Letters to the Editor
Effects of Rivastigmine in a Case of Residual Schizophrenia
Dear Editor:
Among cholinesterase inhibitors, rivastigmine is an acetylcholinesterase and butyrylcholinesterase inhibitor that is widely used in treating Alzheimer’s and subcortical vascular dementias, owing to its beneficial pharmacodynamic property.
Combined with antipsychotics, rivastigmine has been found effective in improving negative schizophrenia symptoms (1,9). We report a case of residual schizophrenia with predominant negative symptoms that responded to rivastigmine and risperidone.
Case Report
Mrs J is an Indian woman, aged 45 years, with residual schizophrenia (according to ICD-10 criteria) of 6 years’ duration. She was treated with risperidone and maintained on 6 mg daily. She presented with marked psychomotor retardation, passivity, lack of initiative, poverty of speech, and poor facial expression. With strong family support, she had maintained good drug compliance and responded to risperidone, which completely controlled her positive symptoms. She developed the presenting complaints during the prior 18 months, despite regularly taking an antipsychotic. Using the clinical interview, patient observation, and additional informant information, we evaluated her baseline negative symptom complex according to the Scale for the Assessment of Negative Symptoms (SANS, 2). We also evaluated her performance in Instrumental Activities of Daily Living (IADL, 3) and on the Satisfaction with Life Scale (SWLS, 4). Further, we administered neurocognitive tests: the Halstead-Reitan Battery (5) for psychomotor speed, attention, and scanning; the Rey Auditory Verbal Learning Test (6); and the Wechsler Memory Scale-Third Edition (7) for learning and memory.
We started the patient on rivastigmine tartrate 1.5 mg twice daily, titrated at monthly intervals to reach a maximum of 6 mg daily in 2 months’ time and maintained along with risperidone 6 mg daily. A second SANS evaluation, done after 4 weeks of drug therapy, showed 10% improvement in negative symptoms. The combined treatment of antipsychotic and rivastigmine continued for 6 months, at which time the patient was reassessed. We found a notable drop of 41% from her baseline SANS score. Similarly, her baseline IADL and SWLS scores improved by 36% and 28%, respectively. Neuro-psychological tests measured after 6 months showed appreciably better cognitive functions, which were directly related to the improvement in her quality of life.
Discussion
The neurotransmitters implicated in the pathogenesis of schizophrenia are dopamine, serotonin, glutamate, and acetylcholine. Cognitive impairment in schizophrenia is partly due to diminished acetylcholine activity in the brain cortex. Patients with schizophrenia and comorbid cognitive dysfunction appeared to show an improvement in their cognitive score when an acetylcholinesterase inhibitor was added to their treatment regimen (8,10). Rivastigmine significantly improved quality of life in subjects with schizophrenia. These benefits are due to the drug’s effects on the cognitive deficits and negative symptoms associated with this condition (9). This finding leads to the hope that acetylcholinesterase inhibitors may have a role as adjunctive treatments for residual schizophrenia. Further studies are needed to help elucidate this issue.
References
1. Van de Graff K, Loonen A, Hovens JE, van Halen L, van Dijke A, Tulen J. Pilot study of the effects of rivastigmine in schizophrenia. J Eur Coll Neuropsychopharmacol 2003;13(Suppl 4):S315.
2. Andreasen N. The Scale for Assessment of Negative Symptoms (SANS). Iowa City (IA): University of Iowa; 1981.
3. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–86.
4. Diener E, Emmons R, Largen J, Griffin S. The Satisfaction with Life Scale. J Personal Assess 1985;49:71–5.
5. Reitan RM, Wolfson D. Conventional intelligence measurements and neuropsychological concepts of adaptive abilities. J Clin Psychol 1992;48:521.
6. Schmidt M. Rey Auditory-Verbal Learning Test. Los Angeles (CA): Western Psychological Services; 1996.
7. Wechsler D. Wechsler Memory Scale-Third Edition. San Antonio (CA): Psychological Corporation; 1997.
8. Stryjer R, Strous RD, Bar F, Werber F, Shaked G, Buhiri Y, and others. Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia. Clin Neuropharmacol 2003;26:12–7.
9. Lenzi A, Maltinti E, Poggi E, Fabrigio L, Coli E. Effects of rivastigmine on cognitive function and quality of life in patients with schizophrenia. Clin Neuropharmacol 2003;26:317–21.
10. Tugal O, Yazici K. A double-blind, placebo controlled, cross-over trial of adjunctive donepezil for cognitive impairment in schizophrenia. J Eur Coll Neuropsychopharmacol 2003;13(Suppl 4):S294.
Janakiraman Raguraman, DIH, DPM
John Vijay Sagar, MD
R Chandrasekaran, MD
Pondicherry, India
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