In terms of pharmacotherapy this guideline includes the following recommendations:
Antidepressants are not recommended for the initial treatment of mild depression, because the risk–benefit ratio is poor.

The use of antidepressants should be considered for patients with mild depression that is persisting after other interventions, and those whose depression is associated with psychosocial and medical problems
The use of antidepressants should be considered when patients with a past history of moderate or severe depression present with mild depression
There is more evidence for the effectiveness of antidepressant medication in moderate to severe depression than in milder depression. Antidepressants are as effective as psychological interventions, widely available and cost less. Careful monitoring of symptoms, side effects and suicide risk (particularly in those aged under 30) should be routinely undertaken, especially when initiating antidepressant medication. Patient preference and past experience of treatment, and particular patient characteristics should inform the choice of drug. It is also important to monitor patients for relapse and discontinuation/withdrawal symptoms when reducing or stopping medication. Patients should be warned about the risks of reducing or stopping medication
When an antidepressant is to be prescribed in routine care, it should be a selective serotonin reuptake inhibitor (SSRI), because SSRIs are as effective as tricyclic antidepressants and are less likely to be discontinued because of side effects.

All patients prescribed antidepressants should be informed that, although the drugs are not associated with tolerance and craving, discontinuation/withdrawal symptoms may occur on stopping, missing doses or, occasionally, on reducing the dose of the drug. These symptoms are usually mild and self-limiting but can occasionally be severe, particularly if the drug is stopped abruptly.

When patients present initially with severe depression, a combination of antidepressants and individual CBT should be considered as the combination is more cost-effective than either treatment on its own.

Patients who have had two or more depressive episodes in the recent past, and who have experienced significant functional impairment during the episodes, should be advised to continue antidepressants for 2 years.

For patients whose depression is treatment resistant, the combination of antidepressant medication with CBT should be considered.

When prescribing an SSRI, consideration should be given to using a product in a generic form. Fluoxetine and citalopram, for example, would be reasonable choices because they are generally associated with fewer discontinuation/withdrawal symptoms. However, fluoxetine is associated with a higher propensity for drug interactions.

Dosulepin, phenelzine, combined antidepressants, and lithium augmentation of antidepressants should only be routinely initiated by specialist mental health professionals, including General Practitioners with a Special Interest in Mental Health.

Venlafaxine treatment should only be initiated by specialist mental health medical practitioners including General Practitioners with a Special Interest in Mental Health.

Venlafaxine treatment should only be managed under the supervision of specialist mental health medical practitioners including General Practitioners with a Special Interest in Mental Health.

Toxicity in overdose should be considered when choosing an antidepressant for patients at significant risk of suicide. Healthcare professionals should be aware that the tricyclic antidepressants (with the exception of lofepramine) are more dangerous in overdose than other equally effective drugs recommended for routine use in primary care
Reasonable choices for a second antidepressant include a different SSRI or mirtazapine, but consideration may also be given to other alternatives, including moclobemide, reboxetine and tricyclic antidepressants (except dosulepin).