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Molecular Psychiatry (2001) 6, 134–142 © 2001 Nature Publishing Group All rights reserved 1359-4184/01 $15.00 www.nature.com/mp

MECHANISMS OF DRUG ACTION

Extrapyramidal symptoms and antidepressant drugs: neuropharmacological aspects of a frequent interaction in the elderly
S Govoni1, M Racchi1, E Masoero1, M Zamboni2 and L Ferini-Strambi2
1

Department of Experimental and AppliedPharmacology, University of Pavia, Pavia, Italy; 2Department of Neurology, Institute San Raffaele, Milano, Italy
Depression is the most prevalent functional psychiatric disorder in late life. The problem of motor disorders associated with antidepressant use is relevant in the elderly. Elderly people are physically more frail and more likely to be suffering from physical illness, and any drug given mayexacerbate pre-existing diseases, or interact with other drug treatments being administered for physical conditions. Antidepressants have been reported to induce extrapyramidal symptoms, including parkinsonism. These observations prompted us to review the neurobiological mechanism that may be involved in this complex interplay including neurotransmitters and neuronal circuits involved in movementand emotion control and their changes related to aging and disease. The study of the correlations between motor and mood disorders and their putative biochemical bases, as presented in this review, provide a rationale either to understand or to foresee motor side effects for psychotropic drugs, in particular antidepressants. Molecular Psychiatry (2001) 6, 134–142. Keywords: elderly; depression;movement disorders; Parkinson’s disease; antidepressant drugs; extrapyramidal symptoms

Introduction Several neuropsychiatric diseases have a characteristic late onset pattern and therefore predominantly affect the elderly. Moreover, aging may be a risk factor for the development of neurological and psychiatric diseases such as motor disorders (in particular Parkinson’s disease), affectivedisorders (depression) and dementia (Alzheimer’s disease or vascular dementia) due to agerelated changes in neurotransmission. A correlation between these disease states may exist as suggested by a significant degree of co-morbidity. Notably, depression in the elderly is an increasingly prevalent problem. All types of depression may be encountered in the population over 60 years: major depression,dysthymic disorder, bipolar depression, and adjustment disorder with depressed mood. The differential diagnosis of depression in the elderly is also more complicated than for younger individuals because of the greater likelihood of concomitant medical problems.1,2 Depression may complicate chronic disorders such as hypertension and diabetes, as well as be caused by the specific treatment of severalmedical disorders. There are also problems concerning drug treatment of depression in older patients. In the elderly

Correspondence: S Govoni, Department of Pharmacology, Viale Taramelli 14, 27100 Pavia, Italy. E-mail: govonis unipv.it Received 10 January 2000; revised 10 July 2000; accepted 14 July 2000

pharmacokinetic changes may delay drug clearance and increase the risk of drug accumulation,elderly people are physically more frail and more likely to be suffering from physical illness, and any drug given may exacerbate pre-existing diseases, or interact with other treatments being administered for these conditions. Treatment studies in old depressed patients have tended to focus on response rate in terms of specific symptoms or rating scale scores, but there is a difference between‘efficacy’ within the specific context of a clinical trial and ‘effectiveness’ in clinical practice. Another, at least partially, neglected area is the impact of drug side effects in terms of increased physical morbidity. Some antidepressants have been reported to induce extrapyramidal symptoms, including parkinsonism.3 This is an important point because depression often accompanies and contributes to...