Why is it so difficult to stop psychiatric drug treatment?
Abstract
In this paper, I argue that the problems that occur after discontinuation or reduction of long-term psychiatric drug treatment may be caused by the process of drug withdrawal itself, rather than representing the course of the underlying illness. Adverse effects induced by discontinuation of psychiatric medication include: (1) a somatic discontinuation syndrome that includes psychological symptoms which may be mistaken for relapse, (2) a rapid onset psychotic reaction after withdrawal of both conventional neuroleptic drugs and some atypicals, notably clozapine (sometimes referred to as supersensitivity psychosis), (3) a psychological reaction to withdrawal, which may be mistaken for relapse or may itself precipitate relapse, (4) a genuine relapse of the underlying condition precipitated by the process of withdrawal. The implications of these effects include the possibility that much of the research on maintenance treatment is flawed and that the recurrent nature of psychiatric conditions may sometimes be iatrogenic. If withdrawal induced adverse effects could be effectively managed, the success of drug discontinuation might be much greater than usually assumed and might outweigh the disadvantages of continued treatment.
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Landmark clinical trials of psychiatric drug treatments for psychosis, depression, and bipolar disorder found discontinuation rates as high as 74%.
“Landmark clinical trials of psychiatric drug treatments for psychosis, depression, and bipolar disorder have found discontinuation rates as high as 74% (8)(9)(10).”
From Discontinuing Psychiatric Medications: A Survey of Long-Term Users (2017) · cites this paper as [10]
High potency and short and intermediate half-life compounds tend to carry greater risks for withdrawal symptoms, in addition to drug dependence.
“High potency and short and intermediate half-life compounds tend to carry greater risks for withdrawal symptoms, in addition to drug dependence [6,9,10] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [6]
Persistent postwithdrawal disorders have been described with different classes of CNS drugs (e.g. protracted insomnia for alcohol and benzodiazepine withdrawal and major depression/dysphoria for cocaine and amphetamine withdrawal), and even more so with specific drugs (e.g. quetiapine and paroxetine) within a drug class.
“Persistent postwithdrawal disorders have been described with different classes of CNS drugs (e.g.protracted insomnia for alcohol and benzodiazepine withdrawal [10,36] and major depression/dysphoria for cocaine and amphetamine withdrawal [10,23] ), and even more so with specific drugs (e.g.quetiapine and paroxetine) within a drug class [6,15,16,33] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [6]
Short-acting antipsychotics such as clozapine and quetiapine, which have fast dissociation from dopamine D2 receptor, have been shown to have a greater risk of rebound.
“This is also true for short-acting antipsychotics, such as clozapine and quetiapine, which have a fast dissociation from do- pamine D 2 receptor, and have been shown to have a greater risk of rebound [6,33] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [6]
There is increasing evidence for postwithdrawal disorders with SSRI long-term use.
“We now have increasing evidence for postwithdrawal disorders with SSRI long-term use [6,15,16,26,37] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [6]
The reinforcing properties of short-acting and short-elimination half-life CNS drugs appear to be the same for all CNS drug classes.
“The reinforcing properties of short-acting and short-elimination half-life CNS drugs appear to be the same for all CNS drug classes [6,9] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [6]
Postwithdrawal disorders may resemble rebound symptoms being more severe than the original symptoms, but these disorders persist at least 6 weeks in contrast to rebound symptoms.
“They may resemble rebound symptoms being more severe than the original symptoms, but these disorders persist at least 6 weeks in contrast to rebound symptoms and [6,15,16,26,37] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [6]
Persistent postwithdrawal panic disorder has been shown to occur following withdrawal of paroxetine, and paroxetine has also been associated with other postwithdrawal disorders.
“Persistent postwithdrawal panic disorder [15,38] has been shown to occur following withdrawal of paroxetine, and paroxetine has also been associated with other postwithdrawal disorders [6,15,16] .”
From New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal (2015) · cites this paper as [6]
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References 38 · Cited by 59
- Authors
- Moncrieff, J.
- Affiliations
- University College London (GB)
- Corresponding author
- Moncrieff, Joanna
- ORCID
- Moncrieff, Joanna
- Venue
- Medical Hypotheses
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 67
- Issue
- 3
- Pages
- 517-523
- ISSN
- 0306-9877 (ISSN-L)
- OpenAlex
- W2148088086
- Cited by
- 59
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medical Hypotheses (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Historical Psychiatry and Medical Practices
- Keywords
- drug withdrawal, maintenance therapy, relapse, clozapine, antipsychotic drugs, atypical antipsychotics, adverse drug reactions
- MeSH terms
- Humans, Models, Psychological, Psychotic Disorders, Substance Withdrawal Syndrome, Antipsychotic Agents, Withholding Treatment
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