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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 47-50

Cervical and axial dystonia secondary to mirtazapine: a case report and literature review


Department of Neurology, Federal University of Santa Maria, Santa Maria, Brazil; Department of Medicine, Federal University of Santa Maria, Santa Maria, Brazil

Date of Submission16-Nov-2019
Date of Decision13-Dec-2019
Date of Acceptance10-Jan-2020
Date of Web Publication01-Apr-2020

Correspondence Address:
Dr. Jamir Pitton Rissardo
Rua Roraima, Santa Maria, Rio Grande do Sul.
Brazil
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AOMD.AOMD_30_19

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  Abstract 

Mirtazapine (MTZ) is an atypical antidepressant frequently prescribed for the management of major depressive disorder. It has multiple mechanisms of action, which probably contribute to the several side effects encountered with this medication. Hyperkinetic movement disorders induced by MTZ have been rarely reported in the literature. To the best of authors’ knowledge, there are five cases of dystonia (DTN) secondary to MTZ use, but this study reports the youngest individual in a nonpsychiatric MTZ indication. We report a case of an adult woman who presented with axial and cervical DTN-type laterocollis after 5 days of MTZ use, which was indicated for hot flashes. A comprehensive review of the cases and a mechanism assumption are performed.

Keywords: Axial dystonia, cervical dystonia, mirtazapine


How to cite this article:
Rissardo JP, Caprara AL. Cervical and axial dystonia secondary to mirtazapine: a case report and literature review. Ann Mov Disord 2020;3:47-50

How to cite this URL:
Rissardo JP, Caprara AL. Cervical and axial dystonia secondary to mirtazapine: a case report and literature review. Ann Mov Disord [serial online] 2020 [cited 2020 Jun 5];3:47-50. Available from: http://www.aomd.in/text.asp?2020/3/1/47/281745




  Introduction Top


Mirtazapine (MTZ) is an atypical antidepressant approved by the US Food and Drug Administration (FDA) in 1996 and is frequently prescribed for the management of the major depressive disorder. This drug is also used for some off-label conditions such as insomnia, post-traumatic stress disorder, and hot flashes. In this context, MTZ has multiple mechanisms of action, which probably contribute to the several side effects encountered with this medication.[1]

Hyperkinetic movement disorders induced by MTZ have been rarely reported in the literature. To the best of authors’ knowledge, there are only five case reports of dystonia (DTN) secondary to MTZ use, but this study reports the youngest individual and in a nonpsychiatric MTZ indication.[2],[3],[4],[5],[6]

Herein, we report a case of an adult woman who was diagnosed with hot flashes. MTZ was started. In 4 days, the patient developed axial and cervical DTN. Then, MTZ was withdrawn and she had a full recovery.


  Case Report Top


A 50-year-old woman was admitted to our hospital presenting with abnormal posture and spasmodic torticollis within 1 day of onset. The patient stated that she had searched a general practitioner 5 days ago because she had experienced episodic sensations of warmth on the chest, neck, and face immediately followed by an outbreak of sweating. Laboratory test results were within normal limits. An electrocardiogram showed no abnormalities. She was diagnosed with hot flashes at the perimenopausal period. MTZ 15mg tab once daily at bedtime was started.

On admission, she reported progressive stiffness and left lateralization of the neck associated with ipsilateral flexion of the trunk. She had hypertension that was well controlled with enalapril 10mg tab daily. Her family history was unremarkable and negative for neurological diseases. On neurological examination, cervical DTN-type laterocollis, moderate lateral flexion of the trunk, and tenderness on palpation of sternocleidomastoid were observed. The axial symptoms worsened while standing or walking and improved with passive mobilization and supine positioning. Other cranial nerve functions were preserved. The muscle strength was 5/5 symmetrically in upper and lower limbs; deep tendon reflexes were normal. There were no tremors, rigidity, or bradykinesia. Laboratory test results were within normal limits. Electromyography, electroencephalography, cranial computed tomography, and brain magnetic resonance imaging were normal. MTZ was withdrawn.

On the fifth admission day, the patient had a full recovery and was discharged. At 1-month and 6-month follow-up, the patient did not complain of abnormal movement symptoms.


  Discussion Top


The main mechanism of MTZ is the antagonism effect in the presynaptic α2 adrenergic receptors that release serotonin and norepinephrine. It also works in other receptors such as histamine receptors and serotonin receptors, which include 5-HT2A, 5-HT2C, and 5-HT3. This is important to know as these explain the several side effects associated with this medication, which occur in more than 10% of the users.[7] Watanabe et al.[8] published a review comparing MTZ with other antidepressants. They found that MTZ is more likely to cause sleepiness and weight gain, but less likely to cause tremors compared to tricyclic antidepressants (TCAs), and far less likely to cause sexual dysfunction compared to selective serotonin reuptake inhibitors (SSRIs).[8] Thus, this medication is clinically important for patients who experienced significant adverse effects with TCAs and SSRIs.

Only a few cases with MTZ-associated DTN have been reported in the literature. We identified five cases after a review of the literature and compared them with the present case [Table 1].[2],[3],[4],[5],[6] A literature search was performed in Embase, Google Scholar, Lilacs, MEDLINE, SciELO, and ScienceDirect, on a set of terms that included dystonia, Pisa syndrome, and mirtazapine. To the best of authors’ knowledge, these cases described individuals with psychiatric disorders. In this way, the present case is the first to describe a subject with hot flashes and MTZ indication.
Table 1: Case reports of patients who developed DTN secondary to MTZ use

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In the cases presented in [Table 1], predominance of a geriatric population is noted, which could be explained by a reduced clearance and may increase the MTZ plasma levels and a major sensibility of the drug. Moreover, most studies showed a higher percentage of side effects in the elderly population compared to a younger population. Therefore, MTZ should be started at a low dose and a close follow-up is recommended, especially for those patients who are aged 65 years or older.[9]

Another interesting fact was that the present case is the first nonpsychiatric indication and in a normal cognitive individual. This is important because it decreases the probability of the association between MTZ and DTN to be a psychogenic movement disorder as in some of the cases already reported the patients were drug users, had severe or recurrent depression, or were affected by severe cognitive impairment.[10] It is worth mentioning that in all the individuals mentioned in [Table 1], the time from MTZ start till DTN, and the time from MTZ withdrawal and recovery was within days to weeks. Also, the prognosis was excellent with all the patients having a full recovery.

DTN is defined by involuntary sustained muscle contractions causing twisting and repetitive movements or abnormal postures. The mechanism of DTN is still poorly understood; as a result, there are many hypotheses in the literature, but we assume that those after stroke may provide a better comprehension for a possible pathway. In this way, an explanation could be the interruption in the cortico–striato–pallido–thalamo–cortical loop. Mitchell et al.[11] proposed that lesions in the pathways that go to the thalamus might interrupt the direct and indirect pathways. However, the indirect pathway subactivity probably predominates, and this disruption could increase the thalamocortical drive and eventually lead to DTN.[11],[12] Therefore, we hypothesized that the use of low-dose MTZ may cause a block of serotonin (5HT) 2A receptors probably localized in the thalamus decreasing the activity of the indirect pathway and leading to an increase of the thalamocortical drive as was already proposed in rat models.[13] To be more specific, it is believed that the antagonism of 5HT2 receptors has a tonic inhibitory influence on dopamine release, and blocking this influence may lead to the induction of hyperkinetic states.[7]

Lu et al.[2] were the first to publish the report on the association between MTZ and DTN, and they estimated an incidence rate of 1/100 to 1/1000. We believed that their incidence was probably overestimated because in the literature there are five cases published more than 20 years after FDA approval. Furthermore, Yoon[6] reviewed all cases of MTZ associated with movement disorders and found only 12 case reports.

In sum, our report suggests that MTZ should be listed as a probable cause of DTN. This adverse effect is assumed to be associated with the antagonism of 5HT2 receptors by MTZ, which causes a tonic inhibitory influence on dopamine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jilani TN, Saadabadi A. Mirtazapine.StatPearls [Internet]. Treasure Island, FL:StatPearls Publishing;2019.  Back to cited text no. 1
    
2.
Lu R, Hurley AD, Gourley M. Dystonia induced by mirtazapine. J Clin Psychiatry 2002;63:452-3.  Back to cited text no. 2
    
3.
Méndez Guerrero A, Llamas S, Murcia FJ, Ruíz J. Acute Pisa syndrome after administration of a single dose of mirtazapine. Clin Neuropharmacol 2013;36:133-4.  Back to cited text no. 3
    
4.
van den Bosch S, Bouckaert F, Peuskens J. [Mirtazapine-induced dystonia in a patient with Alzheimer’s disease]. Tijdschr Psychiatr 2006;48:153-7.  Back to cited text no. 4
    
5.
Yamada Y, Takano H, Yamada M, Satake N, Hirabayashi N, Okazaki M, et al. Pisa syndrome associated with mirtazapine: A case report. BMC Pharmacol Toxicol 2018;19:82.  Back to cited text no. 5
    
6.
Yoon WT. Hyperkinetic movement disorders induced by mirtazapine: Unusual case report and clinical analysis of reported cases. J Psychiatry 2018;21:437.  Back to cited text no. 6
    
7.
Nutt D. Mirtazapine: Pharmacology in relation to adverse effects. Acta Psychiatr Scand Suppl 1997;391:31-7.  Back to cited text no. 7
    
8.
Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev 2011;12:CD006568.  Back to cited text no. 8
    
9.
Schatzberg AF, Kremer C, Rodrigues HE, Murphy GM Jr.; Mirtazapine vs. Paroxetine Study Group. Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Am J Geriatr Psychiatry 2002;10:541-50.  Back to cited text no. 9
    
10.
Kaski D, Bronstein AM, Edwards MJ, Stone J. Cranial functional (psychogenic) movement disorders. Lancet Neurol 2015;14:1196-205.  Back to cited text no. 10
    
11.
Mitchell IJ, Luquin R, Boyce S, Clarke CE, Robertson RG, Sambrook MA, et al. Neural mechanisms of dystonia: Evidence from a 2‐deoxyglucose uptake study in a primate model of dopamine agonist‐induced dystonia. Mov Disord 1990;5:49-54.  Back to cited text no. 11
    
12.
Krystkowiak P, Martinat P, Defebvre L, Pruvo JP, Leys D, Destée A. Dystonia after striatopallidal and thalamic stroke: Clinicoradiological correlations and pathophysiological mechanisms. J Neurol Neurosurg Psychiatry 1998;65:703-8.  Back to cited text no. 12
    
13.
Barre A, Berthoux C, De Bundel D, Valjent E, Bockaert J, Marin P, et al. Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning. Proc Natl Acad Sci USA 2016;113:E1382-91.  Back to cited text no. 13
    



 
 
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