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CASE REPORT Table of Contents  
Ahead of print publication
Neuroleptic-induced tardive dystonia in young patients suffering from psychosis


1 Assistant Professor, Department of Psychiatry, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, Maharashtra, India
2 Senior Resident, Department of Psychiatry, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, Maharashtra, India
3 House Officer, Department of Nuclear Medicine, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, Maharashtra, India

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Date of Submission10-Jan-2022
Date of Acceptance18-Apr-2022
Date of Web Publication17-May-2022
 

  Abstract 


Tardive dystonia is one of the extrapyramidal syndromes that start after long-term use of dopamine receptor antagonists. Tardive dystonia is underdiagnosed and often misdiagnosed; some of the treatment possibilities are hardly known among psychiatrists and are notorious for being resistant to treatment. Here, we present a set of two cases who had come with neuroleptic-induced tardive dystonia, initially given oral tetrabenazine and injectable botulinum toxin, but they did not respond. They got better after treatment with the combination of oral baclofen and electroconvulsive therapy (ECT). ECT is thought to prevent the super sensitization of postsynaptic dopamine receptors that contribute to the development of tardive states. Baclofen is a presynaptic gamma-aminobutyric acid receptor agonist primarily used to treat spasticity. Both may have acted synergistically to treat the dystonia. Tardive dystonia needs to be ruled out in patients with a history of long-term antipsychotic medication use. Consultant liaison with psychiatrists will be of paramount importance in the timely management of these cases. The combination of ECT and baclofen may be an effective choice for patients of schizophrenia with tardive dystonia developed in the course of neuroleptic treatment. However, further controlled studies are needed to develop and refine the guidelines for managing it.

Keywords: Baclofen, electroconvulsive therapy, neuroleptic, tardive dystonia


How to cite this URL:
Angane AY, Anvekar AR, Keshari PK, Unnithan VB. Neuroleptic-induced tardive dystonia in young patients suffering from psychosis. Arch Ment Health [Epub ahead of print] [cited 2022 Nov 29]. Available from: https://www.amhonline.org/preprintarticle.asp?id=345399





  Introduction Top


Dystonia refers to sustained muscle contractions which frequently cause twisting and repetitive movements or abnormal postures.[1] Cervical dystonia (spasmodic torticollis) causes the head to rotate to one side or toward the chest, or back, or a combination of this posture.[2]

Tardive dystonia is an extrapyramidal syndrome occurring after prolonged usage of dopamine receptor antagonists. Tardive dystonia often develops at higher rates in patients receiving neuroleptic agents for long periods.[3] The prevalence of tardive dystonia is 3%–50% in patients who are treated with neuroleptics.[3]

Many different treatment options are available which include physical and occupational therapy; oral medications such as anticholinergics, baclofen, and benzodiazepines, levodopa; atypical antipsychotics such as quetiapine, tetrabenazine, and intramuscular injection of botulinum toxins; and neurosurgical interventions such as peripheral denervation (mainly for cervical dystonia), intrathecal baclofen, ablative procedures (pallidotomy and thalamotomy), and deep brain stimulation.[4]

Here, we would like to present a set of two cases who had come with neuroleptic-induced tardive dystonia. They were initially given oral tetrabenazine and injectable botulinum toxin but failed to respond. As guidelines for the management of recalcitrant neuroleptic-induced tardive dystonia in such patients of schizophrenia are not yet well-developed, a combination of electroconvulsive therapy (ECT) and baclofen was instituted. These cases will serve as important evidence for the development of evidence summaries and future treatment guidelines.


  Case Reports Top


Case 1

Mrs. R, a 29-year-old right-handed female, had been suffering from schizophrenia for the past 10 years. She was maintained on oral olanzapine 15 mg and trihexyphenidyl 6 mg. For the past 9 months, she developed tardive dystonia in the form of twisting of the neck and jaw to the right side. She was treated in the past in liaison with a neurologist for the same by giving her oral clozapine 100 mg, trihexyphenidyl 8 mg, promethazine 100 mg, and tetrabenazine 100 mg, which she took regularly along with two injections of botulinum toxin (Type A) 100 units twice in the space of 2 months with no improvement before admission.

On admission, neurological examination revealed involuntary contraction of the left sternocleidomastoid and deviation of the neck to the right (torticollis) [Figure 1]. Other gross motors and sensory system examinations were within the normal limits. On mental status examination, the patient appeared conscious and oriented with no abnormality in thought and perception. A diagnosis of schizophrenia with tardive dystonia was made.
Figure 1: Involuntary contraction of the left sternocleidomastoid causing deviation of the patient's neck to the right

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On admission, all routine blood investigations were done, which were found to be within normal limits. Other investigations, which helped in ruling out other causes of dystonia, included magnetic resonance imaging of the brain, serum copper levels, and slit-lamp examination for Kayser‒Fleischer ring, all of which were found to be normal. Her clozapine dosage was kept at 100 mg. She was started on baclofen 30 mg which was gradually increased to 90 mg in a time span of 2 weeks. There was almost 50% reduction in symptoms. However, further increases in the dose of baclofen lead to side effects of lethargy and sedation. Hence, a course of ECT was started simultaneously. It was observed that the patient's dystonic movements improved steadily (80% reduction). A total course of 12 ECTs were given. The patient was subsequently well maintained for 6 months post ECTs, on clozapine 100 mg and baclofen 90 mg [Figure 2].
Figure 2: Improvement in patient's dystonia after treatment

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Case 2

Mr. K, a 30-year-old left-handed male, was suffering from schizophrenia for the past 10 years. He was well maintained and functioning on oral trifluoperazine 20 mg and trihexyphenidyl 4 mg.

For the past 3 months, he presented with insidious onset of lateral flexion of the back and neck to the left side during all positions, including sitting, standing, and walking which progressed to the extent where the lateral part of his head would touch his left shoulder. The symptoms progressed despite tapering off all antipsychotic medications and starting the patient on clozapine.

A decision for admitting the patient was made for comprehensive investigation and treatment. On detailed neurological examination, the patient had laterocollis which included involuntary contraction of the truncal muscles of the left side with scoliosis of the thoracic spine with convexity to the right side [Figure 3]. The tone of the right sternocleidomastoid muscle was also increased (torticollis). The rest of the neurological examination and mental status examination was within the normal limits. A diagnosis of schizophrenia with tardive dystonia was made.
Figure 3: Involuntary contraction of the left truncal muscles with scoliosis of the thoracic spine having convexity to the right side. Moreover, the increased tone of the right sternocleidomastoid muscle

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All routine investigations were within the normal limits. Magnetic resonance imaging of the brain was done to rule out any neurological insult, which was found to be normal. The patient was shifted to and maintained on oral clozapine 100 mg. Simultaneously, neurology reference was done, and the patient was administered injectable botulinum toxin Type A 150 units and 100 units at an interval of 4 weeks along with tetrabenazine up to 100 mg. The patient perceived no improvement and so gradually tetrabenazine was tapered and stopped.

Baclofen 30 mg was then added at the beginning of the 7th week and titrated up to 120 mg by the end of the 9th week of treatment. The patient perceived a 30%–40% improvement. As dystonia was still debilitating for the patient in day-to-day life, the patient was started on ECTs. Almost complete improvement in dystonia after a course of 16 ECTs was noted. Worsening of dystonia was not noted thereafter even after 4 months of follow-up. The patient was well maintained on oral clozapine 100 mg and baclofen 120 mg and was socio occupational functioning [Figure 4].
Figure 4: Improvement in dystonia after electroconvulsive therapy

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  Discussion Top


ECT is thought to prevent the supersensitization of the postsynaptic dopamine receptors that contribute to the development of tardive states.[5],[6] These effects only occurred with concurrent neuroleptic administration, which may account for the efficacy of ECT in both hypo and hyperdopaminergic states.[5]

Several mechanisms of action have been proposed for ECT in tardive dyskinesia and tardive dystonia. ECT is known to enhance dopaminergic transmission. It has been proposed that this enhancement occurs at either the receptor or the postreceptor level.[6]

Another explanation involves the disruption of the blood–brain barrier, which is known to occur after ECT.[7] This disruption may allow increased levels of antipsychotics and antidepressants to enter the brain, potentially alleviating the motor symptoms even while the oral dose of the drug remains constant.[8]

Electroconvulsive shock in rats has been found to supersensitize them to dopamine.[9] This may be associated with other changes in the dopamine system, including upregulation of dopamine Type 2 receptors in the striatum which may be the mechanism by which ECT exerts an antiparkinsonian effect. An increase in cerebrospinal fluid dopamine metabolites after ECT is also indicative of increased dopamine neurotransmission. These changes did not appear to be mediated by alterations in the dopamine transporter protein, indicating other mechanisms for the efficacy of ECT.

Baclofen is a presynaptic gamma-aminobutyric acid receptor agonist primarily used to treat spasticity.[10] The exact mechanism of action by which it aids in treating dystonia is yet to be ascertained.[11],[12]

In our cases, patients had developed tardive dystonia due to the neuroleptic drugs. However, there was no improvement seen by changing the antipsychotic medication to clozapine and adding oral tetrabenazine for adequate doses and time, which is generally considered a first-choice treatment in such cases. Patients were even given a trial of botulinum injections locally on the affected muscle, to no avail. Finally, after exhausting all the options, a trial of oral baclofen was considered. Improvement was noticed both subjectively and objectively as soon as tablet baclofen was added. However, when the improvement plateaued even after increasing the dose, ECTs were given simultaneously. The concurrent treatment with baclofen and ECTs seems to have acted synergistically, showing complete improvement which was sustained.

The case report provides additional insight into the need to constantly monitor the development of involuntary movements even with the administration of an atypical antipsychotic like olanzapine which traditionally has a lower risk profile. Further research into better management options needs to be performed.


  Conclusions Top


In summary, tardive dystonia needs to consider among differentials in patients of any age presenting with unusual movement or neuromuscular disorders when there is a history of long-term antipsychotic medication use. Consultant liaison with psychiatrists will be of paramount importance in the effective management of these cases. Early diagnosis of this condition will help in improving the prognosis of these patients by allowing for the rapid institution of an appropriate therapeutic regimen before the condition becomes resistant to treatment. The combination of ECT and baclofen may be an effective choice for patients of schizophrenia with tardive dystonia developed in the course of neuroleptic treatment. Further controlled studies are needed to develop and refine the guidelines for managing tardive dystonia.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

The authors would like to thank Dr. Ajita S. Nayak, Professor and Head, Department of Psychiatry, Seth G.S. Medical College and K.E.M. Hospital, Mumbai

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Skogseid IM. Dystonia-new advances in classification, genetics, pathophysiology and treatment. Acta Neurol Scand Suppl 2014;129:13-9.  Back to cited text no. 1
    
2.
Kaplan SL, Coulter C, Sargent B. Physical therapy management of congenital muscular torticollis: A 2018 evidence-based clinical practice guideline from the APTA Academy of Pediatric Physical Therapy. Pediatr Phys Ther 2018;30:240-90.  Back to cited text no. 2
    
3.
Jesić MP, Jesić A, Filipović JB, Zivanović O. Extrapyramidal syndromes caused by antipsychotics. Med Pregl 2012;65:521-6.  Back to cited text no. 3
    
4.
Cloud LJ, Jinnah HA. Treatment strategies for dystonia. Expert Opin Pharmacother 2010;11:5-15.  Back to cited text no. 4
    
5.
Rosenquist PB, Miller B, Pillai A. The antipsychotic effects of ECT: A review of possible mechanisms. J ECT 2014;30:125-31.  Back to cited text no. 5
    
6.
Dannlowski U, Domschke K, Birosova E, Lawford B, Young R, Voisey J, et al. Dopamine D3 receptor gene variation: Impact on electroconvulsive therapy response and ventral striatum responsiveness in depression. Int J Neuropsychopharmacol 2013;16:1443-59.  Back to cited text no. 6
    
7.
Andrade C, Bolwig TG. Electroconvulsive therapy, hypertensive surge, blood-brain barrier breach, and amnesia: Exploring the evidence for a connection. J ECT 2014;30:160-4.  Back to cited text no. 7
    
8.
Repple J, Meinert S, Bollettini I, Grotegerd D, Redlich R, Zaremba D, et al. Influence of electroconvulsive therapy on white matter structure in a diffusion tensor imaging study. Psychol Med 2020;50:849-56.  Back to cited text no. 8
    
9.
Kimura M, Oda Y, Oishi K, Yoshino K, Kimura H, Niitsu T, et al. Effects of repeated electroconvulsive shocks on dopamine supersensitivity psychosis model rats. Schizophr Res 2021;228:1-6.  Back to cited text no. 9
    
10.
Lake W, Shah H. Intrathecal baclofen infusion for the treatment of movement disorders. Neurosurg Clin N Am 2019;30:203-9.  Back to cited text no. 10
    
11.
Miyazaki Y, Sato K, Koizumi H, Sako W, Asanuma K, Kaji R. New medications for dystonia. Rinsho Shinkeigaku 2012;52:1074-6.  Back to cited text no. 11
    
12.
Overgård TM, Kjærsgaard-Hansen L, Søe M, Illum NO. Positive experience with intrathecal baclofen treatment in children with severe cerebral palsy. Dan Med J 2015;62:A4999.  Back to cited text no. 12
    

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Correspondence Address:
Amey Yeshwant Angane,
Department of Psychiatry, Seth G.S. Medical College and K.E.M. Hospital Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amh.amh_10_22



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