The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Clinical Risk Following Abrupt and Gradual Withdrawal of Maintenance Neuroleptic Treatment
Abstract
BACKGROUND: Abrupt discontinuation of long-term psychotropic medication can be followed by a high risk of early relapse. This study aimed to quantify the relapse risk over time in patients with schizophrenia following discontinuation of maintenance neuroleptic treatment. METHODS: Data on the timing of relapses in patients with schizophrenia after withdrawal from neuroleptic therapy were located by a computerized literature search, combined with new data, and evaluated by survival analysis. RESULTS: Data were found for 1210 schizophrenic subjects: 1006 (795 inpatients and 211 outpatients) were withdrawn abruptly from oral neuroleptic therapy, and 204 discontinued treatment gradually (> or = 3 weeks) or stopped treatment with depot neuroleptic drugs. After abrupt discontinuation of oral medication, the risk of relapse reached 50% within 30 weeks, with remarkably little additional risk thereafter to 3.7 years; inpatients relapsed more rapidly than did outpatients (10 vs 18 weeks to a 25% relapse risk). In studies including subjects whose drug therapy was withdrawn abruptly (n = 49) vs gradually (n = 58), relapse was earlier after abrupt discontinuation (25% risk in 6 vs 10 weeks), with a persistent difference for at least 6 months. CONCLUSIONS: The relapse risk was high within 6 months of discontinuing oral neuroleptic therapy, particularly in hospitalized patients. Most patients who remained stable for 6 months continued to do so for long periods without medication, indicating clinical heterogeneity. Drug-withdrawal stressors, related to long-term pharmacodynamic adaptations, are implicated. Since the risk was lower after gradually discontinuing oral neuroleptic therapy or stopping depot injections, early relapse may be spared by a slow removal of drugs.
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In the citing paper
“Abruptly stopping antipsychotic medication is the method most likely to induce relapse and withdrawal symptoms.3,4”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [3]
In the citing paper
“It appears that relapse rates are raised in the discontinuation group for 1–3 years following a switch to placebo, before converging with relapse rates of medicated patients thereafter.3,56–59”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [3]
In the citing paper
“That is, relapses are not distributed evenly across time but tend to occur predominantly around the point of drug cessation.”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [3]
Citations
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Three-Year Outcomes for Maintenance Therapies in Recurrent Depression
Frank, E. (1990) · Archives of General Psychiatry · doi:10.1001/archpsyc.1990.01810240013002 · Cited by 1,294
Statistical Methods in Epidemiology
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Delattre, O., Zucman‐Rossi, J., Melot, T., Sastre‐Garau, X., Zucker, J., Lenoir, G., Ambros, P. F., Sheer, D., Turc‐Carel, C., Triche, T. J., et al. (1994) · New England Journal of Medicine · doi:10.1056/nejm199408043310503 · Cited by 1,104
One hundred years of schizophrenia: a meta-analysis of the outcome literature
Hegarty, J. D., Baldessarini, R. J., Tohen, M. F., WATERNAUX, C. M., & Oepen, G. (1994) · American Journal of Psychiatry · doi:10.1176/ajp.151.10.1409 · Cited by 771
Oates, J. A., Wood, A. J. J., Baldessarini, R. J., & Frankenburg, F. R. (1991) · New England Journal of Medicine · doi:10.1056/nejm199103143241107 · Cited by 689
The Continuing Unethical Use of Placebo Controls
Rothman, K. J., & Michels, K. B. (1994) · New England Journal of Medicine · doi:10.1056/nejm199408113310611 · Cited by 669
Drug and Sociotherapy in the Aftercare of Schizophrenic Patients
Hogarty, G. E. (1974) · Archives of General Psychiatry · doi:10.1001/archpsyc.1974.01760170005001 · Cited by 573
Significance of Neuroleptic Dose and Plasma Level in the Pharmacological Treatment of Psychoses
Baldessarini, R. J. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800250095013 · Cited by 545
II. A Randomised Controlled Trial of Prophylactic Neuroleptic Treatment
Crow, T. J., Macmillan, J. F., Johnson, A. L., & Johnstone, E. C. (1986) · The British Journal of Psychiatry · doi:10.1192/bjp.148.2.120 · Cited by 491
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Leucht, S., Tardy, M., Komossa, K., Heres, S., Kissling, W., Salanti, G., & Davis, J. M. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60239-6 · Cited by 931
Barnes, T. R. E., Drake, R., Paton, C., Cooper, S. J., Deakin, J. F. W., Ferrier, I. N., Gregory, C. J., Haddad, P. M., Howes, O. D., Jones, I. R., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119889296 · Cited by 615
Viguera, A. C., Nonacs, R., Cohen, L. S., Tondo, L., Murray, A., & Baldessarini, R. J. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.2.179 · Cited by 488
Barnes, T. R. E. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881110391123 · Cited by 369
“DSM-IV diagnostic criteria for schizophrenia include continuous signs of the disturbance for at least 6 months, including at least 1 month of symptoms, and for ICD-10 diagnosis, symptoms must be clearly present for most of the time during a period of 1 month or more.”
BackgroundAntidepressant-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
Metadata
- Authors
- Viguera, A. C.
- Affiliations
- Harvard University (US)
- Corresponding author
- Viguera, Adele C.
- ORCID
- Viguera, Adele C.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1997-01-01
- Volume
- 54
- Issue
- 1
- Pages
- 49
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2153434361
- Cited by
- 246
- References
- 49
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 9 · 2020: 10 · 2019: 10 · 2018: 10 · 2017: 6 · 2016: 6 · 2015: 14 · 2014: 8 · 2013: 13 · 2012: 14
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k05mh047370-25)
- National Institute of Mental Health (P01MH031154, MH-31154, MH47370)
- 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
- schizophrenia, neuroleptic withdrawal, abrupt discontinuation, relapse risk, long-term antipsychotic treatment, depot neuroleptics
- MeSH terms
- Administration, Oral, Ambulatory Care, Delayed-Action Preparations, Drug Administration Schedule, Female, Follow-Up Studies, Hospitalization, Humans, Injections, Intramuscular, Male, Recurrence, Risk Factors, Schizophrenia, Schizophrenic Psychology, Substance Withdrawal Syndrome, Antipsychotic Agents, Survival Analysis
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