Mirtazapine came onto the market in 1994 as a tetracyclic antidepressant, thus being structurally different from the selective serotonin reuptake inhibitors (SSRIs). It has been used to treat depression, posttraumatic stress disorder, obsessive-compulsive disorder, and social anxiety. It is now generic and available in 15mg, 30mg, and 45mg tablets.

Mechanism of Action

Mirtazapine affects a variety of neurotransmitters, including serotonergic, adrenergic, histamine, and muscarinic receptors. In affecting the 5HT-2 serotonergic, but not dopamine, receptors, it bears some resemblance to clozapine.

Use in Schizophrenia

Five small (n=24 to 40), double-blind trials have used mirtazapine 30 mg/d as an adjunct to treat schizophrenia. All the trials lasted between 6 and 8 weeks. Four of the five trials reported statistically significant improvement of the symptoms of schizophrenia, especially the negative symptoms.49-52 Two of the four positive studies also reported a statistically significant improvement in positive symptoms. The fifth study (n=40) reported no improvement in either positive or negative symptoms,53 but had a nonsignificant trend favoring mirtazapine. Mirtazapine was also shown in three studies to be effective in decreasing antipsychotic-induced akathisia.54-56 SMRI is supporting two large, multi-site studies in progress using mirtazapine as an adjunct to treat schizophrenia.

Use in Bipolar Disorder

Mirtazapine has been widely used to treat unipolar depression, and there are reports of its inducing manic episodes in selected patients.57


Given the paucity of effective drugs for treating the negative symptoms of schizophrenia, mirtazapine appears to be promising. For treating depression, mirtazapine has been used in doses up to 120mg/day. The main side effects of mirtazapine are drowsiness, increased appetite, and weight gain. When starting and stopping the drug, the dose should be increased and decreased slowly.