This book has an admirable primary aim: To answer the question, "What to do if the first treatment doesn't work?" In 19 chapters covering mood disorders, anxiety disorders, eating disorders, schizophrenia, personality disorders, ADHD, premenstrual dysphoria disorder, insomnia, and side effects, a large number of authors present us with the facts and give recommendations. I cannot think of a better source of information for these questions. The authors don't distract us with information about diagnosing, or slow us down with clinical vignettes. This is strictly a "nothing-butthe-facts-ma'am" book. My only complaint is that we tend to lose sight of the forest in this long list of the trees, i.e., we don't have our noses rubbed in the shame we should feel that the data base for much of our second and third treatments is just lousy. I shall focus my specific comments on mood disorders, given the journal in which this review appears.
Fava, Kaji, and Davidson present a comprehensive summary of pharmacologic strategies for treatmentresistant major depression. Patients who tolerate their initial antidepressant but don't respond seem good candidates for augmentation, they say. They list 8 studies of lithium augmentation, which seems a respectable amount of data, and give us a box score of 4 positive studies (significantly better than placebo), 3 negative studies, and 1 without a placebo control. Yet, most of these studies had small sample sizes. Five had a total sample of less than 30. The authors don't tell us, but I assume that all the negative studies had inadequate power to detect a clinically important difference. Further, most of the studies used TCAs as the initial drug, leaving the issue rather uncertain since most patients nowadays don't receive TCAs as initial treatment.
The subject gets more complicated in considering whether the subjects received an adequate trial of the initial drug. The authors don't address the lack of adequate pivotal dose-response studies. Does augmentation work regardless of dose of the initial drug? We don't know.
The evidence for other augmenting drugs is less than for lithium. Only 2 studies of T3 have been randomized clinical trials (RCTs), one positive and one negative (which is a crossover study that might not be appropriate for this question). Several dopaminergic augmenting drugs, such as bromocriptine, amantadine, and pergolide, have only anecdotal reports. The same for stimulants.