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Effectiveness of Clozapine in Treating Severe Tardive Dystonia and Associated Pyosis
Narsimha Reddy Pinninti, M.D.; Martin J. DeSantis, D.O.; A. Adityanjee, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2012;24:E5-E6. doi:10.1176/appi.neuropsych.11010020

To the Editor: A 58-year-old African American woman with long-standing schizophrenia, paranoid type, and severe tardive dystonia had history of repeated nonadherence and hospitalization. Multiple medication trials were unsuccessful. She was then treated with clozapine in a dose of 250 mg/day, and dystonia was measured using Burke-Fahn and Marsden Rating Scale. She had near-total resolution of tardive dystonia after initiation of clozapine, and the improvement was sustained over a 3-year follow-up period.

Tardive dystonia (TDt) is an extrapyramidal side effect from first-generation antipsychotics, but it has also been reported with second-generation antipsychotics, including clozapine.1 There are several reports of effectiveness of clozapine in the treatment of TDt.2 We add to the existing literature by reporting a case of clozapine's effectiveness in treating TDt that differs from previous reports in two respects: 1) measuring TDt with standardized rating scales; and 2) having a longer follow-up period (3 years).

A 58-year-old African American woman with diagnosis of schizophrenia, paranoid type, diabetes mellitus type 2, and hypertension, presented with persecutory and grandiose delusions, lack of insight, and severe dystonia. She had history of multiple exacerbations due to non-adherence attributed to medication side effects. The dystonia involved her face, neck, trunk, and arms, causing significant neck pain, dysphonia, and difficulty eating. Dystonia was present for over a year, despite multiple medication trials, the details of which were not known. At presentation, she was on a daily dose of quetiapine 300 mg, clonazepam 2 mg, and benztropine 2 mg. Baseline Abnormal Involuntary Movement Scale (AIMS) and Burke-Fahn and Marsden rating scales showed scores of 29 and 84, respectively.3 she scored 19 out of 30 on the burke-fahn disability scale, indicating a severe degree of dystonia, with functional disability. Medication trials attempted were increasing the dose of quetiapine to 500 mg daily and benztropine to 3 mg daily, but she could not tolerate further dose increases because of sedation and anticholinergic side effects, respectively, and she refused other medication trials. Within 2 months, she was involuntarily hospitalized with an exacerbation of psychosis due to medication nonadherence. Dystonia was unchanged, although she was off all antipsychotic medication. Clozapine was initiated and titrated to a dose of 250 mg/day. Within 3 months, her psychotic symptoms resolved completely, and AIMS and Burke-Fahn and Marsden rating scales showed respective scores of 3 and 7, and disability rating score was 2. For the next 3 years, she was medication-adherent and asymptomatic. Medication adherence was attributed by the patient to effectiveness of clozapine in improving TDt. At the 3-year follow-up, AIMS and Burke-Fahn and Marsden rating scores were 3 and 2, respectively, with a disability score of 0. Respective serum levels of both clozapine and norclozapine were 627 ng/ml and 301 ng/ml (total of 928 ng/ml).

There was improvement of 90% and 92% in AIMS and Burke-Fahn-Marsden rating scale scores, respectively, with clozapine. The long history of TDt, persistence of TDt without antipsychotics, and the temporal relationship with clozapine initiation and improvement support the efficacy of clozapine and make the idea of spontaneous resolution of TDt unlikely. In this particular instance, clozapine improved TDt and thereby contributed to medication adherence in an individual with a long history of nonadherence. Our case report followed the patient for an extended period of 3 years and is only the second report that demonstrates improvement in TDt as shown by standardized rating scales.4

This case report adds to the existing literature on the effectiveness of clozapine in TDt and presents data to support a controlled trial of clozapine in treating TDt.

None of the authors reports any conflicts of interest.

Duggal  HS;  Mendhekar  DN:  Clozapine-induced tardive dystonia (blepharospasm).  J Neuropsychiatry Clin Neurosci 2007; 19:86–87
[PubMed]
[CrossRef]
 
Kwan  Y;  Sim  K:  Resolution of tardive dystonia in a patient with bipolar disorder treated with clozapine: a case report.  Prog Neuropsychopharmacol Biol Psychiatry 2010; 34:238–239
[PubMed]
[CrossRef]
 
Burke  RE;  Fahn  S;  Marsden  CD  et al:  Validity and reliability of a rating scale for the primary torsion dystonias.  Neurology 1985; 35:73–77
[PubMed]
 
Aukst-Margetic  B;  Margetic  B:  Treatment of generalized tardive dystonia with clozapine.  Psychiatr Danub 2008; 20:329–331
[PubMed]
 
References Container
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References

Duggal  HS;  Mendhekar  DN:  Clozapine-induced tardive dystonia (blepharospasm).  J Neuropsychiatry Clin Neurosci 2007; 19:86–87
[PubMed]
[CrossRef]
 
Kwan  Y;  Sim  K:  Resolution of tardive dystonia in a patient with bipolar disorder treated with clozapine: a case report.  Prog Neuropsychopharmacol Biol Psychiatry 2010; 34:238–239
[PubMed]
[CrossRef]
 
Burke  RE;  Fahn  S;  Marsden  CD  et al:  Validity and reliability of a rating scale for the primary torsion dystonias.  Neurology 1985; 35:73–77
[PubMed]
 
Aukst-Margetic  B;  Margetic  B:  Treatment of generalized tardive dystonia with clozapine.  Psychiatr Danub 2008; 20:329–331
[PubMed]
 
References Container
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