Antipsychotic Efficacy of the Antidepressant Trimipramine: A Randomized, Double-blind Comparison with the Phenothiazine Perazine

Bender, Stefan; Olbrich, H. M.; Fischer, W.; Hornstein, C.; Schoene, W.; Falkai, Peter; Haarmann, C.; Berger, M.; Gastpar, Markus

doi:10.1055/s-2003-39043

Cited by 17 publications

(11 citation statements)

References 18 publications

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“…With regard to trimipramine, to our knowledge, its effect on CYP1A2 has not yet been investigated. However, it is likely that it exerts some influence as trimipramine has a chemical structure very similar to imipramine (Bender et al, 2003), and CYP1A2 mediates the N-demethylation of imipramine (Koyama et al, 1997). The kinetics of clozapine are nonlinear which means that after CYP1A2 inhibition (e.g.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of combined clozapine–lithium pharmacotherapy

Bender

Linka

Wolstein

et al. 2004

Int. J. Neuropsychopharm.

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Several case reports described neurotoxic side-effects in the course of a combined clozapine-lithium treatment. Here we report on the safety and efficacy of this combination in a sample of 44 hospital patients. Medical records were retrospectively audited and a subsample of 23 patients was re-assessed. Mean total duration of combined treatment was 23.5 months. The combination (indications: prophylaxis; treatment of affective symptoms or aggression/excitement; augmentation of neuroleptic efficacy) was rated effective in 84% and adverse events were reported in 64% of the patients. Notably, most of the adverse events were benign and transient. However, 8 patients (18%) developed transient neurological adverse events that were genuinely novel in only 3 patients (7%) and coincided with high dosage of medication or high plasma levels or serotonergic (antidepressant) co-medication. Our data suggest that combined clozapine-lithium treatment may appear to be safe and effective when administered within a moderate therapeutic dose range and without serotonergic co-medication or other substances interfering with clozapine metabolism.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of combined clozapine–lithium pharmacotherapy

Bender

Linka

Wolstein

et al. 2004

Int. J. Neuropsychopharm.

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“…This model explains 34% of the variability of the slopes but only 1.5% of the variability of the intercepts, i.e. of the variability of the groups at level 2, according to formula (7). Figure 1, a strong interaction was found between center and therapy.…”

Section: Resultsmentioning

confidence: 91%

“…Nevertheless, these methods are still rarely used in the analysis of clinical trials. Recent literature includes analyses of longitudinal data using the t-test [7] or various kinds of analysis of variance as used [8][9][10][11][12], as an example. If linear mixed models are used, the model building is usually not described in a manner, that is easy to follow [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Data Analysis of Symptom Score Trajectories Using Linear Mixed Models in a Clinical Trial

Engel¹

2013

ijsmr

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In clinical trials, longitudinal data are often analyzed using T-tests, anovas or ancovas instead of the more powerful linear mixed models. The purpose of this paper is to demonstrate how the more sophisticated linear mixed models according to the approach of Singer and Willett, which allows special insight into the behaviour of the data, can be used in clinical trials. Individual trajectories of PANNS-MNS Scores from a controlled clinical trial were used to demonstrate all the steps needed for an analysis of longitudinal data. The model is built step by step, model assumptions are checked, time-variant and time-invariant factors are included and the results are interpreted. The unique needs of a clinical trial, such as the calculation of effect sizes or of an appropriate sample size, are taken into account. Finally, a flow chart is presented that would serve as an instruction tool for the analysis of longitudinal data in clinical trials.

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“…The study was conducted in accordance with the Basic & Clinical Pharmacology & Toxicology policy for experimental and clinical studies . In a 5‐week clinical study, the efficacy of the antidepressant trimipramine was compared to that of perazine in the treatment of schizophrenic patients . Patients who were treated with antipsychotic drugs before the commencement of the study underwent a washout period of 2‐3 days.…”

Section: Methodsmentioning

confidence: 99%

The effect of perazine on the CYP2D6 and CYP2C19 phenotypes as measured by the dextromethorphan and mephenytoin tests in psychiatric patients

Baumann

Eap

Gastpar³

2019

Basic Clin Pharma Tox

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There is evidence that the antipsychotic drug perazine is an inhibitor of CYP2D6. This study aimed at evaluating its effect on CYP2D6 and CYP2C19 activities in submitting psychiatric patients to phenotyping with dextromethorphan and mephenytoin, respectively, substrates of these enzymes, before and during a treatment with perazine. A total of 31 patients were phenotyped with dextromethorphan (CYP2D6) and mephenytoin (CYP2C19) before and after a 2‐week treatment with 450 ± 51 mg/day (mean ± sd) perazine. At baseline, five patients appeared to be poor metabolizers (PM) of dextromethorphan and two patients of mephenytoin. The metabolic ratio (MR) of dextromethorphan/dextrorphan as determined in collected urine increased significantly (Wilcoxon; P < .0001) from baseline (0.39 ± 1.38 [mean ± sd]) till day 14 (1.46 ± 2.22). In 19 out of 26 extensive metabolizers (EM) of dextromethorphan, the phenotype changed from EM to PM. This suggests an almost complete inhibition of CYP2D6 by perazine and/or its metabolites. On the other hand, perazine (or some of its metabolites) did seemingly not inhibit CYP2C19. In conclusion, this study suggests that in patients treated with perazine and co‐medicated with CYP2D6 substrates, there could be an increased risk of adverse effects as a consequence of a pharmacokinetic interaction.

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Antipsychotic Efficacy of the Antidepressant Trimipramine: A Randomized, Double-blind Comparison with the Phenothiazine Perazine

Cited by 17 publications

References 18 publications

Safety and efficacy of combined clozapine–lithium pharmacotherapy

Safety and efficacy of combined clozapine–lithium pharmacotherapy

Longitudinal Data Analysis of Symptom Score Trajectories Using Linear Mixed Models in a Clinical Trial

The effect of perazine on the CYP2D6 and CYP2C19 phenotypes as measured by the dextromethorphan and mephenytoin tests in psychiatric patients

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