Asian Journal of Psychiatry 3 (2010) 235–236

Short communication

Successful treatment of co-morbid schizophrenia and multiple sclerosis

Eesha Sharma, Naren P. Rao *, Ganesan Venkatasubramanian, Rishikesh V. Behere,Shivarama Varambally, Bangalore N. Gangadhar

Department of Psychiatry, National Institute of Mental Health & Neurosciences [NIMHANS], Bangalore, India

A R T I C L E I N F O

Article history:

Received 5 July 2010

Accepted 8 July 2010

Keywords:

Clozapine

Interferon-beta-1a

Multiple sclerosis

Risperidone

Schizophrenia

A B S T R A C T

Multiple sclerosis (MS) has both neurological and psychiatric manifestations. Though depression, bipolar

disorder and la belle indifference are commonly described, schizophrenia-like-psychosis is not widely

reported with MS. Drug interactions and side effects make treatment, in such scenario, challenging. We,

for the first time, report a patient with MS and paranoid schizophrenia successfully treated with

concurrent use of clozapine and risperidone with interferon-beta-1a.

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1. Introduction

Multiple sclerosis (MS), a disseminated demyelinating disease ofthe central nervous system (CNS), has neurological and psychiatricmanifestations (Ghaffar and Feinstein, 2007). Though depression isthe commonest psychiatric presentation, bipolar disorder, la belleindifference and intellectual deterioration are also described(Ghaffar and Feinstein, 2007). However, there are only few reportsof schizophrenia-like-psychosis in MS (Kohler et al., 1988; Feinsteinet al., 1992). Importantly, treatment of schizophrenia with co-morbid MS is challenging, in view of the possibility of antipsychoticsworsening persisting neurological deficits and potential druginteractions. We for the first time report successful concurrentuse of clozapine and risperidone with interferon-beta-1a, in apatient with MS who developed paranoid schizophrenia.

2. Case report

Mrs. A, a 31-year-old lady, presented with 3 years duration illnesscharacterized by delusions of persecution, reference, mindreading,grandiosity, delusion of being controlled, delusion of doubles,delusion of pregnancy, 2nd and 3rd person auditory hallucinations,and socio-occupational dysfunction. She scored 32 on Scale forAssessment of Positive symptoms (SAPS) (Andreasen, 1984) and 0 onScale for Assessment of Negative Symptoms (SANS) (Andreasen,1983); 29 on Mini Mental Status Examination suggesting absence of

* Corresponding author. Tel.: +91 80 26995250.

E-mail address: docnaren@gmail.com (N.P. Rao).

1876-2018/$ – see front matter � 2010 Elsevier B.V. All rights reserved.

doi:10.1016/j.ajp.2010.07.006

significant cognitive deficits (Folstein et al., 1975); 6 (severely ill) onClinical Global Impression-Severity (CGI-S) (Guy, 2008a,b). She haddeveloped dyskinetic movements with antipsychotics, involvinglower jaw, lips and upper limbs and scored 10 on AbnormalInvoluntary Movements Scale (AIMS) (Guy, 2008a,b).

She had also been diagnosed with MS – relapsing remitting type4 years back (McDonald et al., 2001). She had had two episodes ofoptic neuritis and one of paraparesis. Her MRI and cerebrospinalfluid-electrophoresis findings supported the clinical picture for adiagnosis of MS. Acute MS episodes were treated with oral steroids.After the third episode of MS, interferon-beta-1a, for prophylaxis,was started and continued till she presented to us. When shepresented to us, she had ataxic gait and residual weakness in lowerlimb and pelvic girdle muscles such that she could not move herlimbs against moderate force applied by examiner.

MRI, a month before onset of psychosis, revealed multiplevarying sized (average size 4–6 mm) hyper-intense lesions inbrainstem, cerebellar hemispheres, bilateral thalami, and bilateralperiventricular (perpendicular to ventricular surface) areas; fewlesions showed faint ring enhancement and faint restriction in leftperiventricular and fronto-parietal regions. MRI 3 years after onsetof psychosis revealed diffuse cerebral atrophy which was moreprominent in frontal and temporal lobes, subcortical grey mattervolume loss in caudate nucleus and putamen, and ventriculardilatation, findings consistent with those seen in schizophrenia.

Her electrocardiogram, electroencephalogram, liver, renal andthyroid functions, and serum lipid profile were within normallimits. She was earlier treated with adequate trials of olanzapine,amisulpiride and oral risperidone but had not shown muchimprovement in psychopathology. On risperidone-consta 25 mg

E. Sharma et al. / Asian Journal of Psychiatry 3 (2010) 235–236236

intramuscularly, given fortnightly, she had minimal improvementin social functioning, though psychopathology persisted. In view ofthe above, we diagnosed her as having treatment resistantschizophrenia (Meltzer, 1997) and started clozapine 25 mg/day;gradually the dose was increased up to 325 mg/day.

At this dose, she developed persistent tachycardia (PR = 120–140/min) and hypertension (BP = 140/90–150/90 mm Hg) andthus, over the next 3–4 weeks we gradually decreased clozapineto 225 mg/day and augmented it with oral risperidone, doseincreased up to 8 mg/day. Pulse-rate and blood-pressure normal-ized in 2 weeks. She tolerated risperidone–clozapine combinationwell and there were no significant side effects. We continuedInterferon-beta-1a 30 mg per week as prophylaxis for multiplesclerosis, as per neurologist’s advice.

She showed significant improvement and at the end of 11weeks of hospital stay, her SAPS score decreased to 18 and CGI-Simproved to 4 (moderately ill). She scored 2 (much improved) onclinical global impression-improvement. She maintained consis-tent improvement even after 12 weeks of discharge from hospital,with significant improvement especially in socio-occupationalfunctioning.

3. Discussion

To the best of our knowledge, this is the first report ofconcurrent use of risperidone–clozapine and interferon-beta-1a inparanoid schizophrenia with MS. In index patient, though therewas good control of MS after start of interferon-beta-1aprophylaxis, psychotic symptoms persisted. Thus, we consideredan independent diagnosis of Paranoid Schizophrenia. Also, her MRIfindings were suggestive of psychosis (Shenton et al., 2001),possibly unrelated to MS.

Psychosis did not show much improvement with threeadequate trials of antipsychotics, and thus clozapine wasstarted. She developed tachycardia with clozapine and its dosecould not be increased further. Risperidone was added andthough she had not shown improvement with oral risperidoneearlier, she showed significant improvement on risperidone–clozapine combination.

This report demonstrates successful concurrent use of clozapineand risperidone with interferon-beta-1a. However, one need to becautious while using this combination and monitoring is necessarywhile using these drugs in view of potential drug interactions andside effects; neuroleptics, except clozapine, worsen neurologicaldeficits in MS (Davids et al., 2004), and similarly, interferon may

worsen psychosis (Goeb et al., 2006). In addition both can causeagranulocytosis (Tueth, 1994; Rieckmann et al., 2004). However,none of these were seen in this patient with up to 6 months ofcombined use. Thus, our report suggests that the combination ofclozapine and interferon-beta-1a is probably safe and, with regularmonitoring, can possibly be considered in treatment resistantschizophrenia with co-morbid MS.

Conflict of interest

None.

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