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In This Article
 »  Abstract
 » Introduction
 » Case Report
 » Discussion
 »  References

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DRUG WATCH
Year : 2013  |  Volume : 45  |  Issue : 5  |  Page : 532-533
 

Fluvoxamine induced oculogyric dystonia and manic switch in a patient with obsessive compulsive disorder


Department of Psychiatry, Central Institute of Psychiatry, Kanke, Ranchi, Jharkhand, India

Date of Submission05-Feb-2013
Date of Decision23-Apr-2013
Date of Acceptance04-Jul-2013
Date of Web Publication6-Sep-2013

Correspondence Address:
Sai Krishna Tikka
Department of Psychiatry, Central Institute of Psychiatry, Kanke, Ranchi, Jharkhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.117760

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 » Abstract 

Fluvoxamine has a similar spectrum of adverse effects as compared to other selective serotonin reuptake inhibitors. However, fluvoxamine induced oculogyric dystonia is a rare instance in clinical practice. In this report, we present a case of obsessive compulsive disorder that developed oculogyric dystonia during the course of fluvoxamine mono-therapy and subsequently had a manic switch.


Keywords: Induced manic switch, oculogyric dystonia, selective serotonin reuptake inhibitor


How to cite this article:
Tikka SK, Garg S, Das B. Fluvoxamine induced oculogyric dystonia and manic switch in a patient with obsessive compulsive disorder. Indian J Pharmacol 2013;45:532-3

How to cite this URL:
Tikka SK, Garg S, Das B. Fluvoxamine induced oculogyric dystonia and manic switch in a patient with obsessive compulsive disorder. Indian J Pharmacol [serial online] 2013 [cited 2019 Aug 20];45:532-3. Available from: http://www.ijp-online.com/text.asp?2013/45/5/532/117760



 » Introduction Top


Fluvoxamine, a commonly used drug for obsessive compulsive disorder (OCD), has a similar spectrum of adverse events compared to other selective serotonin reuptake inhibitors (SSRIs). Although less frequent, fluvoxamine, like other SSRIs is known to cause various types of movement disorders like akathisia,  Parkinsonism More Details and tardive dyskinesia. [1] Also, fluvoxamine has comparable degree of propensity to precipitate a manic switch to that of other SSRIs like fluoxetine, paroxetine and sertraline. [2] Here, we present a case of OCD that developed oculogyric dystonia during the course of fluvoxamine mono-therapy and subsequently had a manic switch.


 » Case Report Top


A 21-year-old, Muslim male belonging to middle socio-economic status and educated up to intermediate degree had a family history of bipolar affective disorder in his paternal grandfather. He was well adjusted premorbidly and presented with 4 years of illness with no obvious precipitating factor, characterized by repeated, intrusive doubts about symmetry and repeatedly arranging household articles like clothes, shoes, furniture, books etc. He also had doubts on the linearity of the sentences he writes on pages and would write several times before he moved to the next page. He clearly was distressed with these symptoms and for the past 4 months was also complaining of predominant low mood, decreased interest in activities, ideas of decreased self-worth and pessimistic future. He was admitted as an inpatient with a diagnosis of OCD and comorbid moderated depressive episode according to ICD-10. His routine blood investigations including thyroid profile, computed tomography scan brain and electroencephalography were normal. He scored a total of 24 on Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and 15 on Hamilton Depression (HAM-D-17) Rating Scale. He was started on morning dose of fluvoxamine, with an initial dose of 50 mg to be hiked by 50 mg every 4 th day. By the 2 nd week, he started reporting of improvement especially in depressive symptoms (HAM-D-17 scores reduced to 10 whereas on Y-BOCS, he scored 22). On the 11 th day of admission, he complained of oculogyric dystonia characterized by involuntary sustained upward gaze in both his eyes during morning hours. There were no signs and symptoms suggestive of pseudo-parkinsonism or any other movement disorders. He was administered injection promethazine 50 mg stat intramuscularly and the symptom subsided within an hour. Dose of fluvoxamine was decreased to 150 mg and further hiking was planned every 8 th day. This symptom did not recur subsequently. By 25 th day the fluvoxamine dose was increased to 250 mg and he showed significant improvement in both obsessive (Y-BOCS total score -14) and depressive symptoms (HAM-D-17 total score -4). However, 2 days later, mental status examination revealed over familiar manner of relating, over productive speech, euphoric affect and inflated self-esteem. He scored 16 on Young Mania Rating Scale (YMRS). Fluvoxamine dose was reduced to 150 mg and 900 mg lithium was added, which was later increased to 1050 mg to obtain optimal serum level, i.e., 0.72 meq/L. He showed an improvement in manic symptoms within 10 days (YMRS total score -3) and maintained the improvement shown in obsessive symptoms.

There is a clear temporal relationship between the occurrence of dystonia and relatively faster titration in the dose of fluvoxamine to 200 mg. And reduction in the dose and subsequent slow titration was helpful. Also, temporal relationship between the occurrence of manic switch and dose of fluvoxamine was established. This particular class of drugs is known to cause the spectrum of side-effects as in our case. However, specific case of fluvoxamine causing oculogyric dystonia has not been reported in the literature. While considering the manic switch, a positive family history of bipolar illness in this case might have predisposed the patient to a manic switch; but neurobiological mechanisms of fluvoxamine might be sufficient to trigger a manic switch. The Naranjo adverse drug reaction probability score for oculogyric dystonia was -6 and for the induced manic switch was -5; both suggesting a "probable" association with administration of fluvoxamine.


 » Discussion Top


Although, dystonia is found to be a most common type of extrapyramidal symptom induced by SSRIs, [1] apart from a few case reports [3] oculogyric dystonia precipitated by an SSRI is a rare instance in clinical practice. No study has reported of an association between extrapyramidal symptoms induced by SSRI and their potential to precipitate a manic switch. Interestingly, the index case presents a possible association between movement disorders induced by an SSRI (in this case oculogyric dystonia and manic switch with fluvoxamine). Fluvoxamine with a half-life of less than 24 h (i.e., 15.6 h) has a possibility of inter-dose withdrawal. Also, rise and fall of its blood levels in rapid cycles cause rapidly fluctuating biochemical imbalances in the brain. [4] Inhibitory modulation of dopaminergic neurons resulting from the increase in 5-hydroxytryptamine (5-HT) and disturbance in the reciprocal balance between dopaminergic, serotonergic and noradrenergic, or cholinergic activity [1] have been proposed as mechanisms underlying SSRI induced dystonia. On the other hand, fluvoxamine induced manic switch might be related to the inter-dose withdrawal and also to rapid fluctuations in the blood levels of serotonin leading to reciprocal changes in dopamine [4] - implying imbalances in the 5HT 2 to D 2 receptor occupancy. Reciprocal enhancement in the blood levels of norepinephrine also has been suggested as a mechanism underlying a manic switch. [5]

This case suggests that rapid hiking in dose (every 4 th day increase in fluvoxamine by 50 mg) caused a sudden shift in the 5HT 2 :D 2 balance toward D 2 causing oculogyric dystonia; and at higher doses (fluvoxamine 250 mg and above) there might have been a disturbance in the reciprocal balance of serotonin, dopamine and norepinephrine neurotransmission, due to rise and fall in blood levels of fluvoxamine in rapid cycles, resulting in a manic switch. Inter-dose withdrawal might also have played some role also. Moreover, fluvoxamine induced dystonia in a case of OCD could also imply the role of glutaminergic system. Abnormal glutaminergic neurotransmission in cortical-striatal-thalamic circuits underlie both movement disorders (via motor projections) and OCD (via limbic associative projections). [6] SSRIs have been shown to normalize this excessive glutaminergic drive pathology; specifically fluvoxamine reduces N-Methyl-D-aspartate (NMDA) activity via sigma 1 receptors. [7] This report of ours therefore implicate the role of this "sigma enigma" in both fluvoxamine induced oculogyric dystonia and manic switch in a case of OCD.

Interestingly, existing molecular genetic studies reveal a mixed support for the association between SSRI induced extrapyramidal symptoms and manic switch. There are reports that extrapyramidal symptoms induced by SSRIs are associated with the presence of the A1 allele of DRD2 Taq1A polymorphism, [8] which is also implicated in the etiology of bipolar disorder. [9] However, polymorphisms in serotonin transporter genes, which are implicated in antidepressant induced manic switch, [10] have not been found to be significantly associated with SSRI induced extrapyramidal symptoms. [8] Occurrence of oculogyric dystonia and manic switch in a patient of OCD during the course of fluvoxamine therapy suggests further investigation in the association between SSRI induced movement disorders and manic switch.

 
 » References Top

1.Madhusoodanan S, Alexeenko L, Sanders R, Brenner R. Extrapyramidal symptoms associated with antidepressants - A review of the literature and an analysis of spontaneous reports. Ann Clin Psychiatry 2010;22:148-56.  Back to cited text no. 1
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2.Peet M. Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants. Br J Psychiatry 1994;164:549-50.  Back to cited text no. 2
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3.Patel OP, Simon MR. Oculogyric dystonic reaction to escitalopram with features of anaphylaxis including response to epinephrine. Int Arch Allergy Immunol 2006;140:27-9.  Back to cited text no. 3
[PUBMED]    
4.Breggin PR. Fluvoxamine as a cause of stimulation, mania and aggression with a critical analysis of the FDA-approved label. Int J Risk Saf Med 2001;14:71-86.  Back to cited text no. 4
    
5.Bhanji NH, Margolese HC, Saint-Laurent M, Chouinard G. Dysphoric mania induced by high-dose mirtazapine: A case for 'norepinephrine syndrome'? Int Clin Psychopharmacol 2002;17:319-22.  Back to cited text no. 5
[PUBMED]    
6.MacMaster FP, Rosenberg DR. Glutamate and the treatment of obsessive compulsive disorder. Janicak PG, ed. Psychopharm Review 2010;45:33-40.  Back to cited text no. 6
    
7.Hindmarch I, Hashimoto K. Cognition and depression: The effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered. Hum Psychopharmacol 2010;25:193-200.  Back to cited text no. 7
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8.Hedenmalm K, Güzey C, Dahl ML, Yue QY, Spigset O. Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin and dopamine transporter and receptor polymorphisms. J Clin Psychopharmacol 2006;26:192-7.  Back to cited text no. 8
    
9.Huang CC, Chang YH, Lee SY, Chen SL, Chen SH, Chu CH, et al. The interaction between BDNF and DRD2 in bipolar II disorder but not in bipolar I disorder. Am J Med Genet B Neuropsychiatr Genet 2012;159B:501-7.  Back to cited text no. 9
[PUBMED]    
10.Biernacka JM, McElroy SL, Crow S, Sharp A, Benitez J, Veldic M, et al. Pharmacogenomics of antidepressant induced mania: A review and meta-analysis of the serotonin transporter gene (5HTTLPR) association. J Affect Disord 2012;136:e21-9.  Back to cited text no. 10
[PUBMED]    



This article has been cited by
1 Fluvoxamine
Reactions Weekly. 2013; 1475(1): 19
[Pubmed] | [DOI]



 

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