Hostname: page-component-745bb68f8f-v2bm5 Total loading time: 0 Render date: 2025-01-27T10:36:40.701Z Has data issue: false hasContentIssue false
  • English
  • Français

Extrapyramidal Symptoms with Selective Serotonin Reuptake Inhibitors

Published online by Cambridge University Press:  02 January 2018

Dinesh K. Arya
Dinesh K. Arya*
Affiliation:
Peter Hodgkinson Centre, County Hospital, Lincoln LN2 5QY
*
Masterton Hospital, P. O. Box 96, Masterton, New Zealand
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Several case reports in the literature suggest that selective serotonin reuptake inhibitors can produce extrapyramidal symptoms.

Method

Computerised literature searches were used to identify reports on extrapyramidal symptoms and serotonin reuptake inhibitors. Subsequently, manual searches were made for articles in which there was any indication of the mechanisms responsible for these extrapyramidal symptoms.

Results

Only a few reports could be identified in which serotonin reuptake inhibitors were implicated in extrapyramidal symptoms in some patients.

Conclusions

Evidence is discussed from preclinical and clinical studies suggesting the interaction between serotoninergic and dopaminergic neurotransmitter system, as a possible mechanism for production of extrapyramidal symptoms.

Type
Review
Information
The British Journal of Psychiatry , Volume 165 , Issue 6 , December 1994 , pp. 728 - 733
Copyright
Copyright © Royal College of Psychiatrists, 1994 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Arnt, J., Hyttel, J. & Bach-Lauritsen, T. (1986) Further studies on the mechanism behind scopolamine-induced reversal of antistereotypic and cataleptogenic effects of neuroleptics in rats. Acta Pharmacologica et Toxicologica, 59, 319–324.CrossRefGoogle ScholarPubMed
Arya, D. K. & Szabadi, E. (1993) Dyskinesia associated with fluvoxamine. Journal of Clinical Psychopharmacology, 13, 365–366.CrossRefGoogle ScholarPubMed
Ayd, F. J. (1961) A survey of drug-induced extrapyramidal reactions. Journal of the American Medical Association, 175, 1054–1060.CrossRefGoogle ScholarPubMed
azmitia, E. C. (1978) The serotonergic-producing neurons in the midbrain median and dorsal raphe nuclei. In Handbook of Psychopharmacology, Vol. 9: Chemical Pathways in the Brain (eds Iverson, L. L., Iverson, S. D. & Snyder, S. H.), pp. 233–314. New York: Plenum Press.CrossRefGoogle Scholar
Baldessarini, R. J. & Marsh, E. (1990) Fluoxetine and side effects. Archives of General Psychiatry, 47, 191–192.CrossRefGoogle ScholarPubMed
Baldwin, D., Fineberg, N. & Montgomery, S. (1991) Fluoxetine, fluvoxamine and extrapyramidal tract disorders. International Clinical Psychopharmacology, 6, 51–58.CrossRefGoogle ScholarPubMed
Balsara, J. J., Jadhav, J. H. & Chandorkar, A. G. (1979) Effect of drugs influencing central serotonergic mechanisms on haloperidol-induced catalepsy. Psychopharmacology, 62, 67–69.CrossRefGoogle ScholarPubMed
Bernick, C. (1988) Methysergide-induced akathisia. Clinical Neuropharmacology, 11, 87–89.CrossRefGoogle ScholarPubMed
Bersani, G., Grispini, A., Pasini, A., et al (1986) Neuroleptic induced extrapyramidal side effects: clinical perspectives with ritanserin (R 55 667), a new selective 5-HT2 receptor blocking agent. Current Therapeutic Research, 40, 492–499.Google Scholar
Blackburn, T. P., Cox, B. & Lee, T. F. (1982) Involvement of a central dopaminergic system in 5-methoxy-N,N-dimethyltryptamine-induced turning behaviour in rats with lesions of the dorsal raphe nuclei. Psychopharmacology, 78, 261–265.CrossRefGoogle ScholarPubMed
Bleich, A., Brown, S., Kahn, R., et al (1988) The role of serotonin in schizophrenia. Schizophrenia Bulletin, 14, 297–315.CrossRefGoogle ScholarPubMed
Bobillier, P., Seguin, S., Petitjean, F., et al (1976) The raphe nuclei of the cat brain stem: a topographical atlas of their afferent projections as revealed by autoradiography. Brain Research, 113, 449–486.CrossRefGoogle Scholar
Bonate, P. L. (1991) Review. Serotonin receptor subtypes: functional, physiological, and clinical correlates. Clinical Neuropharmacology, 14, 1–16.CrossRefGoogle ScholarPubMed
Bouchard, R. H., Pourcher, E. & Vincent, P. (1989) Fluoxetine and extrapyramidal side effects. American Journal of Psychiatry, 146, 1352–1353.Google Scholar
Bourgoin, S., Enjalbert, A., Adrien, J., et al (1977) Midbrain raphe lesions in the newborn rat: II. Biochemical alteration in serotoninergic innervation. Brain Research, 127, 111–126.CrossRefGoogle ScholarPubMed
Brandon, S. (1969) Unusual effects of fenfluramine. British Medical Journal, 4, 557–558.CrossRefGoogle ScholarPubMed
Brod, T. M. (1989) Fluoxetine and extrapyramidal side effects. American Journal of Psychiatry, 146, 1353.CrossRefGoogle Scholar
Budman, C. L. & Bruun, R. D. (1991) Persistent dyskinesia in a patient receiving fluoxetine. American Journal of Psychiatry, 148, 1403.Google Scholar
Carlsson, A. & Lindquist, M. (1963) Effect of chlorpromazine and haloperidol on formation of 3-methoxytryptamine and normetanephrine in mouse brain. Acta Pharmacologica et Toxicologica, 20, 140–144.CrossRefGoogle ScholarPubMed
Carter, C. J. & Pycock, C. J. (1977) Possible importance of 5-hydroxytryptamine in neuroleptic-induced catalepsy in rats. British Journal of Pharmacology, 60, 267–268.Google ScholarPubMed
Carter, C. J. & Pycock, C. J. (1978) Differential effects of central serotonin manipulation on hyperactive and stereotyped behaviour. Life Sciences, 23, 953–960.CrossRefGoogle ScholarPubMed
Ceulemans, D. L. S., Gelders, Y. G., Hoppenbrouwers, M. L. J. A., et al (1985) Effects of serotonin antagonism in schizophrenia. A pilot study with setoperone. Psychopharmacology, 85, 329–332.CrossRefGoogle ScholarPubMed
Chase, T. N., Ng, L. K. Y. & Watanabe, A. M. (1972) Parkinson's disease. Modification by 5-hydroxytryptophan. Neurology, 22, 479–484.CrossRefGoogle ScholarPubMed
Chen, J., Paredes, W., van Praag, H. M., et al (1992) Serotonin denervation enhances responsiveness of presynaptic dopamine efflux to acute clozapine in nucleus accumbens but not in caudate-putamen. Brain Research, 582, 173–179.CrossRefGoogle ScholarPubMed
Cheshire, R. M., Cheng, J. T. & Teitelbaum, P. (1982) Antiserotonergic drugs reinstate galloping forward locomotion produced by pontine tegmentum damage in rats. In Serotonin in Biological Psychiatry (eds Ho, B. T., Shoolar, J. C. & Usdin, E.), pp. 315–317. New York: Raven Press.Google Scholar
Chouinard, G. & Sultan, S. (1992) A case of Parkinson's disease exacerbated by fluoxetine. Human Psychopharmacology, 7, 63–66.CrossRefGoogle Scholar
Committee on Safety of Medicine (1993) Dystonia and withdrawal symptoms with paroxetine. Current Problems in Pharmacovigilance, 19, 1.Google Scholar
Costall, B., Fortune, D. H., Naylor, R. J., et al (1975) Serotonergic involvement with neuroleptic catalepsy. Neuropharmacology, 14, 859–868.CrossRefGoogle ScholarPubMed
Crespi, F., Martin, K. F. & Marsden, C. A. (1988) Simultaneous in vivo voltametric measurement of striatal extracellular DOPAC and 5HIAA levels: effect of electrical stimulation of dopamine and 5-HT neuronal pathways. Neuroscience Letters, 90, 285–291.CrossRefGoogle Scholar
Davies, J. & Tongroach, P. (1978) Neuropharmacological studies on the nigro-striatal and raphe-striatal system in the rat. European Journal of Pharmacology, 51, 91–100.CrossRefGoogle ScholarPubMed
DeSimoni, M. G., Dal Toso, G., Fodritto, F., et al (1987) Modulation of striatal dopamine metabolism by the activity of dorsal raphe serotonergic afferences. Brain Research, 411, 81–88.CrossRefGoogle Scholar
Downs, D. A., Harringan, S. E. & Heffner, T. G. (1985) Buspirone effects in a primate model of extrapyramidal dysfunction. Society of Neuroscience (abstr.), 11, 426.Google Scholar
Drago, F., Canonico, P. L. & Scapagnini, U. (1986) Neuromodulatori e modelli sperimentali di patologia extrapiramidale. In Norbo di Parkinson e Malattie Extrapiramidali (eds Caraceni, T. & Nappi, G.), pp. 69–78. Pavia: Mediche Italiane.Google Scholar
Dray, A., Gonye, T. J., Oakley, N. R., et al (1976) Evidence for the existence of a raphe projection to the substantia nigra in rat. Brain Research, 113, 45–57.CrossRefGoogle Scholar
Dray, A., & Davis, J., Oakley, N. R., et al (1978) The dorsal and medial raphe projections to the substantia nigra in the rat: electrophysiological, biochemical and behavioural observations. Brain Research, 151, 431–442.CrossRefGoogle Scholar
Ennis, E., Kemp, J. P. & Cox, B. (1981) Characterisation of inhibitors 5-hydroxytryptamine receptors that modulate dopamine release in the striatum. Journal of Neurochemistry, 36, 1515–1520.CrossRefGoogle Scholar
Fallon, B. A. & Liebowitz, M. R. (1991) Fluoxetine and extrapyramidal symptoms in CNS lupus. Journal of Clinical Psychopharmacology, 11, 147–148.CrossRefGoogle ScholarPubMed
Fink, H., Morgenstern, R. & Oelssner, W. (1984) Clozapine – a serotonin antagonist? Pharmacology, Biochemistry and Behaviour, 20, 513–517.CrossRefGoogle ScholarPubMed
Fuller, R. W., Perry, K. W. & Clemens, J. A. (1976) Elevation of 3,4-dihydroxyphenylacetic acid concentration in rat brain and stimulation of prolactin secretion by fenfluramine: evidence of antagonism at dopamine receptor sites. Journal of Pharmacy and Pharmacology, 28, 643–644.CrossRefGoogle ScholarPubMed
Gabay, S. (1981) Serotonergic-dopaminergic interactions: implications for hyperkinetic disorders. In Advances in Experimental Medicine and Biology (eds Haber, B., Gaber, S., Issidorides, M. R., et al), pp. 285–291. New York: Plenum Press.Google Scholar
Garelis, E., Young, S. N., Lal, S., et al (1974) Monoamine metabolites in lumbar CSF: the question of their origin in relation to clinical studies. Brain Research, 79, 1–8.CrossRefGoogle ScholarPubMed
Gately, P. F., Poon, S. L., Segal, D. S., et al (1985) Depletion of brain serotonin by 5, 7-dihydroxytryptamine alters the response to amphetamine and the habituation of locomotor activity in rats. Psychopharmacology, 87, 400–405.CrossRefGoogle ScholarPubMed
Gelders, Y., Ceulemans, D. L. S., Reyntjens, A., et al (1985) The influence of selective serotonin antagonism on conventional neuroleptic therapy. Proceedings of the Fourth World Congress of Biological Psychiatry, Philadelphia, September 1985, p. 417.Google Scholar
Gernaat, H. B., Van de Woude, J. & Touw, D. J. (1991) Fluoxetine and parkinsonism in patients taking carbamazepine. American Journal of Psychiatry, 148, 1604–1605.Google ScholarPubMed
Geyer, M. A., Puerto, A., Menkes, D. B., et al (1976) Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways. Brain Research, 106, 257–269.CrossRefGoogle ScholarPubMed
Goldstein, J. M., Litwin, L. C. & Malick, J. B. (1987a) Ritanserin increases spontaneous activity of A9 and A10 dopamine neurons (abstr.). Federation Proceedings, 46, 966.Google Scholar
Goldstein, J. M., Litwin, L. C., Sutton, E. B., et al (1987b) Effects of ICI 169, 369, a selective 5-HT2 antagonist, in electrophysiological tests predictive of antipsychotic activity. Society of Neuroscience Abstracts, 13, 1649.Google Scholar
Hajdu, F., Hassler, R. & Bak, I. J. (1973) Electron microscopic study of the substantia nigra and the strio-nigral projection in the rat. Zeitschrift für Zellforsch., 146, 207–221.CrossRefGoogle ScholarPubMed
Hall, C. D., Weiss, E. A., Morris, C. E., et al (1972) Rapid deterioration in patients with parkinsonism following tryptophanpyridoxine administration. Neurology, 22, 231–237.CrossRefGoogle ScholarPubMed
Halperin, J. R. & Murphy, B. (1991) Extrapyramidal reaction to ondansetron. Cancer, 69, 1275.CrossRefGoogle Scholar
Hamilton, M. S. & Opler, L. A. (1992) Akathisia, suicidality and fluoxetine. Journal of Clinical Psychiatry, 53, 401–406.Google ScholarPubMed
Herve, D., Pickel, V. M., Joh, T. H., et al (1987) Serotonin axon terminals in the ventral tegmental area of the rat: fine structure and synaptic input to dopaminergic neurons. Brain Research, 435, 71–83.CrossRefGoogle ScholarPubMed
Hetey, L., Kurdin, V. S., Shemanow, A. Y., et al (1985) Presynaptic dopamine and serotonin receptors modulating tyrosine hydroxylase activity in synaptosomes of nucleus accumbens of rats. European Journal of Pharmacology, 113, 1–10.CrossRefGoogle ScholarPubMed
Hetey, L., & Drescher, K. (1986) Influence of antipsychotics on presynaptic receptors modulating the release of dopamine in synaptosomes of the nucleus accumbens of rats. Neuropharmacology, 25, 1103–1109.CrossRefGoogle ScholarPubMed
Jacobs, B. L., Foote, S. L. & Bloom, F. E. (1978) Differential projections of the neurones within the dorsal raphe nucleus of the rat: a horseradish peroxidase (HRP) study. Brain Research, 147, 149–153.CrossRefGoogle Scholar
Jacobs, M. B. (1983) Diltiazam and akathisia. Annals of Internal Medicine, 99, 794–795.CrossRefGoogle Scholar
Jansen, , Steur, E. N. H. (1993) Increase of parkinsonian disability after fluoxetine medication. Neurology, 43, 211–213.CrossRefGoogle Scholar
Jenner, P., Sheehy, M. & Marsden, C. D. (1983) Noradrenaline and 5-hydroxytryptamine modulation of brain dopamine function: implications for the treatment of Parkinson's disease. British Journal of Clinical Pharmacology, 15 (suppl.), 2779–2898.CrossRefGoogle ScholarPubMed
Jones, D. L., Mogenson, G. J. & Wu, M. (1981) Injections of dopaminergic, cholinergic, serotonergic and GABAergic drugs into the nucleus accumbens: effect on locomotor activity. Neuropharmacology, 20, 29–37.CrossRefGoogle Scholar
Knapp, S. & Mandell, A. J. (1976) Coincidence of blockade of synaptosomal 5-hydroxytryptamine uptake and decrease in tryptophan hydroxylase activity: effects of fenfluramine. Journal of Pharmacology and Experimental Therapeutics, 198, 123–132.Google ScholarPubMed
Knott, P. J. & Hutson, P. H. (1982) Stress-induced stereotypy in the rat: neuropharmacological similarities to Tourette Syndrome, pp. 223–238. New York: Raven Press.Google ScholarPubMed
korsgaard, S., Gerlach, J. & Christensson, E. (1985) Behavioural aspects of serotonin-dopamine interaction in monkey. European Journal of Pharmacology, 118, 245–252.CrossRefGoogle ScholarPubMed
korsgaard, S., Gerlach, J. & Friis, T. (1986) Effects of mianserin in neurolepticinduced parkinsonism. Psychopharmacology, 88, 109–111.CrossRefGoogle ScholarPubMed
Lee, E. H. Y. & Geyer, M. A. (1982) Selective effects of apomorphine on dorsal raphe neurons: a cytoflourimetric study. Brain Research Bulletin, 9, 719–725.CrossRefGoogle Scholar
Liebman, J. & Neale, R. (1980) Neuroleptic-induced acute dyskinesias in squirrel monkeys: correlation with propensity to cause extrapyramidal side effects. Psychopharmacology, 68, 25–29.CrossRefGoogle ScholarPubMed
Liebman, J., Gerhardt, S. C. & Gerber, R. (1989) Effects of 5-HT 1A agonists and 5-HT 2 antagonists on haloperidol-induced dyskinesias in squirrel monkeys: no evidence for reciprocal 5-HT-dopamine interaction. Psychopharmacology, 97, 456–461.CrossRefGoogle Scholar
Lipinski, J. F., Mallya, G., Zimmerman, R. N., et al (1989) Fluoxetine-induced akathisia: clinical and theoretical implications. Journal of Clinical Psychiatry, 50, 339–342.Google ScholarPubMed
Ludwig, C. L., Weinberger, D. R., Bruno, G., et al (1986) Buspirone, Parkinson's disease and locus ceruleous. Clinical Neuropharmacology, 9, 373–378.CrossRefGoogle Scholar
Maj, J., Mogilnicka, E. & Przewlocka, B. (1975) Antagonistic effect of cyproheptadine on neuroleptic-induced catalepsy. Pharmacology, Biochemistry and Behavior, 3, 25–27.CrossRefGoogle ScholarPubMed
Marsden, C. A. & Gulberg, H. C. (1973) The role of monoamines in rotation induced or potentiated by amphetamine after nigral, raphe and mesencephalic reticular lesions in the rat brain. Neuropharmacology, 12, 195–211.CrossRefGoogle ScholarPubMed
Meltzer, H. Y., Young, M., Metz, J., et al (1979) Extrapyramidal side effects and increased serum prolactin following fluoxetine, a new antidepressant. Journal of Neural Transmission, 45, 165–175.CrossRefGoogle ScholarPubMed
Miller, J. J., Richardson, T. L., Fibiger, H. C., et al (1975) Anatomical and electrophysiological identification of a projection from the mesencephalonic raphe to the caudate putamen in the rat. Brain Research, 97, 133–138.CrossRefGoogle Scholar
milson, J. A. & Pycock, C. J. (1976) Effects of drugs acting on cerebral 5-hydroxytryptamine mechanisms on dopamine-dependent turning behaviour in mice. British Journal of Pharmacology, 56, 77–85.CrossRefGoogle ScholarPubMed
Nicolaou, N., Garcia-Munoz, M., Arbuthnott, G., et al (1979) Interaction between serotonergic and dopaminergic systems in rats demonstrated by small unilateral lesions of the raphe nuclei. European Journal of Pharmacology, 57, 295–305.CrossRefGoogle ScholarPubMed
Opler, L. A. (1991) Drug treatment in schizophrenia: old issues and new developments. Einstein Quarterly Journal of Biological Medicine, 9, 10–13.Google Scholar
Palkovits, M., Brownstein, M. & Saavedra, J. M. (1974) Serotonin content of the brain stem nuclei in the rat. Brain Research, 80, 237–249.CrossRefGoogle ScholarPubMed
Porsolt, R. D. & Jalfre, M. (1981) Neuroleptic-induced acute dyskinesias in rhesus monkeys. Psychopharmacology, 75, 16–21.CrossRefGoogle ScholarPubMed
Povlsen, U. J., Noring, U., Lund, L. A., et al (1986) Effects of serotonergic and anticholinergic drugs in haloperidol-induced dystonia in Cebus monkeys. Clinical Neuropharmacology, 9, 84–90.CrossRefGoogle ScholarPubMed
Reccoppa, L., Welch, W. A. & Ware, M. R. (1990) Acute dystonia and fluoxetine. Journal of Clinical Psychiatry, 51, 487.Google ScholarPubMed
Samanin, R. & Garattini, S. (1979) The serotonergic system in the brain and its possible functional connections with other aminergic systems. Life Sciences, 17, 1201–1210.CrossRefGoogle Scholar
Sananman, M. L. (1974) Dyskinesia after fenfluramine. New England Journal of Medicine, 291, 422.Google ScholarPubMed
Tate, J. L. (1989) Extrapyramidal symptoms in a patient taking haloperidol and fluoxetine. American Journal of Psychiatry, 146, 399–400.Google Scholar
Teicher, M. H., Glod, C. & Cole, J. O. (1990) Emergence of intense suicidal preoccupation during fluoxetine treatment. American Journal of Psychiatry, 147, 207–210.Google ScholarPubMed
Van der Kooy, D. & Hattori, T. (1980) Dorsal raphe cells with collateral projections to the caudate-putamen and substantia nigra: a fluorescent retrograde double labelling study in rat. Brain Research, 186, 1–7.CrossRefGoogle Scholar
Waldmeier, P. C. & Delini-Stula, A. A. (1979) Serotonindopamine interactions in the nigrostriatal system. European Journal of Pharmacology, 55, 363–373.CrossRefGoogle ScholarPubMed
Westfall, T. C. & Tittermary, V. (1982) Inhibition of the electrically induced release of [3H] dopamine by serotonin from superfused rat striatal slices. Neurosciences Letters, 28, 205–209.CrossRefGoogle ScholarPubMed
Wils, V. (1992) Extrapyramidal symptoms in a patient treated with fluvoxamine. Journal of Neurology, Neurosurgery and Psychiatry, 55, 330–331.CrossRefGoogle Scholar
Yamaguchi, K., Nabeshima, T. & Kameyama, T. (1986) Potentiation of phencyclidine-induced dopamine-dependent behaviours in rats after pretreatments with serotonin-depletors. Journal of Pharmacobiodynamics, 9, 479–489.Google ScholarPubMed
Yamamoto, B. & Freed, C. R. (1984) Asymmetric dopamine and serotonin in nigro-striatal and limbic structures of trained circling rat. Brain Research, 297, 115–119.CrossRefGoogle Scholar
Zubenko, G. S., Cohen, B. M. & Lipinski, J. F. (1987) Antidepressant-induced akathisia. Journal of Clinical Psychopharmacology, 7, 254–257.CrossRefGoogle Scholar
Submit a response

eLetters

No eLetters have been published for this article.