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Apart from commercial reasons, two motivations have led to the introduction of SSRIs to replace the first and second generation antidepressants already available. One was the search for a more rational treatment, based on specific mechanisms, the other the development of effective treatments with fewer side effects, particularly for older patients, who have a greater sensitivity to cardio-vascular and central nervous system effects. The first has been frustrated up to a point, in that SSRIs and other single mechanism drugs do not appear to be more effective than the earliest relatively non-specific antidepressants. The second has been fulfilled, in that SSRIs generally are better tolerated in older patients and in overdose. However, there is a spectrum of other side effects that are particularly relevant in older age and that need attention when treating depression in this particular patient group.

Original publication




Journal article



Publication Date





118 - 123


Antidepressants, CGI, CI, CYP219, Clinical Global Impression (scale), Cytochrome P450 2C19, EPSE, FDA, HAM-D, Hamilton Depression Rating scale, MADRS, MHRA, Major depressive disorder, Medicines and Healthcare products Regulatory Agency, Montgomery-Åsberg Depression Rating scale, NNT, OR, PPIs, QT interval corrected (for heart rate), QTc, RCT, RR, Randomized controlled trials, Risks, SNRI (s), SSRI(s), Side effects, Suicide, TCA(s), US Food and Drug Administration, confidence interval, extrapyramidal side effects, numbers needed to treat, odds ratio, proton pump inhibitors, randomized controlled trial, risk ratio, serotonin reuptake inhibitor(s), serotonin–norepinephrine reuptake inhibitor(s), tricyclic antidepressants(s), Aged, Depression, Humans, Serotonin Uptake Inhibitors