Do antidepressants t(h)reat(en) depressives? Toward a clinically judicious formulation of the antidepressant-suicidality FDA advisory in light of declining national suicide statistics from many countries.

Given that suicidality is a well-known symptom and outcome of untreated or inadequately treated depressive illness, the United States (US) Food and Drug Administration (FDA) warning of emergent suicidality in children and adolescents based on the antidepressant arm of placebo-controlled randomized trials (RCTs) has created understandable concern in clinical practice. The issues involved are of broader public health importance for all age groups. As in other branches of medicine, psychiatrists must always be vigilant of the rare risk of iatrogenesis when prescribing potent agents like antidepressants for patients with depressive disorders where the risk of suicidality is inherent. The overall evidence we review suggests that the widespread use of antidepressants in the new "SSRI-era" appear to have actually led to highly significant decline in suicide rates in most countries with traditionally high baseline suicide rates. The decline is particularly striking for women who, compared with men, seek more help for depression. Recent clinical data on large samples in the US too have revealed a protective effect of antidepressant against suicide. We argue that the discrepancy between RCTs (in children) and national and clinical suicide statistics (in adults) may reside in new provocative data documenting high rates of unrecognized pseudo-unipolar mixed states particularly in juvenile, but also in adult, clinical populations. Such an interpretation accords well with equally provocative data that bipolar II (which is often "mixed" in nature) may well represent a particularly vulnerable clinical substrate for suicidality. In this respect, the widespread (at least in the psychiatric sector) augmentation of antidepressants with benzodiazepines, atypical antipsychotics or mood stabilizers may represent one situation where current practice is superior to evidence-based medicine. We conclude that rather than being a threat, the judicious clinical use of antidepressants actually does serve to effectively treat and indeed protect depressed patients from suicidal outcome. The fact of being in treatment with regular clinical follow-up appears beneficial as well.