Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia. Diazepam in high doses is effective in schizophrenia. Acute high-dose parenteral haloperidol treatment of psychosis. A double-blind comparison of clonazepam and placebo in the treatment of neuroleptic-induced akathisia. Combined drug treatment of newly hospitalized, acutely ill psychiatric patients. Schizophrenics fully remitted on neuroleptics for 3-5 years--to stop or continue drugs? A double-blind comparison of diazepam, chlordiazepoxide and chlorpromazine in psychotic patients. Successful clonazepam treatment of neuroleptic-induced akathisia in older adolescents and young adults: a double-blind, placebo-controlled study. Diazepam treatment of early signs of exacerbation in schizophrenia. Double blind, controlled study of the efficacy and safety of alpidem in the treatment of anxiety in schizophrenic in-patients. Itil TM, Keskiner A, Fink M: Thioridazine and chlordiazepoxide, alone and combined, in the treatment of chronic schizophrenia. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. A double-blind outpatient study of diazepam (Valium) and placebo. Prophylactic effect of neuroleptics in symptom-free schizophrenics. Haloperidol and lorazepam combined: clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis. The use of midazolam in acutely agitated psychiatric patients. Comparative effects of fluphenazine, fluphenazine-chlordiazepoxide and fluphenazine-imipramine. Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior. The effects of chlordiazepoxide (librium) in anxiety states. A multi-blind study. Chlorpromazine-chlordiazepoxide and chlorpromazine-imipramine treatment: side effects and clinical laboratory findings. Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation. The therapeutic effects of lorazepam in psychotic patients treated with haloperidol: a double-blind study.
The efficacy of a benzodiazepine was compared with that of a neuroleptic for the rapid tranquilization of patients presenting at a psychiatric emergency room service. Thirty-seven highly agitated patients exhibiting psychotic symptoms were randomly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed every 30 min for 4 h. Administration route was either intramuscular injection or oral concentrate. Symptom ratings were conducted each hour using double-blind procedures. Both medications reduced symptom ratings on the Brief Psychiatric Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale. Global Clinical Impression scores for the two medication groups did not differ significantly either at baseline or at 4 h after entry into the study. However, Global Clinical Impression scores of patients in the lorazepam group were less severe at intermittent ratings. The groups did not differ on the Brief Psychiatric Rating Scale at any rating time. No differences were found either in the number of doses administered or in the administration route selected. Given the potential for severe extrapyramidal symptoms developing hours or days after a single dose of haloperidol, lorazepam may provide an excellent alternative for the rapid tranquilization of the acutely agitated psychotic patient in the emergency room setting. While neuroleptics remain the mainstay of drug intervention in the emergency management of psychosis, a variety of agents have received study as alternatives or adjuncts to these drugs in an attempt to improve the safety and efficacy of acute treatment. The purposes of this study were to investigate the efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic patients in psychotic relapse and to clarify the effects of combination treatment on specific aspects of the psychotic process.
                Twenty-eight acutely psychotic patients with schizophrenia who were admitted to an emergency psychiatric service were randomly assigned to treatment with either haloperidol and alprazolam or haloperidol with placebo under double-blind conditions. Drug administration lasted 72 hours.
                Both groups improved significantly. The combination-treated group required significantly less medication and had 56% fewer dystonic reactions. The addition of alprazolam was most effective for symptoms of excitement and uncooperativeness, particularly in the initial hours of treatment.
                The combination of alprazolam and haloperidol seems to be the most effective for agitated patients, particularly in the first 48 hours of treatment. It may also result in fewer dystonic reactions. 1. Diazepam in high doses, up to 400 mg per day, was administered to paranoid schizophrenic patients in a double-blind placebo-controlled study. 2. The effects of treatment were assessed by the following: the Brief Psychiatric Rating Scale (BPRS); the Clinical Global Impressions Scale (CGI); the Schizophrenia Subscale of the Present State Examination (SS-PSE); the Simpson-Angus Rating Scale (SARS) for extrapyramidal symptoms; the Nurses' Observation Scale for Inpatient Evaluation (NOSIE); and a 90 item Self-Assessment Questionnaire (SCL-90). 3. Within a few hours to a few days from the onset of diazepam treatment both positive (such as auditory hallucinations and persecutory delusions) and negative (such as emotional withdrawal and blunted affect) schizophrenic symptoms were dramatically eliminated in 5 out of the 6 patients. After 2 days of drug-free observation, 20 newly admitted psychotic patients received 20-35 mg of haloperidol intravenously and 20 patients received 30-40 mg of diazepam intravenously. Posttreatment ratings at 4 and 24 hours with the Brief Psychiatric Rating Scale and the Clinical Global Impressions revealed significant improvement in both groups but no significant differences between the two treatments. The present study was designed to investigate the efficacy of clonazepam in neuroleptic-induced akathisia. Twelve patients were treated during 2 weeks with clonazepam or placebo in a double-blind randomized design. Akathisia was scored by an independent rater before and after treatment, as well as 1 week after medication withdrawal. Clonazepam (0.5-2.5 mg/day) induced a significantly higher reduction in the akathisia scores than placebo (p < 0.05). One week after stopping the drug, there was a partial but significant relapse in the treated group as compared with controls, in whom the symptoms remained stable. In addition, the clinical improvement was significantly correlated with the daily dose of clonazepam (rs = 0.827; p < 0.002). These results support the potential usefulness of clonazepam in the treatment of neuroleptic-induced akathisia and suggest an optimal daily dose in the range of 10-40 micrograms/kg. nan A double-blind comparison between benzodiazepines and neuroleptics was carried out for 1 1/2 years on 30 schizophrenics who had hitherto continuously received neuroleptics and remained apparently in full remission for at least 3-5 years. The benzodiazepine-group had a significantly higher relapse rate than the neuroleptic-group, meaning that we cannot stop neuroleptics for these patients yet. Three possible reasons for this are (1) demand of the natural course of the illness, (2) the fact that the patients agreed to stay in therapy for so long may signify a need for therapy, (3) some of the relapses on stopping neuroleptics may be 'withdrawal psychosis' after prolonged neuroleptic therapy. If withdrawal of neuroleptics is really needed, however, it may be considered for a subgroup of female patients whose illness started after the age of 40. nan In a double-blind, placebo-controlled trial of clonazepam in the treatment of neuroleptic-induced akathisia in older adolescents, clonazepam was significantly more effective at reducing akathisia scores at the end of the first treatment week than placebo (p less than 0.0001). Clonazepam may be a safe and effective treatment for neuroleptic-induced akathisia in this age group. Therapeutic intervention at the earliest phase of symptom exacerbation in schizophrenia is an important clinical need, but specific pharmacotherapeutic interventions for this phase of illness have not been established. This study examined diazepam efficacy for this phase of treatment.
                A double-blind, randomized clinical trial with 53 schizophrenic patients compared diazepam with placebo (with fluphenazine treatment for a comparison group). Treatment was initiated at the earliest signs of exacerbation, and symptom progression was the dependent measure used to evaluate efficacy.
                Diazepam was statistically superior to placebo in preventing symptom progression and was comparable to fluphenazine.
                Efficacy data support the use of diazepam in treating prodromal and early warning signs of symptom exacerbation in schizophrenia. This therapeutic strategy may be especially important for patients who refuse antipsychotic drugs or as a supplemental approach in a treatment plan that emphasizes low-dose antipsychotic therapy. In this double-blind study, alpidem, a new imidazo-pyridine anxiolytic drug, was compared with placebo in order to test its efficacy and safety in chronic schizophrenic in-patients suffering from anxiety not directly related to the schizophrenic process. Sixty-six patients aged from 18 to 65 entered the trial. They also scored at least 18 on the Hamilton Rating Scale for Anxiety (HRSA) after a seven-day placebo run-in. Improvement in symptoms was evaluated by means of the HRSA, the Brief Psychiatric Rating Scale (BPRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression score (CGI). Thirty-three patients were randomly allocated to alpidem and 33 to placebo. Alpidem was significantly more effective (P less than 0.0001) than placebo in improving HRSA scores (total score and factorial scores for somatic and psychic anxiety), BPRS, and VAS. Considering the results of CGI at 21 day, more patients were moderately to markedly improved on alpidem (30/33) than on placebo (2/33) (P less than 0.0001). The efficacy index, according to CGI, was significantly better (P less than 0.001 at least) for alpidem than for placebo. Side-effects were negligible in both groups. nan Rapid tranquilization is a routinely practiced method of calming agitated psychotic patients by use of neuroleptics, benzodiazepines, or both in combination. Although several studies have examined the efficacy of the three approaches, none have compared these treatments in a prospective, randomized, double-blind, multicenter trial. Ninety-eight psychotic, agitated, and aggressive patients (73 men and 25 women) were prospectively enrolled during an 18-month period in emergency departments in five university or general hospitals. Patients were randomly assigned to receive intramuscular injections of lorazepam (2 mg), haloperidol (5 mg), or both in combination. Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours, based on clinical need. They were evaluated hourly after the first injection until at least 12 hours after the last. Efficacy was assessed on the Agitated Behavior Scale (ABS), a modified Brief Psychiatric Rating Scale (MBPRS), Clinical Global impressions (CGI) scale, and an Alertness Scale. Effective symptom reduction was achieved in each treatment group with significant (P < .01) mean decreases from baseline at every hourly ABS evaluation. Significant (P < .05) mean differences on the ABS (hour 1) and MBPRS (hours 2 and 3) suggest that tranquilization was most rapid in patients receiving the combination treatment. Study event incidence (side effects) did not differ significantly between treatment groups, although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms. The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation. nan Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design. Patients were randomly assigned to the following drugs orally administered twice a day: placebo; diazepam 15 mg; imipramine 50 mg; chlorpromazine 75 mg; and haloperidol 3 mg. The number of days of remission for each patient was recorded. Since only two patients received all five drug treatments, the data were analyzed using the number of days allocated to the "first assigned drugs" only and the cross-over aspect of the experimental design was disregarded. All patients treated with either the placebo, diazepam or imipramine relapsed within a year. On the other hand, four patients treated with chlorpromazine, or with haloperidol, were in remission for more than 1 year. Fifty percent of the patients relapsed within 16 days with placebo; 88 days with diazepam; 30 days with imipramine; 165 days with chlorpromazine; and 74 days with haloperidol. Within a year, only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine. At the end of the 3-year trial, both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs. These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics. In 61 acute schizophrenic patients the effects of haloperidol (HPL) and lorazepam combined vs. HPL alone and the interaction between these drugs were evaluated. Patients were assigned to groups randomly. The study design was open. Study duration was 28 days. Psychopathology was evaluated on the basis of BPRS scores. Extrapyramidal side-effects were rated according to Simpson and Angus (1970). Pharmacological parameters included serum levels of lorazepam, HPL, and reduced HPL. Mean daily lorazepam dosage was 0.05 mg/kg, mean HPL dosage 0.5 mg/kg. None of the patients treated with lorazepam and HPL achieved better BPRS total or subscores, nor did their condition improve faster than in patients treated with HPL alone. A significant linear relationship between lorazepam serum levels and oral dosage was found, but none between lorazepam serum levels and BPRS total score, subscore reduction, or extrapyramidal side-effects. The authors conclude that beneficial effects of lorazepam in the treatment of acute psychosis are scant and may not justify the risks incurred with routine comedication of lorazepam. Agents currently used for acutely agitated patients such as sodium amytal and haloperidol are disadvantageous because of their adverse effects on the respiratory and extrapyramidal systems. Because of this, a rapid, safe, well-absorbed agent such as midazolam would be useful. This study compares the effectiveness of midazolam, sodium amytal, and haloperidol in agitated schizophrenic patients. Five male patients between 28 and 59 years were randomly assigned to each group. They were administered intramuscularly either 10 mg of haloperidol, 250 mg of sodium amytal, or 5 mg of midazolam. Over a 2-hour period, patients were rated for motor agitation, hostility, auditory hallucinations, and flight of ideas. Both midazolam and sodium amytal were significantly more effective than haloperidol in controlling motor agitation. There were no treatment differences on any other symptom rated. These results indicate that further studies on the use of midazolam to achieve rapid tranquilization would be useful. nan The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients.
                Twenty-eight actively psychotic inpatients, aged 20-60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale.
                Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes.
                Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings. nan nan The combination of haloperidol, 5 mg, and lorazepam, 4 mg, was both effective and safe for managing agitated behavior in an open trial with acutely psychotic patients. The combination also appeared to be superior to its individual components when studied in a randomized, nonblind trial. The principle of the combined use of antipsychotics and sedative-hypnotics was further tested by comparing two new combinations: thiothixene, 5 mg, and lorazepam, 4 mg, versus haloperidol, 5 mg, and phenobarbital sodium, 130 mg. These combinations had comparable efficacy and safety, and the level of transquilization approached that produced by the haloperidol-lorazepam combination in the preceding studies. nan
There is currently no convincing evidence to confirm or refute the practise of administering benzodiazepines as monotherapy or in combination with antipsychotics for the pharmacological treatment of schizophrenia and schizophrenia-like psychosis. Low-quality evidence suggests that benzodiazepines are effective for very short-term sedation and could be considered for calming acutely agitated people with schizophrenia. Measured by the overall attrition rate, the acceptability of benzodiazepine treatment appears to be adequate. Adverse effects were generally poorly reported. High-quality future research projects with large sample sizes are required to clarify the evidence of benzodiazepine treatment in schizophrenia, especially regarding long-term augmentation strategies.