Dose reduction of high-dose first-generation antipsychotics or switch to ziprasidone in long-stay patients with schizophrenia: A 1-year double-blind randomized clinical trial.

Long-stay patients with severe schizophrenia are frequently treated with high doses of first-generation antipsychotics (FGA). Dose reduction or switching to ziprasidone may reduce the severity of negative symptoms and side effects. We investigated in a randomized double-blind trial whether a dose-reduction strategy to achieve an adequate dose of a FGA (5 mg/day haloperidol equivalents, n = 24) or switching to ziprasidone (160 mg/day, n = 24) in treatment resistant patients would decrease negative symptoms after 1 year of treatment.

Efficacy of imipramine in psychotic versus nonpsychotic depression.

The purpose of the present study is to compare the efficacy of imipramine in the treatment of psychotic versus nonpsychotic depression. Previous studies report varying results of monotherapy with antidepressants in psychotic depression. Because psychotic depression is seriously underinvestigated, performing a post hoc analysis of randomized clinical trials consisting of both psychotic and nonpsychotic depressed patients may contribute to the discussion on the optimal treatment of depressed patients with mood-congruent psychotic features.

Lithium addition in antidepressant-resistant depression: effects on platelet 5-HT, plasma 5-HT and plasma 5-HIAA concentration.

The efficacy of the addition of lithium to an established course of antidepressant treatment can be explained by a synergistic effect of the two drugs on central 5-HT neurotransmission. In the present study we investigated the effect of lithium addition on the 5-HT concentration in plasma and platelets and the concentration of 5-HIAA. Thirty-nine depressed inpatients who fulfilled the DSM-IV criteria for major depressive disorder and who did not respond to monotherapy with either imipramine or fluvoxamine participated in this study.

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.

[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.

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.

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.

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.

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.

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.

Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients.

Background: Alternatives to lithium for prophylactic treatment of patients with bipolar affective disorders are increasingly being advocated. However, trials comparing lithium with alternatives are scarce and often biased.

Method: We studied 94 patients with at least 2 episodes of bipolar disorder (DSM-III-R) during the previous 3 years who were in remission at entry into the study.

Influence of resistance to antidepressant pharmacotherapy on short-term response to electroconvulsive therapy.

Background: Few studies assessing the influence of resistance to antidepressant pharmacotherapy on the response to subsequent electroconvulsive therapy (ECT) are found in the literature. Results are somewhat conflicting and may not be applicable to the population of depressed patients in The Netherlands. The aim of this study is to assess the influence of medication resistance on the short-term response to ECT in a population of severely depressed inpatients in The Netherlands, where ECT is an exceptional treatment, often used as a final treatment option.

Diagnosis at the first episode to differentiate antidepressant treatment responses in patients with mood and anxiety disorders.

Rationale: Co-morbidity of mood and anxiety disorders is often ignored in pharmacotreatment outcome studies and this complicates the interpretation of treatment response. The clinical trials are usually based on single categories from the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Objectives: The present study is a first attempt to differentiate the responses to antidepressants using a design that differs from that used in previous clinical trials.

Trait anxiety and the effect of a single high dose of diazepam in unipolar depression.

In this cross-sectional study we explored in 101 depressive in-patients (DSM III-R) the association between level of trait anxiety and variables that have been investigated previously to discern primary and secondary depression, respectively. Besides, we explored the influence of trait anxiety level on difference in treatment response to either imipramine or mirtazapine. Trait anxiety was measured interviewing a close relative of the patient using a questionnaire related to aspects of psychic anxiety and to aspects of somatic anxiety.

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.

Lithium and carbamazepine in bipolar disorder.

Lithium is considered first choice in the prevention of prospective episodes in patients with bipolar disorder. However, efficacy is not satisfactory in all patients and side effects sometimes prevent the use of lithium. It is argued that efficacy in clinical practice may be less impressive than anticipated from clinical trials, and alternative treatments are beinu advocated increasingly for that reason, such as the anticonvulsants, carbamazepine and valproate.

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 new antidepressants: mirtazapine and venlafaxine].

Mirtazapine and venlafaxine are two novel antidepressants which are pharmacologically different from other new anti-depressants. Mirtazapine blocks the presynaptic alpha 2-adrenoreceptors and has a benign safety profile. Venlafaxine particularly inhibits the reuptake of serotonin and in higher doses it inhibits the reuptake of norepinephrine as well.

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.

Effects of alprazolam and lorazepam on catecholaminergic and cardiovascular activity during supine rest, mental load and orthostatic challenge.

Effects of oral alprazolam (0.5 and 1 mg) and lorazepam (2 mg) on sympathetic adrenomedullary activity and sedation were studied during supine rest, mental load (Color Word Test, CWT) and active standing (OCT), in 12 male volunteers in a randomized double-blind placebo-controlled cross-over design. Compared to placebo, alprazolam significantly increased subjective sedation, reduced plasma adrenaline and noradrenaline concentrations and mean blood pressure (MBP) during supine rest, and attenuated plasma adrenaline responses during the CWT and the OCT; these effects during the CWT and OCT appeared to be dose-dependent.

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.