The many different faces of major depression: it is time for personalized medicine

Eur J Pharmacol. 2015 Apr 15:753:88-104. doi: 10.1016/j.ejphar.2014.11.045. Epub 2015 Jan 12.


First line antidepressants are the so-called SSRIs (selective serotonin reuptake inhibitors), e.g. fluvoxamine, fluoxetine, sertraline, paroxetine and escitalopram. Unfortunately, these drugs mostly do not provide full symptom relief and have a slow onset of action. Therefore other antidepressants are also being prescribed that inhibit the reuptake of norepinephrine (e.g. reboxetine, desipramine) or the reuptake of both serotonin (5-HT) and norepinephrine (e.g. venlafaxine, duloxetine, milnacipran). Nevertheless, many patients encounter residual symptoms such as impaired pleasure, impaired motivation, and lack of energy. It is hypothesized that an impaired brain reward system may underlie these residual symptoms. In agreement, there is some evidence that reuptake inhibitors of both norepinephrine and dopamine (e.g. methylphenidate, bupropion, nomifensine) affect these residual symptoms. In the pipeline are new drugs that block all three monoamine transporters for the reuptake of 5-HT, norepinephrine and dopamine, the so-called triple reuptake inhibitors (TRI). The working mechanisms of the above-mentioned antidepressants are discussed, and it is speculated whether depressed patients with different symptoms, sometimes even opposite ones due to atypical or melancholic features, can be matched with the different drug treatments available. In other words, is personalized medicine for major depression an option in the near future?

Keywords: Amitifadine (DOV 21,947EB-1010) (PubChem CID: 11680542); Bupropion (PubChem CID: 444); DOV 216,303; DOV 216,303 (PubChem CID: 9795276); Depression; Dopamine; Duloxetine (PubChem CID: 60835); Escitalopram (PubChem CID: 146570); Fluoxetine (PubChem CID: 3386); Fluvoxamine (PubChem CID: 5324346); Intracranial self-stimulation; Methylphenidate; Methylphenidate (PubChem CID: 4158); Microdialysis; Milnacipran (PubChem CID: 65833); Reboxetine (PubChem CID: 65856); Selegiline (PubChem CID: 26757); Tesofensine (PubChem CID: 11370864); Venlafaxine (PubChem CID: 5656).

Publication types

  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Brain / drug effects
  • Depressive Disorder, Major / drug therapy*
  • Endophenotypes
  • Humans
  • Neurotransmitter Uptake Inhibitors / pharmacology
  • Neurotransmitter Uptake Inhibitors / therapeutic use
  • Precision Medicine / methods*
  • Reward


  • Antidepressive Agents
  • Neurotransmitter Uptake Inhibitors