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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 2  |  Page : 373-374

Role of 5HT1A and 5HT2A receptors and default mode network in olanzapine-induced somnambulism

1 Antara Psychiatric Centre, Kolkata, West Bengal, India
2 Department of Psychiatry, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India
3 Department of Psychology, Kumaon University, Nainital, Uttarakhand, India

Date of Web Publication10-Mar-2017

Correspondence Address:
Dr. Sourav Das
Department of Psychiatry, Antara Psychiatric Centre, Kolkata - 700 145, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/neuroindia.NI_481_15

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How to cite this article:
Das S, Gupta R, Dhyani M, Sah D, Maity J. Role of 5HT1A and 5HT2A receptors and default mode network in olanzapine-induced somnambulism. Neurol India 2017;65:373-4

How to cite this URL:
Das S, Gupta R, Dhyani M, Sah D, Maity J. Role of 5HT1A and 5HT2A receptors and default mode network in olanzapine-induced somnambulism. Neurol India [serial online] 2017 [cited 2023 Feb 4];65:373-4. Available from: https://www.neurologyindia.com/text.asp?2017/65/2/373/201859


Somnambulism or sleepwalking (SW) is one of the most common forms of parasomnia characterized by various complex motor behaviors (including walking) during stage N3 of non-rapid eye movement (NREM) sleep.[1] The prevalence peaks between 11% to 13.5% between 7 and 12 years of age and decreases to 3–4% in adulthood.[2] Till date, only 13 cases of somnambulism secondary to atypical antipsychotics were reported globally, of which 8 were due to quetiapine, 1 was due to risperidone, and 4 were secondary to olanzapine. Here, we present a case of a 26-year-old male patient diagnosed with schizophrenia, who developed SW after being given olanzapine. To the best of our knowledge, this is the first such case reported from the Indian subcontinent.

A 26-year-old male patient suffering from schizophrenia for the last 2 years presented to us with symptomatic exacerbation even while being treated with oral risperidone (from elsewhere). He was admitted and given injectable haloperidol with promethazine twice daily for 2 days to manage acute agitation and violent behavior and was switched to oral olanzapine from the third day, along with lorazepam on a need basis. Olanzapine was started at 5 mg/day and escalated by 5 mg every 10 days.

He started showing clinical improvement in his psychotic symptoms after 2 weeks of admission, but at 15 mg/day of olanzapine, the fellow inmates complained that he was behaving abnormally during sleep. He was getting up, walking in the ward, trying to pull the pillows and bed sheets of some inmates, and banging his head against walls on a few occasions. On two instances, he also tried to throttle some fellow inmates. Each such episode lasted for 10 to 20 min and occurred before 12 am (the first third duration of sleep). During the episodes, he was appearing confused, with open eyes, and was not arousable. He went to sleep after each episode and had complete amnesia of the events on awakening. There was no stereotypic motor pattern during such episodes. SW was diagnosed and olanzapine was gradually tapered down to 5 mg/day; clonazepam was added at bedtime, which led to resolution of the above symptoms. One week later, olanzapine was gradually escalated again to 15 mg/day, due to worsening of his psychotic symptoms. After 3–4 days, SW appeared again. After two such episodes in a span of three nights, olanzapine was cross tapered with aripiprazole under clonazepam cover. There was no recurrence of SW symptoms with aripiprazole and the patient was discharged after 2 months on attaining clinical stability.

There was no history suggestive of similar occurrences or confusional arousals, night terrors, bruxism, periodic limb movement disorder, restless leg syndrome, and seizure disorder in the past or in the family. The patient had a history of occasional cannabis use, with the last use more than 2 weeks prior to admission.

The diagnosis of SW is mainly clinical.[2] Differential diagnoses considered in this case were REM behavior disorders (RBDs), nocturnal frontal lobe epilepsy (NFLE), and temporal lobe epilepsy (TLE). The presence of amnesia of the event, difficult arousablity, and occurrence within the first third of the night ruled out RBD.[2] NFLE and TLE were ruled out by duration and frequency of the episodes, absence of stereotypic behavior pattern, absence of awakening, and rather spontaneous going-to-bed after the episodes.[3],[4] The resolution of SW after decreasing olanzapine and its relapse after reintroduction in this case confirms the role of olanzapine (15 mg/day) in precipitating SW episodes.

Traditionally, SW has been regarded as a disorder of slow wave sleep (SWS) and/or as a disorder of arousal.[2] Olanzapine and risperidone have been implicated in SW as they are hypothesized to increase SWS by their action on 5-hydroxytryptamine 2C (5HT2C) receptor.[5] Bassetti et al., based on his single-photon emission computed tomography study, proposed that activation of thalamocingulate and anterior cerebellar pathways and persisting deactivation of fronto-parietal associative cortices can be found in SW episodes.[6] Emerging evidence suggests that SW (similar to other disorders such as schizophrenia, Alzheimer's dementia, depression and autism) arise out of an incongruence between task positive and task negative networks of the default mode network (DMN).[7] In this setting, olanzapine precipitating SW by increasing SWS appears to be an oversimplification. 5HT1A receptor agonism acts on nucleus basalis, and 5HT2A and 2C receptor antagonism acts on presynaptic cholinergic terminals to facilitate acetylcholine release which facilitates SWS.[8]

Moreover, 5HT1A receptor via glutamate and gamma-aminobutyric acid modulation has an inverse modulatory effect on posterior cingulate cortex (the strongest hub of resting human brain) and important modulatory effect overall on the DMN.[9] 5HT2A receptors are abundant in the medial prefrontal cortex, which forms an integral part of the DMN.[10] DMN resting-state functional connectivity has a positive correlation with internal awareness.[11] Also, in the cortical pyramidal neurones, 5HT1A and 5HT2A receptor activation have opposing effects with regard to glutamate modulation.[10] Quetiapine has both 5HT1A receptor agonism and 5HT2A receptor antagonism; olanzapine and risperidone have 5HT2A receptor antagonism (and may be causing an indirect 5HT1A receptor agonism due to opposite action of 1A and 2A receptors on glutamatergic transmission). The above data implicate 5HT1A and 5HT2A, rather than 5HT2C receptor action of atypical antipsychotics such as olanzapine and quetiapine as being responsible for the precipitation of SW. Moreover, due to dual action via 5HT1A and 2A receptors of quetiapine, SW is precipitated more commonly (as evident by 8 cases compared to 4 due to olanzapine) and at lower dose of quetiapine (50 mg/day), compared to 15–20 mg/day of olanzapine.[12],[13] Olanzapine treatment has been associated with modulation of DMN in persons with schizophrenia, underlying the hypothesis that olanzapine action can modulate the DMN.[14]

To conclude, we hypothesize that 5HT2A and 5HT1A, rather than 5HT2C receptor modulation, and DMN are involved in SW episodes in olanzapine and other atypical antipsychotic treatment. Given the wide usage of atypical antipsychotics, studies with adequate sample size may be planned in future to find out the true prevalence of SW and other parasomnias in patients taking atypical antipsychotics.

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Conflicts of interest

There are no conflicts of interest.

 » References Top

Juszczak GR, Swiergiel AH. Serotonergic hypothesis of sleepwalking. Med Hypotheses 2005;64:28-32.  Back to cited text no. 1
Zadra A, Desautels A, Petit D, Montplaisir J. Somnambulism: Clinical aspects and pathophysiological hypotheses. Lancet Neurol 2013;12:285-94.  Back to cited text no. 2
Tinuper P, Provini F, Bisulli F, Vignatelli L, Plazzi G, Vetrugno R, et al. Movement disorders in sleep: Guidelines for differentiating epileptic from non-epileptic motor phenomena arising from sleep. Sleep Med Rev 2007;11:255-67.  Back to cited text no. 3
Hughes JR. A review of sleepwalking (somnambulism): The enigma of neurophysiology and polysomnography with differential diagnosis of complex partial seizures. Epilepsy Behav 2007;11:483-91.  Back to cited text no. 4
Sharpley AL, Vassallo CM, Cowen PJ. Olanzapine increases slow-wave sleep: Evidence for blockade of central 5-HT (2C) receptors in vivo. Biol Psychiatry 2000;47:468-70.  Back to cited text no. 5
Bassetti C, Vella S, Donati F, Wielepp P, Weder B. SPECT during sleepwalking. Lancet 2000;356:484-5.  Back to cited text no. 6
Mahowald MW, Schenck CH. Insights from studying human sleep disorders. Nature 2005;437:1279-85.  Back to cited text no. 7
Fink KB, Göthert M. 5-HT receptor regulation of neurotransmitter release. Pharmacol Rev 2007;59:360-417.  Back to cited text no. 8
Hahn A, Wadsak W, Windischberger C, Baldinger P, Höflich AS, Losak J, et al. Differential modulation of the default mode network via serotonin-1A receptors. Proc Natl Acad Sci U S A. 2012;109:2619-24.  Back to cited text no. 9
Aznar S, Klein AB. Regulating prefrontal cortex activation: An emerging role for the 5-HT2A serotonin receptor in the modulation of emotion-based actions? Mol Neurobiol 2013;48:841-53.  Back to cited text no. 10
Vanhaudenhuyse A, Demertzi A, Schabus M, Noirhomme Q, Bredart S, Boly M, et al. Two distinct neuronal networks mediate the awareness of environment and of self. J Cogn Neurosci 2011;23:570-8.  Back to cited text no. 11
Kolivakis TT, Margolese HC, Beauclair L, Chouinard G. Olanzapine-induced somnambulism. Am J Psychiatry 2001;158:1158.  Back to cited text no. 12
Raja M, Raja S. Sleepwalking in four patients treated with quetiapine. Psychiatr Danub 2013;25:80-3.  Back to cited text no. 13
Sambataro F, Blasi G, Fazio L, Caforio G, Taurisano P, Romano R, et al. Treatment with olanzapine is associated with modulation of the default mode network in patients with schizophrenia. Neuropsychopharmacology 2010;35:904-12.  Back to cited text no. 14

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