Dr Yolande Lucire
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Adverse drug reactions are biological & not related to diagnosis

Research: Antidepressant Use and Risk of Suicide and Attempted Suicide or Self Harm in People Aged 20 to 64: Cohort Study Using A Primary Care Database. Yolande Lucire lucire@ozemail.com.au
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h517 (Published 18 February 2015)
Cite this as: BMJ 2015;350:h517


The predicaments for which doctors prescribe antidepressants are not available to persons doing epidemiological studies or meta-analyses, as they do not have access to this patient level information. Accordingly, the reason for prescription should not be assumed to be “depression” – even as understood in its common language meaning. Antidepressants have been trialled for “minor mental disorders”, otherwise known as common human unhappiness, and also approved for anxiety, obsessive-compulsive disorder and menopausal symptoms.

At the United States Food and Drug Administration (US FDA), approval must be granted if a drug can be differentiated from placebo, or sugar pill, in two clinical trials out of any number that have been done, based on whatever criterion of significance the drug company chooses. Approval by FDA guarantees neither safety nor efficacy.

Whether or not the person develops toxic symptoms, worsening depression and sucidality or physical side effects is not at all related to their previous mental state or socially-constructed psychiatric diagnosis. Toxic side effects are biological, and occur in persons treated for non-psychiatric conditions as well.

Adverse effects as listed in each drug’s product information are the outcome of antidepressant toxicity, above the “therapeutic window of opportunity”, and result from several factors, usually acting together.

These include diminishing mutations in metabolizing genes in the cytochrome P450 system, the dose of the drug, synergistic adverse effects, the age of the patient, the drug burden, general and hepatic health, drug-drug and drug-gene interactions resulting from co-prescription of CYP450 inhibitors or withdrawal of inducers and the rate at which the medication is increased or decreased.

Adverse effects correlate well with genotypes but poorly with drug blood levels, which do not necessarily reflect brain levels. Also, once suicidality has set in, it worsens if withdrawal is not undertaken very slowly and persists well after the culprit medication has been ceased, and cannot be detected in blood which is five half-lives of the drug at issue.

Competing interests: No competing interests

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