The asthma drug montelukast (SINGULAIR) is the third most-prescribed brand name drug in the U.S., with 28 million prescriptions filled in 2011. Despite its popularity, the drug has been linked to the occurrence of nightmares, as well as a host of other adverse psychiatric events, which have been well-documented and confirmed by a recent study. These adverse events may be particularly common in children. Because montelukast has only limited benefits and poses some unique risks, such as...
The asthma drug montelukast (SINGULAIR) is the third most-prescribed brand name drug in the U.S., with 28 million prescriptions filled in 2011. Despite its popularity, the drug has been linked to the occurrence of nightmares, as well as a host of other adverse psychiatric events, which have been well-documented and confirmed by a recent study. These adverse events may be particularly common in children. Because montelukast has only limited benefits and poses some unique risks, such as these psychiatric reactions, WorstPills.org has categorized the drug as Do Not Use since its approval.
Montelukast belongs to a family of drugs called leukotriene inhibitors, which when introduced represented the first new family of asthma drugs in 20 years. These drugs work by blocking the function or preventing the production of chemicals called leukotrienes, which are thought to play a role in asthma.
In addition to its Food and Drug Administration (FDA) approval to prevent and treat asthma symptoms, montelukast also is approved to relieve the symptoms of hay fever in adults and children age 2 and older and to prevent exercise-induced bronchoconstriction in patients age 6 and older.
The December 2012 issue of European Respiratory Journal published the results of a study that gathered reports of nightmares in children and adults taking montelukast. These reports were collected by the Spanish System of Pharmacovigilance through December 2011.
Of the 24 patients in whom nightmares were reported, 17 were children age 8 or younger. In addition to nightmares, other psychiatric adverse events, including insomnia, hallucinations, nervousness, irritability, aggressiveness and anxiety, were found in 12 of the 17 children.
In 18 patients, the nightmares appeared within the first day of exposure to montelukast or within the first week of treatment with the drug. In 21 of the 24 patients, the nightmares ended rapidly after discontinuing montelukast. After the nightmares resolved, three patients were then re-exposed to montelukast, and their nightmares reappeared.
This evidence is supported by an earlier study from Sweden that looked at 744 psychiatric adverse reactions, caused by a number of different drugs, in children under the age of 18 over a 10-year period. Montelukast was linked to more such reactions, 92, than any other drug studied. Of these 92 cases, the most common reactions were nightmares (19 cases), aggressiveness (13 cases), sleep disorder (11 cases), personality disorder (nine cases), anxiety (nine cases) and hyperactivity (eight cases). As was true in the Spanish study, the vast majority (93 percent) of these reactions abated when the drug was stopped. In more than one-third of the cases, the reintroduction of montelukast caused a re-emergence of the adverse reaction.
After receiving many reports of adverse drug reactions in patients using montelukast, the FDA changed the drug’s label to state:
Neuropsychiatric events have been reported in adult, adolescent, and pediatric patients taking SINGULAIR. Post-marketing reports with SINGULAIR use include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor. The clinical details of some post-marketing reports involving SINGULAIR appear consistent with a drug-induced effect.
However, because there is no FDA-mandated patient Medication Guide accompanying montelukast, patients may not be informed of this information when filling a prescription for the drug.
The authors of the Spanish study correctly point out that “unexplained nightmares can lead to unjustified psychiatric consultation and possibly to additional treatments, which can add more morbidity. Doctors, patients and their families should be fully informed about this risk.”
What You Can Do
Although montelukast is categorized as Do Not Use on WorstPills.org, you should not stop any asthma medication without first consulting your physician. Abruptly stopping a medication may result in the acute deterioration of asthma control.
The respected French journal Prescrire International has stated that the “more recent classes of antiasthmatic drugs [including leukotriene inhibitors, such as montelukast] have been disappointing thus far and have no established place in routine patient management.”
Inhaled corticosteroids (ICS, such as beclomethasone inhaled steroid [QVAR AEROSOL], fluticasone inhaled steroid [FLOVENT, FLOVENT DISKUS, FLOVENT ROTADISK] and triamcinolone inhalation [AZMACORT AEROSOL CANISTER]) are the mainstay treatment for persistent asthma.
The Cochrane Collaboration, an impartial, independent organization that periodically examines all published studies on a variety of health care topics, notes the superiority of ICS to leukotriene inhibitors, stating:
In symptomatic adults and children with mild or moderate asthma, anti-leukotrienes are less effective than inhaled corticosteroids (ICS) … for preventing exacerbations and achieving asthma control; the superiority of ICS is particularly marked in patients with moderate versus mild airway obstruction but does not appear influenced by age, duration of intervention, or anti-leukotriene used.
The Cochrane review further notes that use of leukotriene inhibitors is tied to increased risks of “exacerbation[s] requiring systemic corticosteroids” as well as hospital admissions and states that ICS drugs perform better in categories such as lung function, quality of life and symptoms.
On this efficacy basis, the Cochrane Collaboration recommends the use of ICS to treat persistent asthma in adults and children. We agree.
 Top-selling drugs (by units sold) of 2011. (Note: Singulair is third most selling brand-name drug, though sixth overall.) Drugs.com. www.drugs.com/stats/top100/2011/units. Accessed June 18, 2013.
 Scow et al. Leukotriene inhibitors in the treatment of allergy and asthma. Am Fam Physician. 2007 Jan 1;75(1):65-70. www.aafp.org/afp/2007/0101/p65.html.
 Merck. Singulair drug label. March 21, 2013. www.accessdata.fda.gov/drugsatfda_docs/label/2013/020829s065,020830s066,021409s042lbl.pdf. Accessed May 29, 2013.
 Cereza G, Garcia Dolade N, Laporte J-R, Nightmares induced by montelukast in children and adults. Eur Resp Jnl. 40;6:1574-75.
 Bygdell M, Brunlöf G, Wallerstedt S, and Kindblom J. Psychiatric adverse drug reactions reported during a 10-year period in the Swedish pediatric population. Pharmacoep and Drug Saf 2012; 21: 79–86.
 Merck. Singulair drug label. March 21, 2013. www.accessdata.fda.gov/drugsatfda_docs/label/2013/020829s065,020830s066,021409s042lbl.pdf. Accessed on May 29, 2013.
 Long-term asthma therapy: Adapt steroid therapy to severity. Prescrire International. 2007;91:211.
 Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database of Systematic Reviews. 2012;5. Art. No.: CD002314. DOI: 10.1002/14651858.CD002314.pub3.