New perspectives on the treatment of depression.
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Benzamides↗
Biomedical subjects
Y D Lapierre
Publications and source records attributed to Y D Lapierre.
A dose-finding study with remoxipride in the acute treatment of schizophrenic patients.
Two hundred and forty-two patients with acute schizophrenia were enrolled in a double-blind, comparative, dose-finding study of a novel antipsychotic, remoxipride. Remoxipride was evaluated in a low (30 to 90 mg), medium (120 to 240 mg) and a high (300 to 600 mg) dose range and compared with a haloperidol (15 to 45 mg), which was administered to a similar group of patients. The results support the antipsychotic effect of remoxipride, with maximum efficacy occurring at daily doses between 120 mg and 600 mg. Side-effects were more frequent at doses of remoxipride over 300 mg. In all groups, remoxipride caused consistently fewer extrapyramidal side-effects than haloperidol. The antipsychotic effect of remoxipride may be derived from specific blockade of dopamine D2 receptors in the mesolimbic tract. The findings also suggest that remoxipride may have a therapeutic effect on negative symptoms of schizophrenia.
Dose-Response Relationship, Drug↗
Temporal segmentation of response speed in depression: neuro-electrophysiological approaches.
1. Depressive psychomotor retardation, as observed by delayed reaction times (RT), may be related to a slowing in information processing speed. 2. Two separate studies compared indices of information processing speed in depressed patients and non-clinical controls by segmenting behavioral RT with brain event-related potentials (ERPs) and electromyographic (EMG) responses. 3. In Study I, slower behavioral RTs in depression were concomitant with slower central processing times (CPT) but not motor execution times (MET). 4. In Study II, P165, a putative early cognitive ERP related to 'stimulus evaluation time', was found to be slower but within normal range in depressed patients.
Acoustic Stimulation↗
Preparatory brain potentials in major depressive disorder.
1. Psychomotor slowing in depression is frequently reflected by delayed reaction times (RT). 2. The role of central arousal mechanisms in response slowing was examined by comparing scalp-recorded slow negative potentials of depressed patients with normal controls in two separate studies. 3. Varying fore-warned RT conditions elicited contingent negative variation (CNV) waveforms and the resultant mid-point amplitudes of these waveforms together with orienting (O-wave), expectancy (E-wave) and post-imperative negative variation (PINV) component amplitudes and sensory evoked responses (N1, P2) were compared between groups. 4. RTs were significantly slowed in depressed patients and the patient group exhibited consistently larger PINV amplitudes. Depending on the RT condition, patients also exhibited larger mid-point CNV amplitudes and smaller N1 and P2 amplitudes.
Adult↗
Controlling acute episodes of depression.
Three 6-8 week comparative studies have shown sertraline to be an effective, safe and well-tolerated treatment for acute depressive illness. The first, a double-blind fixed-dose study, demonstrated the efficacy of sertraline over placebo; the second, a forced upward titration, active- and placebo-controlled, double-blind study, showed that sertraline was of equal efficacy to amitriptyline. The third was a double-blind comparison of sertraline and amitriptyline in elderly depressives, with the dose being increased as necessary and as tolerated. The overall results showed sertraline to be consistently superior to placebo and equivalent in therapeutic effect to amitriptyline on a number of measures including depression, anxiety, insomnia and suicidal ideation. Efficacy was found in both moderately and severely depressed patients whose primary psychiatric diagnoses included single-episode and recurrent major depression, with and without melancholia. Sertraline was also found to be effective in patients with a high baseline anxiety score on the Hamilton Rating Scale for Depression.
1-Naphthylamine↗
Auditory evoked potentials in panic disorder.
Neuroimaging studies of behavioral-induced anxiety in non-patients and of lactate-induced anxiety in panic disorder patients have indicated that normal and pathological anxiety may share a common pathway involving the temporal poles. As panic-related anxiety may reflect faulty temporopolar evaluative processing of input, the objective of this study was to examine sensory reactivity in panic disorder patients via scalp recordings of the late auditory evoked 'vertex' potential (LAEP) which appears to have a predominantly temporal lobe origin. Twelve patients diagnosed according to DSM-III criteria as panic disorder and ten normal controls served as subjects in this study. EEG was recorded from 16 scalp sites using a monopolar fronto-occipital derivation and LAEPs were separately averaged in response to four acoustic intensities. Analysis focused on group and electrode-site differences in the negative (N1) and positive (P2) component amplitudes of the LAEPs. Panic disorder patients were found to exhibit significantly larger N1 amplitudes across all stimulus intensities and across all recording sites. No significant group differences were observed with P2. Although the results provide indirect support for a temporal focus, other modulating influences must be considered in data interpretation.
Adult↗
Keratodermia: side effects of lithium.
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Bipolar Disorder↗
Introduction: advances in the pharmacotherapy of depression.
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Antidepressive Agents↗
Prediction of steady-state plasma levels of doxepin and imipramine from single dose levels in depressed outpatients.
We have investigated the predictive value of single dose levels for steady state levels of two commonly used antidepressants, doxepin (DOX) and imipramine (IMI) in a population of 40 outpatients with unipolar depression. After a wash-out period, patients were given 75 mg of either doxepin or imipramine and blood samples were drawn 16 h after the dose. Treatment was continued for 2 weeks on a fixed 100 mg/day dose and after that the dose was adjusted according to patients' response. Drugs and their demethylated metabolites were determined weekly using a GC technique. There was a large (more than 5-fold) inter-individual variation in both the single dose and steady-state levels of the two drugs. However, a significant correlation was found between the single-dose levels and initial steady-state levels for both. The respective linear regression equations were: DOX (parent drug & demethylated metabolite): y = 1.4x + 16.8; r = 0.75, p less than 0.001; IMI (parent drug & demethylated metabolite): y = 3.1x + 4.9; r = 0.85; p less than 0.001. These results confirm, in a population of depressed outpatients, previous findings of a significant correlation between single dose and steady state plasma levels of imipramine, and indicate for the first time that such a correlation also exists for another commonly used tricyclic antidepressant, doxepin. From this relationship, dose requirement can be estimated for individual patients to achieve a desired steady-state concentration of total tricyclics (parent drug & metabolite).
Adolescent↗
Selective dopamine D2 antagonist and prolactin response in acute schizophrenia--results from remoxipride studies. The Canadian Remoxipride Study Group.
1. In a double-blind dose finding study prolactin was assessed at baseline and end of treatment in three groups of acute schizophrenics receiving low, intermediate and high doses of remoxipride as compared to a controlled group that received haloperidol. 2. Remoxipride only in high doses (300-600 mg daily) has produced a modest increase in prolactin levels at endpoint as compared to the much higher increase in prolactin secretion that accompanied haloperidol treatment. 3. The weak effects on prolactin as well as the previously reported low incidence of extrapyramidal side effects confirm the profile of remoxipride as a selective dopamine D2 antagonist with preferential effects on the mesolimbic and mesocortical tracts. 4. Male responders to either remoxipride or haloperidol treatment had significantly higher baseline prolactin levels regardless of dose and drug used. In females, there was no difference in baseline prolactin between responders and nonresponders.
Adult↗
Lithium as an adjunct in the treatment of major depression.
This paper reports a double-blind cross-over study (1) to investigate the efficacy of lithium carbonate to produce rapid relief of major depression in patients who were previously unresponsive to at least 4 weeks of antidepressant therapy; (2) to study the effect of acute lithium administration on antidepressant blood levels. In contrast to other studies, lithium was found to be no more effective than placebo. The effect of lithium adjunct on antidepressant levels was not significant.
Antidepressive Agents↗
Cis- and trans-isomers of doxepin and desmethyldoxepin in the plasma of depressed patients treated with doxepin.
Plasma levels of doxepin and desmethyldoxepin were measured in split samples of 20 depressed patients treated with doxepin by using a conventional extraction and gas chromatography method on a packed column (method 1) and derivation of secondary amine and gas chromatography on a capillary column, allowing the separation and simultaneous quantitation of the cis- and trans-isomers of the two compounds (method 2). We have found that significantly higher levels of desmethyldoxepin and of total drug are detected in plasma when the two isomers are separated and measured by method 2. We concluded that the plasma levels of doxepin reported in most previous studies were underestimated since the cis- and trans-isomers were not separated and included in the total drug concentration. Because the activity of the two isomers is different and their proportion varies in individual patients, we suggest that in future studies correlating plasma levels and the clinical effects of doxepin, both the cis- and the trans-isomers of doxepin and desmethyldoxepin be determined.
Chromatography, Gas↗
Plasma concentration of remoxipride in relation to antipsychotic effect and adverse symptoms. The Canadian Remoxipride Study Group.
The possible relationship between plasma concentration of remoxipride and antipsychotic effect/adverse symptoms has been evaluated in a 6-week double-blind dose-finding study in schizophrenic patients. The study comprised 3 parallel groups with fixed daily doses of 30-90 mg, 120-240 mg or 300-600 mg, divided in order to be given three times a day. A total of 79 patients from the three groups, who were treated with the maximum dose for 4 weeks or more, were included in the analysis. All patients had reached steady-state at week 2 and the intra-individual trough remoxipride plasma levels remained stable over the study period. The mean steady-state trough concentrations were found to be linearly related to the dose. Responders to remoxipride treatment were observed over the total concentration range of 0.24-13.50 mumols/l. Reductions of dose or discontinuations of treatment due to adverse symptoms were not associated with elevated remoxipride concentrations. In conclusion, no obvious relationship between plasma concentration of remoxipride and its antipsychotic effect or adverse symptoms was established.
Adolescent↗
A controlled dose-ranging study of remoxipride and haloperidol in schizophrenia--a Canadian multicentre trial.
The efficacy and side-effect profile for three dose ranges of remoxipride were compared with haloperidol in 242 schizophrenic inpatients in 13 centres. All patients were in a productive phase of schizophrenia according to DSM-III criteria. Relative efficacy of low dose (30-90 mg daily) vs middle dose (120-240 mg daily) vs high dose (300-600 mg daily) was compared with the standard dose of haloperidol (15-45 mg daily), as were the side effects. It was concluded that the therapeutic efficacy of remoxipride was comparable to that of haloperidol for acute episodes of schizophrenia; that the low dose range was significantly less effective than the higher ranges; that there was a clear advantage of remoxipride over haloperidol with respect to incidence and severity of extrapyramidal symptoms. The general safety profile of remoxipride as assessed from clinical chemistry, haematology, and cardiovascular variables suggests that remoxipride in the dose ranges studied can be used safely for the treatment of schizophrenic patients.
Acute Disease↗
A review of trimipramine. 30 years of clinical use.
The hybrid chemical structure of trimipramine incorporates an imipramine nucleus and levomepromazine side chain. This structure predicts much of the clinical profile of trimipramine. The initial studies on trimipramine date back nearly 30 years. It now has a well-recognised clinical profile with some characteristics akin to other tricyclic antidepressants (TCA) and others which are quite distinct. It is well established as a highly effective antidepressant with an efficacy profile similar to the other TCAs. Clinically, its anxiolytic and sedative properties distinguish it from most other TCAs. Its effects on sleep architecture are unique and explain some of its unique properties. The side effect profile of trimipramine is in some ways similar to those of the tertiary amine TCAs with a preponderance of anticholinergic and sedative effects. Its cardiotoxic properties are minimal, with some findings suggesting a very favourable profile. Interactions with other drugs, psychotropic or non-psychotropic, are compatible with its pharmacological profile. These are reviewed with its clinical applications in mind. The pharmacokinetic characteristics of trimipramine differ from those of many of the other TCAs. The application of this to clinical situations is addressed. Based on experience using trimipramine, a profile of 'ideal' patient characteristics has been built up. Finally, the use of trimipramine in selected patient populations is reviewed.
Depressive Disorder↗
Therapeutic monitoring of treatment with antidepressants.
The present status of the relationship between blood plasma concentrations of tricyclic antidepressants and clinical outcome is reviewed. Plasma levels of imipramine, desmethylimipramine and nortriptyline are generally accepted as useful clinically but it is more difficult to establish a well-defined relationship between clomipramine and amitriptyline blood levels and clinical outcome. These assays are clinically relevant, particularly in cases of treatment failure, but also in the treatment of the elderly and of overdosage. The technical problems of the assay have practically been solved with the development of new analytic methods.
Antidepressive Agents, Tricyclic↗
Pharmacotherapy of affective disorders in children and adolescents.
The pharmacotherapeutic management of affective disorders in children and adolescents follows the same general principles as for adults. In addition to the adult principles and guidelines, children present a specific challenge in diagnosis because of the specifics of symptomatology to development. The immaturity of the organism results in less responsivity to biologic therapies because of the poorly established biologic basis of the illness at this stage of life. The metabolic aspects of pharmacotherapy modify dosage and necessitate special attention to the effects of pharmacotherapeutic agents on physical and emotional development.
Adolescent↗