MIRTAZAPINE - AN ANTIDEPRESSANT WITH NORADRENERGIC AND SPECIFIC SEROTONERGIC EFFECTS

Mirtazapine is a unique antidepressant that refines the specificity of effects on noradrenergic and serotonergic systems. It is an antagonis t of presynaptic alpha(2)-adrenergic autoreceptors and heteroreceptors on both norepinephrine and serotonin (5-HT) presynaptic axons, plus i s a potent antagonist of postsynaptic 5-HT2 and 5-HT3 receptors. The n et outcome of these effects is increased noradrenergic activity togeth er with specific increased serotonergic activity, especially at 5-HT1A receptors. This mechanism of action maintains equivalent antidepressa nt efficacy but minimizes many of the adverse effects common to both t ricyclic antidepressants and selective serotonin reuptake inhibitors. Mirtazapine has an onset of clinical effect in 2-4 weeks similar to ot her antidepressants, although sleep disturbances and anxiety symptoms may improve in the first week of treatment. It has minimal cardiovascu lar and anticholinergic effects, and essentially lacks serotonergic ef fects such as gastrointestinal symptoms, insomnia, and sexual dysfunct ion. Sedation, increased appetite, and weight gain are more common wit h mirtazapine than with placebo. An elimination half-life of 20-40 hou rs enables once-daily bedtime dosing. The recommended initial dosage i s 15 mg once/day at bedtime, with an effective daily dosage range of 1 5-45 mg. Cases of overdose of up to 975 mg caused significant sedation but no cardiovascular or respiratory effects or seizures.