The STAR*D trial: revealing the need for better treatments.
ABSTRACT STAR*D (Sequenced Treatment Alternatives to Relieve Depression) continues to stimulate debate. The landmark trial demonstrated the feasibility of large-scale, community-based studies conducted without pharmaceutical company support. The results provided insight into nonresponse to initial treatment with selective serotonin reuptake inhibitors and alternatives for second- and third-line treatment options and suggested opportunities for personalized approaches to depression care. However, initial and one-year remission rates (28% and 70%, respectively) suggest that important goals for treatment of this disabling disease remain out of reach and that the bar for antidepressants has been set far too low.
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ABSTRACT: Purpose. To investigate the reasons behind difficulties in recruiting patients to randomized controlled trials (RCTs) in psychiatry and to examine a database of RCTs for differences between studies in mental health and other specialities. Methods. A discussion of recent changes in research governance in the UK and Europe followed by an examination of the database of all trials supported by the Health Technology Assessment programme of the National Institute of Health Research in the UK between 1993 and 2007 to determine if three different measures, (i) time between grant approval and study start date, (ii) percentage of additional time given to extend recruitment and (iii) percentage of planned recruitment achieved, changed over the time period studied and differed between mental health, cancer and other medical disciplines. Findings. Despite attempts in the UK to accelerate the process of clinical trials in recent years, there was a significant increase in the extension time for trials to be completed (p = 0.038) and the percentage of planned recruitment to mental health studies (71%) was significantly less than for cancer (90.3%) and other studies (86.1%) (p = 0.032). Summary. These results suggest that, despite the priority afforded to the advancement of RCTs in healthcare, such studies are encountering increasing difficulty in recruiting to time and target. We suggest that this difficulty can be attributed, at least in part, to the excessively byzantine regulation and governance processes for health research in the UK, and unnecessary bureaucracy in the current National Health Service system. Mental health studies appear particularly vulnerable to delay and better systems to facilitate recruitment are required urgently for the evidence base to be improved and facilitate new cost-effective interventions.Epidemiology and Psychiatric Sciences 05/2013; 22(4):1-8. DOI:10.1017/S2045796013000255 · 3.36 Impact Factor
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ABSTRACT: Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin - an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain's susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted.Frontiers in Psychology 04/2012; 3:117. DOI:10.3389/fpsyg.2012.00117 · 2.80 Impact Factor
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ABSTRACT: Recent research aims at developing a biomarker to predict antidepressant treatment outcomes in major depressive disorder. The Antidepressant Treatment Response (ATR) index has been correlated with response to antidepressant medication (, ) but has not been assessed in a placebo-controlled trial. EEGs recorded at pretreatment baseline and after 1 week of randomized treatment were used to calculate ATR index for 23 subjects with major depressive disorder who were treated for 8 weeks with fluoxetine (FLX) 20 mg (n = 12) or placebo (n = 11). The 17-item Hamilton Depression Rating Scale (HamD17) assessed symptom severity; ATR index was assessed as a predictor of percent change in HamD17 score, endpoint response (≥ 50% improvement) and remission (HamD17 score ≤ 7). The ATR index was significantly associated with improvement on FLX (r = 0.64, P = 0.01), with a higher mean ATR index for FLX responders than for nonresponders (t(10) = -2.07, P = 0.03). Receiver operating characteristic analysis found a 0.83 area under the curve (P = 0.03), for ATR index as a predictor for FLX, while an optimized ATR index cutoff of 47.3 yielded 100% sensitivity, 66.7% specificity, 75% positive predictive value, and 100% negative predictive value. Importantly, ATR index did not correlate significantly with placebo outcomes. Results extend ATR index findings to include predictive validity with fluoxetine, suggesting that this biomarker has specificity for drug effects.Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 09/2011; 28(5):478-82. DOI:10.1097/WNP.0b013e318230da8a · 1.60 Impact Factor