Antidepressants are now among the most widely used prescription medicines in both Great Britain and the US. During the last 20 years, as depression has become recognized as a medical condition rather than mere melancholia, drug companies have sought to refine the 'chemical coshes' of the 1950s into sophisticated drugs that target specific brain chemicals.
The best-known TCA drugs are amitriptyline and imipramine. Yet, despite more than 30 years of use, it's only recently that researchers have set about determining whether they actually work. The embarrassing news is that they generally don't. One study found that only 29 per cent of patients responded to tricyclics. After a major review of the evidence, a further embarrassment is that, for years, psychiatrists have been prescribing dosages that are just too high. At the standard dose of 125 mg/day, the side-effects become so intolerable that many patients simply give up, clearly preferring to be depressed than to lose their appetite and libido, or suffer constipation, dehydration and confusion, the classically depressing side-effects of tricyclic drugs.
Selective serotonin reuptake inhibitors, or SSRIs, act by interfering with (blocking) the brain chemical serotonin, believed to be involved in depression. SSRIs have been heavily and cleverly marketed, such that Prozac, the drug family's brand leader, is now almost as common a word for antidepressants as 'Hoover' is for vacuum cleaners.
But SSRIs are not all they're cracked up to be. Indeed, at least two major review studies have shown SSRIs to be similarly as ineffective as the tricyclics they were designed to replace. Similarly, a recent meta-analysis (a comparative survey of all the clinical data available so far) found that "there are no clinically significant differences in effectiveness between SSRIs and trIcyclic antidepressants". Their adverse effects may be considerably worse. All SSRIs are associated with 'extrapyramidal' reactions (the part of the brain that controls movement), causing a range of disturbing symptoms. One of the worst effects is manic, violent behaviour.