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Treatment of Narcolepsy Complicated by Psychotic Symptoms

TO THE EDITOR: Narcolepsy is a syndrome with an unknown etiology, characterized by excessive daytime sleepiness and usually accompanied with other symptoms, such as cataplexy, hypnagogic / hypnopompic hallucinations, sleep paralysis, and abnormal sleep patterns.¹ Investigators have discussed its association with schizophrenia and the possible confusion between these entities, because they share a number of features, including age at onset and overlapping symptoms.^2–4

Narcolepsy can be related to psychosis in three ways:^2,4 1) narcolepsy could coexist, by chance, with a psychiatric disorder that manifests with psychotic features; 2) central stimulants used in narcolepsy treatment may lead to drug-induced psychotic symptoms;⁵ or 3) sensory misperceptions and other narcolepsy symptoms may form into delusions simulating a psychotic disorder, or, what some authors have called, the "psychotic form of narcolepsy."^2–4

We report here on a patient with narcolepsy complicated by psychotic symptoms, treated with an atypical antipsychotic.

Case Report

A 27-year-old male student, "Mr. A," presented to our psychiatric hospitalization unit because of disorganized behavior and auditory hallucinations.

He had been studied in the neurology service’s sleep unit 6 years earlier because he showed excessive daytime sleepiness and cataplexy. A nocturnal polysomnogram was performed, which showed a REM sleep latency of 3 minutes, followed by a Multiple Sleep Latency Test (MSLT), presenting five sleep-onset REM-sleep periods (SOREM). A human leukocyte antigen (HLA) histocompatability test showed the DQB1*0602 subtype. Narcolepsy with cataplexy was diagnosed, and treatment with central stimulants (methylphenidate) was initiated. Mr. A responded favorably to treatment, but abandoned medication and medical follow-up a few months later.

About a month before his admission to our unit, Mr. A had begun hearing threatening voices, which appeared anytime during the day and were not necessarily related to sleeping periods. He had also experienced two episodes of complex hypnagogic visual hallucinations in which he described a "demon" standing inside his room. He started neglecting his personal care, became more isolated, and had stopped eating before his admission. He was not taking any medication, denied drug use, and reported only occasional moderate alcohol consumption.

On mental examination, Mr. A was suspicious and irritable, and notably anxious. At one point, we had to stop the clinical interview because he showed sudden excessive sleepiness. His speech had frequent derailments and was tangential. He exhibited paranoid and mystical delusions. He described second- and third-person auditory hallucinations in the form of voices that commented on his behavior, gave him orders, and affected his will. His affect was flat.

Mr. A’s physical examination, blood analysis, toxicological screening, and MRI of the brain did not exhibit significant alterations.

The working diagnosis was Schizophreniform Disorder (DSM–IV-TR: 295.40), and olanzapine was prescribed in doses titrated up to 20 mg per day. During this period, he had an extreme increase in daytime sleepiness. For this reason, having accomplished 2 weeks of medication with olanzapine, we decided to suspend it gradually and prescribed aripiprazole in doses titrated up to 30 mg per day instead.

Mr. A had a favorable response to the change in medication, showing less daytime sleepiness and being less distressed by psychotic symptoms. At 6-month follow-up, he was continuing treatment with aripiprazole with good tolerance, and his psychotic symptoms were in remission. He still experienced moderate diurnal somnolence but with less effect on daily-life activities, and he had not started treatment with stimulants.

Discussion

Antipsychotic medication can make narcoleptic symptoms worse.² This finding is consistent with the fact that maintenance of wakefulness is probably promoted by dopaminergic circuits,⁶ and dopamine antagonism can produce sleep.² Central nervous system (CNS) stimulants used to treat narcolepsy lead to a hyperdopaminergic state, which can worsen psychotic symptoms.⁵ This confronts us with a therapeutic dilemma.

Mr. A’s worsening of daytime somnolence after being prescribing olanzapine led us to believe that aripiprazole might be a more suitable drug, because it does not act primarily as a dopaminergic blocker like other known antipsychotics, but acts more as a stabilizer.^4,7 It is a partial dopamine agonist, which means that in situations of high extracellular dopamine concentrations, it acts as an antagonist, whereas in situations where extracellular dopamine concentrations are low, it behaves as an agonist.⁷ These properties and its serotonergic activity as a 5HT₂ antagonist and 5HT_1A partial agonist⁷ meant a better secondary effect-profile for our patient.

Despite the fact that the incidence of drug-induced psychosis from CNS stimulants seems low,⁵ we thought it would be better not to prescribe them in an acute phase with prominent psychotic symptoms, but to prescribe them after discharge, if necessary.

REFERENCES

1. Benca RM: Narcolepsy and excessive daytime sleepiness: diagnostic considerations, epidemiology, and comorbidities. J Clin Psychiatry 2007; 68(suppl 13):5-8
2. Kishi Y, Konishi S, Koizumi S, et al: Schizophrenia and narcolepsy: a review with case report. Psychiatry Clin Neurosci 2004; 58:117–124[Medline]
3. Szucs A, Janszky J, Hollo A, et al: Misleading hallucinations in unrecognized narcolepsy. Acta Psychiatr Scand 2003; 108:314–316; Discussion 316-317[CrossRef][Medline]
4. Kondziella D, Arlien-Soborg P: Diagnostic and therapeutic challenges in narcolepsy-related psychosis. J Clin Psychiatry 2006; 67:1817–1819[Medline]
5. Auger RR, Goodman SH, Silber M: Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: a case-control study. Sleep 2005; 28:667–672[Medline]
6. Rye DB: The two faces of Eve: dopamine’s modulation of wakefulness and sleep (review). Neurology 2004; 63(8; suppl 3):S2-S7
7. Tamminga CA, Carlsson A: Partial dopamine agonists and dopaminergic stabilizers in the treatment of psychosis (review). Curr Drug Targets CNS Neurol Disord 2002; 1:141–147[CrossRef][Medline]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Undurraga, J. Articles by Parellada, E. Search for Related Content PubMed Citation Articles by Undurraga, J. Articles by Parellada, E. Other Neuropsychiatric Disorders Schizophrenia Spectrum Disorders

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