The existence of discontinuation syndromes following treatment with neuroleptic (antipsychotic) drugs was first outlined in the mid-1960s but the effects of such syndromes have been neglected since then. We have pursued evidence for the existence and nature of discontinuation syndromes following neuroleptics through reports of difficulties following the use of dopamine blocking anti-emetics, the use of chlorpromazine to treat tuberculosis, the use of antidepressant-neuroleptic combinations in affective disorders, the occurrence of tardive syndromes and studies designed to establish the existence of discontinuation syndromes in schizophrenia. Combined these bodies of data point strongly to the existence of discontinuation syndromes after cessation of treatment with neuroleptics which may involve features other than motor dyskinesias. There is at present little evidence on the relative frequency of such syndromes or predisposing factors. The area needs research input to establish the nature of the syndromes that may result, their frequency, predisposing factors and best methods of treatment.
Antkiewicz-Michaluk L., Karolewicz B., Michaluk J., Vetulani J. (1995) Differences between haloperidol and pimozide-induced withdrawal syndrome: a role for Ca2+ channels. Eur J Pharmac294: 459-467
2.
Baldessarini R.J., Viguera A.C. (1995) Neuroleptic withdrawal in schizophrenic patients . Archs Gen Psychiat52: 189-192
3.
Baldessarini R.J., Gardner D.M., Garver D.L. (1995) Conversions from clozapine to other antipsychotic drugs. Archs Gen Psychiat52: 1071-1072
4.
Barrow N., Childs A. (1986) Anti-tardive dyskinesia effect of verapamil. Am J Psychiat143:1485
5.
Battegay R. (1966) Drug dependence as a criterion for differentiation of psychotropic drugs. Comp Psychiat7: 501-509
6.
Battegay R. (1967) Drug dependence as a criterion for differentiation of psychotropic drugs. In Brill H, Cole J O, Deniker P, Hippius H, Bradley P B (eds), NeuropsychopharmacologyExcerpta Medica, Amsterdam, pp. 244-252
7.
Carlsson A., Svensson A., Carlsson M.L. (1993) Future strategies in the discovery of new antipsychotic drugs. In Brunello N, Medlewicz J, Racagni G (eds), New generation of antipsychotic drugs: novel mechanisms of action . Karger, Basel, pp. 103-117
8.
Carpenter W.T., Tamminga CA (1995) Why neuroleptic withdrawal in schizophrenia? Archs Gen Psychiat52: 192-193
9.
Chouinard G., Jones B. (1980) Neuroleptic induced supersensitivity psychosis: clinical and pharmacologic characteristics. Am J Psychiat137: 16-21
Dilsaver S.C., Fienberg M., Greden J.F. (1983) Antidepressant withdrawal syndromes treated with anticholinergic agents. Am J Psychiat140: 249-251
13.
Gallant D.M., Edwards C.G., Bishop M.P., Galbraith G.C. (1964) Withdrawal symptoms after abrupt cessation of antipsychotic compounds: clinical confirmation in chronic schizophrenics. Am J Psychiat121: 491-493
14.
Gilbert PL, Harris J., McAdams LA, Jeste DV (1995) Neuroleptic withdrawal in schizophrenic patients . Archs Gen Psychiat52: 173-188
15.
Goode D.J., Corbett W T, Schey H M, Suh S.H., Woodie B., Morris D.L., Morrissey L. (1981) Breast cancer in hospitalized psychiatric patients . Am J Psychiat138: 804-806
16.
Goodwm G.M. (1994) Recurrence of manic-depression after lithium withdrawal . Br J Psychiat164: 149-152
17.
Greden J.F., Tandon R. (1995) Long-term treatment for lifetime disorders : Archs Gen Psychiat52:197-200
18.
Greenberg L.M., Roth S. ( 1966) Differential effects of abrupt versus gradual withdrawal of chlorpromazine in hospitalized chronic schizophrenic patients. Am J Psychiat123: 221-226
19.
Grimes J.D. (1981) Parkinsonism and tardive dyskinesia associated with longterm metoclopramide therapy. N Engl J Med305: 1417
20.
Hollister L. (1998) From hypertension to psychopharmacology. A serendipitous career. In Healy D (ed.), The psychopharmacolgists, Vol. 2. Chapman and Hall, London
21.
Hollister L.E., Eikenberry D.T., Raffel S. (1960) Chlorpromazine in nonpsychotic patients with pulmonary tuberculosis. Am Rev Resp Dis81: 562-566
22.
Jeste D.V., Caligiuri M.P. (1993) Tardive dyskinesia. Schizophr Bull19: 303-315
Lader M. (1983) Benzodiazepine withdrawal states. In Trimble M R (ed.), Benzodiazepines divided . John Wiley, New York, pp.17-31
25.
Melnyk WT, Worthington AG, Laverty SG (1965) Abrupt withdrawal of chlorpromazine and thioridazine from schizophrenic inpatients. Can Psychiat Ass J11: 410-413
26.
Meltzer HY (1995) Neuroleptic withdrawal in schizophrenic patients. An idea whose time has come. Archs Gen Psychiat52; 200-202
27.
Meltzer H.Y. (1997) Clozapine withdrawal: serotonergic or dopaminergic mechanisms? Archs Gen Psychiat54: 760-761
28.
Meltzer H.Y., Lee M.A., Ranjan R., Mason E.D., Cola PA ( 1996) Relapse following clozapine withdrawal: effect of cyproheptadine plus neuroleptic. Psychopharmacology124: 176-187
29.
Noll A.M., Pinsky D. (1991) Withdrawal effects of metoclopramide. West J Med154: 726-728
30.
Nuechterlein K.H., Gitlin M.J., Subotnik K.L. (1995) The early course of schizophrenia and long-term maintenance neuroleptic therapy. Archs Gen Psychiat52: 203-205
31.
O'Brien ET, McKinnon I. (1972) Propranolol withdrawal in hypertension : propranolol and polythiazide in the treatment of hypertension. Br Heart J34: 1042-1044
32.
Patel M. (1986) Long term neurologic complications of metoclopramide . N Y St J Med86: 210
33.
Sachdev P. (1995) The epidemiology of drug-induced akathisia: Part II. Chronic, tardive and withdrawal akathiasis. Schizophr Bull21: 451-461
34.
Shearer R.M., Bownes I.T., Curran P. (1984) Tardive akathisia and agitated depression during metoclopramide therapy. Acta Psychiat Scan70: 428-431
35.
Simpson G.N., Amin M., Kunz E. ( 1965) Withdrawal effects of phenothiazines. Comp Psychiat6: 347-351
36.
Suppes T., Baldessarini R.J., Faedda G.L., Tohen M. (1991) Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Archs Gen Psychiat48: 1082-1088
37.
Viguera A.C., Baldessarini R.J., Hegarty J.D., van Kammen D.P., Tohen M. (1997) Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment. Archs Gen Psychiat54: 49-55
38.
Wang D.Y., Stepniewska K.A., Allen D.S., Fentiman I.S., Bulbrook R.D., Kwa H.G., De Stavola B.L., Reed M.J. (1995) Serum prolactin levels and their relationship to survival in women with operable breast cancer. J Clin Epidemiol48: 959-968
39.
World Health Organization (1965) Expert Committee on Dependence Producing Drugs, 14th Report, WHO Technical Report cir. 312. World Health Organization, Geneva
40.
Wyatt R.J. (1995) Risk of withdrawing antipsychotic medications. Archs Gen Psychiat52: 205-298
