Background: This paper examines the current status of research on the efficacy and effectiveness of antidepressants. Methods: This paper reviews four meta-analyses of efficacy trials submitted to America’s Food and Drug Administration (FDA) and analyzes STAR*D (Sequenced Treatment Alternatives to Relieve Depression), the largest antidepressant effectiveness trial ever conducted. Results: Meta-analyses of FDA trials suggest that antidepressants are only marginally efficacious compared to placebos and document profound publication bias that inflates their apparent efficacy. These meta-analyses also document a second form of bias in which researchers fail to report the negative results for the pre-specified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure as though it was their primary measure of interest. The STAR*D analysis found that the effectiveness of antidepressant therapies was probably even lower than the modest one reported by the study authors with an apparent progressively increasing dropout rate across each study phase. Conclusions: The reviewed findings argue for a reappraisal of the current recommended standard of care of depression.

Monkeys were trained with food reinforcement in a chamber containing four groups of three levers. For each session the monkey's task was to learn a new four-response chain by pressing the correct lever in each group. A stable pattern of learning resulted, and the number of errors reached a steady state from session to session. The technique was then used to determine how various durations of timeouts, following errors, affected the acquisition of new chains. With no timeout, the monkeys made a great many errors, due in large part to superstitious responses within the reinforced chain. Timeout durations ranging from 1 sec to 4 min reduced the number of errors substantially. A second experiment investigated the effects upon acquisition errors of presenting a single light (an "instruction" stimulus) over the correct lever. When this light did not influence the monkeys' responses to the three alternatives, the chains were learned as without it. When the light did control responding, the monkey pressed the appropriate sequence of levers but did not learn the sequence. Thus, when the light was removed, the monkey performed as if learning that sequence for the first time.

No abstract

No abstract

Variability of response location was studied in monkeys performing in a six-lever chamber. Fixed-ratio schedules, ranging from FR 1 to FR 300, generated a high degree of stereotypy of response location. In contrast, fixed-interval schedules of comparable reinforcement frequencies (0.06 to 4 minutes) generated much greater variability. These results failed to confirm any simple relationship between response variability and intermittence of reinforcement. Rather, variability seems to be determined by the particular characteristics of the reinforcement schedule.