Antidepressants reduce the destruction of serotonin and noradrenaline in the brain. These are “neurotransmitters” – compounds that brain cells use to communicate with each other, especially about matters to do with emotion. They are reduced in the brains of depressed people, which means the brain cannot function normally.
Antidepressants are not addictive and don’t damage the brain, even if taken continuously for many years. In fact, one of their main actions is to encourage the brain to produce more of its own natural “fertiliser” proteins, known as “neurotrophins” (from the Greek neuron, nerve, and trophe, nourishment). Neurotrophins help brain cells repair damage caused by depression. They also support an increase of the number of connections between brain cells back to normal levels. The mind uses these richly connected neural cell networks to think, remember and feel. Interestingly, other treatments such as psychotherapy and exercise also boost neurotrophins to some extent.
Tricyclic antidepressants are the most powerful commonly used antidepressants, and also the cheapest. Used since the 1950s, they include nortriptyline (Allegron), amitriptyline (Endep), and dothiepin (Prothiaden, Dothep). They are taken at night because they have a sedative effect and can cause dizziness and falls, especially in the elderly. They’re also dangerous if overdosed on. On the upside, they cause fewer sexual side effects than most of the weaker antidepressants, and also alleviate chronic pain.
Selective Serotonin Reuptake Inhibitors (SSRIs) Less effective in severe depression, these are useful in mild depression or anxiety disorders. They include fluoxetine (Prozac, Lovan), sertraline (Zoloft), citalopram (Cipramil) and escitalopram (Lexapro). They’re all equally effective, and their rates of side effects are similar. SSRIs are quite safe in overdose and cause less dizziness in the elderly, but people may have less interest in sex than usual or find it harder to maintain an erection or reach climax (sexual health clinics use them to treat premature ejaculation). SSRIs can cause “fuzzy head” syndrome, meaning people feel less depression but less of everything else as well.
Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs) A newer class of antidepressants, these include venlafaxine (Effexor) and duloxetine (Cymbalta). SNRIs have similar side effects to SSRIs and seem to be roughly as effective, although venlafaxine at a high dose can also be effective in more severe depression.
Electroconvulsive therapy (ECT) If all else fails, or if the depression is exceptionally severe, ECT can be used. It works in the brain similarly to antidepressants, by restoring the levels of neurotransmitters to normal and boosting the brain’s own neurotrophins – but it does these things much better than tablets and so is more likely to treat an episode of depression successfully. Most people need eight to 12 treatments to get better; these are given two or three times a week under a general anaesthetic. The major disadvantage is that ECT must be carried out in a hospital. Its main side effect is that many people who have ECT do not store new memories well during the course (for example, they may forget particular conversations or forget meals), though this ability quickly returns to normal after the treatment finishes.
St John's Wort
Clinical trials have found St John’s wort improves symptoms more effectively than a placebo for people with mild to moderate depression over a period of one to three months. More than half the people treated with St John’s wort experienced improved mood after this period. It’s also been found to work just as well as tricyclic antidepressants and SSRIs in some cases.
However, most of these studies didn’t compare the same St John’s wort pills. Instead, there was a lot of variation in what dosage the pills contained and how they were made – which could well explain the large variation in how well it worked in different studies. Also, the studies tended to be short – usually less than six weeks – so long-term effectiveness isn’t known. While side effects tended to be milder than for conventional antidepressants, most studies did not look properly at them. The most common appear to be stomach problems (feeling sick or having diarrhoea), dizziness or confusion, tiredness and a dry mouth. People in some studies also said St John’s wort gave them headaches or reduced their enjoyment of sex.
The biggest issue with St John’s wort is that it interferes with other medications, including contraceptive pills, simvastatin, triptans, anti-epileptics, warfarin, some HIV drugs and other antidepressants. Always let your GP or specialist know if you’re taking St John’s wort.