Other and Newer Antidepressants

Agomelatine

Agomelatine is a new antidepressant with MT₁ and MT₂ melatonergic agonist and 5-HT_2C antagonist actions which has been shown to be effective in severe depression (see Mongomery and Kasper, 2007). These properties, together with its lack of major effects on the uptake of dopamine, serotonin, and noradrenaline, may account for its relative lack of adverse side-effects. As Sansone and Sansone (2011) have commented regarding agomelatine:

‘The melatonergic function appears to improve sleep patterns, whereas the serotonergic antagonism results in the release of norepinephrine [noradrenaline] and dopamine. Given the current information, the overall side-effect profile of agomelatine appears relatively mild. For example, agomelatine has no discontinuation syndrome, exhibits infrequent sexual dysfunction, and is generally weight neutral. The drug appears to be relatively safe in overdose.’

Structure

The structure of agomelatine is shown in Fig. 10.1.

Fig. 10.1 The structure of agomelatine.

Dose

The initial adult (>18 years) oral antidepressant dose is 25mg nocte. This can be increased, according to clinical response, to 50mg nocte after 2 weeks. Liver function tests should be carried out prior to treatment and then at the 6-, 12-, and 24-week time-points, and then as appropriate. If the serum transaminase is higher than 3× the reference range upper limit, then treatment with agomelatine should be stopped.

Side-effects

The commonest side-effects are:

nausea
diarrhoea
constipation
abdominal pain
increased serum transaminases
headache
dizziness
drowsiness
insomnia
fatigue
anxiety
back pain
sweating.

Less common side-effects include:

paraesthesia
eczema
blurred vision.

Caution should be exercised in the following cases:

elderly patients
(hypo)mania
concomitant use of drugs associated with hepatic injury
excessive intake of alcohol.

Contraindications include:

dementia
hepatic impairment
breastfeeding.

Duloxetine

This drug inhibits the central re-uptake of serotonin and noradrenaline (norepinephrine).

Structure

The structure of duloxetine is shown in Fig. 10.2.

Fig. 10.2 The structure of duloxetine.

Dose

The adult (>18 years) oral antidepressant dose is 60mg once daily.

For the treatment of generalized anxiety disorder, the initial adult (>18 years) dose is 30mg daily, which may be increased as clinically appropriate to 60mg once daily. The maximum dose is 120mg daily.

Side-effects