Bias in the evaluation of antidepressants.

Tricyclic antidepressants TCAs) are no longer widely prescribed as first choice treatments for depression. In their place have come the selective serotonin reuptake inhibitors (SSRIs). Sales of SSRIs and other new antidepressants have grown massively partly at the expense of tricyclics and partly because of burgeoning antidepressant prescribing in general (Lawrenson et al, 2000; Middleton et al, 2001; Rosholm et al, 2001; Isacsson et al, 1999; Ciuna et al, 2004). Are the SSRIs really so much better? SSRIs have been marketed as being as effective as tricyclics, but better tolerated and safer in overdose. There are probably numerous other perceived advantages they may be less sedating so cause fewer psychomotor symptoms, and as "cleaner" drugs are less likely to have pharmacodynamic interactions with other drugs. However if one examines evidence purely from the accepted gold standard to compare two treatments, any advantages are insignificant. It is true that for every 30 or so patients started on an antidepressant, under trial conditions, one more will remain on the antidepressant at six weeks if an SSRI was prescribed, indicating a small advantage in terms of tolerability (Hotopf et al, 1997a; Barbui et al, 2000). In terms of efficacy, TCAs seem to have the edge in comparison with SSRIs. Perry, who reviewed the Hamilton scores in trials comparing TCAs with SSRIs, found TCAs more effective than SSRIs in patients suffering from severe depression with melancholic features