ANTIDEPRESSANTS are used to relieve the symptoms of depressive illness, an affective disorder. There are three main groups of drugs used for the purpose. All interfere with the function of monoamine neurotransmitters, and the considerable delay before antidepressants become effective is taken as evidence of a down-regulation of noradrenergic or serotonergic systems (rather than the opposite, as advanced in Schildkraut’s original amine theory of depression).

Tricyclic antidepressants are the oldest group (named after the chemical structure of the original members) .e.g. imipramine. They act principally as CNS monoamine (re-) UPTAKE INHIBITORS. Although far from ideal, this is still the most-used antidepressant group. Chemically, they have gone through transformations from the dibenzazepines (e.g. imipramine, desipramine), to dibenzcycloheptenes (e.g. amitriptyline, nortryptyline), dibenzoxepines (e.g. doxepin) and some recent members are not strictly tricyclics. They are effective in alleviating a number of depressive symptoms, though they have troublesome anticholinergic and other side-effects. Most drugs of this class also have sedative properties, which is more pronounced in some, especially amitriptyline, which may be beneficial in some anxious and agitated patients.

Monoamine-oxidase inhibitors (MAOIs) make up the second group and include, isocarboxazid, tranylcypromine and phenelzine, which are now used less commonly due to severe side-effects, especially through a potentially dangerous interaction with foodstuffs. A newer agent, moclobemide (a RIMA, reversible, selective type A monoamine-oxidase inhibitor) is said to give less dangerous interactions with foodstuffs. See MONOAMINE-OXIDASE INHIBITORS.

SSRIs are the most recent class, named after the drugs’ mechanisms of action (Selective Serotonin Reuptake Inhibitors), of which fluoxetine is the archytype. Other examples include cianopramine, citalopram, fluvoxamine, mirtazapine and paroxetine. Later members, such as venlafaxine, differ in being serotonin (re) UPTAKE INHIBITORS that also inhibit noradrenaline reuptake (but are weaker against dopamine uptake). The SSRIs show less side-effects, particularly less sedative actions, than the other classes.

Lastly, given the uncertainty about how antidepressants actually work, there is a group of drugs that seem to be of value, but do not readily fit into any of the above categories. These include nomifensine (now withdrawn), which blocks dopamine uptake (see uptake inhibitors), and the amino acid tryptophan, which is sometimes used where other classes of antidepressant have not been effective.

In manic-depressive and related illnesses, lithium (e.g. lithium carbonate) is the normal treatment for dealing with the manic phase (see ANTIMANIC AGENTS), and for preventing certain types of recurrent depression.

ANTIPSYCHOTICS (e.g. flupenthixol) may also be used, at a much lower dose, as antidepressants.