Pragmatic Trial of Obsessive-compulsive Disorder

Official title

A Pragmatic Trial of Pharmacotherapy Options Following Unsatisfactory Initial Treatment in OCD

Overview

This study includes a sequenced clinical trial in order to assess the efficacy of several switching or augment strategies when initial treatment is ineffective，and to provide strong evidence for clinical practice and international guidelines for Obsessive-Compulsive Disorder treatments.

Detailed description

Selective Serotonin Reuptake Inhibitors(SSRIs) are the first line pharmacotherapy for Obsessive-Compulsive Disorder (OCD) according to APA（American Psychological Association）guideline. Nevertheless, a large proportion (40% or more) of patients response only partially or not at all to treatment with a SSRI. On the basis of the existing sparse literature, several pharmacotherapy options for OCD patients who do not respond, or who respond but do not remit, have been outlined in current treatment guidelines. These include 1) treatment with higher than usual doses of an SSRI, 2) switch to a different SSRI, 3) switch to a different class of medication, 4) augmentation with a dopamine blocker, and 5) augmentation with a glutamatergic agent. There is a need for additional data, particularly real-world data, on how best to choose between these options.

This proposed Randomized Controlled Trial (RCT) study is a multi-center clinical study with a total of 13 centers that specialize in OCD patients. A randomized block design will be used in this study and all eligible participants accepted into this study will undergo an initial course of pharmacotherapy (phase I), and non-remmitters will be randomly allocated to five treatment arms (phase II). In phase I all participants will be treated with sertraline for 12 weeks.In phase II,The 5 arms will comprise 1) treatment with higher than usual doses of sertraline, 2) switch to fluvoxamine, 3) switch to venlafaxine, 4) augmentation with memantine, and 5) augmentation with aripiprazole. Clinicians and patients will know which treatment arm is being employed, but raters will be kept blind to treatment group.

Interventions

• Drug Sertraline 200 milligram(mg)
  All included participants will receive sertraline, initially at 50mg/d, with a weekly 50mg/d further increase, to the maximum recommended dosage (200mg/d) or to the maximum tolerated dosage (less than 200mg/d). Patients will be on their maximum dose by week 4, so allowing an assessment of response at 12 weeks
• Drug Sertraline 300 milligram(mg)
  In experimental phase II, the patients in this group will remain on sertraline (higher dosage): where sertraline 200mg has been tolerated, dosage will be increased by 50mg fortnightly to a maximal dose of 300mg/d or to the maximum tolerable dose (less than 300mg/d).
• Drug Fluvoxamine
  Fluvoxamine will be initiated at a dose of 50mg/d, increasing quickly to a maximal dose of 300mg/d or the maximum tolerated dose by week 4.
• Drug Venlafaxine
  venlafaxine will be initiated at 75mg/d, increasingly weekly by 75mg/day, to a maximal dose of 300 mg/d or the maximum tolerated dose.
• Drug Augment with Memantine
  Sertraline will be augmented with memantine initially at 5mg/d, and increasing by 5mg/d weekly to a maximal dose of 20mg/d (10mg twice daily) or the maximum tolerated dose
• Drug Augment with Aripiprazole
  Sertraline will be augmented with aripiprazole, initially at 5mg/d, and increasing by 5mg/d weekly to a maximal dose of 20mg/d or the maximum tolerated dose

Primary outcome measures

• Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [Time frame: from baseline to 12 weeks, and 12 weeks to month 6.]

Secondary outcome measures (6)

• The Clinical Global Impression (CGI) [Time frame: from 2 weeks to 12 weeks, and 12 weeks to month 6.]
• Beck Anxiety Inventory (BAI) [Time frame: from baseline to 12 weeks, and 12 weeks to month 6.]
• Beck Depression Inventory(BDI) [Time frame: from baseline to 12 weeks, and 12 weeks to month 6.]
• Obsessive-Compulsive Inventory-Revised(OCI-R) [Time frame: from baseline to 12 weeks, and 12 weeks to month 6.]
• Treatment Emergent Symptom Scale (TESS) [Time frame: from 2 weeks to 12 weeks , and 12 weeks to month 6.]
• Tolerability scale [Time frame: from 2 weeks to 12 weeks , and 12 weeks to month 6.]

Eligibility criteria

Inclusion criteria:They

• meet DSM-5 diagnostic criteria for OCD as the primary diagnosis ;
• are in the age range from 18 to 65 years;
• have a score of at least 20 on Yale-Brown Obsessive-Compulsive Scale (Y-BOCS);
• have never received medication for OCD, and have not received any form of psychotherapy for OCD in the past 1 month;
• have provided written informed consent.

exclusion criteria: They

• have met the DSM-5 diagnostic criteria for Schizophrenia Spectrum and Other Psychotic Disorders, or the Bipolar and Related Disorders;
• have a moderate or higher risk of suicide (⩾9 on the Suicide Module in the Mini-International Neuropsychiatric Interview (MINI));
• have substance use that is sufficiently severe to possibly impact negatively on treatment adherence in the past 1 year;
• have severe depression with Beck Depression Inventory (BDI) score of ≥29;
• have comorbid psychiatric or medical disorders that may impact negatively on adherence to or on the efficacy of medication (eg borderline personality disorder, CNS disorders)；
• are pregnant or lactating females.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Mental Health Center — Shanghai

Publications

• Wang P, Gu W, Gao J, Wang C, Fang J, Hu M, Xiang H, Li B, Liu N, Tang W, Wang X, Jia Y, Li Y, Cheng Y, Tang Z, Simpson HB, Stein DJ, Wang Z. Protocol for a Pragmatic Trial of Pharmacotherapy Options Following Unsatisfactory Initial Treatment in OCD (PROCEED). Front Psychiatry. 2022 May 16;13:822976. doi: 10.3389/fpsyt.2022.822976. eCollection 2022. PMID 35651818

Identifiers

NCT: NCT04539951 · CRC2018ZD03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗