Management Of Depressive Disorders Pharmacologic Treatments For Depression Copyright © 2011. World Psychiatric Association

Management Of Depressive Disorders

Pharmacologic Treatments For Depression

Copyright © 2011. World Psychiatric Association

Classification of Antidepressant Medications

• Tricyclic Antidepressants• Monoamine Oxidase Inhibitors• Selective Serotonin Reuptake Inibitors• Selective Serotonin and Noradreline Reuptake Inibitors• Selective Noradrenaline Reuptake Inhibitors• Serotonin Modulating Antidepressants• Dopamine and Noradrenaline Reuptake Inhibitors• Noradrenergic and Specific Serotonergic Antidepressants• Melatonergic Antidepressants


Tricyclic Antidepressants (TCAs)

• Mechanism of action:– Inhibition of serotonin and/or noradrenaline reuptake

• Classification:– Mixed serotonergic/noradrenergic TCAs (Amitryptiline, Imipramine..)

– Predominant serotonergic TCAs (Clomipramine..)

– Predominant noradrenergic TCAs (Desipramine, Nortriptyline…)

• Effective in depressive disorders, independently of the subtype or severity of depression

• Most common side effects:– Anticholinergic and antihistaminergic side effects

– Postural hypothension

• Low safety in overdose


Monoamine Oxidase Inhibitors (MAOIs)

• Mechanism of action:– Inhibition of monoamine oxidase A and/or B

• Classification:– Non-selective and irreversibile MAOI (Phenelzine, Tranylcypromine..)

– Selective and reversible MAO-A inhibitor ( Moclobemide)

• Efficacy is highest in patients suffering from atypical depression

• Interactions of predominantly irreversible MAOIs with:– Sympathomimetic medications or tyramine-containing foods (such as

cheese, red wine, and smoked or pickled meats) can precipitate potentially life-threatening hyperthermia and hypertensive crisis

– Serotonin-enhancing antidepressants can precipitate the serotonin syndrome


Selective Serotonin Reuptake Inhibitors (SSRIs)

• Mechanism of action:– Inhibition of serotonin reuptake (Fluoxetine, Paroxetine, Citalopram,

Escitalopram, Sertraline, Fluvoxamine)

• As effective in depressive disorders as the TCAs, although some evidence exists that SSRIs may not be as efficacious as the TCAs in severely depressed inpatients

• Side effect profile:– During short-term treatment: nausea, vomiting, restlessness, headache,

sleep disturbances

– During long-term treatment: sexual dysfunctions

– Anticholinergic side effects are not common (except for Paroxetine)

– Safety in overdose


Selective Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)

• Mechanism of action:– Inhibition of serotonin and noradrenaline reuptake (Venlafaxine,

Duloxetine)

• Similar efficacy as SSRIs, although a superior efficacy of venlafaxine in terms of percentage of patients acheiving remission has been proposed

• Side effect profile:– Similar to SSRIs

– Hypertension (with high doses of Venlafaxine)

• Toxicity index in overdose:– Between that of the SSRIs and the TCAs (Venlafaxine)


Selective Noradrenaline Reuptake Inhibitors (SNRIs)

• Mechanism of action:– Inhibition of noradrenaline reuptake (only one compound: Reboxetine)

• Efficacy:– At least as effective as other classes of antidepressants except than in

melancholic depression

• Side effect profile:– Safer and more tolerated than TCAs

– Agitation, nervousness, anxiety, sexual dysfunction and gastrointestinal events less frequent than SSRIs

– Most common side effects: tachicardia and hypertension


Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs)

• Mechanism of action:– Blockade of noradrenergic α2 and serotonergic 5HT2-receptors resulting

in potentiation of 5HT action at 5HT1A receptor (Mianserine, Reboxetine)

• Efficacy:– At least as effective as other classes of antidepressants

• Side effect profile:– More tolerated than TCAs

– Sexual dysfunction and gastrointestinal complaints less frequent than SSRIs

– Most common side effects: somnolence and weight gain because of their antihistaminergic action


Serotonin Modulating Antidepressants

• Mechanism of action:– Blockade of serotonin reuptake and 5HT2-receptors resulting in

potentiation of 5HT action at 5HT1A receptor (Trazodone, Nefazodone)

• Efficacy:– At least as effective as other classes of antidepressants

• Side effect profile:– More tolerated than TCAs

– Most common side effects: sedation, dry mouth, nausea, somnolence and dizziness

– Potential of nefazodone to cause severe hepatotoxicity and even fulminant hepatic failure (withdrawn from the market in several countries)

– Trazodone may induce priapism


Dopamine and Noradrenaline Reuptake Inhibitors

• Mechanism of action:– Blockade of dopamine and noradrenaline reuptake (Bupropion)

• Efficacy:– Antidepressant efficacy at least equal to the SSRIs– Recommended especially in bipolar depression because of an

observed lower rate of mood switches as compared to SNRIs

• Side effect profile:– Sexual dysfunction, gastrointestinal complaints, agitation and

insomnia less frequent than SSRIs– The risk of seizures must be taken into account


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Management Of Depressive Disorders Pharmacologic Treatments For Depression Copyright © 2011. World Psychiatric Association