Side effects
A 2011 Cochrane review found that, compared with other antidepressants, it is more likely to cause weight gain and sleepiness, but it is less likely to cause tremor than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than SSRIs.Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite (17%) and weight gain (>7% increase in <50% of children).Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, fasciculations (muscle twitches), peripheral edema (swelling, usually of the lower limbs), and negative lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the SSRIs, and may actually improve certain ones when taken in conjunction with them. (Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhoea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.) In general, some antidepressants, especially selective serotonin reuptake inhibitors (SSRI), can paradoxically exacerbate some peoples depression or anxiety or cause suicidal ideation.
Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to tricyclic antidepressants.Twelve reported fatalities have been attributed to mirtazapine overdose. The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2). This is similar to that observed with SSRIs. Interactions
Concurrent use with inhibitors or inducers of the cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and/or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism. As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them. Liver impairment and moderate chronic kidney disease have been reported to decrease the oral clearance of mirtazapine by about 30%; severe kidney disease decreases it by 50%.Mirtazapine in combination with an SSRI, SNRI, or TCA as an augmentation strategy is considered to be relatively safe and is often employed therapeutically, with a combination of venlafaxine and mirtazapine, sometimes referred to as "California rocket fuel". Several case reports document serotonin syndrome induced by the combination of mirtazapine with other agents (olanzapine, quetiapine, tramadol and venlafaxine).