Most treatment guidelines suggest that antidepressants may take many weeks to work. It is argued that even if the current treatment seems ineffective, it should be persisted with for several weeks or even months. The Mood Disorders Unit interprets the evidence differently.
If medication is likely to be effective, evidence of at least some improvement should appear in the first ten days or so, whether it is an improvement in mood, sleep, or other features. For melancholic and psychotic depression, the rate of improvement is generally slower (but relatively constant). It may, in fact, appear painfully slow.
If no improvement is noted in the first two weeks after commencing an antidepressant, the dose of that drug may need to be increased, a change to another class of antidepressant may be required, or ‘augmenting’ strategies (the addition of quite differing drugs) may need to be introduced. Unfortunately, when changing from one drug to another, days to weeks may pass before success can be established. It might also be the case that non-drug strategies will be more effective in bringing the depression to an end.

Augmentation of antidepressant drugs
The effectiveness of some antidepressants can be increased by the use of adjunctive or augmentation drugs, for example, thyroid hormones or lithium.
There is increasing evidence to suggest that the new ‘atypical’ antipsychotic drugs may also have augmenting effects on antidepressants, often working rapidly and also being able to be ceased rapidly in many instances. While not investigated formally, the benefits of such augmenting drugs may only be relevant to melancholic and psychotic depression.