Treating symptoms in depression


Six classes of antidepressant treatments are available for depression therapy, and all affect the concentrations of monoamine neurotransmitters either within the neuron or in the synaptic cleft.  However, each class also offers differences in efficacy, tolerability, pharmacodynamics and pharmacokinetics.

The table below provides an overview of the different classes of antidepressant treatments, presented in chronological order of introduction to the clinic:



Monoamine oxidase inhibitors (MAOIs)

MAOIs inhibit activity of the monoamine oxidase isozymes, with differing selectivities and binding characteristics depending on each therapeutic molecule.1 They reduce breakdown of monoamine neurotransmitters at the synapse, and therefore increase their concentration in the synaptic cleft.1 Undesirable adverse event profiles led to them being used largely as a last resort therapy, although recent research suggests that newer and reversible MAOIs can offer a more tolerable experience of therapy, and that these drugs can still play an important role in the treatment of depression.2

Tricyclic antidepressants (TCAs)

TCAs exhibit inhibitory activity at both serotonin and norepinephrine reuptake channels, often in addition to antagonist efficacy at serotonin, histamine, α-adrenaline and/or muscarinic acetylcholine receptors.3 As a result of this lack of selectivity, TCAs exhibit a diverse adverse event profile, producing side effects which increase patients’ likelihood of discontinuing treatment.3,4 Consequently, TCAs are typically reserved for patients not responding to other therapies.4

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs selectively block the serotonin reuptake channel at the synaptic terminal to raise serotonin concentration, with low or negligible affinity for norepinephrine channels or monoamine receptors. SSRIs were therefore the first rationally designed therapies in psychiatry, and are recommended as the first line clinical treatment for depression.4,5

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

While SSRIs are selective for the serotonin reuptake channel, SNRIs show selectivity for both serotonergic and norepinephrinergic reuptake inhibition. Compared to other classes of antidepressants, the SNRIs are considered to exhibit simpler pharmacology, as they have relatively short half-lives and few active metabolites.6

Norepinephrine reuptake inhibitors (NRIs)

As the antidepressant effects of TCAs are attributed to their blockade of norepinephrine reuptake, a newer class of antidepressants were developed with the same mode of action.7 This leads to augmentation of synaptic norepinephrine concentrations, which can alleviate depressive symptoms. As serotonin and norepinephrine systems have different roles in the brain, SSRIs and NRIs exhibit variances in their clinical efficacy profiles.7


In recent years, an additional class of antidepressants has emerged with heterogeneous yet specific molecular targets. There are now several drugs in the clinical repertoire which are described as having ‘multimodal’ modes of action. This means that they exert their therapeutic effects through a combination of targets including ion channels, receptors and neurotransmitter reuptake channels. This broadens our existing clinical spectrum of antidepressants, offering an increased variety of pharmacotherapies for the treatment of depression.8

  1. Fiedorowicz JG, Swartz KL. The role of monoamine oxidase inhibitors in current psychiatric practice. J Psychiatr Pract 2004; 10(4): 239-248
  2. Zajecka JM, Zajecka AM. A Clinical Overview of Monoamine Oxidase Inhibitors: Pharmacological Profile, Efficacy, Safety/Tolerability, and Strategies for Successful Outcomes in the Management of Major Depressive Disorders. Psychiatric Annals 2014; 44(11): 513.
  3. Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 2007; 151(6):
  4. The treatment and management of depression in adults, NICE clinical guideline 90. 2009.
  5. Hiemke C, Härtter. S. Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther 2000; 85: 11–28.
  6. Sansone RA, Sansone LA. Serotonin-Norepinephrine Reuptake Inhibitors: A Pharmacological Comparison. Innov Clin Neurosci 2014; 11: 37–42.
  7. Hajós M et al. The selective norepinephrine reuptake inhibitor antidepressant Reboxetine: pharmacological and clinical profile. CNS drug reviews 2006; 10(1): 23–44.
  8. Baghai TC et al. Individualised pharmacological treatment of depressive disorders: state of the art and recent developments. J Depress Anxiety 2014; 3(2): 1000154
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