scholarly journals Antipsychotic Dose in Acute Schizophrenia: A Meta-analysis

2020 ◽  
Vol 46 (6) ◽  
pp. 1439-1458
Author(s):  
Hiroyoshi Takeuchi ◽  
Nicole E MacKenzie ◽  
Dominic Samaroo ◽  
Ofer Agid ◽  
Gary Remington ◽  
...  
Keyword(s):  
Side Effects ◽  
Meta Analysis ◽  
Positive Symptom ◽  
Fixed Dose ◽  
Double Blind ◽  
Acute Schizophrenia ◽  
Second Generation Antipsychotics ◽  
Oral Antipsychotic ◽  
Relationship Of ◽  
Higher Doses

Abstract Little is known regarding optimal antipsychotic doses in the acute phase of schizophrenia. The aim of the present study was to employ the concept of minimum effective dose (MED) in examining efficacy and tolerability within this population. MED was identified for each antipsychotic through a previous systematic review. We then identified double-blind placebo-controlled randomized trials that involved fixed-dose antipsychotic monotherapy in acute schizophrenia and compared the identified MED vs higher doses of the same oral antipsychotic. Studies were selected from a recent meta-analysis examining dose–response relationship of second-generation antipsychotics and haloperidol. We extracted the data on study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events. For each antipsychotic, we conducted a meta-analysis to compare outcomes between MED and 2-fold MED, and MED and 3-fold MED. A total of 26 studies involving 5618 patients were included in the meta-analysis. In terms of study discontinuation, significant differences were found in study discontinuation due to lack of efficacy between MED and higher doses, in favor of 2-fold and 3-fold MEDs. Regarding psychopathology, both 2-fold and 3-fold MEDs were superior to MED for total and positive symptom scores. As for side effects, 2-fold MED proved inferior to MED for parkinsonism scores and diarrhea, whereas 3-fold MED was inferior for akathisia, somnolence, and vomiting. Findings suggest that clinicians can dose an antipsychotic at 2-fold or 3-fold MED for patients with acute schizophrenia but should closely monitor side effects.

Evaluation of the Effect of Timolol Alone and in Combination with Hydrochlorothiazide and Amiloride in the Treatment of Mild to Moderate Arterial Hypertension: A Double-Blind, Controlled Study

1976 ◽  
Vol 51 (s3) ◽  
pp. 529s-531s ◽  
Author(s):  
G. Muiesan ◽  
B. Magnani ◽  
E. Agabiti-Rosei ◽  
C. Alicandri ◽  
E. Ambrosioni ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Side Effects ◽  
Moderate Essential Hypertension ◽  
Fixed Dose ◽  
Controlled Study ◽  
Double Blind ◽  
Combination Tablet ◽  
Group A ◽  
Group B

1. The effects of timolol alone and in combination with a fixed dose of hydrochlorothiazide and amiloride have been studied in a double-blind, controlled study in fifty-four patients with mild to moderate essential hypertension. 2. After a 4 weeks placebo period patients were randomly assigned to enter groups receiving timolol alone (group A), hydrochlorothiazide + amiloride (group B) or timolol + hydrochlorothiazide + amiloride (group C). Each treatment was carried out for 6 weeks. 3. The use of timolol (10 mg), hydrochlorothiazide (25 mg) and amiloride (2·5 mg) in a combination tablet given twice daily gave better control of blood pressure in patients with mild to moderate essential hypertension than did equivalent dosages of timolol alone or of hydrochlorothiazide and amiloride. 4. Clinical and laboratory side effects were minimal.

Antipsychotic Effects of Cannabidiol

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
F.M. Leweke ◽  
D. Koethe ◽  
F. Pahlisch ◽  
D. Schreiber ◽  
C.W. Gerth ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Paranoid Schizophrenia ◽  
Treatment Strategies ◽  
Endocannabinoid System ◽  
Psychotic Symptoms ◽  
Controlled Clinical Trial ◽  
Antipsychotic Treatment ◽  
Double Blind ◽  
Acute Schizophrenia

Background:In contrast to delta-9-tetrahydrocannabinol, the phytocannabinoid cannabidiol does not exert psychotomimetic effects. Cannabidiol was suggested a re-uptake inhibitor of anandamide and potential antipsychotic properties have been hypothesized for it. We therefore performed a clinical trial to investigate thesis hypothesis and to clarify the underlying link to the neurobiology of schizophrenia.Methods:We performed an explorative, 4-week, double-blind, controlled clinical trial on the effects of purified cannabidiol in acute schizophrenia compared to the antipsychotic amisulpride. The antipsychotic properties of both drugs were the primary target of the study. Furthermore, side-effects and anxiolytic capabilities of both treatments were investigated.Results:42 patients fulfilling DSM-IV criteria of acute paranoid schizophrenia participated in the study. Both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by BPRS and PANSS. However, there was no statistical difference between both treatment groups. In contrast, cannabidiol induced significantly less side effects (EPS, increase in prolactin, weight gain) when compared to amisulpride.Conclusions:Cannabidiol revealed substantial antipsychotic properties in acute schizophrenia. This is in line with our suggestion of an adaptive role of the endocannabinoid system in paranoid schizophrenia, and raises further evidence that this adaptive mechanism may represent a valuable target for antipsychotic treatment strategies.The Stanley Medical Research Institute (00-093 to FML) and the Koeln Fortune Program (107/2000 + 101/2001 to FML) funded this study.

A Multicentre Double Blind Trial of Fluoxetine versus Amitriptyline in the Treatment of Depressive Illness

1993 ◽  
Vol 27 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Fiona K. Judd ◽  
Kate Moore ◽  
Trevor R. Norman ◽  
Graham D. Burrows ◽  
Ramesh K. Gupta ◽  
...  
Keyword(s):  
Side Effects ◽  
Side Effect ◽  
Serotonin Reuptake ◽  
Depressive Illness ◽  
Fixed Dose ◽  
Side Effect Profile ◽  
Double Blind Trial ◽  
Double Blind ◽  
Antidepressant Efficacy ◽  
To Receive

The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline.

Efficacy and safety of brexpiprazole in schizophrenia: Meta-analysis of three double-blind, randomized, placebo-controlled phase 3 studies

2016 ◽  
Vol 33 (S1) ◽  
pp. S109-S109 ◽  
Author(s):  
C. Weiss ◽  
P. Zhang ◽  
M.J. Hakala ◽  
A. Skuban ◽  
E. Weiller
Keyword(s):  
Partial Agonist ◽  
Meta Analysis ◽  
Placebo Treatment ◽  
Phase 3 ◽  
Double Blind ◽  
Treatment Groups ◽  
Acute Schizophrenia ◽  
Three Phase ◽  
Flexible Dosing ◽  
Competing Interest

IntroductionBrexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors.ObjectivesTo evaluate the efficacy, safety, and tolerability of brexpiprazole in patients with acute schizophrenia in a meta-analysis of three phase 3 studies with brexpiprazole.AimThe primary endpoint was change from baseline to week 6 in PANSS total score.MethodsData from the 3 clinical studies in patients with acute schizophrenia were combined and analyzed using individual patient data meta-analysis. In two similarly designed studies (NCT01396421; NCT01393613), patients with acute schizophrenia were randomized to fixed-doses of brexpiprazole 2 mg/day, 4 mg/day or placebo (a low-dose treatment group was included in each study [0.25 mg and 1.0 mg]; not included in the meta-analysis). In the third study (NCT01810380), patients were randomized to flexible dosing of brexpiprazole (2 to 4 mg/day), placebo, or an active reference (quetiapine extended release). Changes from baseline for brexpiprazole vs. placebo were analyzed using an MMRM approach.ResultsBrexpiprazole 2–4 mg (n = 868) was superior to placebo (n = 517) in change from baseline in PANSS total score (−20.1 vs. −14.3; estimated treatment difference to placebo: −5.8 [95% CI: −8.0; −3.6]; P < 0.001). The proportions of patients reporting TEAEs were similar between the brexpiprazole and placebo treatment groups (57.9% vs. 57.5%). No unexpected safety concerns were observed.ConclusionThis meta-analysis supports evidence from three individual trials that brexpiprazole is efficacious and safe in treating patients with acute schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Étude Comparative de la Butapérazine et de la Prochlorpérazine Chez le Schizophrène Chronique

1965 ◽  
Vol 10 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Paul Rajotte ◽  
J.-M. Bordeleau ◽  
Léon Tétreault
Keyword(s):  
Side Effects ◽  
Significant Positive Correlation ◽  
Global Evaluation ◽  
Double Blind Trial ◽  
Double Blind ◽  
Significant Difference ◽  
Duration Of Hospitalization ◽  
Schizophrenic Patients ◽  
Parametric Statistics ◽  
Higher Doses

A comparative double-blind trial of butaperazine and prochlorperazine was carried out in 40 chronic schizophrenic patients. Subjects were matched in 20 pairs according to sex, age, duration of hospitalization, staff, ward and score on the B.P.R.S. Drugs were randomly allocated within each pair of patients and their effects evaluated according to the B.P.R.S. Posology was progressively increased up to 200 mg. daily but remained always equal for all patients. Results were analysed by non-parametric statistics for the B.P.R.S. and by an χ2 test for the global evaluation. Butaperazine and prochlorperazine showed a significant therapeutic efficacy throughout the twelve-week period. At the fourth and tenth week, prochlorperazine was significantly superior to butaperazine. However, at the twelfth week there was no significant difference in the efficacy of both drugs, as measured by the B.P.R.S. and the global evaluation. Beyond 100 mg. daily of both drugs a plateau was reached which higher doses did not influence. Side effects made their appearance sooner with butaperazine but at the end of the trial the frequency of side effects was comparable with both drugs. A highly significant positive correlation between raters adds weight to our results*.

Influence of Ibuprofen on Oral Anti-Coagulation with Phenprocoumon

1974 ◽  
Vol 2 (4) ◽  
pp. 279-283 ◽  
Author(s):  
M J Boekhout-Mussert ◽  
E A Loeliger
Keyword(s):  
Side Effects ◽  
Oral Anticoagulants ◽  
The Other ◽  
Reverse Order ◽  
Fixed Dose ◽  
Double Blind ◽  
Number Of Patients

Twenty-four patients on long-term anti-coagulant treatment with phenprocoumon (Marcoumar®) took part in a study designed to investigate the possible interaction between phenprocoumon and ibuprofen (Brufen®). Prior to entry into the study, the anti-coagulant state of each patient was adequately controlled on a dose of phenprocoumon which remained unchanged throughout the study. Under double-blind conditions, half of the total number of patients received ibuprofen 600 mg a day in three divided doses for two weeks followed by two weeks without therapy; then two weeks of placebo, again followed by two weeks without therapy. The other patients received the drugs in the reverse order. The anti-coagulant state was measured using the Thrombotest, the results being expressed as a percentage of the normal. The results indicated that the effects of a fixed dose of phenprocoumon, as measured by the Thrombotest, did not alter significantly throughout the study, and no serious side-effects were noted. These findings suggest that in general, ibuprofen can safely be given to patients receiving oral anticoagulants without the risk of interfering with their anti-coagulant state.

Old versus new: weighing the evidence between the first- and second-generation antipsychotics

2005 ◽  
Vol 20 (1) ◽  
pp. 7-14 ◽  
Author(s):  
John M. Davis ◽  
Nancy Chen
Keyword(s):  
Side Effects ◽  
Evidence Based Medicine ◽  
Second Generation ◽  
Psychotic Patient ◽  
Evidence Based ◽  
Random Assignment ◽  
Double Blind ◽  
Second Generation Antipsychotics ◽  
First And Second Generation ◽  
Based Medicine

AbstractIn our opinion the best guide to prescribing antipsychotics is the clinician’s experience with his patients and in particular the patient being treated. If treatment works, stick with it. We feel it is also important for the clinician to consider the evidence from well-controlled double-blind random-assignment studies because in “evidence-based medicine,” biases both known and unknown are controlled by blinding and randomization. The purpose of this paper is to summarize and discuss the evidence on efficacy. Choice of antipsychotic, in our opinion, is probably the most important decision that the clinician makes for the psychotic patient. This involves the choice of drug, its dose, balancing efficacy, side-effects and cost.

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