These widely used drugs include a range of different preparations which relieve DEPRESSION. All the antidepressants available at the time of writing are more or less equally eﬀective. In studies where patients agree to take either antidepressants or identical dummy PLACEBO pills (without knowing which), at least two-thirds of those who receive antidepressants feel much better within three months, while fewer than one-third of those on placebos recover naturally in the same period. In general these drugs are useful for severe and moderate depression including postnatal illness; they are not eﬀective in milder forms of depression although they may be tried for a short time if other therapies have failed.
The most widely prescribed type of antidepressants are the tricyclics, so-called because their molecular structure includes three rings. The other commonly used types are named after the actions they have on chemicals in the brain: the SELECTIVE SEROTONIN-REUPTAKE INHIBITORS (SSRIS) and the MONOAMINE OXIDASE INHIBITORS (MAOIS) – see also below. All types of antidepressant work in similar ways. Tricyclic antidepressants have cured depression in millions of people, but they can cause unpleasant side-eﬀects, particularly in the ﬁrst couple of weeks. These include SEDATION, dry mouth, excessive sweating, CONSTIPATION, urinary problems, and impotence (inability to get an erection). Up to half of all people prescribed tricyclic drugs cannot tolerate the side-eﬀects and stop treatment before their depression is properly treated. More seriously, tricyclics can upset the rhythm of the heart in susceptible people and should never be given in the presence of heart disease.
The SSRIs are newer, coming into wide use in the late 1980s. They increase the levels in the brain of the chemical messenger SEROTONIN, which is thought to be depleted in depression. Indeed, the SSRIs are as eﬀective as tricyclics and, although they can cause nausea and excessive sweating at ﬁrst, they generally have fewer side-eﬀects. Their main disadvantage, however, is that they cost much more than the most commonly used tricyclic, amitriptyline. On the other hand, they are more acceptable to many patients and they cause fewer drop-outs from treatment – up to a quarter rather than a half. The money saved by completed, successful treatment may outweigh the prescribing costs. SSRIs have been reported as associated with an increased risk of suicide.
Another group of antidepressants, the MAOIs, have been in use since the late 1950s.
They are stimulants, rather than sedatives, and are particularly helpful for people who are physically and mentally slowed by depression. They work well but have one big disadvantage – a dangerous interaction with certain foods and other drugs, causing a sudden and very dangerous increase in blood pressure. People taking them must carry an information card explaining the risk and listing the things that they should avoid. Because of this risk, MAOIs are not used much now, except when other treatments have failed. A new MAOI, moclobemide, which is less likely to interact and so cause high blood pressure, is now available.
LITHIUM CARBONATE is a powerful antidepressant used for intractable depression. It should be used under specialist supervision as the gap between an eﬀective dose and a toxic one is narrow.
St John’s Wort is a popular herbal remedy which may be eﬀective, but which is handicapped by diﬀerences of strength between diﬀerent preparations or batches. It can interact with a number of conventional drugs and so needs to be used cautiously and with advice.
In general, antidepressants work by restoring the balance of chemicals in the brain. Improved sleep and reduced anxiety are usually the ﬁrst signs of improvement, particularly among people taking the more sedative tricyclic drugs. Improvement in other symptoms follow, with the mood starting to lift after about two weeks of treatment. Most people feel well by three months, although a few residual symptoms, such as slowness in the mornings, may take longer to clear up. People taking antidepressants usually want to stop them as soon as they feel better; however, the risk of relapse is high for up to a year and most doctors recommend continuing the drugs for around 4–6 months after recovery, with gradual reduction of the dose after that.
Withdrawal reactions may occur including nausea, vomiting, headache, giddiness, panic or anxiety and restlessness. The drugs should be withdrawn gradually over about a month or longer (up to six months in those who have been on maintenance treatment).
A wide range of antidepressant drugs is described in the British National Formulary. Examples include:
Tricyclics: amitryptyline, imipramine, doxepin.
MAOIs: phenelzine, isocarboxazid.
SSRIs: citalopram, ﬂuoxetine, paraxtene. (Antidepressant drugs not in these three
groups include ﬂupenthixol, mertazapine and venlafaxine.)