Criterion	Evaluation of the literature
1. Were there clearly defined patient groups that were similar in all ways other than exposure to an antidepressant?	No comparison group in case studies. Comparison groups differ across other studies.
2. Were treatments and manic symptoms measured the same way in both groups? Was the assessment of mania objective or blinded to antidepressant exposure status?	Open-label trials and case studies not blinded.
3a. Was the follow-up period sufficiently long for mania to occur?	Variable, but often sufficient (extending out to a year or more).
3b. Was retention adequate? How were missing data treated?	Straus et al. [28] offer a rule of thumb of ignoring any study with more than 20% lost to follow-up, because this will likely introduce bias. Missing data are often not discussed in published reports on antidepressants and mania.
4. Do the results satisfy some of the diagnostic tests for antidepressants causing mania?
4a. Is it clear that antidepressant exposure preceded the onset of the outcome?	If assessment of mania is not rigorous at baseline, then prior hypomania can escape detection.
4b. Is there a dose–response gradient?	Dose–response has not been demonstrated for antidepressant induction of mania yet.
4c. Is there any positive evidence from a withdrawal–rechallenge study?	We have not found a rechallenge study in the literature. There is a blinded withdrawal study [98].
4d. Is the association between antidepressants and mania consistent from study to study?	No. Results run the full gamut from increased rates of mania, to no difference in rates, to significant decreases in rates of mania.
4e. Does the association between antidepressants and mania make biological sense?	Yes, clearly.
Adapted from [28].