed no significant difference in their BPRS scores.
                These findings suggest that adjunctive nadolol may be useful in the treatment of acutely aggressive schizophrenic patients by inducing a more rapid and consistent decrease of overall psychiatric symptoms and by reducing the extrapyramidal effects. Our results raise the possibility that the mechanism of action of nadolol on psychiatric symptoms in schizophrenic patients may be different from the mechanism of improvement of neuroleptic-induced extrapyramidal symptoms and akathisia. Nadolol may be a helpful adjunctive treatment for schizophrenic patients in general and not just for those with a high hostility level. Preliminary evidence indicates a beneficial effect of serotonin 2A (5-HT(2A)) receptor antagonists in antipsychotic-induced akathisia (AIA). We investigated the antiakathisia effect, safety, and tolerability of low-dose mirtazapine, an agent with marked 5-HT(2A) antagonism.
                In a 7-day double-blind trial, 90 antipsychotic-treated patients meeting DSM-IV criteria for AIA were randomly assigned to mirtazapine (n = 30; 15 mg), propranolol (n = 30; 80 mg), or placebo (n = 30). Primary outcome measures were between-group differences in Barnes Akathisia Scale (BAS) global scores and in the proportion of responders (reduction of > or = 2 points on BAS). Analysis was by intention to treat.
                Twenty-four patients (26.6%) who were assigned treatment did not complete the study (7 mirtazapine, 8 propranolol, 9 placebo), due to lack of response (n = 19) and adverse events (n = 5). Both mirtazapine and propranolol significantly reduced AIA severity (BAS: -34% mirtazapine and -29% propranolol vs. placebo -11%; p = .012 and p = .023, respectively). Thirteen (43.3%) mirtazapine and 9 (30.0%) propranolol-treated patients versus 2 (6.7%) placebo-treated patients responded (the corresponding odds ratios 10.7 [95% confidence interval (CI), 2.1-53.3] and 6.0 [95% CI, 1.1-30.7]). Five (16.7%) of 30 propranolol-treated patients and none in the mirtazapine and placebo groups (p = .0195 for both) prematurely discontinued the study due to clinically significant hypotension or bradycardia.
                The comparable efficacy and better tolerability of low-dose mirtazapine versus propranolol, the current first-line treatment for AIA, position mirtazapine as a favorable candidate for the treatment of acute AIA and may improve current therapeutic practices. nan Considerable evidence indicates that the lipophilic beta-blocker propranolol is useful in treating organically based aggression. This study looked at the efficacy of a more hydrophilic beta-blocker, nadolol, to treat aggression in chronic psychiatric inpatients.
                Forty-one chronic psychiatric inpatients with an average of one aggressive outburst per week (defined by the Overt Aggression Scale [OAS]) were entered into a double-blind, placebo-controlled study lasting 17 weeks. The OAS was used to track aggression on a per-incident basis, while the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions scale (CGI) were used to track clinical status.
                Nadolol subjects showed a significant decline in frequency of aggression compared with controls (p = .026) and a significant decline in the BPRS total score (p = .007) and in the subfactors "hostility and suspicion," "negative symptoms," and "signs of hyperarousal/tension." There was no significant change in CGI "severity of illness" ratings between groups, although the nadolol group was significantly improved from baseline at every subsequent time period while the placebo group was unchanged throughout the study.
                Nadolol is of significant benefit in the treatment of aggression in chronic psychiatric inpatients. This drug does penetrate the brain over time, but the success of a drug whose primary locus of action is peripheral may implicate a bimodal mechanism of action, i.e., a role for the CNS and the soma in the maintenance of aggression. Although propranolol has been documented to be useful in treatment of neuroleptic-induced akathisia, preliminary anecdotal reports on the efficacy of nadolol in treatment of this condition are contradictory.
                To evaluate the efficacy of nadolol in treatment of this condition, a double-blind, placebo-controlled trial was conducted in 20 psychiatric inpatients. Patients with akathisia of at least moderate severity were randomly assigned to receive nadolol 40 to 80 mg/day or placebo. Patients were rated daily for 4 days, then every other day for 15 days by means of the Extrapyramidal Symptom Rating Scale.
                No significant differences were found between or within groups in subjective restlessness scores. In objective akathisia scores, there were no significant differences between groups; however, beginning at Day 9, both groups showed significant improvement compared with Day 1. There was no difference between groups in number of responders.
                The authors' data do not support the efficacy of nadolol in the treatment of neuroleptic-induced akathisia and do not provide support for a peripheral site of action for beta-blockers in treatment of this condition.
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.