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Biomedical subjects

Walter W van den Broek

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

17 recordsLinked to original sources

Influence of episode duration of major depressive disorder on response to electroconvulsive therapy.

BACKGROUND: Longer duration of major depressive episode is supposed to decrease response to electroconvulsive therapy (ECT). Most studies on the subject are dated and their population differs from ours, therefore their results may not be applicable to our population of severely depressed inpatients. METHODS: We reviewed the records of 56 consecutive inpatients with major depressive disorder according to DSM-III-R criteria and assessed each patient's episode duration. We examined whether episode duration has an effect on response to ECT. RESULTS: Episode duration has no significant effect on response to ECT, according to both a reduction on the Hamilton Rating Scale for Depression (HRSD) of at least 50% and a post-treatment HRSD score <or=7 as outcome criteria. Concerning each patient's absolute change in HRSD score pre-treatment compared to post-treatment, again episode duration has no significant effect. LIMITATIONS: The present study has a limited sample size and concerns a rather homogeneous population of severely depressed inpatients. Episode duration was established retrospectively. CONCLUSIONS: ECT is an effective treatment for severely depressed inpatients, independent of episode duration.

Adult↗

Imipramine is effective in preventing relapse in electroconvulsive therapy-responsive depressed inpatients with prior pharmacotherapy treatment failure: a randomized, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of imipramine versus placebo in preventing relapse after successful electroconvulsive therapy (ECT) in depressive inpatients with pharmacotherapy treatment failure prior to ECT. METHOD: During a 6-month period, the incidence of relapse was assessed. Two centers, both inpatient units for treatment of depressed patients, participated in this trial. Patients with DSM-IV-diagnosed major depressive disorder resistant to an anti-depressant and subsequent lithium addition and/or a monoamine oxidase inhibitor were included. Patients were randomly assigned to double-blind treatment with imipramine with adequate plasma levels (N=12) or placebo (N=15) after successful ECT. The mean imipramine dosage was 209 mg/day (standard deviation: 91.7, range: 75-325 mg/day). The main outcome measure was relapse defined as at least "moderately worse" compared with baseline score on the Clinical Global Impressions-Improvement scale. Treatments were compared with survival analysis using the Cox proportional hazards model, including psychotic features and the score on the Hamilton Rating Scale for Depression (HAM-D) at baseline as prespecified covariables. Patients were enrolled in the study from April 1997 to July 2001. RESULTS: In the placebo group, 80% (12/15) of the patients relapsed compared with 18% (2/11) in the imipramine group. The Cox regression analysis showed a significant reduction in the risk of relapse of 85.6% with imipramine compared to placebo (p=.007; 95% confidence interval [CI]=24.6% to 97.2%) adjusted for the covariables. There was an 18% increase in the relapse rate (p=.032; 95% CI=2% to 36%) per unit increase in HAM-D score before the start of the trial; psychotic features had no significant effect (p=.794). CONCLUSIONS: Depressed patients with pharmacotherapy treatment failure may benefit from the prophylactic effect of the same class of drug during maintenance therapy after response to ECT.

Adult↗

Outcome of a 4-step treatment algorithm for depressed inpatients.

OBJECTIVE: The aim of this study was to examine the efficacy and the feasibility of a 4-step treatment algorithm for inpatients with major depressive disorder. METHOD: Depressed inpatients, meeting DSM-IV criteria for major depressive disorder, were enrolled in the algorithm that consisted of sequential treatment steps (washout period, anti-depressant monotherapy, lithium addition, treatment with a nonselective monoamine oxidase inhibitor, electroconvulsive therapy). Definition of nonresponse and progression through the steps of the algorithm was dependent on the score on the 17-item Hamilton Rating Scale for Depression (HAM-D) at predefined evaluation times. Patients were admitted from April 1997 through July 2001. RESULTS: Of the 203 patients studied, 149 were treated according to the full algorithm, and 54 patients were immediately entered into step 3. Of the 203 patients, 165 (81%) achieved response (> or = 50% reduction in HAM-D score) and 101 (50%) remitted (final HAM-D score < or = 7). Of the 149 patients treated according to the full algorithm, 129 (87%) responded and 89 (60%) remitted. Twenty-four patients (16%) dropped out from the algorithm. CONCLUSION: Although response with antidepressant monotherapy was less than 50%, successive treatment according to the 4-step algorithm was very effective in a sample of depressed inpatients. The adherence to the algorithm was good as shown by a low dropout rate. This study emphasizes the importance of persisting with standardized antidepressant treatment in patients who are initially nonresponders to the first antidepressant. By the end of the study, more than 80% of the patients responded and 50% achieved full remission.

Adult↗

Does power matter with ECT?

BACKGROUND: To assess the incidence of depressed inpatients requiring high output ECT and the response of this group compared with a group requiring standard output ECT. METHODS: We reviewed the records of 59 consecutive inpatients that were treated with bilateral ECT between January 2001 and January 2004. Diagnosis of major depression was based on DSM IV criteria. Response and remission to ECT (respectively defined as a 50% reduction in score and a score of < or = 7 on the Hamilton Rating Scale for Depression; HRSD) of both groups were compared. RESULTS: Of the 59 patients, 13 (22%) required high output ECT. These patients needed significantly more ECT treatments than patients in the standard dose group (16.4+/-7.1 versus 10.4+/-4.5; p=0.01). In total, 31 of 46 patients (67%) requiring standard output ECT and 11 of the 13 patients (85%) requiring high output ECT responded to ECT. This difference is not significant. LIMITATIONS: This study has a retrospective nature and a rather homogenous sample. CONCLUSION: In this study 1 in 5 of the depressed inpatients needs a high dose energy of bilateral ECT to induce an adequate seizure. The efficacy of ECT in these patients is similar to that in the standard dose group. Considering these facts, high output ECT devices should be available for use in routine clinical practice.

Adult↗

Imipramine dose in relation to therapeutic plasma level: are clinical trials using imipramine as a positive control flawed?

RATIONALE: Imipramine has often been used as positive control in studies investigating the efficacy of new antidepressants. Imipramine-controlled studies in general employ a fixed-dose design. It is unclear how many patients would achieve effective plasma levels with such a design. OBJECTIVES: The objectives of this study were to assess the range of doses necessary to attain a therapeutic plasma level in the imipramine arms of two double-blind, fixed-plasma-level studies and to compare them with doses administered in efficacy studies with imipramine as a positive control. METHOD: During two double-blind studies, imipramine doses were adjusted to a predefined fixed plasma level. Here we report an analysis of the range of doses necessary to attain that level in the imipramine arms of the studies. We also computed the cumulative percentage of patients with therapeutic plasma levels (> or = 200 ng/ml) at various imipramine doses in order to compare them with doses administered in efficacy studies with imipramine as a positive control. RESULTS: Target plasma levels were attained with a mean daily dose of 248 mg, with a dose range of 50-450 mg. We calculated a possible increase in efficacy of imipramine of about 20% if doses had been adjusted to therapeutic plasma levels in clinical trials using it as a positive control. CONCLUSIONS: The absence of significant differences in efficacy between selective serotonin re-uptake inhibitors (SSRIs) and imipramine in these trials is at least in part due to improper dosing of the latter; imipramine with therapeutic drug monitoring may be more effective than SSRIs.

Adult↗

One-year outcome of psychotic depression after successful electroconvulsive therapy.

BACKGROUND: Psychotic depression is thought to have a higher relapse frequency after electroconvulsive therapy (ECT) compared with nonpsychotic depression, although this observation is contradicted by previous studies that have found the opposite. In this study, the 1-year risk of relapse after successful ECT was determined prospectively in patients with psychotic depression and compared with the risk of relapse observed for depressed patients without psychotic features. METHOD: Fifty-nine responders to ECT (a decrease in Hamilton Rating Scale for Depression [HAM-D] score > or = 50%) were followed for 1 year: 29 with and 30 without psychotic features. Relapse was defined as meeting DSM-IV criteria for major depressive disorder and a HAM-D score > or = 16. The frequency of relapse after 4 and 12 months was compared between both samples, adjusted for the co-variables duration of the index episode and type of post-ECT pharmacotherapy. RESULTS: : At both 4 and 12 months after ECT, instances of relapse were significantly lower in patients with psychotic depression compared with nonpsychotic patients: 3/28 (11%) versus 16/27 (59%) and 4/27 (15%) versus 19/28 (68%), respectively. CONCLUSIONS: The main finding of the present study is the favorable 1-year outcome for patients with psychotic depression after response to ECT with a trend toward the same result at 4 months. The 1-year outcome of the total sample is also more favorable than expected.

Chi-Square Distribution↗

Fluvoxamine for fatigue in primary biliary cirrhosis and primary sclerosing cholangitis: a randomised controlled trial [ISRCTN88246634].

BACKGROUND: Fatigue is a major clinical problem in many patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). An effective treatment has not been defined. Recently, a large proportion of patients with these diseases was found to have symptoms of depression. Because fatigue is a frequent symptom of depression and there is some evidence that treatment with an antidepressant improves fatigue in patients with fibromyalgia, we hypothesised that the antidepressant fluvoxamine might improve fatigue related to PBC and PSC. METHODS: Fatigued patients were randomised to receive fluvoxamine (75 mg BID) or placebo for a six-week period. Fatigue and quality of life were quantified using a visual analogue scale, the Fisk Fatigue Severity Scale, the Multidimensional Fatigue Inventory and the SF-36. RESULTS: Seventeen and 16 patients were allocated to fluvoxamine and placebo, respectively. There was no statistically significant beneficial effect of fluvoxamine on fatigue or quality of life. The median VAS scores in the fluvoxamine and placebo groups were 7.40 and 7.45 at day 0, 6.9 and 7.15 at day 14, 7.45 and 7.65 at day 42 and 7.8 and 8.0 four weeks after treatment discontinuation. CONCLUSION: We found no evidence for a beneficial effect of fluvoxamine on fatigue in these patients with cholestatic liver disease and severe chronic fatigue.

Cholangitis, Sclerosing↗

A double-blind randomized study comparing imipramine with fluvoxamine in depressed inpatients.

OBJECTIVE: To compare the efficacy of imipramine and fluvoxamine in inpatients from two centers suffering from a depressive disorder according to DSM IV criteria. METHODS: The study included 141 patients with a depressive disorder according to DSM IV criteria. After a drug-free and placebo run-in period of 1 week, patients were randomized to imipramine or fluvoxamine; doses of both drugs were adjusted to a predefined target blood level. Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level. RESULTS: The mean age of the study group (47 males, 94 females) was 51.8 (range 19-65) years. Of these 141 patients, 56 had episode duration longer than 1 year, 48 had mood congruent psychotic features, and 138 patients received medication. Seven patients did not complete the medication trial. The total number of patients using concurrent medication was 12/138 (8.6%). On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI (chi2 exact trend test=4.089, df=1, P=-0.048). There was no significant difference in 50% or more reduction on the HRSD, the other primary outcome criterion. On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group (mean difference=3.1, standard error (SE)=1.4, t=2.15, df=136, P=0.033). There was no significant difference in the number of patients with an HRSD < or =7 at the final evaluation. CONCLUSIONS: In depressed inpatients imipramine is more efficacious than fluvoxamine. Both drugs were well tolerated by all patients.

Adult↗

Double-blind placebo controlled study of the effects of etomidate-alfentanil anesthesia in electroconvulsive therapy.

The effect of etomidate and alfentanil on heart rate, systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure was compared with etomidate and placebo during electroconvulsive therapy (ECT). We also studied the influence of alfentanil on seizure duration using both the cuff method and 2-lead electroencephalographs on the prevention of myoclonus induction by etomidate, on duration of apnea and on postictal agitation after ECT. We enrolled 21 consecutive patients in a prospective placebo-controlled, within patient blocked randomized study. Alfentanil significantly reduced heart rate, diastolic arterial pressure, and mean arterial pressure both before and after the stimulus. The increase in these variables during the convulsion was not affected, compared with placebo. Alfentanil had no effect on seizure duration. However, apnea duration was prolonged during the alfentanil sessions as compared with placebo (73 seconds). Alfentanil did not significantly reduce the occurrence of myoclonus after etomidate as compared with placebo, nor did postictal agitation after ECT appear more often with alfentanil. Alfentanil could be useful to reduce tachycardia and hypertension during ECT in high-risk patients without effects on seizure duration. Alfentanil itself has no proconvulsive effect in combination with etomidate.

Adult↗

Effect of antidepressant medication resistance on short-term response to electroconvulsive therapy.

This prospective study assessed the influence of resistance to antidepressant pharmacotherapy on the short-term response to subsequent electroconvulsive therapy (ECT). Previous research has shown that patients with medication resistance were less likely to respond to ECT. This finding may be applicable to the population of depressed inpatients in The Netherlands, where ECT is often preceded by several medication trials. Eighty-five patients (61 female and 24 male patients) with DSM-IV criteria for depressive disorder, both with and without mood congruent psychotic features, were included for analysis. Medication resistance was rated with the Antidepressant Treatment History Form. Medication resistance was predefined in accordance with the previous research in this field. When a reduction of at least 50% on the 17-item version of the Hamilton Rating Scale for Depression (HRSD) between pre- and post-ECT is used as response criterion, medication-resistant patients were equally likely to respond to subsequent ECT (30/48 = 82.5%) than patients without medication resistance (30/37 = 81.1%). Even when post-ECT HRSD score < or = 7 was used (full remission), there was no significant difference between medication-resistant patients (21/48 = 43.8%) and patients without medication resistance (15/37 = 40.5%). When potential confounding variables were taken into account, these differences remain nonsignificant. In contrast to earlier research, medication resistance does not influence short-term response to subsequent ECT and it can still be of considerable efficacy.

Adult↗

Comparison of two-phase treatment with imipramine or fluvoxamine, both followed by lithium addition, in inpatients with major depressive disorder.

OBJECTIVE: This study was designed to compare the efficacy of two two-phase pharmacological treatment strategies for inpatients with DSM-IV major depressive disorder. METHOD: During phase I, patients participated in a double-blind study of the effects of imipramine versus fluvoxamine, with final evaluation of response 4 weeks after patients attained the target plasma level. In phase II, for patients without treatment response or with partial response in phase I, lithium was added to imipramine or fluvoxamine. Final evaluation of response was made 3 weeks after the patients attained the target plasma level of lithium (0.6-1.0 mmol/liter). RESULTS: One hundred thirty-eight patients were enrolled in the study. At the end of phase I, remission, defined as a final Hamilton Depression Rating Scale score < or =7, was achieved by 16 (23%) of 70 imipramine-treated patients and 10 (15%) of 68 fluvoxamine-treated patients. At the end of phase II, 41 (59%) of 70 imipramine-treated patients versus 27 (40%) of 68 fluvoxamine-treated patients qualified for remission, a significant difference in favor of the imipramine strategy. Only a small minority of both groups received concomitant medication. In both phase I and phase II, the discontinuation rate was low (5% and 10%, respectively). CONCLUSIONS: Imipramine with subsequent lithium addition is superior to a similar strategy with fluvoxamine for treatment of severely depressed inpatients. Both strategies were well tolerated.

Adult↗

Efficacy and tolerability of tranylcypromine versus phenelzine: a double-blind study in antidepressant-refractory depressed inpatients.

BACKGROUND: The aim of this study was to examine whether phenelzine is a suitable alternative to tranylcypromine in antidepressant-resistant depression. METHOD: A total of 77 severely depressed in-patients, meeting the DSM-IV criteria for major depressive disorder, who failed to respond to fixed plasma level treatment with either tricyclic antidepressants or fluvoxamine were withdrawn from psychotropic medication and included in a double-blind flexible-dose 5-week comparison of tranylcypromine and phenelzine. RESULTS: Of the 77 patients, 67 (87%) completed the trial, of whom 35 (52%) responded. No significant differences in response between both drugs were observed. Seventeen (44%) of 39 patients responded to tranylcypromine and 18 (47%) of 38 to phenelzine (> or = 50% reduction in Hamilton Rating Scale for Depression [HAM-D] score). The mean reduction in HAM-D score was 10.4 +/- 8.3 for the tranylcypromine sample versus 8.3 +/- 8.4 for the phenelzine-treated patients. Only a few patients (10%) used concomitant psychotropic medication. A substantial number of patients experienced severe side effects, mainly dizziness, agitation, and insomnia; the incidence was the same in both samples (21%). CONCLUSION: No difference in efficacy was observed between both monoamine oxidase inhibitors in a sample of patients with severe antidepressant-refractory depression. Phenelzine appears to be a suitable alternative to tranylcypromine.

Antidepressive Agents↗

Motor activity and autonomic cardiac functioning in major depressive disorder.

BACKGROUND: The daily pattern of motor activity and the autonomic cardiovascular regulation were studied in major depression to quantify changes in psychomotor function and autonomic cardiac functioning. Additionally, relationships between motor activity parameters, cardiovascular measures and specific clinical features were examined. METHODS: Wrist-actigraphy was used to monitor 24-h motor activity for 67 unmedicated (unipolar) depressed inpatients and 64 control subjects. During supine rest, spectral analysis was applied to assess HR and SBP variability, a baroreflex sensitivity (BRS) index and the respiratory frequency, in addition to mean heart rate (HR) and blood pressure (BP) levels for the patient group and a second control group (N=51). RESULTS: The patients showed a lower motor activity level and a reduced fragmentation of motor activity during wake, and a higher motor activity level and a decreased immobility during sleep. The mean HR and DBP level and the respiratory frequency were higher in the patient group than in the control group, but no differences in HR and SBP variability or BRS were found. Furthermore, motor activity parameters and cardiovascular measures of the patients were related to agitation and retardation and overall, patients with lower motor activity levels demonstrated lower SBP levels. CONCLUSIONS: This study confirms that the 24-h pattern of motor activity is altered in unmedicated depressed inpatients, but limited evidence was found for an autonomic cardiac dysfunction. Within the patient group there were relationships between motor activity parameters, cardiovascular measures, and clinical features, but the underlying neurobiological pathways need to be further explored.

Adult↗

Fatal interaction between tranylcypromine and imipramine.

This case report describes a patient on tranylcypromine who erroneously received a single dose of imipramine and subsequently developed a fatal serotonin syndrome. Both the clinical features and the pathophysiology of the serotonin syndrome are discussed.

Adrenergic Uptake Inhibitors↗

CPT performance in major depressive disorder before and after treatment with imipramine or fluvoxamine.

Numerous neuropsychological studies have reported deficits in cognitive and attentional functioning in depressed patients. However, there are limited data available about unmedicated depressed patients and the effects of antidepressant treatment on attentional performance. In this study, a Continuous Performance Test (CPT) was employed to evaluate the attentional performance of depressed inpatients during a drugfree period (n = 52) in comparison to healthy control subjects (n = 73). After 4 weeks of double-blind treatment with imipramine (TCA) or fluvoxamine (SSRI) at adequate plasma levels the CPT performance was studied again. We found that the unmedicated patients had a significantly impaired performance on all CPT parameters (reaction time, omission errors and commission errors) in comparison to the controls. None of the CPT parameters correlated with the severity of the depression or the level of psychomotor retardation. However, the CPT performance in the patient group was significantly related to subjective mood state (depression, tension). Double-blind treatment with imipramine or fluvoxamine resulted in an improvement of the CPT performance. In the imipramine treatment group the mean reaction time decreased significantly, and after treatment with fluvoxamine a significant decrease of the mean reaction time and the number of omission errors was detected. Both antidepressants induced a significant improvement of clinical state, but we did not find a relationship between the altered CPT performance and the changes on the clinical scales. Future studies should investigate other mechanisms underlying the improved attentional performance after treatment.

Adult↗