25 In conclusion, higher doses of antidepressants might be tried in some treatment-resistant patients, but the risk is that they might not tolerate the side effects. Does the effect of antidepressants wear off with time? Loss of clinical

efficacy for antidepressants has been described in patients receiving tricyclic antidepressants,29 MAOIs,30 as well as recent antidepressants.31,32 This loss of efficacy could occur in up to a third of all depressed patients, for example, those having responded Inhibitors,research,lifescience,medical to fluoxetine33; it often manifests itself as apathy, fatigue, as well as depression. It seems to represent a truly pharmacological and physiological problem, possibly tied to secondary changes in the dopaminergic system, although the fact that it. reflects the evolution of the psychiatric disorder cannot be ruled out. Clinically, an increase in dosage can lead to remission

as well as to further aggravation of symptoms. After a period with no medication, the same medication can be reintroduced, often with success.34 Improvement seen with Inhibitors,research,lifescience,medical placebo in clinical trials seems to have a strong tendency to disappear over time.35 What is the clinical relevance of antidepressants for subsyndromal mood or anxiety disorders? Subsyndromal or subthreshold disorders are clinical entities in which the presence of a psychiatric disorder is suggested by minor symptoms, within a continuum Inhibitors,research,lifescience,medical between normal state and an axis I diagnosis based on Diagnostic and find more Statistical

Manual of Mental Disorders, 4th edition (DSM-IV).36 Although the efficacy Inhibitors,research,lifescience,medical of antidepressants has not been extensively evaluated in these conditions, there are epidemiological data showing that a subsyndromal state or the failure to achieve complete remission predicts the occurrence of a first episode or the recurrence of an axis I disorder.37,38
Transcranial magnetic stimulation (TMS) was introduced by Barker in 19851 as a tool Inhibitors,research,lifescience,medical for noninvasively stimulating the central nervous system (CNS). The first experiments by Barker et al were aimed at inducing motor movements and measuring nerve conduction. These authors based their studies on previous reports that electromagnetic coils placed near the human head can give rise to neurological Histone demethylase phenomena such as phosphenes and vertigo, and cause some to feel faint.2 The dramatic implications of this initial demonstration by Barker et al are becoming apparent with the exponential increase in the number of studies that, use TMS as a tool for exploring CNS function in normal individuals and in disease.3,4 TMS is based on Faraday’s principle of mutual induction, which states that electrical energy can be converted into magnetic energy, and vice versa. During TMS, a bank of capacitors repeatedly and rapidly discharges into an electric coil and produces a timevarying magnetic pulse.