My Papers

July 20, 2022
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were...
Mark Abie Horowitz, PhD Prof David Taylor, PhD
March 5, 2019
All classes of drug that are prescribed to treat depression are associated with withdrawal syndromes. SSRI withdrawal syndrome occurs often and can be severe, and might compel patients to recommence their medication. Although the withdrawal syndrome can be differentiated from recurrence of the underlying disorder, it might also be mistaken for recurrence, leading to long-term unnecessary medication. Guidelines recommend short tapers, of between 2 weeks and 4 weeks, down to...
Mark Abie Horowitz, Sameer Jauhar, Sridhar Natesan, Robin M Murray, David Taylor
March 23, 2021
The process of stopping antipsychotics may be causally related to relapse, potentially linked to neuroadaptations that persist after cessation, including dopaminergic hypersensitivity. Therefore, the risk of relapse on cessation of antipsychotics may be minimized by more gradual tapering. There is converging evidence that suggests that adaptations to antipsychotic exposure can persist for months or years after stopping the medication—from animal studies, observation of tardive dyskinesia in patients, and the clustering...
Mark Abie Horowitz and Joanna Moncrieff
May 27, 2020
Esketamine has been licensed for ‘treatment-resistant depression’ in the USA, UK and Europe. Licensing trials did not establish efficacy: two trials were negative, one showed a statistically significant but clinically uncertain effect, and a flawed discontinuation trial was included, against Food and Drug Administration precedent. Safety signals – deaths, including suicides, and bladder damage – were minimised.
No data was found (Work in progress. Ignore this message)
SUMMARY We now recognise that withdrawal symptoms from antidepressants are common, and can be severe and long-lasting in some people. Many withdrawal symptoms overlap with symptoms of anxiety or depression, making it difficult to distinguish withdrawal from relapse. We describe how their onset soon after dose reduction, the association of psychological with physical symptoms, their prompt response to reinstatement, and their typical ‘wave’ pattern of onset, peak and resolution can...
Abstract Background Depression and anxiety are the most frequent indication for which antidepressants are prescribed. Long‐term antidepressant use is driving much of the internationally observed rise in antidepressant consumption. Surveys of antidepressant users suggest that 30% to 50% of long‐term antidepressant prescriptions had no evidence‐based indication. Unnecessary use of antidepressants puts people at risk of adverse events. However, high‐certainty evidence is lacking regarding the effectiveness and safety of approaches to discontinuing long‐term...
Approaches for discontinuation versus continuation of long‐term antidepressant use for depressive and anxiety disorders in adults
Ruth Cooper, Lisa Grunwald and Mark Abie Horowitz
February 19, 2020
ABSTRACT The UK’s National Institute for Health and Care Excellence (NICE) is in the process of writing guidelines for “Medicines Associated with Dependence or Withdrawal Symptoms: Safe Prescribing and Withdrawal Management for Adults”. NICE has excluded antipsychotics, despite inclusion having been requested by all four groups participating in the guideline scoping workshop, as well as the Royal College of Psychiatrists, the All-Party Parliamentary Group for Prescribed Drug Dependence, the International...
Anne Guy, Marion Brown, Stevie Lewis and Mark Abie Horowitz
November 9, 2020
Background: Stopping antidepressants commonly causes withdrawal symptoms, which can be severe and long-lasting. National Institute for Health and Care Excellence (NICE) guidance has been recently updated to reflect this; however, for many years withdrawal (discontinuation) symptoms were characterised as ‘usually mild and self-limiting over a week’. Consequently, withdrawal symptoms might have been misdiagnosed as relapse of an underlying condition, or new onset of another medical illness, but this has never...
Mark Abie Horowitz and David Taylor
July 1, 2019
We thank Sudhakar Selvaraj and colleagues1 for their interest in our work. They offer several critiques of the relevance of PET occupancy data to withdrawal effects. However, we think their claim that changes in plasma levels of drug would not be associated with withdrawal symptoms has little evidential support. The more abrupt reduction in plasma levels of antidepressants with shorter half-lives is understood to cause their more severe and quick-onset withdrawal...
Mark Abie Horowitz, Robin M. Murray, David Taylor
August 5, 2020
Antipsychotics are recommended for long-term treatment of schizophrenia because they reduce risk of relapse. However, antipsychotics have many adverse effects, including metabolic complications, tardive dyskinesia, and probable brain volume reduction.1 Patients may ask to reduce or stop their medication or do so abruptly without professional support, sometimes with dire consequences. As there is some evidence that not all patients need lifelong antipsychotic treatment and some may have improved social functioning...
Joanna Moncrieff, Swapnil Gupta and Mark Horowitz
July 6, 2020
Abstract Most guidelines recommend long-term, indefinite neuroleptic (or antipsychotic) treatment for people with schizophrenia, recurrent psychosis or bipolar disorder, on the basis that these medications reduce the chance of relapse. However, neuroleptics have significant adverse effects, including sexual dysfunction, emotional blunting, metabolic disturbance and brain shrinkage, and patients often request to stop them. Evidence for the benefits of long-term treatment is also not as robust as generally thought. Short-term randomised...
Mark Abie Horowitz and David Taylor
November 1, 2019
We read with interest the Article by Fredrick Hieronymus and colleagues in The Lancet Psychiatry.1 The authors showed that SSRIs significantly improve scores in a subset of items in the 17-item Hamilton Depression Rating Scale (HDRS-17), over and above placebo, after a treatment period of 6 weeks, irrespective of baseline depression severity. However, we think that some uncertainties exist that should temper the authors’ conclusion that the “claim that antidepressants are useless...
David Taylor and Mark Abie Horowitz
December 2, 2020
Nobody can fail to be intrigued by, if not sceptical of, studies which appear to show that the prescribing of antipsychotics [which can cause weight gain, metabolic disturbance, QT prolongation, akathisia-linked suicide (Salem, Nagpal, Pigott, & Teixeira, 2017) and dose-related sudden cardiac death (Ray, Chung, Murray, Hall, & Stein, 2009)] results in people living longer than those not prescribed these drugs. The expectation, of course, is that people taking antipsychotics...