The DOI matches its Crossref record; 62 of the 64 references it cites were found in a registry or an index.
Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal‐related relapse
Abstract
Objective: To examine the evidence that discontinuation of long‐term antipsychotic medication, including clozapine, may provoke a psychotic episode. Method: Databases were searched and citations scrutinised. Results: Evidence for a rapid onset psychosis (supersensitivity psychosis) following clozapine withdrawal was found and weaker evidence that this might occur with some other antipsychotic drugs. Some cases were reported in people without a psychiatric history. It appears that the psychosis may be a feature of drug withdrawal rather than the re‐emergence of an underlying illness, at least in some patients. Meta‐analyses of withdrawal studies have suggested that antipsychotic discontinuation may also increase the risk of relapse over and above the risk because of the underlying disorder, but not all individual studies show this effect. Mechanisms may relate to brain adaptations to long‐term drug use but data are sparse. Conclusion: These effects require further urgent research. Interventions to reduce morbidity after drug withdrawal need to be developed.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Ketamine (intravenous anesthetic) and esketamine (nasal spray) potentially produce psychological dependence and rapidly induce pharmacological tolerance [136-139].”
From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [137]
Citations
Cites
Neuroleptic Withdrawal in Schizophrenic Patients
Gilbert, P. L. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950150005001 · Cited by 434
Risk of Recurrence Following Discontinuation of Lithium Treatment in Bipolar Disorder
Suppes, T. (1991) · Archives of General Psychiatry · doi:10.1001/archpsyc.1991.01810360046007 · Cited by 392
Antidepressant-Induced Sexual Dysfunction
Gregorian, R. S., Golden, K. A., Bahce, A., Goodman, C., Kwong, W. J., & Khan, Z. M. (2002) · Annals of Pharmacotherapy · doi:10.1345/aph.1a195 · Cited by 320
Silvestri, S., Seeman, M. V., Negrete, J.-C., Houle, S., Shammi, C. M., Remington, G. J., Kapur, S., Zipursky, R. B., Wilson, A. A., Christensen, B. K., et al. (2000) · Psychopharmacology · doi:10.1007/s002130000532 · Cited by 311
Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics
(1980) · American Journal of Psychiatry · doi:10.1176/ajp.137.1.16 · Cited by 301
Dopaminergic supersensitivity after neuroleptics: time-course and specificity
Muller, P., & Seeman, P. (1978) · Psychopharmacology · doi:10.1007/bf00429171 · Cited by 271
Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment
Viguera, A. C. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830130055011 · Cited by 246 · cited 7×
“Dopamine receptor supersensitivity has been suggested as one such possible adaptation (48).”
BackgroundInfluentialSeeman, P., & Tallerico, T. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.6.876 · Cited by 237
Gitlin, M. J., Nuechterlein, K. H., Subotnik, K. L., Ventura, J., Mintz, J., Fogelson, D. L., Bartzokis, G., & Aravagiri, M. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.11.1835 · Cited by 216
Neuroleptic Withdrawal in Schizophrenic Patients
Baldessarini, R. J. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950150021002 · Cited by 194
Gitlin, M. J., Nuechterlein, K. H., Subotnik, K. L., Ventura, J., Mintz, J., Fogelson, D. L., Bartzokis, G., & Aravagiri, M. (2004) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/foc.2.1.122 · Cited by 183
Discontinuing lithium maintenance treatment in bipolar disorders: risks and implications
Baldessarini, R. J., Tondo, L., & Viguera, A. C. (1999) · Bipolar Disorders · doi:10.1034/j.1399-5618.1999.10106.x · Cited by 152
Lehtinen, V., Aaltonen, J., Koffert, T., Räkköläinen, V., & Syvälahti, E. K. G. (2000) · European Psychiatry · doi:10.1016/s0924-9338(00)00400-4 · Cited by 137
Gäebel, W., Jänner, M., Frommann, N., Pietźcker, A., Köpcke, W., Linden, M., Müller, P., Müller-Spahn, F., & Tegeler, J. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(01)00182-7 · Cited by 133
Severe cases of neuroleptic-induced supersensitivity psychosis
Chouinard, G. (1991) · Schizophrenia Research · doi:10.1016/0920-9964(91)90050-2 · Cited by 123
Diazepam Treatment of Early Signs of Exacerbation in Schizophrenia
Carpenter, W. T., Buchanan, R. W., Kirkpatrick, B. W., & Breier, A. F. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.2.299 · Cited by 117
A new bipolar spectrum concept: a brief review
Angst, J., & Gamma, A. (2002) · Bipolar Disorders · doi:10.1034/j.1399-5618.4.s1.1.x · Cited by 108
Drs. Chouinard and Jones Reply
Chouinard, G., & Jones, B. (1980) · American Journal of Psychiatry · doi:10.1176/ajp.137.8.992-a · Cited by 104
Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal
Shiovitz, T. M., Welke, T. L., Tigel, P. D., Anand, R., Hartman, R. D., Sramek, J. J., Kurtz, N. M., & Cutler, N. R. (1996) · Schizophrenia Bulletin · doi:10.1093/schbul/22.4.591 · Cited by 104 · cited 2×
“(31) may be because of the fact that subjects were only taking clozapine as part of pharmacokinetic studies for 28 days at a relatively low dose (200 mg daily) and the patient’s previous antipsychotic was restarted after 2 days.”
BackgroundThe Natural Course of Schizophrenia and Effective Maintenance Drug Treatment
Davis, J. M., & Andriukaitis, S. M. (1986) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-198602001-00002 · Cited by 98
Psychopathology Induced by “Speed Drugs”
Schiørring, E. (1981) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(81)80018-4 · Cited by 91
Supersensitivity psychosis in schizophrenic patients after sudden clozapine withdrawal
Ekblom, B., Eriksson, K., & Lindstr�m, L. H. (1984) · Psychopharmacology · doi:10.1007/bf00464798 · Cited by 88
Clozapine Withdrawal Resulting in Delirium With Psychosis
Stanilla, J. K., de León, J., & Simpson, G. M. (1997) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v58n0603 · Cited by 87
van Reekum, R., Conn, D. K., Clarke, D. E., Cohen, T., Ostrander, L., Herrmann, N., & Eryavec, G. M. (2002) · International Psychogeriatrics · doi:10.1017/s1041610202008396 · Cited by 74
WITHDRAWAL FROM NEUROLEPTIC DRUGS
Brooks, G. W. (1959) · American Journal of Psychiatry · doi:10.1176/ajp.115.10.931 · Cited by 73
Relapse following clozapine withdrawal: effect of neuroleptic drugs and cyproheptadine
Meltzer, H. Y., Lee, M. A., Ranjan, R., Mason, E. A., & Cola, P. A. (1996) · Psychopharmacology · doi:10.1007/bf02245619 · Cited by 68
Margolese, H. C., Chouinard, G., Beauclair, L., & Bélanger, M.-C. (2002) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200208000-00003 · Cited by 61
Maina, G., Albert, U., Ziero, S., & Bogetto, F. (2003) · International Clinical Psychopharmacology · doi:10.1097/01.yic.0000047784.24295.2b · Cited by 61
Clozapine withdrawal effects and receptor profiles of typical and atypical neuroleptics
Verghese, C., de León, J., Nair, C., & Simpson, G. M. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00215-4 · Cited by 59
Pharmacological long-term treatment strategies in first episode schizophrenia
Gäebel, W., Möller, H., Buchkremer, G., Ohmann, C., Riesbeck, M., Wölwer, W., von Wilmsdorff, M., Bottlender, R., & Klingberg, S. (2004) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-004-0509-y · Cited by 57
Clozapine withdrawal rebound psychosis.
Borison, R. L., Diamond, B. I., Sinha, D., Gupta, R. P., & Ajiboye, P. O. (1988) · PubMed · Cited by 56
Effects of switching inpatients with treatment-resistant schizophrenia from clozapine to risperidone
Still, D. J., Dorson, P. G., Crismon, M. L., & Pousson, C. (1996) · Psychiatric Services · doi:10.1176/ps.47.12.1382 · Cited by 54
Rebound psychosis: Effect of discontinuation of antipsychotics in Parkinson's disease
Fernandez, H. H., Trieschmann, M. E., & Okun, M. S. (2004) · Movement Disorders · doi:10.1002/mds.20260 · Cited by 51
Tollefson, G. D., Dellva, M. A., Mattler, C. A., Kane, J. M., Wirshing, D. A., & Kinon, B. J. (1999) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199910000-00007 · Cited by 50
Practical Psychiatric Epidemiology
Prince, M., Stewart, R., Ford, T., & Hotopf, M. (2003) · Oxford University Press eBooks · doi:10.1093/med/9780198515517.001.0001 · Cited by 50
Neuronal basis of neuroleptic-induced extrapyramidal side effects.
Ossowska, K. (2002) · PubMed · Cited by 48
The effect of lithium in bipolar disorder: a review of recent research evidence
Maj, M. (2003) · Bipolar Disorders · doi:10.1034/j.1399-5618.2003.00002.x · Cited by 47
RESULTS OF SIMULTANEOUS ABRUPT WITHDRAWAL OF ATARAXICS IN 500 CHRONIC PSYCHOTIC PATIENTS
Judah, L. N., JOSEPHS, Z. M., & Murphree, O. D. (1961) · American Journal of Psychiatry · doi:10.1176/ajp.118.2.156 · Cited by 46
Supersensitivity psychosis and tardive dyskinesia: a survey in schizophrenic outpatients.
Chouinard, G., Annable, L., & Ross‐Chouinard, A. (1986) · PubMed · Cited by 45
Is there a limbic system equivalent of tardive dyskinesia?
Kl, D., & Rosenberg, G. S. (1979) · PubMed · Cited by 45
The Concept of Supersensitivity Psychosis
Kirkpatrick, B. W., Alphs, L. D., & Buchanan, R. W. (1992) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-199204000-00009 · Cited by 41
Intermittent medication ‐ an alternative?
Gäebel, W. (1994) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1994.tb05863.x · Cited by 32
Conversions From Clozapine to Other Antipsychotic Drugs
Gardner, D. M. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950240089014 · Cited by 31
Supersensitivity psychosis in patients with schizophrenia after sudden olanzapine withdrawal.
Llorca, P., Vaïva, G., & Lançon, C. (2001) · PubMed · Cited by 31
Neuroleptic‐induced supersensitivity psychosis in patients with bipolar affective disorder
Steiner, W., Laporta, M., & Chouinard, G. (1990) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1990.tb05477.x · Cited by 26
What is the clinical significance of the discontinuation syndrome seen with clozapine?
Goudie, A. J. (2000) · Journal of Psychopharmacology · doi:10.1177/026988110001400212 · Cited by 24
Lack of Behavioral Supersensitivity to d-Amphetamine After Pimozide Withdrawal
van Kammen, D. P. (1980) · Archives of General Psychiatry · doi:10.1001/archpsyc.1980.01780160057006 · Cited by 23
Neuroleptic-induced supersensitivity psychosis: retrospective study of schizophrenic inpatients.
Hunt, J. I., Singh, H., & Simpson, G. M. (1988) · PubMed · Cited by 21
Neuroleptic withdrawal in patients meeting criteria for supersensitivity psychosis.
Singh, H., Ji, H., Vitiello, B., & Gm, S. (1990) · PubMed · Cited by 21
Drug Withdrawal in Chronic Schizophrenic Patients
Weinberger, D. R., Bigelow, L. B., KLEIN, S. T., & Wyatt, R. J. (1981) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-198105000-00002 · Cited by 20
Reserpine Withdrawal Psychosis
Kent, T. A., & WILBER, R. D. (1982) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-198208000-00011 · Cited by 20
Basic and clinical studies of neuroleptic-induced supersensitivity psychosis and dyskinesia.
Diamond, B. I., & Borison, R. L. (1986) · PubMed · Cited by 19
Reserpine withdrawal psychosis: the possible role of denervation supersensitivity of receptors.
Kent, T. A., & Wilber, R. D. (1982) · PubMed · Cited by 18
Psychosis after neuroleptic withdrawal in a manic-depressive patient
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.1.105 · Cited by 16
Melaine Johns Cupp, Toxicology and Clinical Pharmacology of Herbal Products
Sarker, S. D. (2002) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357021778358 · Cited by 15
Switching between Clozapine and Risperidone Treatment
Gardner, D. M., Baldessarini, R. J., Benzo, J., Zarate, C. A., & Tohen, M. F. (1997) · The Canadian Journal of Psychiatry · doi:10.1177/070674379704200419 · Cited by 15
Rebound Psychoses following the Discontinuation of a High Potency Neuroleptic
Kahne, G. J. (1989) · The Canadian Journal of Psychiatry · doi:10.1177/070674378903400312 · Cited by 14
Long-term maintenance treatment in chronic schizophrenia. Some observations on outcome and duration.
Johnson, D. A. (1981) · PubMed · Cited by 10
Apud, J. A., Egan, M. F., & Wyatt, R. J. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(02)00338-9 · Cited by 8
Conventional Antipsychotic Prescription in Unipolar Depression, II
Mortimer, A. M., Martin, M., Vega, J. A. W., & Tyson, P. J. (2003) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v64n0608 · Cited by 8
Medical Effects of Abrupt Withdrawal of Neuroleptic Therapy
Lacoursiere, R. B. (1978) · JAMA · doi:10.1001/jama.1978.03290020031010 · Cited by 1
Medical effects of abrupt withdrawal of neuroleptic therapy
Lacoursiere, R. (1978) · JAMA · doi:10.1001/jama.240.2.109c · Cited by 1
Research works printed but not linked: 2
- Franks MA, 2005, The consequences of suddenly stopping psychotropic medication in bipolar disorder, Bipolar Disorders, 4, 11
- 10.1345/aph.1A440 · DOI · Paper page
Cited by
Sorted by citations
The nature of relapse in schizophrenia
Emsley, R. A., Chiliza, B., Asmal, L., & Harvey, B. H. (2013) · BMC Psychiatry · doi:10.1186/1471-244x-13-50 · Cited by 481
Huhn, M., Tardy, M., Spineli, L. M., Kissling, W., Förstl, H., Pitschel-Walz, G., Leucht, C., Samara, M., Dold, M., Davis, J. M., et al. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.112 · Cited by 333
What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?
Correll, C. U., Rubio, J. M., & Kane, J. M. (2018) · World Psychiatry · doi:10.1002/wps.20516 · Cited by 324
The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal
Brissos, S., Veguilla, M. R., Taylor, D., & Balanzá-Martinez, V. (2014) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125314540297 · Cited by 297
Maintenance treatment with antipsychotic drugs for schizophrenia
Leucht, S., Tardy, M., Komossa, K., Heres, S., Kissling, W., & Davis, J. M. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008016.pub2 · Cited by 293
Metadata
- Authors
- Moncrieff, J.
- Affiliations
- University College London (GB)
- Corresponding author
- Moncrieff, J.
- ORCID
- Moncrieff, J.
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2006-03-23
- Volume
- 114
- Issue
- 1
- Pages
- 3-13
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W2168608597
- Cited by
- 231
- References
- 64
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 23 · 2020: 14 · 2019: 13 · 2018: 10 · 2017: 8 · 2016: 18 · 2015: 19 · 2014: 13 · 2013: 14 · 2012: 11
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- antipsychotic withdrawal, clozapine, antipsychotic discontinuation, psychosis relapse, drug withdrawal
- MeSH terms
- Clozapine, Humans, Long-Term Care, Psychoses, Substance-Induced, Psychotic Disorders, Recurrence, Risk Factors, Substance Withdrawal Syndrome, Antipsychotic Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review