Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are typical antidepressants that are also widely used to treat major depressive disorder (MDD), anxiety disorders, and other mental disorders. While these drugs are highly useful, the safety profile of each antidepressant varies widely. 1 Furthermore, it has long been pointed out that they can cause withdrawal symptoms after decrease or discontinuing. 2 A recent systematic review 3 found that 40% of patients experience withdrawal symptoms after reducing or discontinuing SSRIs. However, withdrawal symptoms can be confused with a relapse or recurrence of the original disorder, and reintroduction of the antidepressant that was initially used or switching from one antidepressant to a different one may actually worsen symptoms. 4 Clinicians are therefore required to carefully assess the emergence of psychiatric symptoms following the decrease or discontinuation of SSRIs or SNRIs. In 2015, Chouinard and Chouinard outlined a comprehensive new classification of SSRI/SNRI withdrawal symptoms and proposed specific diagnostic criteria, 5 later refined by Cosci and Chouinard. 6 This classification allows the formulation of the diagnosis of three withdrawal syndromes: new symptoms, rebound symptoms, and persistent post‐withdrawal disorders. The Diagnostic clinical Interview for Drug Withdrawal 1 (DID‐W1) 7 is a semi‐structured clinical interview designed to make the diagnosis of these three withdrawal symptoms. Cosci et al. found high inter‐rater reliability of the DID‐W1, indicating that the DID‐W1 may be useful in clinical practice to diagnose clinical phenomena associated with reducing or discontinuation of SSRIs and SNRIs and to distinguish them from relapse. 8 , 9
Since the DID‐W1 was translated into Japanese, the aim of the present study was to verify whether the Japanese version of the DID‐W1 has similar inter‐rater reliability to the original version. The study was approved by the Ethics Committee of the Kurume University School of Medicine, Kurume, Japan and all patients provided written informed consent. The Japanese version of the DID‐W1 (see Supporting Information S1; the original version of the DID‐W1 is presented in Cosci and Guidi 9 ) was developed using translation and back‐translation by two different bilingual psychiatrists with the permission of the author of the original scale.
The study included outpatients who received treatment at Kurume University Hospital or Uematsu Mental Clinic between April 2020 and March 2023, and who had a history of decrease or discontinuation of SSRI/SNRI. Participants were assessed via the Japanese version of the DID‐W1 by two independent psychiatrists at different times on the same day. Mental disorders were also assessed using the Mini‐International Neuropsychiatric Interview (ver7.0.0). 10
A total of 16 patients participated in this study to assess the inter‐rater reliability of the Japanese version of the DID‐W1. Of them, 14 (87.5%) were females and had a mean age (standard deviation) of 38.6 ± 14.1 years. They had received a SSRI/SNRI treatment for social anxiety (n = 8, 50%), major depressive disorder (n = 7, 43.8%), and dissociative disorder (n = 1, 6.3%). The patients had been treated with escitalopram (n = 7, 43.8%), paroxetine (n = 3, 18.8%), duloxetine (n = 3, 18.8%), sertraline (n = 1, 6.3%), fluvoxamine (n = 1, 6.3%), and venlafaxine (n = 1, 6.3%).
The percentage inter‐rater agreement for the Japanese version of the DID‐W1 was 88.9%, the Cohen's kappa was 0.9 (standard error = 0.09), the 95% confidence interval was 0.72–1, and the squared correlation coefficient was 0.84. Detailed results for each diagnosis are shown in Table 1. Among the study participants, we did not find any patients with the diagnosis of persistent post‐withdrawal disorder. Except for that category, high concordance was observed.
Table 1.
Inter‐rater reliability per diagnosis.
| Agreement (%) | Cohen's kappa (SE) | 95% CI | Squared correlation coefficient | |
|---|---|---|---|---|
| Current new withdrawal symptoms | 100 | 1 (0) | – | 1 |
| Lifetime new withdrawal symptoms | 75 | 0.81 (0.17) | 0.47–1 | 0.6 |
| Current rebound symptoms | – | – | – | – |
| Lifetime rebound symptoms | 100 | 1 (0) | – | 1 |
| Current persistent post‐withdrawal disorder | – | – | – | – |
| Lifetime persistent post‐withdrawal disorder | – | – | – | – |
Abbreviations: 95% CI, 95% confidence interval; SE, standard error.
The present study showed high inter‐rater reliability of the Japanese version for the DID‐W1; the results are consistent with those of the original version of the instrument. 8 , 9 The present results suggest that the Japanese version of the DID‐W1 may be useful in making an appropriate diagnosis and determining the subsequent treatment options of patients who are decreasing or have discontinued SSRIs/SNRIs.
The limitations of this study include that, although the number of participants was similar to the pilot study conducted for the original version of the DID‐W1, 7 these preliminary findings are in need of replication in larger Japanese speaking samples. In addition, it was not possible to verify the characteristics of the module devoted to persistent post‐withdrawal disorder due to the lack of this diagnosis in the current sample. 8 Large‐scale research using the Japanese version of the DID‐W1 is required because this may help to clarify the classification of the syndrome after SSRI/SNRI decrease or discontinuation, aid in treatment decisions, and even contribute to epidemiological understanding.
AUTHOR CONTRIBUTIONS
Conception and design of the study: Tomoyuki Nakamura and Misari Oe. Translation: Tomoyuki Nakamura, Misari Oe, Ken Uematsu, and Hikaru Hori. Acquisition of data: Tomoyuki Nakamura, Misari Oe, and Ken Uematsu. Analysis of data: Tomoyuki Nakamura. Drafting the tables: Tomoyuki Nakamura, Misari Oe, and Hikaru Hori. Providing suggestions regarding the manuscript: Tomoyuki Nakamura, Misari Oe, Hikaru Hori, Motohiro Ozone, and Fiammetta Cosci. All authors reviewed the manuscript and approved it for submission.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
FUNDING INFORMATION
None.
ETHICS APPROVAL STATEMENT
This study was approved by the ethics committee of Kurume University Hospital (approval number: 19024) and was conducted in accordance with the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects.
PATIENT CONSENT STATEMENT
All patients provided written informed consent.
CLINICAL TRIAL REGISTRATION
N/A.
Supporting information
SUPPORTING INFORMATION S1 DID‐W1: Diagnostic clinical Interview for Drug Withdrawal 1 New Symptoms of SSRI and SNRI.
ACKNOWLEDGMENTS
The authors have nothing to report.
DATA AVAILABILITY STATEMENT
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
SUPPORTING INFORMATION S1 DID‐W1: Diagnostic clinical Interview for Drug Withdrawal 1 New Symptoms of SSRI and SNRI.
Data Availability Statement
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.