The prevalence of a return of depressive symptoms during maintenance AD treatment was 9–57% in published trials [6], pointing to an occurrence of tolerance phenomena during AD treatment [7–10]. This increases with the duration of treatment; in a meta-analysis of maintenance treatment studies, the risk of relapse progressively increased from 23% within 1 year over 34% within 2 years to 45% within 3 years [10]. The term ‘tachyphylaxis’(the progressive decrease in response to a given dose after repetitive administration of a pharmacologically or physiologically active substance) has also been used to designate the relapse during maintenance treatment or clinical deterioration characterized by symptoms such as apathy and fatigue [11, 12]. The effectiveness of a drug increase in relapse during maintenance treatment of major depression was assessed in a controlled study concerned with fluoxetine administered at 20 mg daily or 90 mg weekly [13]; 57% of the patients on the daily dosage and 72% on the weekly dosage

A rational use of drugs depends on the balance of potential benefits and adverse effects applied to the individual patient [1]. A problem in achieving such a balance derives from the different sources of information that need to be integrated. Guidelines tend to place emphasis on systematic reviews and meta-analyses of randomized controlled trials that are uniquely geared to detecting benefits [1]. Observational studies tend to be considered to have less validity, despite evidence to call such a view into question [2]. The appraisal of adverse effects relies primarily on observational studies and data from routine clinical practice and may not emerge from randomized controlled trials, unless these effects occur early in treatment and are specifically investigated [1]. The use of antidepressant drugs (AD) exemplifies the discrepancy between different sources of information. Adverse events that may be subsumed under the rubric of tolerance [3] and that may be overlooked by guidelines, such as those of the American Psychiatric Association [4], will be critically examined. Clinical decisions concerned with the provision of knowledge to the individual patient need to be placed within the framework of risk (the likelihood of poor outcomes of an index disorder if the therapy is withheld), responsiveness to the treatment option, and vulnerability to the adverse effects of treatment [5]. How such a framework may affect prescription practices in mood and anxiety disorders will be discussed.