antidepressant treatment

Last edited 03/2023 and last reviewed 03/2023

Antidepressant drugs modify the levels of monoaminergic neurotransmitters in the brain. The raphe nucleus in the brain stem contains the cell bodies of these serotonergic and noradrenergic neurones which innervate wide areas of the brain. Synaptic levels of monoamines, particularly serotonin, are thought to be decreased in depression.

The main classes of antidepressants are:

• tricyclic antidepressants
• serotonin-selective reuptake inhibitors
• noradrenergic and and specific serotonergic antidepressants

Monoamine oxidase A inhibitors are no longer in routine use.

Lithium is used in bipolar affective disorder and in cases of resistant depression.

Antidepressant drugs in mild depression:

• randomised controlled trial (RCT) evidence indicates that for many patients there is little clinically important difference between antidepressants and placebo, and the placebo response is greatest in mild depression
• antidepressants are not recommended for the initial treatment of mild depression, because the risk-benefit ratio is poor
• mild or persistent subthreshold depression
  • do not use antidepressants routinely to treat persistent subthreshold depressive symptoms or mild depression because the risk–benefit ratio is poor, but consider them for people with:
    • a past history of moderate or severe depression or
    • initial presentation of subthreshold depressive symptoms that have been present for a long period (typically at least 2 years) or
    • subthreshold depressive symptoms or mild depression that persist(s) after other interventions
• do not use antidepressants routinely to treat subthreshold depressive symptoms or mild depression in patients with a chronic physical health problem (because the risk–benefit ratio is poor), but consider them for patients with:
  • a past history of moderate or severe depression or
  • mild depression that complicates the care of the physical health problem or
  • initial presentation of subthreshold depressive symptoms that have been present for a long period (typically at least 2 years) or
  • subthreshold depressive symptoms or mild depression that persist(s) after other interventions

Antidepressant drugs in moderate or severe depression

• in moderate to severe depression there is more evidence for the effectiveness of antidepressant medication than in milder depression
• for routine care, a selective serotonin reuptake inhibitor is the first choice drug - because SSRIs are as effective as tricyclic antidepressants and are less likely to be discontinued because of side effects
• careful monitoring of symptoms, side effects and suicide risk (particularly in those aged under 30) should be routinely undertaken, especially when initiating antidepressant medication
• moderate or severe depression
  • for people with moderate or severe depression, provide a combination of antidepressant medication and a high-intensity psychological intervention (CBT or interpersonal therapy [IPT])
• when an antidepressant is to be prescribed for a patient with depression and a chronic physical health problem, take into account the following:
  • the presence of additional physical health disorders
  • the side effects of antidepressants, which may impact on the underlying physical disease (in particular, SSRIs may result in or exacerbate hyponatraemia, especially in older people)
  • that there is no evidence as yet supporting the use of specific antidepressants for patients with particular chronic physical health problems
  • interactions with other medications

For more detailed guidance then refer to full updated NICE guideline (2).

Reference:

1. NICE (April 2007). Management of depression in primary and secondary care.
2. NICE (April 2018). Depression
3. Anderson IM et al (2000). Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. J Psychopharmacol;14: 3-20.