Narcolepsy Can Masquerade as Schizophrenia

Narcolepsy in childhood and adolescence can present with excessive sleepiness, hallucinations, sleep attacks, and/or cataplexy. Patients can have trouble falling asleep at night and/or they can fall asleep suddenly regardless of the situation. They can also present with what appears to be a psychiatric disorder because hallucinations and illusions are common in patients with narcolepsy as well as those with schizophrenia. The shared symptoms may reflect a shared pathophysiology in the histamine system.

The relationship between psychiatric illness and narcolepsy is so strong that experts suggest that any patient with atypical and refractory psychiatric illness should be considered as possibly having narcolepsy (references below). The recommendations should especially be heeded for individuals with refractory psychosis and/or schizophrenia. Unfortunately, the diagnosis of narcolepsy in patients with mental illness can be further complicated by the fact that the use of anti-psychotics in schizophrenia can worsen symptoms of narcolepsy and stimulant therapy for narcolepsy may enhance symptoms of psychosis.

A recent case study describes a six-year-old girl who presented to Jersey Shore Medical Center in the United States with sleep attacks, snoring, and hypnopompic/hypnagogic hallucinations that dated back approximately two years. The authors wrote up this case study as an example of a child with narcolepsy with cataplexy who easily could have been diagnosed with a psychiatric disorder. In their case study, they describe the child’s sleep study results which were not completely consistent with narcolepsy.

The multiple sleep latency test (MSLT) test takes place after the overnight sleep study and is used to measure excessive daytime sleepiness. It does this by measuring how quickly an individual falls asleep in a quiet environment during the day. A mean sleep latency of ≤ 8 minutes is considered consistent with narcolepsy. Individuals suspected of narcolepsy are also examined for sleep onset REM periods (SOREMPS) on the MSLT. If REM sleep happens within 15 minutes at least two times out of the five naps plus overnight sleep study, the patient meets the diagnostic criteria for narcolepsy.

While the child in the case study had a mean sleep latency of 3.2 minutes, she did not have any sleep onset REM periods (SOREMPS) on the multiple sleep latency test (MSLT). The young patient thus failed the SOREMP component of the diagnostic criteria for narcolepsy. The physicians decided, however, that her history and objective data were strong enough to make an official diagnosis of narcolepsy with cataplexy. This diagnosis was confirmed by her excellent clinical response to narcolepsy medications.

The New Jersey physicians prescribed the six-year-old girl sodium oxybate (Xyrem) off-label at a reduced dose in an attempt to control both the cataplexy and the severe hypersomnia. They also prescribed dextroamphetamine-amphetamine (Adderall) in the morning as well as in the afternoon as needed. The patient’s symptoms were well-controlled on this regimen. In their case study, the authors note that, while the histamine 3 receptor inverse agonist pitolisant is not yet available in the United States, it is a treatment option available in Europe.

The case study described above is only one of many case studies that have found that patients treated for narcolepsy experienced remission of psychotic symptoms as well as significant improvement in behavior. Unfortunately, psychotic symptoms in narcolepsy may increase in response to sodium oxybate such that patient experience hallucinations that resemble those seen in schizophrenia. Physicians have found that, when patients have sodium oxybate-induced psychotic symptoms, a reduction of the dose of sodium oxybate or addition of an antipsychotic medication can be helpful. Thus far, pitolisant does not appear to trigger psychotic symptoms. Moreover, pitolisant appears to be uniquely poised to address the psychiatric issues associated with narcolepsy, particularly since recent evidence suggests that histamine plays an important role in schizophrenia.

References:

1. Hu W and Chen Z. The Roles of Histamine and Its Receptor Ligands in Central Nervous System Disorders: An Update. Pharmacol Ther. 2017. 175:116-32.

2. Miskoff JA and Chaudhri M. Off-label Sodium Oxybate in Childhood Narcolepsy. Cureus. Published online April 24, 2018.

3. Morse AM and Sanjeev K. Narcolepsy and Psychiatric Disorders: Comorbidities or Shared Pathophysiology? Med Sci. 2018. 6:16.

4. Piazzi G, Fabbri C, Pizza F, et al. Schizophrenia-like Symptoms in Narcolepsy Type 1: Shared and Distinctive Clinical Charactristics. Neuropsychobiology. 2015. 71:218-24.

5. Talih FR. Narcolepsy Presenting as Schizophrenia: A Literature Review and Two Case Reports. Innov Clin Neurosci. 2011. 8:30-34.

6. Sarkanen T, Niemela V, Landtblom A-M, et al. Psychosis in Patients with Narcolepsy as an Adverse Effect of Sodium Oxybate. Front Neurol. 2014. 5:article 136.