The Use and Clinical Significance of Transcranial Magnetic Stimulation in the Treatment of Major Depression

Abstract

M ajor depression is among the most common and disabling of human diseases. The Global Burden of Disease Study notes that by the year 2020, the societal impact of unipolar major depression alone will be exceeded by only that of ischemic heart disease as estimated by a measure of disease morbidity, disability-adjusted life years. While modern pharmaceutical options have a clear record of success in randomized, controlled clinical trials, real-world experience in their use leaves room for improvement. The percentage of all patients who seek treatment for whom current options do not provide an acceptable solution ranges to 30%. The results of the Sequenced Treatment Alternatives to Relieve Depression (or STAR*D) trial have recently been reported. This study used a semi-naturalistic treatment algorithm designed to model as closely as possible the sequence of treatment options most commonly used in clinical practice. Among the observations are that for patients who may generally be expected to respond to treatment, the likelihood of achieving remission of symptoms (defined by a Hamilton Depression Rating Scale score of < 8) after either one (Level 1) or two (Level 2) sequential treatment trials ranges over 50%. However, once prospective evidence of failure to achieve benefit has been demonstrated, the likelihood of good clinical outcome drops precipitously, and hovers at exceedingly low levels after three prospective treatment failures. For example, the reported incidence of categorical remission in patients treated with tranylcypromine was 6.9%, which was observed after patients had failed to receive benefit from any of the three preceding adequately administered antidepressants. Equally informative is a review of the information in the STAR*D study regarding overall tolerability of treatments. For instance, as patients proceeded through the sequential treatment levels, the discontinuation rate due to treatment intolerance or adverse events rose steadily (8.6% at Level 1; 20.5% [range: 12.5%–27.2%] at Level 2; 35.2% [range: 34.2%–36.2%] at Level 3; and 32.1% [range 21.6%–41.4%] at Level 4). In other words, as the expectations of efficacy diminished with increasing resistance to prior treatment, the non-adherence to, and likely intolerability of, treatment options increased quite dramatically. Overall, these data paint a picture of measurable but limited benefit with the most commonly used pharmaceutical treatments. Does this picture improve over the longer term for individuals who achieve acceptable acute benefit? Unfortunately, it appears that, similar to the acute outcomes, as the degree of prior treatment non-response increases, the likelihood that any efficacy will be lost After reading this article, the practitioner should be able to: