Depression - Major Depressive DisorderPhase 4DISCARDNCT07393919
Discontination of Antidepressants in Remitted Depression
A Phase 4 study testing Hyperbolic tapering and Linear tapering in people with Depression - Major Depressive Disorder, run by Universita di Verona.
Trial summary
Overprescribing and long-term use of antidepressants (ADs) are common and may increase the risk of adverse effects and withdrawal symptoms when discontinuation is attempted. Although several discontinuation strategies have been proposed, empirical evidence comparing different tapering approaches is limited. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression - Major Depressive Disorder
- What is being tested?
- Hyperbolic tapering and Linear tapering
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2026to 30 Sep 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years old or above;
- diagnosed with a depressive disorder, single episode (ICD-11, 6A70) or recurrent (ICD-11, 6A71);
- currently taking a selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), or vortioxetine for the treatment of depression;
- the current AD has been taken for at least 6 months;
- the current AD has been on a stable dose over the last 2 months;
- a score ≤9 on the PHQ-9 and ≤5 on the GAD-7 at study enrolment;
Show all 11Show fewer
- DSM-5-TR criteria for a depressive episode are not met at the time of recruitment;
- no clinical evidence of moderate-to-severe symptoms in the last 6 months, as assessed by the recruiting clinician;
- discontinuing the AD is clinically indicated by the recruiting clinician, and agreed to by the participant in a shared decision-making process;
- uncertainty about which discontinuation strategy would be best for the participant;
- the participant is willing to sign the informed consent to participate to the study.
Who cannot join
- comorbid schizophrenia-spectrum disorders, bipolar disorder, or dementia, as formally diagnosed by a psychiatrist, neurologist, geriatrician, or other specialists;
- current treatment with more than one AD at therapeutic doses;
- current treatment with ADs of other classes (e.g., mirtazapine, agomelatine, bupropion, for which the evidence on the risk of withdrawal is unclear), alone or in combination with other ADs;
- conditions or medications that contraindicate the use of any AD according to the Summary of Product Characteristics of included ADs (synthetically reported in Table 1) (e.g., current symptoms of mania);
- current treatment with benzodiazepines above the dose of 2.5 mg equivalents of lorazepam per day (corresponding to clonazepam 1.2 mg/day; alprazolam 1.2 mg/day; diazepam 19 mg/day);
- pregnancy or willingness to become pregnant.
About this study
Official title: Safe Discontinuation of Antidepressants in Individuals With Clinically Remitted Depressive Disorders
Overprescribing and long-term use of antidepressants (ADs) are common and may increase the risk of adverse effects and withdrawal symptoms when discontinuation is attempted. Although several discontinuation strategies have been proposed, empirical evidence comparing different tapering approaches is limited. In particular, hyperbolic tapering has been suggested as a potentially safer and more effective alternative to standard linear tapering, but no randomized trials have directly compared these strategies.
This study is a pragmatic, multicentre, open-label, parallel-group, superiority randomized trial designed to compare two antidepressant discontinuation strategies-linear tapering and hyperbolic tapering-in adults with remitted depressive disorders. Eligible participants are adults aged 18 years or older with currently remitted depressive disorders who have been taking antidepressants for at least six months and are considered clinically appropriate candidates for discontinuation.
Read more
Participants will be recruited in outpatient psychiatric settings, with the involvement of general practitioners and other medical specialists. After baseline assessment, participants will be randomized to either a linear tapering strategy, consisting of dose reductions of 50% of the minimal effective dose every two weeks until discontinuation, or a hyperbolic tapering strategy, consisting of proportional dose reductions of approximately 20-25% every two weeks until discontinuation. Follow-up assessments will be conducted regularly over a 36-week period.
The primary outcome is the proportion of participants who fail to discontinue the antidepressant within the predefined tapering schedule (allowing a limited tolerance period) or who re-initiate antidepressant treatment during the 16 weeks following discontinuation. Secondary outcomes include measures of safety, tolerability, acceptability, clinical effectiveness, and cost-effectiveness, as well as withdrawal symptoms, relapse of depressive or anxiety symptoms, and adherence to the tapering schedule.
Participants and recruiting clinicians will not be blinded to treatment allocation, while outcome assessors and the biostatistician will remain blinded until completion of the study to minimize detection bias. The study aims to provide pragmatic evidence to inform clinical practice and guideline development regarding optimal strategies for antidepressant discontinuation.
Read the detailed description
Antidepressants (ADs) are effective in the treatment of moderate-to-severe depression and anxiety disorders and are recommended by national and international clinical guidelines, although concerns about over-prescribing persist. In Italy, AD consumption increased by over 10% between 2014 and 2020. Selective serotonin reuptake inhibitors (SSRIs) account for approximately 70% of AD prescriptions and around half of total AD-related expenditure. Across most countries, AD prescribing has increased steadily, largely driven by use in general practice and by longer treatment duration.
For individuals experiencing a first depressive episode, evidence-based guidelines recommend continuing AD treatment for 6-9 months after clinical response. Meta-analytic evidence suggests a similar risk of relapse for maintenance periods ranging from six months to over one year. Treatment duration may vary according to illness severity and recurrence, with at least two years commonly recommended in cases of multiple episodes with functional impairment. In Italy, approximately one in three individuals continue AD treatment beyond 12 months, raising concerns about potentially inappropriate long-term or indefinite prescribing.
Prolonged AD use is associated with an increased risk of long-term adverse effects, including sexual dysfunction, weight gain, emotional blunting, and cardiovascular conditions. Discontinuation of ADs may also lead to withdrawal symptoms, which can be clinically relevant in a substantial proportion of patients. Several clinical factors appear to increase the risk of withdrawal, and it has been suggested that, for some individuals, disabling withdrawal symptoms rather than relapse may be the primary reason for unsuccessful discontinuation.
Randomized controlled trials indicate that discontinuing ADs is associated with a higher risk of relapse compared with continuation. However, discontinuation schedules used in many trials are rapid or abrupt, potentially increasing withdrawal symptoms that may be misclassified as relapse and thereby inflating relapse estimates. There is broad agreement that gradual tapering may reduce withdrawal symptoms, but most clinical guidelines provide only generic recommendations, often implying a linear dose reduction approach that remains standard in routine practice.
Alternative tapering strategies have been proposed, most notably hyperbolic tapering, which involves proportional dose reductions over longer periods. This approach is based on the nonlinear relationship between dose and receptor occupancy and may require tapering periods ranging from several months to over one year. Hyperbolic tapering often necessitates very low doses that are not readily achievable with standard marketed formulations, raising feasibility, regulatory, and policy challenges. To date, no randomized trials have directly compared different tapering strategies.
Against this background, there is a clear need for experimental evidence comparing hyperbolic and linear tapering approaches in routine clinical practice. The DISCARD study is a pragmatic, multicentre randomized trial designed to address this gap by comparing hyperbolic versus linear tapering in adults with currently remitted depressive disorders who have been taking ADs for at least six months and for whom discontinuation is clinically appropriate.
Participants will be recruited across four university psychiatric units in Italy, with methodological support provided by a fifth academic centre. General practitioners and other specialists will be involved in identifying potentially eligible individuals. After providing informed consent and completing baseline assessments, participants will be randomized to either a linear or a hyperbolic tapering strategy according to predefined schedules tailored to the starting dose. Follow-up assessments will be conducted regularly over a 36-week period using validated measures of depressive symptoms, anxiety symptoms, withdrawal symptoms, quality of life, and social functioning. Outcome assessors and the biostatistician will remain blinded to treatment allocation.
The primary outcome is the proportion of participants who fail to discontinue the AD within the predefined tapering schedule or who re-initiate AD treatment during the 16 weeks following discontinuation. Secondary outcomes include non-adherence to the tapering schedule, occurrence and severity of withdrawal symptoms, clinical relapse, early study discontinuation, and use of predefined rescue strategies. This study is designed to generate pragmatic evidence on the comparative effectiveness, feasibility, safety, and cost-effectiveness of hyperbolic versus linear tapering strategies in everyday clinical practice.
- Conditions
- Depression - Major Depressive Disorder
- Being tested
- Hyperbolic tapering, Linear tapering
- Keywords
- depression, antidepressants, clinically remitted depressive disorder, discontinuation of the antidepressant
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperbolic taperingDrug
The dose will be reduced by 20-25% every 2 weeks.
Linear taperingDrug
Dose will be reduced by fixed amounts (generally 50% of the minimum effective dose) every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Linear tapering | Active comparator | Antidepressant (AD) dose will be reduced by fixed amounts (generally 50% of the minimum effective dose) every 2 weeks, according to pre-defined schedules, with the aim of reaching 50% of the minimum effective dose (as defined in the AIFA Summary of Product Characteristics), and finally discontinuing the AD after 4 to 10 weeks (depending on the initial dose). This approach is similar to the tapering schedules commonly used in current clinical practice. Any SSRI, SNRI, tricyclic antidepressant, and vortioxetine will be allowed. Receives: Drug: Linear tapering |
| Hyperbolic tapering | Active comparator | Antidepressant (AD) dose will be reduced by 20-25% every 2 weeks, according to pre-defined schedules adapted from the Maudsley Hospital Guidelines (Taylor, 2021), with the aim of reaching at least 20% of the minimum effective dose (as defined in the AIFA Summary of Product Characteristics), and finally discontinuing the AD after 12 to 20 weeks (depending on the initial dose). Any SSRI, SNRI, tricyclic antidepressant, and vortioxetine will be allowed. Receives: Drug: Hyperbolic tapering |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants Who Do Not Successfully Discontinue Antidepressant Treatment Within 16 Weeks
Proportion of participants who fail to successfully discontinue the antidepressant treatment, defined as either:
- continued use of the antidepressant beyond the predefined tapering schedule (allowing a tolerance period of up to 15% of the total tapering duration), or
- re-initiation of any antidepressant medication for any reason (e.g., withdrawal symptoms, recurrence of depressive or anxiety symptoms).
Measured: 16 weeks
Secondary outcomes (5)
Proportion of Participants Who Fail to Discontinue Antidepressant Treatment by the End of the Predefined Tapering Schedule
Proportion of participants who do not complete antidepressant discontinuation by the end of the predefined tapering schedule, regardless of reason
Measured: Up to the end of the predefined tapering period
Proportion of Participants Who Re-initiate Antidepressant Treatment Within 16 Weeks After Discontinuation
Proportion of participants who restart any antidepressant medication for any reason after successful completion of the tapering schedule.
Measured: Up to 16 weeks after complete antidepressant discontinuation
Proportion of Participants Non-adherent to the Predefined Antidepressant Tapering Schedule
Proportion of participants who deviate from the predefined tapering schedule for any reason.
Measured: Up to the end of the predefined tapering period
Mean of DESS highest overall scores
A mean of the highest scores reached by each patient on the modified Discontinuation-Emergent Signs and Symptoms Scale (DESS)
Measured: Up to the end of the 16-weeks follow-up period
Proportion of participants leaving the study early due to any reason without meeting criteria for the primary outcome
This includes people who do not attend follow-up visits and cannot be contacted, people who refuse to be involved in follow-up assessments, or people who die during the tapering or the follow-up for reasons unrelated to withdrawal symptoms or relapse.
Measured: Up to the end of the 16-weeks follow-up period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2026
- Study start1 Feb 2026 (estimated)
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depression - Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Individuals will be randomized 1:1 to linear or hyperbolic tapering, The sequence of treatments will be randomly permuted in blocks of constant size. The allocation will be stratified by (a) recruiting centre; (b) individuals at high- vs. low-risk of withdrawal symptoms,
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universita di Verona
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliera Universitaria Integrata Verona, Centro Ricerche Cliniche di Verona
- Responsible party
- Principal investigator, Giovanni Ostuzzi, Universita di Verona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07393919
- Sponsor's protocol ID
- OSTUZZI_PRIN_PNRR2022_M4C2_INV
- Other IDs
- 2023-509377-23, 2023
- Acronym
- DISCARD
- Status last verified
- Jan 2026
- First submitted
- 21 Jan 2026
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Once the dataset is completed, it will be uploaded to the online repository EUDAT-B2-SHARE, and will be made available after a motivated request, which will be discussed by the study's leading authors.
Publications
Ostuzzi G, Gastaldon C, Zaccoletti D, Bartoli F, Belnome G, Carra G, Cavallotti S, Cristea I, D'Agostino A, De Fazio P, de Filippis R, Gottardi C, Novara C, Papola D, Riboldi I, Tedeschi F, Amaddeo F, Barbui C. Safe discontinuation of antidepressants in individuals with clinically remitted depressive disorders: study protocol for a randomised controlled trial. BMJ Open. 2026 Jul 15;16(7):e119492. doi: 10.1136/bmjopen-2026-119492.
PubMed 42463208
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safe Discontinuation of Antidepressants in Individuals With Clinically Remitted Depressive Disorders
- ClinicalTrials.gov ID
- NCT07393919
- Acronym / sponsor ID
- DISCARD / OSTUZZI_PRIN_PNRR2022_M4C2_INV
- Conditions
- Depression - Major Depressive Disorder
- Keywords
- depression, antidepressants, clinically remitted depressive disorder, discontinuation of the antidepressant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Universita di VeronaUniversity, hospital or other
- Collaborators
- Azienda Ospedaliera Universitaria Integrata Verona, Centro Ricerche Cliniche di Verona
- Study start
- 1 Feb 2026 (estimated)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 6 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Overprescribing and long-term use of antidepressants (ADs) are common and may increase the risk of adverse effects and withdrawal symptoms when discontinuation is attempted. Although several discontinuation strategies have been proposed, empirical evidence comparing different tapering approaches is limited. In particular, hyperbolic tapering has been suggested as a potentially safer and more effective alternative to standard linear tapering, but no randomized trials have directly compared these strategies.
This study is a pragmatic, multicentre, open-label, parallel-group, superiority randomized trial designed to compare two antidepressant discontinuation strategies-linear tapering and hyperbolic tapering-in adults with remitted depressive disorders. Eligible participants are adults aged 18 years or older with currently remitted depressive disorders who have been taking antidepressants for at least six months and are considered clinically appropriate candidates for discontinuation.
Participants will be recruited in outpatient psychiatric settings, with the involvement of general practitioners and other medical specialists. After baseline assessment, participants will be randomized to either a linear tapering strategy, consisting of dose reductions of 50% of the minimal effective dose every two weeks until discontinuation, or a hyperbolic tapering strategy, consisting of proportional dose reductions of approximately 20-25% every two weeks until discontinuation. Follow-up assessments will be conducted regularly over a 36-week period.
The primary outcome is the proportion of participants who fail to discontinue the antidepressant within the predefined tapering schedule (allowing a limited tolerance period) or who re-initiate antidepressant treatment during the 16 weeks following discontinuation. Secondary outcomes include measures of safety, tolerability, acceptability, clinical effectiveness, and cost-effectiveness, as well as withdrawal symptoms, relapse of depressive or anxiety symptoms, and adherence to the tapering schedule.
Participants and recruiting clinicians will not be blinded to treatment allocation, while outcome assessors and the biostatistician will remain blinded until completion of the study to minimize detection bias. The study aims to provide pragmatic evidence to inform clinical practice and guideline development regarding optimal strategies for antidepressant discontinuation.
Detailed description
Antidepressants (ADs) are effective in the treatment of moderate-to-severe depression and anxiety disorders and are recommended by national and international clinical guidelines, although concerns about over-prescribing persist. In Italy, AD consumption increased by over 10% between 2014 and 2020. Selective serotonin reuptake inhibitors (SSRIs) account for approximately 70% of AD prescriptions and around half of total AD-related expenditure. Across most countries, AD prescribing has increased steadily, largely driven by use in general practice and by longer treatment duration.
For individuals experiencing a first depressive episode, evidence-based guidelines recommend continuing AD treatment for 6-9 months after clinical response. Meta-analytic evidence suggests a similar risk of relapse for maintenance periods ranging from six months to over one year. Treatment duration may vary according to illness severity and recurrence, with at least two years commonly recommended in cases of multiple episodes with functional impairment. In Italy, approximately one in three individuals continue AD treatment beyond 12 months, raising concerns about potentially inappropriate long-term or indefinite prescribing.
Prolonged AD use is associated with an increased risk of long-term adverse effects, including sexual dysfunction, weight gain, emotional blunting, and cardiovascular conditions. Discontinuation of ADs may also lead to withdrawal symptoms, which can be clinically relevant in a substantial proportion of patients. Several clinical factors appear to increase the risk of withdrawal, and it has been suggested that, for some individuals, disabling withdrawal symptoms rather than relapse may be the primary reason for unsuccessful discontinuation.
Randomized controlled trials indicate that discontinuing ADs is associated with a higher risk of relapse compared with continuation. However, discontinuation schedules used in many trials are rapid or abrupt, potentially increasing withdrawal symptoms that may be misclassified as relapse and thereby inflating relapse estimates. There is broad agreement that gradual tapering may reduce withdrawal symptoms, but most clinical guidelines provide only generic recommendations, often implying a linear dose reduction approach that remains standard in routine practice.
Alternative tapering strategies have been proposed, most notably hyperbolic tapering, which involves proportional dose reductions over longer periods. This approach is based on the nonlinear relationship between dose and receptor occupancy and may require tapering periods ranging from several months to over one year. Hyperbolic tapering often necessitates very low doses that are not readily achievable with standard marketed formulations, raising feasibility, regulatory, and policy challenges. To date, no randomized trials have directly compared different tapering strategies.
Against this background, there is a clear need for experimental evidence comparing hyperbolic and linear tapering approaches in routine clinical practice. The DISCARD study is a pragmatic, multicentre randomized trial designed to address this gap by comparing hyperbolic versus linear tapering in adults with currently remitted depressive disorders who have been taking ADs for at least six months and for whom discontinuation is clinically appropriate.
Participants will be recruited across four university psychiatric units in Italy, with methodological support provided by a fifth academic centre. General practitioners and other specialists will be involved in identifying potentially eligible individuals. After providing informed consent and completing baseline assessments, participants will be randomized to either a linear or a hyperbolic tapering strategy according to predefined schedules tailored to the starting dose. Follow-up assessments will be conducted regularly over a 36-week period using validated measures of depressive symptoms, anxiety symptoms, withdrawal symptoms, quality of life, and social functioning. Outcome assessors and the biostatistician will remain blinded to treatment allocation.
The primary outcome is the proportion of participants who fail to discontinue the AD within the predefined tapering schedule or who re-initiate AD treatment during the 16 weeks following discontinuation. Secondary outcomes include non-adherence to the tapering schedule, occurrence and severity of withdrawal symptoms, clinical relapse, early study discontinuation, and use of predefined rescue strategies. This study is designed to generate pragmatic evidence on the comparative effectiveness, feasibility, safety, and cost-effectiveness of hyperbolic versus linear tapering strategies in everyday clinical practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Individuals will be randomized 1:1 to linear or hyperbolic tapering, The sequence of treatments will be randomly permuted in blocks of constant size. The allocation will be stratified by (a) recruiting centre; (b) individuals at high- vs. low-risk of withdrawal symptoms,
| Arm | Type | Receives |
|---|---|---|
| Linear tapering | Active comparator | Drug: Linear taperingAntidepressant (AD) dose will be reduced by fixed amounts (generally 50% of the minimum effective dose) every 2 weeks, according to pre-defined schedules, with the aim of reaching 50% of the minimum effective dose (as defined in the AIFA Summary of Product Characteristics), and finally discontinuing the AD after 4 to 10 weeks (depending on the initial dose). This approach is similar to the tapering schedules commonly used in current clinical practice. Any SSRI, SNRI, tricyclic antidepressant, and vortioxetine will be allowed. |
| Hyperbolic tapering | Active comparator | Drug: Hyperbolic taperingAntidepressant (AD) dose will be reduced by 20-25% every 2 weeks, according to pre-defined schedules adapted from the Maudsley Hospital Guidelines (Taylor, 2021), with the aim of reaching at least 20% of the minimum effective dose (as defined in the AIFA Summary of Product Characteristics), and finally discontinuing the AD after 12 to 20 weeks (depending on the initial dose). Any SSRI, SNRI, tricyclic antidepressant, and vortioxetine will be allowed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 18 years old or above;
- diagnosed with a depressive disorder, single episode (ICD-11, 6A70) or recurrent (ICD-11, 6A71);
- currently taking a selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), or vortioxetine for the treatment of depression;
- the current AD has been taken for at least 6 months;
- the current AD has been on a stable dose over the last 2 months;
Key exclusion criteria (6 listed)
- comorbid schizophrenia-spectrum disorders, bipolar disorder, or dementia, as formally diagnosed by a psychiatrist, neurologist, geriatrician, or other specialists;
- current treatment with more than one AD at therapeutic doses;
- current treatment with ADs of other classes (e.g., mirtazapine, agomelatine, bupropion, for which the evidence on the risk of withdrawal is unclear), alone or in combination with other ADs;
- conditions or medications that contraindicate the use of any AD according to the Summary of Product Characteristics of included ADs (synthetically reported in Table 1) (e.g., current symptoms of mania);
- current treatment with benzodiazepines above the dose of 2.5 mg equivalents of lorazepam per day (corresponding to clonazepam 1.2 mg/day; alprazolam 1.2 mg/day; diazepam 19 mg/day);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperbolic taperingThe dose will be reduced by 20-25% every 2 weeks. | Drug | Hyperbolic tapering |
| Linear taperingDose will be reduced by fixed amounts (generally 50% of the minimum effective dose) every 2 weeks. | Drug | Linear tapering |
Primary outcome
Proportion of Participants Who Do Not Successfully Discontinue Antidepressant Treatment Within 16 Weeks
Time frame: 16 weeks
Proportion of participants who fail to successfully discontinue the antidepressant treatment, defined as either: 1. continued use of the antidepressant beyond the predefined tapering schedule (allowing a tolerance period of up to 15% of the total tapering duration), or 2. re-initiation of any antidepressant medication for any reason (e.g., withdrawal symptoms, recurrence of depressive or anxiety symptoms).
5 secondary outcomes
Proportion of Participants Who Fail to Discontinue Antidepressant Treatment by the End of the Predefined Tapering Schedule
Time frame: Up to the end of the predefined tapering period
Proportion of Participants Who Re-initiate Antidepressant Treatment Within 16 Weeks After Discontinuation
Time frame: Up to 16 weeks after complete antidepressant discontinuation
Proportion of Participants Non-adherent to the Predefined Antidepressant Tapering Schedule
Time frame: Up to the end of the predefined tapering period
Mean of DESS highest overall scores
Time frame: Up to the end of the 16-weeks follow-up period
Proportion of participants leaving the study early due to any reason without meeting criteria for the primary outcome
Time frame: Up to the end of the 16-weeks follow-up period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Derived from this study: PubMed 42463208Ostuzzi G, Gastaldon C, Zaccoletti D, Bartoli F, Belnome G, Carra G, Cavallotti S, Cristea I, D'Agostino A, De Fazio P, de Filippis R, Gottardi C, Novara C, Papola D, Riboldi I, Tedeschi F, Amaddeo F, Barbui C. Safe discontinuation of antidepressants in individuals with clinically remitted depressive disorders: study protocol for a randomised controlled trial. BMJ Open. 2026 Jul 15;16(7):e119492. doi: 10.1136/bmjopen-2026-119492.
- Individual participant dataSharing planned: Yes. Once the dataset is completed, it will be uploaded to the online repository EUDAT-B2-SHARE, and will be made available after a motivated request, which will be discussed by the study's leading authors.
Related trials for Depression - Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hyperbolic tapering and Linear tapering in people with Depression - Major Depressive Disorder, run by Universita di Verona.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Who Do Not Successfully Discontinue Antidepressant Treatment Within 16 Weeks (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07393919, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.