Montelukast — How Dangerous It Is, Side Effects and Psychiatric Disorders

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Names under which montelukast is available: the international nonproprietary name is montelukast, and the Latin name is montelukast. Medicinal products contain montelukast sodium. Available dosage forms include film-coated tablets, chewable tablets, and granules for oral administration. The best-known brand name is Singulair. The medicine is also sold under the names Montelukast, Montelar, Singlon, Ektalust, Almont, Monkasta, and other brand names depending on the country and manufacturer. Combination products containing montelukast together with levocetirizine, desloratadine, fexofenadine, bilastine, or other antiallergic components are also available on the pharmaceutical market. Before taking several medicines at the same time, it is necessary to check the “active ingredient” line: a separate montelukast medicine must not be unknowingly duplicated by a combination tablet.

Why montelukast is considered harmless and where the real risk begins: the medicine is often perceived as a safe, non-hormonal tablet for allergy, cough, and bronchial asthma. It is prescribed to children, taken once daily, and is often continued for months without regular reassessment of whether treatment is still necessary. This everyday confidence can be dangerous: montelukast can cause sleep disorders, anxiety, irritability, aggression, depressive symptoms, hallucinations, attention disorders, obsessive thoughts, suicidal thoughts, and suicidal behavior. These reactions have been reported in patients both with and without a history of psychiatric illness, during treatment and after discontinuation. In 2020, the FDA required information about serious neuropsychiatric adverse effects to be placed in its strongest Boxed Warning and restricted the use of montelukast for allergic rhinitis to cases in which other treatments are ineffective or not tolerated.

A person may fail to associate the first symptoms with the medicine. Nightmares may be attributed to stress, a child’s irritability to age or upbringing, reduced concentration to school workload, and anxiety or low mood to the underlying illness. Taking several allergy medicines at the same time creates a risk of hidden duplication of montelukast. Alcohol, stimulants, and psychoactive substances may further worsen sleep, mood, and behavioral control, making a drug-related reaction more difficult to recognize.

Side effects after the first dose and during a short course: the most common reactions include headache, abdominal pain, dyspepsia, nausea, diarrhea, fatigue, and symptoms of upper respiratory tract infections. Children may experience fever, abdominal pain, cough, and irritability. These reactions are usually not life-threatening but may lead to discontinuation of treatment.

Clinically significant neuropsychiatric reactions may appear after the first doses or within several days. These include insomnia, unusually vivid dreams, nightmares, sleepwalking, anxiety, psychomotor agitation, aggression, hostility, tremor, impaired attention, disorientation, tics, stuttering, memory impairment, and marked behavioral changes. More severe reactions include depression, hallucinations, obsessive-compulsive symptoms, suicidal thoughts, and suicidal actions. The official FDA prescribing information explicitly warns about serious neuropsychiatric events and calls for discontinuation of the medicine when new symptoms appear.

Rare but potentially life-threatening complications include anaphylaxis, angioedema, severe skin reactions including Stevens–Johnson syndrome and toxic epidermal necrolysis, as well as clinically significant liver injury. Swelling of the face or larynx, difficulty breathing, widespread blistering rash, impaired consciousness, or suicidal behavior requires emergency medical care rather than observation at home.

Side effects with long-term and repeated use: montelukast does not cause classic physical drug dependence, but a prolonged course increases the duration of exposure to the medicine and the likelihood that gradually developing changes will go unnoticed. Sleep disturbances, night terrors, anxiety, low mood, aggression, tics, reduced concentration, and behavioral changes may persist for weeks or months. In many patients, symptoms decrease after discontinuation, but cases have been reported in which they persisted or appeared only after treatment had been stopped.

Epidemiological studies have produced inconsistent results. In a 2025 Swedish study involving 74,291 children and adolescents, the overall risk of neuropsychiatric events with montelukast did not differ from the risk associated with long-acting β₂-agonists. Other observational studies have found an increased incidence of certain neuropsychiatric diagnoses, sleep disorders, or behavioral symptoms. This inconsistency means that a severe reaction does not occur in every patient, but it does not justify ignoring an individual temporal association between the start of treatment and changes in mental state.

With prolonged treatment, increased liver enzyme activity, drug-induced hepatitis, and other liver function abnormalities have also been described. Rarely, systemic eosinophilia and eosinophilic granulomatosis with polyangiitis may occur, accompanied by worsening breathing, vascular inflammation, peripheral neuropathy, skin manifestations, and cardiac involvement. Particular attention is given to patients whose symptoms appear while the dose of systemic glucocorticosteroids is being reduced.

Montelukast does not cause tolerance requiring continuous dose escalation and does not have a classic withdrawal syndrome. However, long-term use may mask inadequate asthma control if the patient continues taking the tablet instead of adjusting effective maintenance inhaled therapy.

Contraindications and high-risk groups: the absolute contraindication is hypersensitivity to montelukast or to excipients in the dosage form. Before prescribing the medicine, it is necessary to determine whether the patient has depression, anxiety disorders, psychosis, self-harm, suicidal thoughts or attempts, severe sleep disorders, or marked behavioral disorders. However, the absence of a psychiatric history does not protect against a neuropsychiatric reaction. The FDA recommends discussing this risk with all patients and their relatives before treatment begins.

Particular caution is required in children. A young child is not always able to describe anxiety, hallucinations, obsessive thoughts, or changes in perception. The first manifestations may include crying at night, fear of falling asleep, unusual aggression, enuresis, sleepwalking, tics, a sudden deterioration in behavior, or statements about death. Parents should consider these symptoms as a possible drug-related reaction rather than only a psychological problem.

In patients with liver disease, monitoring for symptoms of hepatotoxicity and laboratory abnormalities becomes more important. Chewable tablets from some manufacturers contain aspartame, so the composition of the specific medicine must be checked in patients with phenylketonuria. Montelukast is not intended to relieve an acute asthma attack and is dangerous when used as a replacement for a rapid-acting inhaled bronchodilator.

Dangerous interactions: phenobarbital and other potent enzyme inducers may accelerate the metabolism of montelukast and reduce its concentration, thereby decreasing its therapeutic effect. The official prescribing information reports an approximately 40% reduction in the area under the pharmacokinetic curve when montelukast is combined with phenobarbital. If asthma control worsens, increasing the dose of montelukast without assessing the interaction is a mistake.

Gemfibrozil, a potent CYP2C8 inhibitor, significantly increases systemic exposure to montelukast. The official prescribing information does not require automatic dose adjustment, but the combination requires clinical monitoring, particularly if unusual neuropsychiatric or other adverse reactions occur. Similar caution is justified with other clinically significant CYP2C8 inhibitors.

A specific direct interaction with alcohol is not considered established, but alcohol may worsen insomnia, anxiety, irritability, depressive manifestations, impulsivity, and impaired behavioral control. If psychiatric symptoms appear, this combination is especially undesirable because it makes it more difficult to determine the cause of the reaction.

Concurrent use of psychostimulants, sedatives, hypnotics, antidepressants, and other medicines affecting the central nervous system is not always formally contraindicated, but it complicates the assessment of insomnia, agitation, aggression, anxiety, and mood changes. The most practical danger is hidden duplication of montelukast: a separate tablet may be taken together with a combination antiallergic medicine that already contains the same active ingredient.

Patient mistakes: a common mistake is self-treatment with montelukast for any runny nose, cough, prolonged infection, or occasional wheezing. The medicine is not a universal antiallergic treatment and does not treat bacterial or viral infections. For isolated allergic rhinitis, its use should be limited to situations in which safer options are insufficiently effective or are not tolerated.

A second mistake is expecting immediate relief of an attack of breathlessness. Montelukast is not an emergency medicine and does not replace a rapid-acting inhaler. Repeatedly taking a tablet or increasing the dose during bronchospasm does not provide the rapid bronchodilation that is required and may delay effective treatment.

Self-directed dose increases, shortening the interval between doses, simultaneous use of several montelukast-containing medicines, and unjustified prolongation of treatment are dangerous. Nightmares, insomnia, sudden irritability, aggression, depression, hallucinations, or suicidal statements must not be ignored. Prescribing a sedative or psychotropic medicine without evaluating the role of montelukast may result in treating a drug-induced complication with another medicine instead of removing its cause.

Overdose and poisoning: no universal toxic single dose of montelukast has been established. Clinical studies and post-marketing reports have described cases in which doses far above therapeutic levels were taken without severe poisoning, but this does not mean that overdose is safe for a particular child or adult. The most common manifestations were abdominal pain, drowsiness, thirst, headache, vomiting, and psychomotor agitation.

Hidden overdose may occur when different family members administer the same dose more than once, when a child accidentally swallows tablets, when the wrong dosage form is selected, when separate montelukast is combined with a combination product, or when a dosing calculation is incorrect. Because there is no specific antidote, treatment is symptomatic and supportive. There are no reliable data showing that montelukast can be effectively removed by hemodialysis or peritoneal dialysis.

After accidental ingestion of an excessive dose, one should not wait for a pronounced clinical picture to develop. Consultation with a poison control service or medical assessment is necessary, especially if the overdose occurred in a child. Emergency care is required in cases of impaired consciousness, marked agitation, hallucinations, seizures, repeated vomiting, difficulty breathing, swelling of the face or larynx, or a severe skin reaction.

A safe integrative alternative to montelukast: the choice of replacement depends on the reason the medicine was prescribed. For allergic rhinitis, chronic rhinosinusitis, postnasal drip, allergic cough, and combined airway inflammation, an integrative regimen may include Allergy Mixture LH, Rhinitis and Rhinosinusitis Mixture LH, and ABP-153.

Allergy Mixture LH is the primary systemic antiallergic alternative. The complex contains Andrographis paniculata, Schefflera leucantha, and Murdannia loriformis. Its pharmacological action is associated with reducing allergic airway inflammation, regulating Th2- and Th17-dependent responses, suppressing proinflammatory signaling pathways, and reducing eosinophilic infiltration, release of allergy mediators, mucus hypersecretion, and bronchial hyperreactivity. It is not a selective CysLT1 receptor antagonist but rather a multicomponent intervention affecting the inflammatory cascade.

The pharmacological rationale for the complex is based on data regarding its botanical components, the mechanisms of action of their constituent compounds, and clinical observations. Large direct randomized trials comparing the finished complex with montelukast are insufficient. This limitation must be taken into account, but it does not make the herbal regimen inherently ineffective: it should be assessed according to its composition, therapeutic focus, observed clinical effect, tolerability, and suitability for the specific disease phenotype.

Rhinitis and Rhinosinusitis Mixture LH is a specialized systemic medicine for cases in which nasal obstruction, rhinorrhea, mucosal swelling, chronic rhinosinusitis, and postnasal drip predominate. If montelukast was prescribed primarily because of nasal symptoms, targeted treatment of upper airway pathology may be more rational than systemic use of a medicine with limited effectiveness in rhinitis and a serious neuropsychiatric warning.

ABP-153 is the primary local intranasal medicine in the regimen, not a secondary addition. It is applied directly to the nasal mucosa for inflammation, irritation, dryness, swelling, damage to the local barrier, and chronic rhinosinusitis. Local treatment makes it possible to act directly at the site of the pathological process without systemic blockade of leukotriene receptors and without the neuropsychiatric risk characteristic of montelukast. ABP-153 can replace the local component of treatment for rhinitis and rhinosinusitis, but it is not intended for independent control of bronchial asthma and does not relieve bronchospasm.

Complete replacement of montelukast with this regimen is most justified when the medicine was prescribed for allergic rhinitis, chronic rhinosinusitis, postnasal drip, or a combination of nasal symptoms with mild allergic cough. In controlled mild asthma of an allergic phenotype, the decision is individualized based on assessment of symptoms and pulmonary function. In persistent, unstable, or severe asthma, an integrative regimen must not independently replace maintenance inhaled therapy and emergency medication.

Sodium thiosulfate is not included in the main alternative regimen. It is not a herbal medicine, is not a pharmacological analogue of a leukotriene receptor antagonist, and does not provide comparable control of allergic airway inflammation.

The real effectiveness of montelukast: the medicine is a selective CysLT1 receptor antagonist. Blocking the action of cysteinyl leukotrienes reduces bronchoconstriction, mucosal swelling, and mucus secretion. Montelukast is indeed used for the prevention and long-term treatment of asthma, prevention of exercise-induced bronchospasm, and reduction of symptoms of seasonal or perennial allergic rhinitis. It does not treat the cause of allergic disease and does not stop an asthma attack that has already begun.

In asthma, the medicine may be useful as an additional component of treatment in selected patients, particularly when asthma is combined with allergic rhinitis, exercise-induced bronchospasm, or a particular leukotriene-dependent phenotype. However, its anti-inflammatory effect is on average less pronounced and less predictable than that of maintenance inhaled therapy. Montelukast should not be used as a convenient tablet substitute for effective inhaled treatment simply because the patient or parents do not want to use an inhaler.

In allergic rhinitis, the benefit of the medicine is usually modest. For this reason, the FDA recommends prescribing it only to patients who have not obtained sufficient benefit from alternative treatments or who cannot tolerate them. Prescribing montelukast for an ordinary runny nose without clarifying the diagnosis, assessing symptom severity, and attempting targeted local therapy represents an unjustified expansion of its indications.

Medical errors include prescribing montelukast for cough of unclear origin, failing to confirm asthma, ignoring psychiatric history, failing to inform the patient about the Boxed Warning, continuing treatment after nightmares and behavioral changes appear, and substituting it for an inhaled anti-inflammatory medicine without assessing disease control.

Safety monitoring during treatment: before therapy begins, the baseline state of sleep, mood, behavior, and cognitive function should be documented. The presence of depression, anxiety disorders, psychosis, obsessive thoughts, self-harm, suicidal thoughts, tics, sleepwalking, and severe sleep disorders should be clarified. The patient and their relatives should know which symptoms may be related to the medicine.

During treatment, monitoring should include nightmares, insomnia, nighttime awakenings, sleepwalking, anxiety, agitation, aggression, low mood, attention disorders, unusual fears, hallucinations, obsessive thoughts, and suicidal statements. If new neuropsychiatric symptoms occur, the FDA recommends stopping montelukast and contacting a healthcare professional immediately.

In children, monitoring is carried out by parents or other adults who observe the child daily. A sudden change in personality, refusal to sleep, nighttime crying, fears, aggression, tics, deterioration in school behavior, or statements about death require assessment of a possible relationship with treatment.

Routine laboratory monitoring of liver function is not necessary for every patient, but it becomes mandatory in patients with pre-existing liver disease, when other hepatotoxic medicines are used, or when symptoms of liver injury appear. ALT, AST, bilirubin, and other parameters should be measured in cases of marked weakness, persistent nausea, pain in the right upper abdomen, jaundice, dark urine, pale stools, or generalized itching.

Emergency care is required for suicidal actions, acute psychosis, hallucinations accompanied by dangerous behavior, seizures, marked confusion, swelling of the face or larynx, difficulty breathing, widespread blistering rash, skin detachment, and signs of anaphylaxis. Waiting at home may lead to self-harm, asphyxia, or progression of a severe skin reaction.

Correct discontinuation of montelukast: gradual dose reduction is usually not required because the medicine does not cause classic physical dependence or a typical withdrawal syndrome. If neuropsychiatric symptoms appear, it should be stopped immediately. Treatment should not be continued for several more days simply to see whether aggression, depression, or nightmares disappear on their own.

The patient’s condition should continue to be monitored after discontinuation. In most patients, adverse manifestations decrease, but neuropsychiatric symptoms may persist or first appear after treatment has been stopped. In cases of suicidal thoughts, psychosis, severe depression, or dangerous behavior, discontinuing the medicine alone is insufficient and urgent professional assessment is required.

The absence of a withdrawal syndrome does not mean there is no risk that the underlying disease will return. After montelukast is stopped, allergic rhinitis, cough, bronchial hyperreactivity, or asthma symptoms may worsen. In asthma, the subsequent maintenance regimen, availability of an emergency inhaler, and criteria for seeking urgent medical care should be determined in advance. For nasal allergy, montelukast may be replaced with an approved systemic and local integrative regimen while symptoms are monitored.

A rational approach to treatment: montelukast is justified when its specific effect is genuinely needed and the expected benefit outweighs the risk. It may be used for confirmed chronic asthma, exercise-induced bronchospasm, and certain combined allergic phenotypes. In an acute asthma attack, the medicine is ineffective as a means of immediate relief, while in isolated allergic rhinitis its use should be limited to cases in which safer alternatives are ineffective or not tolerated.

For allergic rhinitis, rhinosinusitis, postnasal drip, and associated allergic cough, an integrative regimen may include Allergy Mixture LH as the primary systemic antiallergic therapy, Rhinitis and Rhinosinusitis Mixture LH as a specialized systemic medicine, and ABP-153 as the primary local intranasal component.

The aim of such replacement is not to abandon necessary treatment, but to eliminate unjustified use of montelukast, reduce the systemic medication burden, and lower the risk of neuropsychiatric complications. Complete replacement is possible when the condition is predominantly nasal. In mild controlled asthma, the decision is individualized. In severe, unstable, or poorly controlled asthma, full maintenance anti-asthma therapy is necessary, while herbal medicines may be considered only as part of a comprehensive approach.

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