Letter to the Editor

Memory function is seriously affected in patients with schizophrenia [1]. Although this is a stable and wide-ranging deficit, anticholinergic medication can aggravate the impairment. Mori et al. [2] recently reported on the effects of anticholinergic drug withdrawal on memory, regional cerebral blood flow, and extra-pyramidal side effects in patients with schizophrenia. Unfortunately, this study is affected by a number of significant limitations that were not addressed by the authors and that may compromise a reliable interpretation of the data.

First, the authors maintain that memory performance improved after withdrawal of anticholinergic drugs, but they failed to include a control group or control condition. Thus, it is possible that the improvement might have been merely due to repeated testing [3]. Second, the authors used simple regression analyses to show that BPRS score is significantly associated with verbal working memory on one hand and significantly with anticholinergic drug dose on the other hand. Multiple regression analysis could have indicated whether one of the factors accounts primarily for the observed variance or whether they contribute additively. Third, the important question of whether improved memory due to anticholinergic withdrawal might be mediated by an improvement in general psychopathology (BPRS ratings) was not addressed, although the data were available.

Clearly, the preliminary findings reported by Mori et al. call for a more thorough investigation of the precise effects of anticholinergic withdrawal in a randomized design with a matched control group. In addition, the use of functional MRI or PET may potentially shed more light on the brain systems involved.

References

• 1 Aleman A, Hijman R, De Haan E HF, Kahn R S. Memory impairment in schizophrenia: a meta-analysis.  Am J Psychiatry. 1999;  156 1358-1366
• 2 Mori K, Yamashita H, Nagao M, Horiguchi J, Yamawaki S. Effects of anticholinergic drug withdrawal on memory, regional cerebral blood flow and extra-pyramidal side effects in schizophrenic patients.  Pharmacopsychiatry. 2002;  35 6-11
• 3 Wilson B A, Watson P C, Baddeley AD; Emslie H, Evans J J. Improvement or simply practice? The effects of twenty repeated assessments on people with and without brain injury.  J Int Neuropsychol Soc. 2000;  6 469-79

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