When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.

SynopsisThe psychometric properties of the 28- and 30-item versions of the Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) are reported in a total of 434 (28-item) and 337 (30-item) adult out-patients with current major depressive disorder and 118 adult euthymic subjects (15 remitted depressed and 103 normal controls). Cronbach's α ranged from 0·92 to 0·94 for the total sample and from 0·76 to 0·82 for those with current depression.Item total correlations, as well as several tests of concurrent and discriminant validity are reported. Factor analysis revealed three dimensions (cognitive/mood, anxiety/arousal and vegetative) for each scale. Analysis of sensitivity to change in symptom severity in an open-label trial of fluoxetine (N = 58) showed that the IDS-C and IDS-SR were highly related to the 17-item Hamilton Rating Scale for Depression. Given the more complete item coverage, satisfactory psychometric properties, and high correlations with the above standard ratings, the 30-item IDS-C and IDS-SR can be used to evaluate depressive symptom severity. The availability of similar item content for clinician-rated and self-reported versions allows more direct evaluations of these two perspectives.

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Objective: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method:A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N ϭ 3,671) to four (N ϭ 123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of Յ5 on the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR 16 ) (equivalent to Յ7 on the 17-item Hamilton Rating Scale for Depression [HRSD 17 ]) defined remission; a QIDS-SR 16 total score of Ն11 (HRSD 17 Ն14) defined relapse. Results: The QIDS-SR 16 remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. Conclusions: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.

In contrast to the vast literature on stress effects on the brain, relatively little is known about the molecular mechanisms of resilience, the ability of some individuals to escape the deleterious effects of stress. Here we show that the transcription factor, ΔFosB, mediates an essential mechanism of resilience in mice. Induction of ΔFosB in the nucleus accumbens, a key brain reward region, in response to chronic social defeat stress is both necessary and sufficient for resilience. ΔFosB induction also is required for the ability of the standard antidepressant, fluoxetine, to reverse behavioral pathology induced by social defeat. ΔFosB produces these effects through the induction of the GluR2 AMPA glutamate receptor subunit, which decreases the responsiveness of nucleus accumbens neurons to glutamate, and through other synaptic proteins. Together, these findings establish a novel molecular pathway underlying both resilience and antidepressant action.

Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare.

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