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Biomedical subjects

W W van den Broek

Publications and source records attributed to W W van den Broek.

At least 19 recordsLinked to original sources

[Comparison of the effectiveness of two treatment strategies in inpatients with a depressive disorder. A double-blind study of imipramine followed by lithium addition versus fluvoxamine followed by lithium addition].

BACKGROUND: There is still uncertainty regarding the best treatment optionfor depressed inpatients and the best strategy to follow if patient response is insufficient. AIM: To compare the efficacy of imipramine and fluvoxamine in depressed inpatients who subsequently received lithium supplement in case of poor response. METHOD: After a drug-free period and four days of placebo use, patients were randomised either to imipramine or to fluvoxamine (phase 1); the antidepressant dosage was fixed according to a predetermined plasma level. The efficacy of the antidepressant was evaluated four weeks after the predetermined plasma level had been attained. If patient response was inadequate, the antidepressant was augmented with lithium (phase 2). Patient response to the lithium addition was evaluated three weeks after an adequate lithium level had been attained. RESULTS: The study involved 138 inpatients. At the end of phase 1, imipramine was found to be superior tofluvoxamine according to the Clinical Global Impression of Improvement. Remission was achieved by 6 (23%) patients on imipramine and by 10 (15%) patients on fluvoxamine; this difference was not statistically significant. At the end of phase 2, 41 (9%) patients on imipramine and 27 (40%) patients on fluvoxamine achieved remission, this significant difference demonstrating the superiority of the imipramine strategy. CONCLUSION: Imipramine with subsequent lithium addition is superior to a similar strategy with fluvoxamine.

Adult↗

[The practice guideline 'Depressive disorder' (first revision) from the Dutch College of General Practitioners; a response from the perspective of psychiatry].

The first revision of the Dutch guidelines for the treatment of depressive disorders by general practitioners adapted the international psychiatric nomenclature for the diagnosis of depressive disorders. This enhances collaboration between general practitioners and psychiatrists. The use of selective serotonin reuptake inhibitors in this guideline is an advantage compared to the earlier version. The distinction between the indication for cognitive therapy and for antidepressant treatment is not very clear in this guideline. Overall the guideline represents a scientific and conservative stance in the treatment of depressed patients, which is commendable. The use of target plasma level concentrations with tricyclic antidepressants, better guidelines for the use of antidepressants or cognitive therapy, and the use of severity rating scales during treatment could further improve the next version of this guideline.

Antidepressive Agents↗

Effects of imipramine, fluvoxamine and depressive mood on autonomic cardiac functioning in major depressive disorder.

OBJECTIVE: Diminished HR variability is considered to be associated with depression and the increased risk of cardiovascular disease. The pharmacological effects of antidepressants and depressive mood itself may contribute to alterations in autonomic cardiac functioning, but a limited amount of data is available. We studied the effects of two different types of antidepressant treatments (imipramine and fluvoxamine), in addition to the effect of depressive mood, on the cardiovascular system in depressed patients. METHODS: Depressed inpatients were studied during a drug-free period and after 4 weeks of adequate treatment with imipramine (n = 17) or fluvoxamine (n = 24). Heart rate variability, blood pressure variability, and a baroreflex sensitivity index during supine rest and orthostatic challenge were analyzed by means of spectral techniques to obtain noninvasive parameters of sympathetic and parasympathetic activity. RESULTS: Both imipramine and fluvoxamine reduced sympathetic and parasympathetic activity, although the effects of imipramine were much more pronounced. Severity of depression was positively related to mean levels of heart rate and blood pressure in the total patient group. There was no convincing evidence that these relationships differed between depressed patients treated with imipramine and those treated with fluvoxamine. CONCLUSION: Our findings suggest that alterations in mean heart rate and blood pressure in depressed patients after antidepressant treatment are the result of a combined effect of pharmacological actions of antidepressants and improvement of depressive mood state. The present study did not confirm the relationship between clinical state and cardiovascular variability or baroreflex sensitivity.

Adult↗

Effect of electroconvulsive therapy on biopterin and large neutral amino acids in severe, medication-resistant depression.

Biopterin, neopterin and the large neutral amino acids (LNAA), i.e. phenylalanine, tyrosine, tryptophan, isoleucine, leucine and valine were measured in plasma of 20 severely depressed inpatients before and after a course of electroconvulsive therapy (ECT). These patients showed a significantly lower plasma biopterin concentration at baseline in comparison with healthy controls. After treatment an increase in biopterin was found, which was statistically significant in the depressed patients with psychotic features. The plasma phenylalanine-tyrosine ratio, which previously increased, normalised after ECT. Mean tryptophan concentration was lower in depressed patients than in normal controls. The patients who responded to ECT showed an increase in the tryptophan concentration and its ratio (tryptophan/LNAA) after treatment. Our results suggest that ECT increases biopterin, which probably results in synthesis of amino acids, especially tyrosine. Furthermore, ECT seems to increase cerebral tryptophan availability because of less tryptophan catabolism parallel with biopterin activation. More research is required to see if biopterin could be useful as a biological marker for the depressive state in this subgroup of patients, because this compound seems to play an important role in the etiology and treatment of depression.

Adult↗

Treatment of mood-congruent psychotic depression with imipramine.

BACKGROUND: Most studies report a poor response of psychotic depressed patients to treatment with a tricyclic antidepressant alone compared to combined treatment with an antipsychotic preparation and compared to non-psychotic depressed patients. However, the issue of optimal treatment of psychotic depressed patients has not been resolved as yet. Previously, we reported a significant difference in response to mirtazapine compared to imipramine in a randomised, double-blind, fixed-blood-level study with in-patients with major depression. In the current study we focus on the treatment response to imipramine in a group of patients with psychotic depression and compare this to patients who manifest no psychotic features. Our aim in presenting these findings was to contribute to the discussion on the optimal treatment of psychotic depressed patients. METHODS: Fifty-two patients with a unipolar major depression (DSM-IIIR), comprising 15 patients with mood-congruent psychotic features and 37 patients with no psychotic features, were commenced on treatment with imipramine after a drug-free and placebo-washout period of 7 days. The dose of imipramine was adjusted for all patients to a predetermined blood level. The Hamilton (HRSD) and Montgomery-Asberg (MADRS) Depression Rating Scales were used to evaluate treatment response. RESULTS: Of the 45 patients who completed the study, nine of the 13 psychotic patients (69.2%) and 14 of the 32 non-psychotic patients (43.8%) responded to treatment. The patients with psychotic features demonstrated a lower mean final HRSD score, together with a greater fall in MADRS score over time, compared to the non-psychotic group. Both these findings remained statistically significant after controlling for a number of possible confounding factors. CONCLUSIONS: These results demonstrate that, in this group of patients with mood-congruent psychotic depression, imipramine used on its own together with strict control of serum drug levels produced a high treatment response rate of 70%. CLINICAL IMPLICATIONS: If replicated, these findings suggest that imipramine with control of blood levels of medication may be a useful first-line treatment for depressed patients with mood-congruent psychotic features. LIMITATIONS: Our sample size was modest. This fact may caution against generalisation of the results.

Adolescent↗

Is delirium after cardiac surgery related to plasma amino acids and physical condition?

The authors studied interrelationships between plasma levels of amino acids, physical condition (as apparent from cortisol, albumin, and thyroid hormone concentrations), and postoperative delirium in 296 patients undergoing elective cardiac surgery. Both plasma tryptophan (Trp) and ratio of Trp to the other large neutral amino acids (oLNAA) were reduced in delirious patients compared with control patients. The lower availability of Trp for the brain in delirious patients may lead to decreased serotonergic function. Besides, the ratio of phenylalanine (Phe) to the oLNAA was increased in delirium, which may result in a higher synthesis of cerebral dopamine and norepinephrine. Delirious patients were also in poorer physical condition than nondelirious patients, having decreased albumin level and increased ratio of inactive reverse triiodothyronine (T3) to active T3. Decreased Trp and increased Phe availability may give rise to an imbalance in cerebral neurotransmitters and thus contribute to delirium.

Adult↗

Incidence of and preoperative predictors for delirium after cardiac surgery.

Incidence of and preoperative predictors for postoperative delirium were studied in 296 patients (age 26-83 years, mean age 63 years) undergoing elective cardiac surgery. Delirium occurred in 40 (13.5%) patients. Predictors included old age, low level of albumin, poor physical condition, use of nifedipine, and a high ratio of the amino acids phenylalanine to the sum of isoleucine, leucine, valine, tyrosine, and tryptophan. These findings suggest that preoperative physical condition and amino acid disturbances may be related to delirium after cardiac surgery in the elderly.

Adult↗

Depressed in-patients respond differently to imipramine and mirtazapine.

Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression. After a previous report of a marked difference in the response to mirtazapine compared to imipramine, we report here an analysis of different symptom clusters. One hundred seven consecutive in-patients with major depression (Diagnostic and Statistical Manual III-R, DSM-III-R) and a Hamilton Rating Scale for Depression (HRS-D) score of 18 points or more were randomly assigned to double-blind treatment. Two and four weeks after predefined blood levels had been obtained, the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine, the latter being in excess of the 15-45 mg/day range currently advised. Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients (79%) who were not receiving any co-medication. Imipramine was more effective against the clusters related to core symptoms of depression: "depression and guilt", "retardation", and "melancholia", respectively. Mirtazapine showed a biphasic response with regard to the clusters "sleep" and "anxiety/agitation", respectively, which consisted of a marked response after two weeks of predefined blood level, but with a waning of this effect at four weeks. Imipramine produced a more gradual response on these clusters, which was more pronounced at four weeks than with mirtazapine. Two aspects of the present study could be related to this finding: blood level control resulted in optimal treatment with imipramine but not mirtazapine, and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication. These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in-patients.

Adrenergic alpha-Antagonists↗

Low-dose esmolol bolus reduces seizure duration during electroconvulsive therapy: a double-blind, placebo-controlled study.

We have measured the effect of a bolus dose of esmolol 80 mg i.v. on heart rate, and systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures during electroconvulsive therapy (ECT). We also assessed seizure duration using both the cuff method and two-lead EEG. We studied 20 patients in a double-blind, placebo-controlled, within-patient blocked randomized study. No patient was receiving psychotherapeutic drugs or had cardiovascular disease. Esmolol significantly reduced heart rate, SAP and MAP before the stimulus, and also significantly reduced the increases in these variables during the convulsion, compared with placebo. However, seizure duration was also significantly reduced, possibly making ECT less effective. The reduction in seizure duration was 5.83 s when monitored clinically and 9.9 s when measured by the EEG. Because of the reduction in seizure duration, routine administration of esmolol is not advisable because it may interfere with the efficacy of ECT, but administration of esmolol during ECT could be useful to reduce tachycardia and hypertension in high-risk patients.

Adrenergic beta-Antagonists↗

[A successful treatment of drug-resistant depression with electroconvulsive therapy].

A woman aged 56 had been treated at the age of 23 for a psychotic depression with vital characteristics in the context of a bipolar disorder. The treatment included electroconvulsive therapy (ECT). From the age of 47, she suffered relapses; drug treatment proved inadequate. For the last 3 years, ECT was administered, which resulted in a good condition. ECT is an effective treatment in patients with depression resistant to medication. However, in spite of continuation pharmacotherapy, the proportion of patients relapsing within 6 months after successful ECT is large. For these patients, continuation ECT may be an efficacious method.

Adult↗

Comparison of 2 treatment strategies for depressed inpatients: imipramine and lithium addition or mirtazapine and lithium addition.

BACKGROUND: The purpose of this study was to compare the overall effectiveness of 2 treatment strategies for inpatients with severe major depressive episode (DSM-III-R): (1) mirtazapine (phase 1) and subsequent lithium addition (phase 2) or (2) imipramine (phase 1) and subsequent lithium addition (phase 2). We previously reported the results of phase 1. METHOD: In phase 1, patients were randomly assigned to treatment with either mirtazapine or imipramine, and doses were adjusted to obtain predefined blood drug levels. Nonresponders had lithium added to the double-blind mirtazapine or imipramine medication. The dose was adjusted to obtain a blood lithium level of 0.5-1.0 mmol/L. Treatment effects were evaluated weekly by the Montgomery-Asberg Depression Rating Scale for up to 2 weeks on this blood lithium level. RESULTS: Data for 100 patients were available for comparison of the 2 treatment strategies. 80 patients received no comedication. By the end of phase 2, 24 (48%) of 50 had responded to mirtazapine and 32 (64%) of 50 had responded to imipramine (intent-to-treat analysis). A survival analysis of the total patient group intent-to-treat showed a significant difference in favor of the treatment strategy with imipramine and subsequent lithium addition. CONCLUSION: Efficacy of imipramine and subsequent lithium addition for nonresponders is superior to the same treatment strategy with mirtazapine. This applies to the patient sample studied, which consisted of 100 severely depressed inpatients, 29 of whom were psychotically depressed. More serious side effects of imipramine, however, led to discontinuation of imipramine in 5 patients. No serious side effects were observed during the phase of lithium addition to either imipramine or mirtazapine. We, therefore, prefer to start treatment with imipramine and test for fixed blood drug levels, and, if necessary, add lithium. In the case of prohibitive side effects, patients are switched to a modern antidepressant such as mirtazapine, and, if necessary, lithium is added to this antidepressant.

Adult↗

[Cerebrovascular lesions and depression].

In this article the authors describe two different ways in which the relationship between affective disorders and cerebrovascular disease can be studied. First, the occurrence of so called 'post stroke depression' offers an opportunity to study this relationship. Second, neuroradiological investigations in patients with a major depressive disorder can be performed. The authors review the literature on both subjects. Until now, unequivocal conclusions concerning vascular lesions on CT or MRI and depressive features in the elderly cannot be drawn from research data available. Moreover, the so-called Post-stroke depression is still not fully understood. Some difficulties encountered in this area of research are also addressed. The authors suggest a neurological cause for the late onset types of major depressive illness and also suggest that these depressions are phenomenologically different from the early onset subtypes of depressive illness. The post stroke depression also seems to differ phenomenologically from major depression according to DSM-criteria.

Brain↗

[Temporary results only in electroconvulsive therapy in therapy-resistant depression; retrospective study].

OBJECTIVE: To evaluate the use and efficacy of electroconvulsive therapy (ECT) in refractory major depression according to DSM-III-R criteria, and to look for factors predicting response in the acute phase and the occurrence of relapse or recurrence after recovery. DESIGN: Retrospective. SETTING: University Hospital Rotterdam, The Netherlands. METHODS: Of all patients who received ECT between January 1988 and July 1993 data were collected by study of clinical records and of information by treating physicians after discharge. Every patient was visited once, or received an outpatient department appointment, to obtain informed consent, take a follow-up history and evaluate social functioning by scoring Global Assessment of Functioning and Sickness Impact Profile rating scales. RESULTS: 35 patients received ECT. In clinical practice, the guidelines of the Netherlands Psychiatric Association were not violated; most patients had received adequate pharmacological pretreatment before the decision to start ECT was made. Two patients died in hospital (not from ECT). In the acute phase 25 of the 33 patients still alive upon discharge showed good recovery. Seven of these suffered relapse within six months. The number of patients with a return of depressive symptoms rose to 12 by the end of the first year of follow-up. Sociodemographic variables and treatment characteristics did not appear to influence the result of treatment in the acute phase, nor the occurrence of relapse or recurrence. With less intensive pre- and post-ECT drug treatment the chances of relapse were increased. CONCLUSIONS: ECT is an effective treatment in the acute phase of a depression. Results after a longer period of follow-up are less satisfactory.

Adult↗

Exposure and participant modelling in a case of injection phobia.

BACKGROUND: From the literature it appears that there may be two types of injection phobia, (1) the 'vasovagal' type, and (2) the 'resistant' type. The first type is characterized by a diphasic cardiovascular response during or after injection and by a tendency to react in a passive, nonresisting way when injected. The second type is characterized by strong, sometimes violent resistance and no vasovagal reaction to an injection. Characteristics of blood injury phobia apply to the first type, but not to the second. The possibility is considered that exposure may be an effective treatment in the first type, and participant modelling in the second type. METHOD: A single case study was carried out with a case of injection phobia of the second type in which exposure with modelling, followed by participant modelling of the injection, was applied. Measures of state anxiety (STAI) and heart rate were obtained. RESULTS: According to expectation, participant modelling of injections was effective in eliminating the fear of injections in a patient of the second type of injection phobia. CONCLUSIONS: The results of this study warrant further investigation of the model in a group design in which the differential treatment effects of exposure and participant modelling are tested.

Adult↗

A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients.

Antidepressant effects of mirtazapine and imipramine were compared in a randomized, double blind, fixed blood-levels study with in-patients in a single centre. Patients with a DSM-III-R diagnosis of major depression and a Hamilton (17-item) score of > or = 18 were selected. After a drug-free and a placebo-washout period of 7 days in total, 107 patients still fulfilling the HRSD criterion of > or = 18, started on active treatment. The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine. Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms. Eight patients dropped out and two were excluded from analyses because of non-compliance; 97 completed the study. According to the main response criterion (50% or more reduction on the HRSD score) 11/51 (21.6%) patients responded on mirtazapine and 23/46 (50%) on imipramine after 4 weeks' treatment on the predefined blood level. Such a dramatic difference in efficacy between antidepressants has not often been reported before. The selection of (severely ill) in-patients, including those with suicidal or psychotic features, may have significance in this respect. Optimization of treatment with the reference drug imipramine through blood level control, exclusion of non-compliance for both drugs, exclusion of most concomitant medication and a low drop-out rate may also have contributed. It is concluded that imipramine is superior to mirtazapine in the patient population studied.

Adult↗

Facilitation of ECT by intravenous administration of theophylline.

Seven patients with major depression who developed seizure inhibition during a course of ECT, were given intravenous theophylline to increase seizure duration. Infusion of 100-200 mg of theophylline, administered slowly over several minutes approximately 30 min before seizure induction, was found to effectively and safely prolong seizure durations. In a total of 55 treatment sessions, no cardiovascular or other complications were seen. On one occasion, seizure duration was prolonged to 220 s.

Aged↗