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Placebo and nocebo effects in gambling disorder pharmacological trials: a meta-analysis

Placebo and nocebo effects in gambling disorder pharmacological trials: a meta-analysis
Placebo and nocebo effects in gambling disorder pharmacological trials: a meta-analysis
Background: placebo and nocebo effects are widely reported across psychiatric conditions, yet have seldom been examined in the context of gambling disorder. Through meta-analysis, we examined placebo effects, their moderating factors, and nocebo effects, from available randomised, controlled pharmacological clinical trials in gambling disorder.

Methods: we searched, up to 19 February 2024, a broad range of databases, for double-blind randomised controlled trials (RCTs) of medications for gambling disorder. Outcomes were gambling symptom severity and quality of life (for efficacy), and drop outs due to medication side effects in the placebo arms.

Results:
We included 16 RCTs (n = 833) in the meta-analysis. The overall effect size for gambling severity reduction in the placebo arms was 1.18 (95%CI 0.91–1.46) and for quality of life improvement was 0.63 (0.42-0.83). Medication class, study sponsorship, trial duration, baseline severity of gambling and publication year significantly moderated effect sizes for at least some of these outcome measures. Author conflict of interest, placebo run-in, gender split, severity scale choice, age of participants or unbalanced randomisation did not moderate effect sizes. Nocebo effects leading to drop out from the trial were observed in 6% of participants in trials involving antipsychotics, while this was less for other medication types.

Conclusion: placebo effects in trials of pharmacological treatment of gambling disorder are large, and there are several moderators of this effect. Nocebo effects were measureable and may be influenced by medication class being studied. Practical implications of these new findings for the field are discussed, along with recommendations for future clinical trials.

1601-5215
Ioannidis, Konstantinos
8ad30a4f-7b70-4189-a06c-e327caed8b2c
Huneke, Nathan T.M.
d1be843a-7aab-4978-9b4d-5bcc69b178a7
Solly, Jeremy E.
0422396e-a1d6-46a9-a8d8-348e95a31780
Veronesi, Guilherme Fusetto
42ca67f5-c4f0-4a0c-b573-9849cca7ece5
Tzagarakis, Charidimos
925d72b9-a24c-4ec0-bc53-75d36d3e686e
Parlatini, Valeria
6cdfb200-40ce-43ce-84da-dcb6eba0f67a
Westwood, Samuel J.
4683dcf1-f7bb-4d3a-beea-6e554a3d538b
Giovane, Cinzia Del
d56c8930-a1aa-4506-804c-bc38c204d250
Baldwin, David S.
1beaa192-0ef1-4914-897a-3a49fc2ed15e
Grant, Jon E.
07372bd5-8a0d-42b4-b41b-e376c652acf3
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Ioannidis, Konstantinos
8ad30a4f-7b70-4189-a06c-e327caed8b2c
Huneke, Nathan T.M.
d1be843a-7aab-4978-9b4d-5bcc69b178a7
Solly, Jeremy E.
0422396e-a1d6-46a9-a8d8-348e95a31780
Veronesi, Guilherme Fusetto
42ca67f5-c4f0-4a0c-b573-9849cca7ece5
Tzagarakis, Charidimos
925d72b9-a24c-4ec0-bc53-75d36d3e686e
Parlatini, Valeria
6cdfb200-40ce-43ce-84da-dcb6eba0f67a
Westwood, Samuel J.
4683dcf1-f7bb-4d3a-beea-6e554a3d538b
Giovane, Cinzia Del
d56c8930-a1aa-4506-804c-bc38c204d250
Baldwin, David S.
1beaa192-0ef1-4914-897a-3a49fc2ed15e
Grant, Jon E.
07372bd5-8a0d-42b4-b41b-e376c652acf3
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f

Ioannidis, Konstantinos, Huneke, Nathan T.M., Solly, Jeremy E., Veronesi, Guilherme Fusetto, Tzagarakis, Charidimos, Parlatini, Valeria, Westwood, Samuel J., Giovane, Cinzia Del, Baldwin, David S., Grant, Jon E., Cortese, Samuele and Chamberlain, Samuel R. (2024) Placebo and nocebo effects in gambling disorder pharmacological trials: a meta-analysis. Acta Neuropsychiatrica, 37, [e40]. (doi:10.1017/neu.2024.52).

Record type: Article

Abstract

Background: placebo and nocebo effects are widely reported across psychiatric conditions, yet have seldom been examined in the context of gambling disorder. Through meta-analysis, we examined placebo effects, their moderating factors, and nocebo effects, from available randomised, controlled pharmacological clinical trials in gambling disorder.

Methods: we searched, up to 19 February 2024, a broad range of databases, for double-blind randomised controlled trials (RCTs) of medications for gambling disorder. Outcomes were gambling symptom severity and quality of life (for efficacy), and drop outs due to medication side effects in the placebo arms.

Results:
We included 16 RCTs (n = 833) in the meta-analysis. The overall effect size for gambling severity reduction in the placebo arms was 1.18 (95%CI 0.91–1.46) and for quality of life improvement was 0.63 (0.42-0.83). Medication class, study sponsorship, trial duration, baseline severity of gambling and publication year significantly moderated effect sizes for at least some of these outcome measures. Author conflict of interest, placebo run-in, gender split, severity scale choice, age of participants or unbalanced randomisation did not moderate effect sizes. Nocebo effects leading to drop out from the trial were observed in 6% of participants in trials involving antipsychotics, while this was less for other medication types.

Conclusion: placebo effects in trials of pharmacological treatment of gambling disorder are large, and there are several moderators of this effect. Nocebo effects were measureable and may be influenced by medication class being studied. Practical implications of these new findings for the field are discussed, along with recommendations for future clinical trials.

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Accepted/In Press date: 9 October 2024
Published date: 20 November 2024

Identifiers

Local EPrints ID: 500172
URI: http://eprints.soton.ac.uk/id/eprint/500172
ISSN: 1601-5215
PURE UUID: 8132d400-fb17-4ce0-a72a-49677c74838d
ORCID for Konstantinos Ioannidis: ORCID iD orcid.org/0000-0002-1537-5425
ORCID for Jeremy E. Solly: ORCID iD orcid.org/0000-0003-1401-5919
ORCID for Guilherme Fusetto Veronesi: ORCID iD orcid.org/0009-0005-0117-6571
ORCID for Valeria Parlatini: ORCID iD orcid.org/0000-0002-4754-2494
ORCID for David S. Baldwin: ORCID iD orcid.org/0000-0003-3343-0907
ORCID for Samuele Cortese: ORCID iD orcid.org/0000-0001-5877-8075
ORCID for Samuel R. Chamberlain: ORCID iD orcid.org/0000-0001-7014-8121

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Date deposited: 22 Apr 2025 16:50
Last modified: 27 Sep 2025 02:33

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Contributors

Author: Konstantinos Ioannidis ORCID iD
Author: Nathan T.M. Huneke
Author: Jeremy E. Solly ORCID iD
Author: Guilherme Fusetto Veronesi ORCID iD
Author: Charidimos Tzagarakis
Author: Valeria Parlatini ORCID iD
Author: Samuel J. Westwood
Author: Cinzia Del Giovane
Author: Jon E. Grant
Author: Samuele Cortese ORCID iD
Author: Samuel R. Chamberlain ORCID iD

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