W. W. van den Broek

Treatment of unipolar psychotic depression: a randomized, double-blind study comparing imipramine, venlafaxine, and venlafaxine plus quetiapine.

Wijkstra J, Burger H, van den Broek WW, Birkenhäger TK, Janzing JGE, Boks MPM, Bruijn JA, van der Loos MLM, Breteler LMT, Ramaekers GMGI, Verkes RJ, Nolen WA. Treatment of unipolar psychotic depression: a randomized, double‐blind study comparing imipramine, venlafaxine, and venlafaxine plus quetiapine.

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.

Influence of gender and menopausal status on antidepressant treatment response in depressed inpatients

The present study investigated the influence of gender and menopausal status on treatment response in depressed inpatients, treated with either imipramine or fluvoxamine. The patients were divided into three groups: men, premenopausal women and postmenopausal women. A multivariate analysis was performed using the difference in Hamilton score (pretreatment — post-treatment) for imipramine and fluvoxamine as dependent variable. The following independent variables were used: the baseline Hamilton score, the antidepressant used, the gender-group and the interaction between the type of antidepressant and gender. In total, 138 patients with a DSM IV diagnosis of depressive disorder were analysed. Men responded more favorably to imipramine (B = 7.12, P = 0.005). Premenopausal women had a better response rate to fluvoxamine than men (B = −8.66, P = 0.027). In depressed inpatients, men respond more favorably to imipramine than to fluvoxamine. Premenopausal women respond more frequently to fluvoxamine than men.

Efficacy of venlafaxine compared with tricyclic antidepressants in depressive disorder: a meta-analysis

Abstract With respect to the pharmacological characteristic, venlafaxine is comparable with tricyclic antidepressants (TCAs), and venlafaxine might be comparable in efficacy. We performed a systematic review investigating the relative efficacy and tolerability of venlafaxine compared with TCAs (imipramine, clomipramine, amitriptyline, nortriptyline and desipramine). Relevant double-blind randomised trials were identified from systematic searches of electronic databases. An exact analysis of the estimated odds ratios of response of the TCA relative to venlafaxine showed no overall significance of treatment effect (P = 0.38). The odds ratios were not homogenous across studies (P = 0.0213). The average dose of venlafaxine was 103.5 mg/day and for the TCA 106.1 mg/day. An exact analysis of the estimated odds ratios of the withdrawals and side effects in the trials with a TCA relative to venlafaxine showed no overall significance of withdrawal. From our review, no significant difference in treatment effect between low dose of both venlafaxine and the TCAs could be found. In our opinion, because of the heterogeneity of the odds ratios, one cannot conclude that they are of equal efficacy.

The course of depressive symptoms in unipolar depressive disorder during electroconvulsive therapy: a latent class analysis.

BACKGROUND Research examining the course of depressive symptoms during electroconvulsive therapy (ECT) is relatively scarce. OBJECTIVE To classify patients according to the course of their depressive symptoms while receiving ECT. METHODS The sample consisted of 156 consecutive patients receiving ECT for unipolar depressive disorder. Depressive symptoms were measured weekly with the Montgomery-Asberg Depression Rating Scale. Latent class analysis was applied to identify distinct trajectories of symptom improvement. RESULTS We identified five classes of different trajectories (improvement rates) of depressive symptoms, i.e. fast improvement (39 patients), intermediate improvement (47 patients), slow improvement (30 patients), slow improvement with delayed onset (18 patients), and finally a trajectory with no improvement (20 patients). The course of depressive symptoms at the end of the treatment within the trajectories of intermediate improvement, slow improvement and slow improvement with delayed onset, was still improving and did not achieve a plateau. CONCLUSION The different courses of depressive symptoms during ECT probably contribute to mixed results of prediction studies of ECT outcome. Data suggest that for a large group of patients no optimal clinical endpoint can be identified, other than full remission or no improvement at all, to discontinue ECT.

A randomized clinical trial comparing two two-phase treatment strategies for in-patients with severe depression

To compare the efficacy of two antidepressant treatment strategies in severely depressed in‐patients, that is, imipramine vs. venlafaxine, both with subsequent lithium addition in non‐responders.

Prevalence of trait anxiety in a sample of depressed inpatients and its influence on response to antidepressants

Depression and anxiety frequently occur together or in extension of each other. According to a previous study in depressed inpatients, a high trait anxiety level correlated with a positive response to the diazepam test (DT) and a low trait anxiety level with a negative response to the test. The aim of this study is to investigate whether positive reaction to the DT is related to a positive response to fluvoxamine and whether a negative reaction to the test is related to positive response to imipramine. The DT was performed in 130 patients diagnosed with a depressive disorder. Following the DT, the patients were randomly assigned to double-blind treatment with either imipramine or fluvoxamine. Doses of both antidepressants were adjusted to attain predefined blood levels, and the outcome was evaluated 4 weeks after attaining these blood levels. Twenty-two patients had a positive response to the DT, whereas 108 patients had a negative response. Although a positive DT is correlated with a high level of trait anxiety, no differences in depressive symptomatology and antidepressant response were found between patients with a positive and a negative DT.