DUAL ACTION SELECTIVE SEROTONIN RE-UPTAKE INHIBITORS

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:

(i) It inhibits the re-uptake of serotonin into the presynaptic neurone

(ii) It selectively blocks postsynaptic 5-HT2 receptors.

(b) Indication

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.).

(c) Adverse effects

1. Less gastrointestina1 side effects.

2. Less sexual dysfunction. SSRIs

3. Frequently reported side-effects are visual disturbances (including amblyopia) and lightheadedness.

4. Promotes sleep - owing to the blockade of 5-HT receptors.

5. 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.

V. SEROTONIN AND NORADRENA~ LINE RE-UPTAKE INHIBITORS (SNRIs)

Venlafaxine (the first SNRI) was introduced into the UK in 1995.

(a) Mode of action

]. Structurally a bicyclic antidepressant.

2. It selectively inhibits the re-uptake of both serotonin and noradrenaline into the presynaptic neurone.

(b) Indication

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).

2. Some evidence for treatment of resistant depression.

(c) Adverse effects

1. Less anticholinergic side-effects.

2. Less clinically significant cardiovascular cf. TCAs

side-effects.

3. Safer in overdosage. } cf. TCAs

4. Less likely to cause weight gain.

5. Gastrointestinal side-effects (e.g. nausea) - these are dose related and occur with a similar prevalence to those observed with SSRIs.

6. Hypertension - blood pressure should be monitored in patients taking 225 mg daily or more.

7. May precipitate hypomania in patients with bipolar affective disorder.

8. Frequently reported side-effects are sweating and headache.

9. 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).