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Biomedical subjects

J M Perel

Publications and source records attributed to J M Perel.

At least 73 records · Page 4Linked to original sources
PubMed1994

Metabolic and physiologic consequences of nortriptyline treatment in the elderly.

The challenge in the pharmacotherapy of affective disorders is shifting to maintenance treatment. Hence, there is a need for systematic data on the somatic effects of long-term medication use. Twenty-six depressed patients (age > 60 yr) treated with therapeutic concentrations of nortriptyline were evaluated after an average of 7 months for changes in lipoproteins and cardiovascular parameters. Twelve patients were tested for debrisoquine (P450 2D6) metabolic status and creatinine clearance at these same intervals. There was no significant change in cholesterol levels, but triglycerides and very-low-density lipoproteins (VLDL) were significantly increased. Heart rate was also elevated by a mean of 15 beats per minute, and there were modest but significant increases in cardiac conduction parameters. Creatinine clearance declined significantly (by 34%), and blood pressure was unchanged. Small decrements in P450 2D6 could be quantitated. Older patients treated with maintenance psychotropic medications should be evaluated at the regular intervals, particularly with regard to the age-related complications of multiple illness and medications.

Aged↗
PubMed1994

Dose-response characterization of the antipanic effects of imipramine.

This article presents panic diary results of a dose-response study with imipramine hydrochloride in panic disorder with agoraphobia patients. Analysis of variance revealed significant time effects on panic frequency and severity measures, but group x time interaction effects were present for the severity measures only. Results also provided evidence for a positive dose-response relationship with 20 percent of patients in the placebo group, 31 percent in the low-dose group (0.5 mg/kg/day), 54 percent in the medium-dose group (1.5 mg/kg/day), and 70 percent in the high-dose (3 mg/kg/day) group being free of recurrent or severe panic attacks at posttreatment. Further stratified and logistic regression analyses revealed a direct linear relationship between total plasma tricyclic concentration and response. These findings affirm the dose-dependent nature and the specificity of imipramine's antipanic effects.

Dose-Response Relationship, Drug↗
PubMed1993

Efficacy of phenelzine and haloperidol in borderline personality disorder.

OBJECTIVE: To compare the efficacy of a neuroleptic (haloperidol) to a monoamine oxidase inhibitor antidepressant (phenelzine sulfate) against the affective, cognitive, and impulsive-aggressive symptoms of criteria-defined borderline inpatients in an effort to dissect apart affective and schizotypal symptom patterns or subtypes using medication response. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient unit of a tertiary care university psychiatric hospital serving a large public catchment area. PATIENTS: One hundred eight consecutively admitted borderline inpatients defined by Gunderson's Diagnostic Interview for Borderline Patients and DSM-III-R criteria, randomly assigned to 38 phenelzine, 36 haloperidol, and 34 placebo trials. INTERVENTIONS: Following 1 week free of medication, haloperidol (average dose, 4 mg/d), phenelzine sulfate (average dose, 60 mg/d), or placebo were given for 5 weeks with weekly symptom ratings and plasma drug level determinations. MAIN OUTCOME MEASURES: Efficacy was measured on depression (Hamilton Rating Scale, Beck Depression Inventory), global severity (Global Assessment Scale, Symptom Checklist-90 items [SCL-90]), anxiety, anger-hostility (SCL-90, Inpatient Multidimensional Psychiatric Scale [IMPS], Buss-Durkee Hostility Inventory), psychoticism (Schizotypal Symptom Inventory, SCL-90, IMPS), impulsivity (Ward Scale, Barratt Impulsiveness Scale, Self-Report Test of Impulse Control), and borderline psychotherapy (Borderline Syndrome Index). RESULTS: Three-way comparisons between groups indicated superior efficacy for phenelzine, followed by placebo and haloperidol on measures of depression, borderline psychopathologic symptoms, and anxiety. Pairwise comparisons between medication and placebo revealed significant efficacy for phenelzine against anger and hostility but no efficacy against atypical depression or hysteroid dysphoria. We were unable to replicate prior reports of efficacy for the neuroleptic. CONCLUSIONS: Pharmacologic dissection of borderline personality disorder patients into affective and schizotypal subtypes could not be demonstrated.

Adult↗
PubMed1993

Comparison of full-dose versus half-dose pharmacotherapy in the maintenance treatment of recurrent depression.

Recent evidence points to the prophylactic efficacy of maintaining recurrent unipolar patients on the same dose of antidepressant medication that was used to treat the acute episode (Frank et al., 1990; Kupfer et al., 1992). Therefore, the question of whether such patients should be tapered to a lower maintenance dose after successful resolution of an acute episode is clearly important. In this report we describe a small randomized clinical trial in which patients were assigned to either full-dose or half-dose maintenance treatment for a period of 3 years. Survival analysis suggests that superior prophylaxis can be achieved with a full-dose as compared to a half-dose maintenance treatment strategy (p < 0.07). Mean survival time for the full-dose subjects was 135.17 (SE 19.75) weeks as compared to 74.94 (SE 19.78) weeks (median of 43.1 weeks) for the half-dose subjects. We conclude that for patients who have suffered several recurrences, full-dose maintenance treatment is the more effective prophylactic strategy.

Adult↗
PubMed1993

Tricyclic dose requirements across pregnancy.

In a series of eight pregnant women, the authors found that the doses of tricyclic antidepressants required to achieve remission of symptoms and adequate serum levels increased during the second half of pregnancy. During the final trimester, the mean dose required was 1.6 times the mean dose required when the patients were not pregnant.

Adult↗
PubMed1993

Continuation pharmacotherapy of borderline personality disorder with haloperidol and phenelzine.

OBJECTIVE: The aim of this study was to assess the effectiveness of low-dose neuroleptic medication and monoamine oxidase inhibitor (MAOI) antidepressant medication in continuation pharmacotherapy of patients with borderline personality disorder. METHOD: The authors conducted a double-blind, placebo-controlled study comparing continuation therapy with a neuroleptic (up to 6 mg/day of haloperidol), an MAOI antidepressant (up to 90 mg/day of phenelzine), and placebo in 14 men and 40 women with borderline personality disorder. Continuation medication trials lasted 16 weeks, following 5 weeks of acute therapy. RESULTS: Continuing haloperidol demonstrated efficacy only for the treatment of irritability. Higher levels of depression, hypersomnia, and leaden paralysis were noted in the patients who received haloperidol than in those who received phenelzine and those who received placebo. The dropout rate during the first 8 weeks of the continuation study was significantly higher for the patients receiving haloperidol (64%) than for those receiving placebo (28%). Continued phenelzine demonstrated only modest efficacy for the treatment of depression and irritability. An activating effect of phenelzine was shown on measures of excitement and reactivity. CONCLUSIONS: No evidence of efficacy was found for continuation therapy with haloperidol in the treatment of borderline personality disorder other than in the treatment of irritability. Little evidence of efficacy was found for continuation therapy with phenelzine for borderline personality disorder other than modest improvements in irritability and depressive symptoms. There is currently no clear pharmacological treatment of choice for the continuation therapy of borderline personality disorder.

Adult↗
PubMed1993

Early response patterns associated with successful clomipramine treatment.

Two different initial dosing regimens with clomipramine (CMI) were compared with particular attention to early response indicators. Thirty-two inpatients with major depressive disorder were randomized in a double-blind protocol. The pulse-loading (P-L) group received 150 and 200 mg of CMI on two consecutive evenings, then placebo for 8 days; the traditional group began at 50 mg, followed by gradual increases every second day until 200 mg was reached. Both groups were then placed on an adjustable dosing schedule of CMI, initially set at 200 mg for an additional 2 weeks. After the completion of P-L, the improvement in scores on the Hamilton Rating Scale for Depression across protocol days 7 to 13 (the P-L placebo period) was equivalent for both dosage regimens and was significantly associated with therapeutic response at the end of the study (p = 0.0186). Desmethylclomipramine levels were significantly greater in P-L nonresponders (p = 0.0039), and a ratio of desmethylclomipramine/CMI of 2 or more after P-L was strongly associated with failure to respond to CMI (p = 0.02). Early, acute responses and assessments of metabolism observed with targeted doses of CMI may be predictive of later successful treatment.

Adult↗
PubMed1993

Fluoxetine trial in suicidal depressed alcoholics.

The selective serotonergic agonist fluoxetine has demonstrated efficacy in the treatment of depression and has suggested efficacy in the treatment of alcoholism. However, no trials with any selective serotonin agonist have been reported in patients who display both major depression and alcoholism. In this study, 12 patients with DSM-III-R diagnoses of major depressive disorder and alcohol dependence were treated openly with fluoxetine for 8 weeks, with doses ranging from 20 mg to 40 mg p.o. qAM. All 12 patients reported prominent suicidal ideation upon admission to our hospital; 6 had made serious suicide attempts shortly before admission. Statistically significant improvements were noted on measures of depression and postdischarge alcohol consumption. No paradoxical increases in suicidality were noted. These findings suggest that fluoxetine has potential for treating the depressive symptoms and the excessive alcohol intake of depressed alcoholics.

Adult↗
PubMed1993

Haloperidol vs. phenelzine in continuation therapy of borderline disorder.

We report the first double-blind, placebo-controlled continuation study comparison of a neuroleptic (haloperidol < or = 6 mg), monoamine oxidase inhibitor (MAOI) antidepressant (phenelzine < or = 90 mg), and placebo in 54 patients with borderline personality disorder. Continuation medication trials of 16 weeks followed 5 weeks of acute therapy. Haloperidol continued to be effective beyond the acute phase only for the treatment of irritability. Higher levels of depression, hypersomnia, and leaden paralysis were noted in the haloperidol group than in the phenelzine and placebo groups. The dropout rate during the first half (8 weeks) of the continuation study was significantly higher for the haloperidol group (64%) than for the placebo group (28%) (p < .05). Phenelzine demonstrated very modest efficacy beyond that noted in the acute phase for the treatment of depression and irritability. Phenelzine was shown to have an activating effect on measures of excitement and reactivity.

Borderline Personality Disorder↗
PubMed1992

Nocturnal urinary excretion of 6-hydroxymelatonin sulfate in prepubertal major depressive disorder.

Levels of the melatonin metabolite, 6-hydroxymelatonin sulfate, were measured in overnight urine from 31 prepubertal children with major depressive disorder and 15 normal control children with very low family loading for affective disorder. The two groups did not differ with regard to their nocturnal excretion of this compound, nor was any depressive subgroup identified whose 6-hydroxymelatonin sulfate excretion differed from that of the control group. Previous studies of pineal function in depression are reviewed and discussed in the context of the present investigation.

Adolescent↗
PubMed1992

Five-year outcome for maintenance therapies in recurrent depression.

After conducting a randomized, 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy, we asked those individuals who survived the 3-year trial receiving active medication (with or without psychotherapy) to continue in a 2-year additional randomized trial of active medication vs placebo. The question was whether maintaining antidepressant medication at the dosage used to treat the acute episode beyond 3 years would continue to provide a significant prophylactic effect compared with medication discontinuation after the 3 years of effective maintenance treatment. Survival analysis demonstrated a highly significant continued prophylactic effect for active imipramine hydrochloride treatment maintained at an average dose of 200 mg. We conclude that active imipramine treatment is an effective means of preventing recurrence beyond 3 years and that patients with previous episodes less than 2 1/2 years apart, therefore, merit continued prophylaxis for at least 5 years.

Adult↗
PubMed1992

Neuroendocrine response to L-5-hydroxytryptophan challenge in prepubertal major depression. Depressed vs normal children.

The neuroendocrine response to L-5-hydroxytryptophan was compared in 37 prepubertal children who met the Research Diagnostic Criteria for major depressive disorder with that in 23 normal children with no lifetime history of any psychiatric disorder and very low rates of depression in both first- and second-degree relatives. Intravenous L-5-hydroxytryptophan (0.8 mg/kg) was given over a 1-hour interval after preloading with oral carbidopa, an inhibitor of peripheral but not central L-5-hydroxytryptophan metabolism. L-5-Hydroxytryptophan, a precursor of serotonin, increases serotonin turnover in the central nervous system when given after carbidopa. Seven (19%) of the 37 children with major depressive disorder and two (9%) of the 23 normal children had nausea or vomiting and therefore did not complete the full infusion. They were subsequently excluded from data analysis. After this stimulation, prolactin, cortisol, and growth hormone secretion were compared between diagnostic groups. The depressed children secreted significantly less cortisol (effect size, 0.70) and significantly more prolactin (effect size, 0.83). There was a sex-by-diagnosis interaction in prolactin response to L-5-hydroxytryptophan and, on examination, the prolactin hypersecretion was seen in depressed girls but not in depressed boys compared with same-sex controls. There was no significant stimulation of growth hormone in either group. These findings are consistent with dysregulation of central serotonergic systems in childhood major depression.

Adult↗
PubMed1992

Clinical experiments in maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia.

Several issues remain to be ascertained beyond the acute response to imipramine hydrochloride in patients with panic disorder. Study 1 consisted of a prospective, systematic characterization of half-dose 12-month maintenance in patients with panic disorder with agoraphobia who had shown marked and stable response to 6 months of acute-phase treatment with imipramine. Study 2 assessed the 6-month cumulative relapse rate following discontinuation of acute-phase imipramine treatment in a comparable sample of patients. The same assessment battery was used in both studies, and the integrity of experimental drug conditions was verified by plasma drug level determinations. In contrast to the high relapse rate following discontinuation of acute-phase treatment, none of the patients showed relapse or had sustained worsening in panic or phobia measures during the half-dose maintenance period. The results underscore the importance of pharmacological prophylaxis and provide empirical guidelines for a successful low-dose maintenance regimen for patients with panic disorder and agoraphobia who respond markedly to imipramine.

Adult↗
PubMed1992

Imipramine and 2-hydroxyimipramine: comparative cardiotoxicity and pharmacokinetics in swine.

The hemodynamic, cardiographic, and initial pharmacokinetic characteristics of the de novo administration of the 2-hydroxymetabolite (2-OH-IMI) of imipramine (IMI), compared with its parent was studied in a swine preparation. Cardiac output, arterial pressure, and the continuous electrocardiogram were assessed after the intravenous administration of the drug or its metabolite. Plasma, sampled over 120 min and CSF sampled at 60 min were analyzed by reverse phase HPLC with spectroflurometric detection. Equilibrium dialyses were performed on plasma sampled at 60 min. 2-OH-IMI, in doses of 5-6 mg/kg, compared to dosages of IMI up to 8.5 mg/kg, produced a significantly greater incidence of life-threatening arrhythmias, and caused profound and significant decreases in blood pressure and cardiac output. 2-OH-IMI had a smaller volume of distribution (Vd) and shorter half-life. CNS penetration, as estimated by CSF/plasma ratios, was significantly greater for 2-OH-IMI. These phenomena were partly accounted for by significantly less protein binding for the hydroxymetabolite. It is concluded that 2-OH-IMI has increased penetrance into the CNS despite a smaller Vd and that it is significantly more cardiotoxic than its parent.

Animals↗
PubMed1992

Pharmacodynamics of pemoline in attention deficit disorder with hyperactivity.

The onset, duration, and offset of pemoline action to improve cognitive performance is examined intensively in 25 prepubescent males suffering from attention-deficit disorder with hyperactivity (ADDH). The purpose was to characterize the pharmacodynamics of pemoline in ADDH patients through correlation of plasma pemoline concentration with psychometric measures of memory search efficiency and paired-associates learning, with the physiological effect of pemoline on dopaminergic transmission concurrently measured by analysis of plasma prolactin response. The effect of pemoline on neuroprocessing is apparent within the first 2 hours after administration with an inverse relationship between plasma pemoline and prolactin concentration present at hour one only (r = 0.84; p = 0.005). Pemoline therapy for 3 weeks does not significantly affect area under the curve for pemoline or prolactin nor did the effect on memory search efficiency decrease, suggesting no apparent tolerance.

Attention↗
PubMed1992

Combined pharmacotherapy and psychotherapy in the acute and continuation treatment of elderly patients with recurrent major depression: a preliminary report.

OBJECTIVE: The authors examined the rate of response to the combination of nortriptyline and interpersonal psychotherapy for acute and continuation treatment of elderly patients with recurrent major depression. METHOD: The subjects were 73 elderly patients, 61 of whom completed treatment. Nortriptyline steady-state blood levels were maintained at 80-120 ng/ml, and interpersonal psychotherapy was administered weekly for 9.1 weeks (medium) of acute therapy and was decreased from biweekly to triweekly during 16 weeks of continuation therapy. During acute treatment nonresponding patients also received brief adjunctive pharmacotherapy with lithium or perphenazine. RESULTS: Of the 61 subjects given adequate trials of nortriptyline and interpersonal psychotherapy, 48 (78.7%) achieved full remission (Hamilton depression rating of 10 or lower over 16 weeks of continuation therapy), 10 patients (16.4%) did not respond (Hamilton rating never below 15), and three achieved only partial remission (Hamilton rating of 11-14). Early versus late onset was not associated with a difference in response rate. During the placebo-controlled, double-blind transition to maintenance therapy, 19 (76.0%) of the 25 patients randomly assigned to placebo maintenance conditions showed continued recovery and six relapsed. None of the 24 patients assigned to nortriptyline conditions relapsed. CONCLUSIONS: Use of nortriptyline plus interpersonal psychotherapy for 9.1 weeks (median) of acute and 16 weeks of continuation therapy appears to be associated with good response and relatively low attrition but about a 25% chance of relapse during double-blind discontinuation of nortriptyline. These data require confirmation in a controlled clinical trial of acute and continuation therapy.

Age Factors↗