xerostomia
Mirtazapine (Remeron) Adverse Reactions
In US controlled clinical trials, about 16% of mirtazapine-treated patients discontinued mirtazapine therapy because of drowsiness (10.4% vs. 2.2% for placebo vs. 60% for amitriptyline) or nausea/vomiting (1.5%/0% vs. 0% for placebo vs. 14%/0% for amitriptyline). The most commonly reported adverse reactions occurring at an incidence of >= 5% for mirtazapine and at least twice the incidence for placebo were drowsiness/sedation (54% vs. 18% for placebo), appetite stimulation (17% vs. 2%), weight gain (12% vs. 2%), and dizziness (7% vs. 3%). Weight gain of greater than 7% of body weight was reported in 7.5% of mirtazapine-treated patients compared to 0% for placebo.
Other adverse reactions occurring in >= 1% of mirtazapine-treated patients and at a greater incidence than in placebo in controlled trials include asthenia (8% vs. 5% for placebo), flu syndrome (5% vs. 3%), back pain (2% vs. 1%), xerostomia (25% vs. 15%), constipation (13% vs. 7%), peripheral edema (2% vs. 1%), edema (1% vs. 0%), myalgia (2% vs. 1%), abnormal dreams (4% vs. 1%), abnormal thinking (3% vs. 1%), tremor (2% vs. 1%), confusion or impaired cognition (2% vs. 0%), dyspnea (1% vs. 0%), and increased urinary frequency (2% vs. 1%).
All effective antidepressants can precipitate mania in predisposed individuals suffering from depression. In U.S. studies, approximately 0.2% of mirtazapine-treated patients developed mania/hypomania, so the occurrence is relatively rare. If mania occurs, the antidepressant should be held and appropriate therapy to treat the manic symptoms initiated.
Suicidal ideation has been reported in antidepressant clinical trials. The symptoms of aggressiveness, akathisia (psychomotor restlessness), agitation, anxiety, insomnia, irritability, hostility, mania, hypomania, impulsivity, and panic attacks have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidal ideation. A change or discontinuation of the therapeutic regimen should especially be considered if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Many of these adverse symptoms have been reported in clinical trials and have not always been associated with suicidality. Rapid discontinuation of SSRIs may also result in many of these adverse CNS events.
The following adverse events have also been reported to occur in 1% of mirtazapine-treated patients, except those already listed for controlled trials. These events come from data in all trials, including open-label and uncontrolled studies. It is important to emphasize that although the events reported occurred during treatment with mirtazapine, they were not necessarily caused by it. Some events occurred at rates similar to placebo in controlled clinical trials. The following events are listed by body system. Body as a whole: abdominal pain, malaise. Cardiovascular: hypertension, vasodilation (flushing). Digestive/GI: anorexia, vomiting. Metabolic: polydipsia (increased thirst). Musculoskeletal: arthralgia, myasthenia. Nervous system/Psychiatric: agitation, anxiety, amnesia, apathy, depression, dyskinesia (reported as either hypokinesia or hyperkinesia), hypoesthesia, paresthesias, twitching, and vertigo. Respiratory: increased cough, sinusitis. Skin and Appendages: pruritus, rash (unspecified). Urogenital system: urinary tract infection. NOTE; additional reported infrequent side effects (0.1 - 1% of patients) and rare events (<= 0.1% of patients) in which a causal relationship to mirtazapine has not been established are listed in the manufacturer’s prescribing information.
The following events were reported in at least 1% of mirtazapine-treated patients, but occurred in placebo-treated groups at an equal or greater incidence: amblyopia, chest pain (unspecified), diaphoresis (sweating), dysgeusia, dyspepsia, diarrhea, flatulence, infection, insomnia, hypertonia, nervousness, libido decrease, orthostatic hypotension, palpitation, pharyngitis, rhinitis, sinus tachycardia, and tinnitus. During pharmacology trials, orthostatic hypotension due to mirtazapine was observed in normal volunteers, however, orthostatic hypotension was infrequently observed in controlled clinical trials of depressed patients. In ECG studies, changes from baseline occurred in equal rates in placebo- and mirtazapine-treated groups and were generally non-clinically significant.
During short-term U.S. controlled trials, clinically significant elevated hepatic enzymes were observed in 2% of mirtazapine-treated patients compared to 0.3% of placebo-treated patients. Most patients with transaminase elevations did not develop signs or symptoms associated with impaired hepatic function. Mirtazapine was discontinued in some patients, while in other cases, the enzyme levels returned to normal even with continued treatment with mirtazapine. If jaundice occurs during mirtazapine treatment, discontinue the drug.
Three cases of agranulocytosis were reported during premarketing clinical trials of mirtazapine. Agranulocytosis (ANC < 500/mm3 with associated signs and symptoms) developed in 2 (one with Sjogren’s syndrome) out of 2,796 patients being treated with mirtazapine. A third patient developed severe neutropenia (ANC < 500/mm3 without any associated symptoms). For these three patients, onset of severe neutropenia was detected on days 61, 9, and 14 of treatment, respectively. Following discontinuation of mirtazapine, all three patients recovered. If a patient develops sore throat, fever, stomatitis, or other signs of infection, along with neutropenia, mirtazapine therapy should be discontinued.
Mirtazapine may increase hypercholesterolemia or hypertriglyceridemia. Nonfasting cholesterol increases to >= 20% above the upper limits of normal were observed in 15% of patients treated with mirtazapine in U.S. controlled studies compared to 7% for placebo and 8% for amitriptyline. In the same studies, nonfasting triglyceride increases to >= 500 mg/dl were observed in 6% of mirtazapine-treated patients compared to 3% for placebo and 3% for amitriptyline. A suspected case of hypertriglyceridemia and hypercholesterolemia, with resultant acute pancreatitis and diabetic ketoacidosis (hyperglycemia) has been reported with the use of mirtazapine 45 mg/day. The patients serum lipid profile and pancreatic enzyme levels returned to normal 2 months after discontinuing mirtazapine. The authors suggest that serum glucose and lipid levels, particularly triglycerides, be monitored at baseline and regularly throughout maintenance treatment.).
In clinical trials with mirtazapine, apart from excessive sedation no clinically relevant effects have been observed following overdose. Toxicity studies demonstrate that clinically relevant cardiotoxic effects will not occur after overdosing with mirtazapine.
Although unlikely to occur with use of mirtazapine alone, the coadministration of other medications that potentiate the actions of serotonin could theoretically result in serotonin syndrome. A case report of serotonin syndrome from an interaction of mirtazapine with fluoxetine has been described.
[ Last revised: 11/10/2005 2:54:00 PM ]
References
. Chen JL, Spinowitz N, Karwa M. Hypertriglyceridemia, acute pancreatitis and diabetic ketoacidosis possibly associated with mirtazapine: A case report. Pharmacotherapy 2003;23:940 - 4.
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