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<p class="ltrs-br-ltr-br-title"><span class="bold"><a id="_idTextAnchor000"></a>Lurasidone-Induced Dystonia</span></p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold">To the Editor:</span> Lurasidone is a novel antipsychotic that differs from other atypical antipsychotics in having a potent 5-hydroxytryptamine 7 (5-HT<span class="subscript">7</span>) and 5-HT<span class="subscript">1A</span> receptor activity.<span class="htm-cite"><a href="#ref1">1</a>,<a href="#ref2">2</a></span> Dystonic reactions have not been commonly described, with only 1 report<span class="htm-cite"><a href="#ref3">3</a></span> of glossopharyngeal dystonia with lurasidone-fluoxetine combination. We present the case of a patient who developed episodes of recurrent oculogyric crises with lurasidone use.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold-ital">Case report.</span> Ms A is a 28-year-old woman with a 12-year history of schizophrenia (<span class="italic">DSM-5 </span>criteria). She has had several hospital admissions with acute psychosis related to partial compliance with antipsychotics following intolerance of side effects. Ms A has received trials of risperidone, quetiapine, aripiprazole, and amisulpride. While taking amisulpride, Ms A experienced jaw stiffness and oculogyric crisis, so the medication was stopped, and lurasidone 40 mg/d was initiated. Her psychotic symptoms subsequently worsened with increased auditory hallucinations and paranoia, so the lurasidone dose was increased to 80 mg/d. Three weeks after the increased dose was initiated, Ms A presented to the emergency department with an oculogyric crisis. She was administered benztropine 2 mg with good effect and was admitted to the hospital for further monitoring and treatment of her psychosis. Ms A requested to remain on lurasidone and was maintained on 80 mg for 7 days with no recurrence of dystonia.</p>
<p class="ltrs-br-ltr-br-body-text">The lurasidone dose was uptitrated, aiming for a better antipsychotic response. With each dose increment of 40 mg, Ms A experienced a mild episode of oculogyric crisis within 3 to 4 days, which resolved rapidly with benztropine 2 mg. Given that each oculogyric episode resolved rapidly and the patient preferred to keep taking lurasidone, the dose increment increase continued. On a dose of 160 mg/d, Ms A experienced the most severe episode, which resolved 45 minutes after she was given benztropine 2 mg. As a consequence of the recurrent oculogyric crises, lurasidone was stopped, and she was started on monthly depot aripiprazole (after establishing tolerability) with no further dystonic reactions and good antipsychotic response.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text">Oculogyric crisis is an acute dystonic reaction characterized by conjugate upward eye deviation usually associated with antipsychotic medications. Drug-related risk factors include high potency, high doses, and rapid dose increments. The pathophysiology of acute dystonia is poorly understood. Hyperdopaminergic mechanisms are widely supported; research<span class="htm-cite"><a href="#ref4">4</a></span> has suggested that compensatory increase in dopamine turnover in response to the antipsychotic-induced dopamine blockade contributes to the pathogenesis of acute dystonic reactions. This increase in dopamine is short lived and is replaced by postsynaptic supersensitivity<span class="htm-cite"><a href="#ref4">4</a></span> and reduction of dystonic episodes. However, hypodopaminergic mechanisms have also been implicated, as other studies<span class="htm-cite"><a href="#ref5">5</a></span> have suggested that acute dystonic reactions occur due to dopamine hypofunction, leading to a relative hyperactivity of cholinergic mechanisms.</p>
<p class="ltrs-br-ltr-br-body-text">Ms A’s first episode of oculogyric crisis occurred 3 weeks after increasing lurasidone from 40 mg to 80 mg orally, with further episodes occurring with each dose increase. The most severe episode occurred at the highest dose of 160 mg/d. Each episode was responsive to benztropine, and the episodes resolved completely when lurasidone was stopped. The reaction scored an 8 on the Naranjo Adverse Drug Reaction Probability Scale,<span class="htm-cite"><a href="#ref6">6</a></span> indicating that lurasidone was the probable cause of Ms A’s oculogyric crises.</p>
<p class="ltrs-br-ltr-br-body-text">Ms A was subsequently stabilized on aripiprazole depot with no further dystonic episodes, despite that aripiprazole has similarly low anticholinergic properties and is known to cause acute dystonias.<span class="htm-cite"><a href="#ref5">5</a></span> We postulate that her dystonic reactions were due to rapid dose increment and lurasidone’s additional proserotonergic effects, as high serotonin levels are also implicated in dystonia.<span class="htm-cite"><a href="#ref7">7</a></span></p>
<p class="ltrs-br-ltr-br-body-text">Conventionally, first-generation antipsychotics are more implicated in acute dystonia. However, newer second-generation antipsychotics like lurasidone can also cause dystonia, and clinicians should be aware of this, especially when serious dystonic reactions have occurred in the same patient with previous antipsychotic use.</p>
<p class="references_references-heading"><span class="smallcaps">References</span></p>
<p class="references-references-text-1-9"><a name="ref1"></a><span class="htm-ref"> 1.	</span>Nakamura M, Ogasa M, Guarino J, et al. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. <span class="italic">J Clin Psychiatry</span>. 2009;70(6):829–836. <a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=19497249&dopt=Abstract"><span class="pubmed-crossref">PubMed</span></a> <a href="
http://dx.doi.org/10.4088/JCP.08m04905"><span class="pubmed-crossref">doi:10.4088/JCP.08m04905</span></a></p>
<p class="references-references-text-1-9"> 2.	Ishibashi T, Horisawa T, Tokuda K, et al. Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. <span class="italic">J Pharmacol Exp Ther.</span> 2010;334(1):171–181. <a href="
http://dx.doi.org/10.1124/jpet.110.167346"><span class="pubmed-crossref">doi:10.1124/jpet.110.167346</span></a></p>
<p class="references-references-text-1-9"><a name="ref3"></a><span class="htm-ref"> 3.	</span>Paul S, Cooke BK, Nguyen M. Glossopharyngeal dystonia secondary to a lurasidone-fluoxetine CYP-3A4 interaction. <span class="italic">Case Report Psychiatry</span>. 2013;2013:136194. <a href="
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https://dx.doi.org/10.1155/2013/136194"><span class="pubmed-crossref">doi:10.1155/2013/136194</span></a></p>
<p class="references-references-text-1-9"><a name="ref4"></a><span class="htm-ref"> 4.	</span>Owens D. <span class="italic">A Guide to the Extrapyramidal Side-Effects of Antipsychotic Drugs</span>. 1st ed. Cambridge, UK: Cambridge University Press; 1999. <a href="
http://dx.doi.org/10.1017/CBO9780511544163"><span class="pubmed-crossref">doi:10.1017/CBO9780511544163</span></a></p>
<p class="references-references-text-1-9"><a name="ref5"></a><span class="htm-ref"> 5.	</span>Bhachech JT. Aripiprazole-induced oculogyric crisis (acute dystonia). <span class="italic">J Pharmacol Pharmacother</span>. 2012;3(3):279–281. <a href="
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http://dx.doi.org/10.4103/0976-500X.99446"><span class="pubmed-crossref">doi:10.4103/0976-500X.99446</span></a></p>
<p class="references-references-text-1-9"><a name="ref6"></a><span class="htm-ref"> 6.	</span>Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. <span class="italic">Clin Pharmacol Ther</span>. 1981;30(2):239–245. <a href="
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http://dx.doi.org/10.1038/clpt.1981.154"><span class="pubmed-crossref">doi:10.1038/clpt.1981.154</span></a></p>
<p class="references-references-text-1-9"><a name="ref7"></a><span class="htm-ref"> 7.	</span>Karakaş Uğurlu G, Onen S, Bayındırlı D, et al. Acute dystonia after using single dose duloxetine: case report. <span class="italic">Psychiatry Investig</span>. 2013;10(1):95–97. <a href="
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http://dx.doi.org/10.4306/pi.2013.10.1.95"><span class="pubmed-crossref">doi:10.4306/pi.2013.10.1.95</span></a></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Prashant Tibrewal, MD, FRANZCP</span><span class="superscript">a</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Rachel Cheng, MBBS</span><span class="superscript">b</span></p>
<p class="ltrs-br-ltr-br-author"><a href="
mailto:rachel.cheng@student.adelaide.edu.au">
rachel.cheng@student.adelaide.edu.au</a></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Tarun Bastiampillai, MBBS, FRANZCP</span><span class="superscript">c</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Rohan Dhillon, MBBS, FRANZCP, MClinSc</span><span class="superscript">a</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Angela Okungu, MBBS, FRANZCP</span><span class="superscript">a</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Josephine Campbell, MBBS</span><span class="superscript">b</span></p>
<p class="end-matter"><span class="superscript">a</span>Cramond Clinic, The Queen Elizabeth Hospital, Woodville, SA, Australia</p>
<p class="end-matter"><span class="superscript">b</span>University of Adelaide, Adelaide, SA, Australia</p>
<p class="end-matter"><span class="superscript">c</span>Department of Psychiatry, Flinders University, Bedford Park, SA, Australia</p>
<p class="end-matter"><span class="bold-italic">Potential conflicts of interest:</span> None.</p>
<p class="end-matter"><span class="bold-italic">Funding/support: </span>None.</p>
<p class="end-matter"><span class="bold-italic">Patient consent:</span> Consent was obtained from the patient to publish this case.</p>
<p class="end-matter"><span class="bold-italic">Published online:</span> June 29, 2017.</p>
<p class="end-matter"><span class="italic">Prim Care Companion CNS Disord 2017;19(3):16l02053</span></p>
<p class="doi-line"><span class="italic">
https://doi.org/</span><span class="doi">10.4088/PCC.16l02053</span></p>
<p class="end-matter"><span class="italic">© Copyright 2017 Physicians Postgraduate Press, Inc.</span></p>
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