Response to treatment in minor and major depression: results of a double-blind comparative study with paroxetine and maprotiline

Abstract

Several concepts of minor depression in the sense of acute but less severe symptomatology than major depression have been proposed in the literature, but currently none of them is generally accepted. For the treatment of these conditions, only few recommendations based on empirical data are available. We conducted a randomized double-blind multicentre study in depressed outpatients comparing paroxetine and maprotiline in both patients with minor (n=245) and major depression (n=298). For the diagnosis, Research Diagnostic Criteria were used in a modified version. Two response criteria were applied: a reduction of 50% or more in total HAMD-17 scores from baseline (criterion 1), and a reduction of the HAMD-17 total score to 9 points or less (criterion 2). A completer and an endpoint analysis was performed. For patients with minor depression, remarkably high response rates were found for paroxetine (criterion 1: 90.9% completer, 82.1% endpoint; criterion 2: 89.1% completer, 82.4% endpoint), while the respective rates for maprotiline tended to be lower (criterion 1: 80.4% completer, 71.4% endpoint; criterion 2: 84.9% completer; 76.1% endpoint). Response rates in patients with major depression were for paroxetine: criterion 1: 74.3% completer, 62.8% endpoint; criterion 2: 76.4% completer, 65.2% endpoint; and for maprotiline: criterion 1: 82.4% completer, 68.5% endpoint; criterion 2: 80.6% completer; 66.0% endpoint, which resembles rates reported from previous antidepressant trials. Both drugs were generally well tolerated. Though no placebo control was carried out, our results suggest that minor depression is a disorder that is very likely to respond to antidepressant pharmacotherapy with paroxetine, but also with maprotiline at a favourable risk/benefit ratio.

Introduction

There has been growing recent scientific interest in patients who clinically suffer from depressive symptoms, but fail to meet the criteria for major depression. Some of the patients may fit into some other classification categories such as dysthymia or adjustment disorder with depressed mood. However, a substantial proportion of patients will nevertheless fail to fit into an official diagnostic category other than the residual category `depressive disorder not otherwise specified', though they clinically may suffer substantially from depressive symptoms.

Minor depression is one term sometimes applied in the context of different classification concepts for the diagnosis of some of these patients. Unfortunately, currently there is no general consensus about what to subsume under the concept of minor depression. The term minor depression has been used by different authors for the description of different phenomena.

Several definitions represent a dimensional approach for the concept of minor depression. The concepts of `subthreshold depression' (Sherbourne et al., 1994) `subsyndromal symptomatic depression' (Judd et al., 1994), the criteria set for minor depression in the Appendix B of DSM-IV, as well as the Research Diagnostic Criteria (RDC) category of minor depression are examples hereof. Also, the concept of minor depression used in this study points into the same direction. It is defined according to modified RDC-criteria and follows the idea that a similar pattern of symptomatology is present in major and minor depression (therefore the same list of criteria is used), but the threshold for the diagnosis major depression is higher than in minor depression. The definition is based on previous empirical data, where we found that defining minor depression as the presence of 3 or 4 criteria out of the RDC catalogue for major depression in a sample of depressed outpatients substantially reduced the amount of patients that would have been classified as `depressive disorder not otherwise specified' according to the DSM-III-R system (Winter et al., 1991, Philipp et al., 1992, Philipp, 1993).

The important general implication of these concepts is that many patients suffering from acute but symptomatologically less pronounced depression experience considerable impairment (Jaffe et al., 1994, Tannock and Katona, 1995). The occurrence of several symptoms of depression not sufficient for the diagnosis of major depression nevertheless seems to constitute a clinically relevant state that occurs frequently, often disables individuals, makes them seek treatment, complicates the course of other axis I disorders, poses costs on the community and therefore cannot be regarded as a trivial or ubiquitous phenomenon (Broadhead et al., 1990, Rosenberg et al., 1991, Horwath et al., 1992, Skodol et al., 1994, Judd et al., 1994, Sherbourne et al., 1994)

Unfortunately, preliminary data indicate that minor depression or similar clinical conditions are widely underrecognized as a disabling disorder. Moreover, treatment guidelines, especially for pharmacological strategies based on empirical studies are hardly available for patients with minor depression. One important issue that needs to be clarified is the possible benefit of pharmacological treatment strategies in this indication (Paykel et al., 1988). Tricyclic antidepressants known to be effective in the treatment of major depression often cause substantial adverse effects. In the past, this may have restricted their use in the indication of less pronounced depressive states (Lapierre, 1994). Moreover, some clinicians even do not consider minor depressive states as an indication for antidepressant drug treatment. With the availability of selective serotonin reuptake inhibitors like paroxetine, which often are better tolerated by patients and which have been found to be effective antidepressant drugs, it seems possible that also minor depression can be treated with a favourable risk/ benefit ratio with antidepressant drugs in a majority of patients (Bech, 1993).

The present study was carried out to compare the efficacy and tolerability of paroxetine and the tetracyclic noradrenaline reuptake inhibitor maprotiline in the acute treatment of outpatients with either major or minor depression. As a definition for major and minor depression, we used the above mentioned modified RDC criteria. In addition to an initial HAMD-17 score of at least 13 points as a dimensional inclusion criterion, we hypothesized that such characterized patients with minor depression would benefit from antidepressant drug treatment. Moreover, a comparison to a sample of patients with major depression was intended. In this report, we present the treatment results differentiating between major and minor depression.