Practice Therapeutics

Newer antidepressants for the treatment of depression in adults

BMJ 2012; 344 doi: (Published 19 January 2012) Cite this as: BMJ 2012;344:d8300
  1. Simon Hatcher, associate professor of psychiatry 1,
  2. Bruce Arroll, professor of general practice2
  1. 1Department of Psychological Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand
  2. 2General Practice and Primary Health Care, University of Auckland, Private Bag 92019, Auckland
  1. Correspondence to: S Hatcher s.hatcher{at}

Antidepressants are prescribed mainly for people with depression, although some are also used for anxiety disorders and other conditions, including chronic pain and enuresis. They are one of the most commonly prescribed medications (more than 43 million prescriptions were written for them between April 2010 and March 2011 in England1).

Antidepressants were developed in the 1950s, and their mechanism of action is thought to be by increasing the levels of extracellular synaptic neurotransmitters such as serotonin, noradrenaline, and dopamine; they also have other effects, including increasing hippocampal neurogenesis. The original antidepressants were known as tricyclics because of their chemical structure. Since the 1980s a new generation of antidepressants has been developed and marketed based on their mode of action. The nomenclature for referring to these newer drugs is confusing as they can be classified by several criteria, including the target molecule and the number of neurotransmitter sites involved.2 Box 1 lists antidepressants grouped according to the current nomenclature used by the World Health Organization.

Box 1 World Health Organization’s current nomenclature for antidepressants, with examples of current drugs

Non-selective monoamine reuptake inhibitors
  • Tricyclic antidepressants: imipramine, amitriptyline*, clomipramine, lofepramine, amoxapine

  • Noradrenaline reuptake inhibitors: desipramine, nortriptyline, maprotiline

Selective serotonin reuptake inhibitors
  • Fluoxetine*, fluvoxamine, zimelidine, paroxetine, sertraline, citalopram, escitalopram

Monoamine oxidase inhibitors (non-selective)
  • Phenelzine, tranylcypromine, isocarboxazid

Monoamine oxidase A inhibitors
  • Moclobemide, toloxatone

Other antidepressants
  • Serotonin noradrenaline reuptake inhibitors: venlafaxine, duloxetine

  • Noradrenaline dopamine reuptake inhibitors: nomifensine, buproprion

  • Noradrenaline and selective serotonin antagonists: mirtazapine

  • Serotonin antagonist and reuptake inhibitor: trazadone

  • Melatonin receptor agonist with 5-HT2C receptor antagonist properties: agomelatine

  • Serotonin partial agonist: gepirone

  • *Listed in the WHO’s list of essential medicines for use in depressive disorders

The focus of this article is on selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants (using the World Health Organization’s nomenclature (box 1)) and their use in adults presenting with depressive disorders. We have excluded non-reversible monoamine oxidase inhibitors such as phenelzine as recent guidelines recommend these should usually be prescribed only by specialist mental health professionals. …

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