Treatments that do not fit into a single drug class include the tetracyclic antidepressants mirtazapine and mianserin; vortioxetine, which affects serotonin levels in a number of ways; and agomelatine, which is a melatonin-receptor agonist and a selective serotonin-receptor antagonist.

If a patient’s symptoms do not appear to improve after two to four weeks, adherence should be checked. If this isn’t an issue, the level of support should be increased – for example, a weekly phone call or appointment can help – and the dose increased within licensing restrictions if there are no significant side effects. Otherwise, treatment should be continued with reviews at decreasing intervals if the response continues to be good.

Switching antidepressant is appropriate if there are side effects, the response is inadequate or the patient expresses a desire to change treatment. As a general rule, the first time a change is made it should be to a different SSRI or a better-tolerated newer-generation antidepressant, and only if another change is required should it be to a different drug class. The shift from one antidepressant to another can usually be achieved within one week if the two drugs have short half-lives.