Nefazodone (Dutonin), the first dual action SSRI was introduced into the UK in 1995.
Structurally, it is a derivative of trazodone, which itself is an antidepressant drug related to the TCAs. It exhibits a dual action on both the neurotransmitter serotonin and its receptors:
It inhibits the re-uptake of serotonin into the presynaptic neurone
It selectively blocks postsynaptic 5-HT2 receptors.
Treatment of depressive disorders (dosage: 50 mg b.d. for I week, then 100 mg b.d. for 1 week, then stepping it up to the usual therapeutic dose of 200 mg b.d.).
Less gastrointestina1 side effects.
Less sexual dysfunction. SSRIs
Frequently reported side-effects are visual disturbances (including amblyopia) and lightheadedness.
Promotes sleep - owing to the blockade of 5-HT receptors.
It requires twice daily dosing, cf. once daily dosing with SSRJs;
this may reduce compliance in patients taking nefazodone for the long-term treatment of depression, cf. patients taking SSRIs.
SEROTONIN AND NORADRENALINE RE-UPTAKE INHIBITORS (SNRIs)
Venlafaxine (the first SNRI) was introduced into the UK in 1995.
Mode of action
Structurally a bicyclic antidepressant.
It selectively inhibits the re-uptake of both serotonin and noradrenaline into the presynaptic neurone.
1.Treatment of depressive disorders (dosage: 37.5 mg b.d.; this may be increased to 75 mg b.d. in mild to moderate depression; it may be further increased by 75 mg increments every 2-3 days to a maximum of 375 mg daily in hospitalized severe depression).
Some evidence for treatment of resistant depression.
Less anticholinergic side-effects.
Less clinically significant cardiovascular cf. TCAs
Safer in over dosage. cf. TCAs
Less likely to cause weight gain.
Gastrointestinal side-effects (e.g. nausea) - these are dose related and occur with a similar prevalence to those observed with SSRIs.
Hypertension - blood pressure should be monitored in patients taking 225 mg daily or more.
May precipitate hypomania in patients with bipolar affective disorder.
Frequently reported side-effects are sweating and headache.
It requires twice daily dosing, cf. once daily dosing with SSRIs;
this may relatively reduce compliance in patients taking venlafaxine for the long-term treatment of depression, cf. patients taking SSRIs.
N.B. A once-a-day formulation of venlafaxine was launched in the UK in 1997 (dosage: 75 mg daily; if further clinical improvement is required, this may be increased to 150 mg daily; it may be further increased to a maximum of 225mg daily if required).