Drug Profile

Mirtazapine (REMERON) is used to treat major depression. Mirtazapine resembles a hybrid of other types of antidepressants, namely tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Mirtazapine blocks receptors of the neurotransmitters serotonin and norepinephrine.

We have designated mirtazapine as Limited Use. For patients who need an antidepressant drug, we recommend trying one of the newer SSRIs (for example, fluoxetine [PROZAC, SARAFEM, SELFEMRA]) first, as these are the safest antidepressants. If symptoms do not improve sufficiently with use of an SSRI and remain severe, further treatment with other antidepressants is warranted.

Published information about this drug is sparse. With so many other antidepressants available, it is wiser to use an antidepressant with better-known safety and effectiveness.

Mirtazapine is not recommended for women who are pregnant or for children younger than 18.

Adverse effects

Older adults and those with liver or kidney problems may need a lower dose of mirtazapine. More than half of the people who take mirtazapine experience prolonged, and often severe, drowsiness.

Agranulocytosis

Mirtazapine can cause a blood disorder that lowers the number of white blood cells. Called agranulocytosis, it is a serious, sometimes fatal, adverse effect. The Adverse Drug Reactions Advisory Committee of Australia reported in 2007 that since 2001 it had received reports of 36 patients with blood disorders associated with mirtazapine. Agranulocytosis was reported in five of these patients.[5]

Serotonin syndrome

Another potentially life-threatening effect of mirtazapine is serotonin syndrome, which happens when there is an excess of serotonin, a naturally occurring nerve transmitter. Excess serotonin is usually the result of taking two or more drugs that have an effect on serotonin — such as SSRIs. Symptoms of serotonin syndrome include sweating, shivering and incoordination. (Read more in the April 2008 issue of Worst Pills, Best Pills News.)

Neuroleptic malignant syndrome

In December 2011, the Food and Drug Administration (FDA) updated the product label of mirtazapine to warn that potentially life-threatening neuroleptic malignant syndrome (NMS) could occur as a result of using the drug alone or with subsequent use of serotonergic drugs (such as triptans), drugs that make the metabolism of serotonin more difficult, or antipsychotics or other dopamine antagonists.[6]

Symptoms of NMS can include extremely high body temperature (hyperthermia), heavy sweating, fast heart rate, fast respiratory rate, rapidly fluctuating blood pressure, impaired consciousness, tremor, and rigid, stiff muscles.

Antidepressants and pregnancy

On Aug. 9, 2004, Health Canada, an agency similar to the FDA, issued a public advisory warning to Canadians that newborns may be adversely affected when their mothers take an SSRI or other newer antidepressants during the third trimester of pregnancy. Health Canada reported that some newborns whose mothers took these drugs during pregnancy have developed complications at birth requiring prolonged hospitalization, breathing support and tube feeding. The symptoms reported include feeding and breathing difficulties, seizures, muscle rigidity, jitteriness and constant crying. In most cases, the mothers were prescribed newer antidepressants during the third trimester of pregnancy.[7]

Studies show ...

A randomized, double-blind, placebo-controlled study found that the use of mirtazapine in patients diagnosed with generalized social anxiety disorder was not effective. The study was reported in the September 2010 International Clinical Psychopharmacology journal and included 60 patients.[8]

In 2011, the medical journal Lancet published a randomized, multicenter, double-blind, placebo-controlled study that evaluated the effects of sertraline (ZOLOFT) and mirtazapine on depression in patients with dementia. The results of the study demonstrated that, in patients with dementia who are depressed, the use of these antidepressant drugs did not show a benefit over the use of a placebo.[9]

In March 2014, Health Canada and the manufacturer of mirtazapine issued safety information noting that cases of abnormal heart rhythm or irregular heartbeats have been reported in patients taking mirtazapine.[10]

In May 2014, Prescrire International published an article with information from the World Health Organization pharmacovigilance database on 47 reported cases of rhabdomyolysis, a condition involving breakdown of muscle tissue that causes acute kidney failure, associated with mirtazapine use.[11]

In 2021, The Lancet published results of a randomized, placebo-controlled clinical trial showing that mirtazapine was not was not effective for treating agitation and led to a higher risk of death in patients with dementia.[12]

In 2021, The British Journal of Clinical Pharmacology published a study showing that mirtazapine was associated with an increased risk of developing low levels of thyroid hormone in the blood .[13]

In 2023, Journal of Psychiatric Practice published a systematic review of nine case reports of pancreatitis (inflammation of the pancreas) associated with mirtazapine.[14]

Other regulatory actions surrounding mirtazapine

2004: In October, the FDA issued a public health advisory requiring manufacturers to add a black-box warning (see "FDA Black-Box Warning" at the top of this page) to the product label for all antidepressants that included information on adverse effects such as suicidal thoughts, agitation and impulsivity. A black-box warning is the strongest type of warning that the FDA can require.

The FDA also required that a Medication Guide be given to patients receiving this drug, advising them of the risks and of precautions that can be taken. Click here to view the Medication Guide for mirtazapine.

2007: The FDA announced in May that it would require new warnings concerning the increased risk of suicidal thoughts and behavior in young adults ages 18 to 24 during the first one to two months of treatment with antidepressants. The agency required the new warnings to be black-box warnings printed on the product labels for all antidepressants sold in the United States. The warnings amended an existing black-box warning for children and adolescents.[15]

The FDA-approved product label for antidepressant drugs sold in the United States carries the following statement:

Suicide: The possibility of a suicide attempt is inherent in major depressive disorder and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy. Prescriptions for Drug X should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.