Title
Pragmatic Trial of Obsessive-compulsive Disorder
A Pragmatic Trial of Pharmacotherapy Options Following Unsatisfactory Initial Treatment in OCD
Phase
Phase 2Lead Sponsor
Jiao Tong UniversityStudy Type
InterventionalStatus
RecruitingIndication/Condition
Obsessive-Compulsive DisorderIntervention/Treatment
Sertraline 200 milligram(mg) Sertraline 300 milligram(mg) Fluvoxamine Venlafaxine Augment with Memantine [memantine (47023), sertraline (32536)] Augment with Aripiprazole [aripiprazole (102384), sertraline (32536)]Study Participants
1600This 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.
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.
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
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).
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.
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.
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
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
In experimental phase I, all recruited subjects provide written informed consent before any related procedures. 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
If participants in In Experimental phase I do not achieve remission, they will be will be randomly assigned to the second-step treatment (Experimental phase II). The second-step therapy will consist of five treatment options including higher-than-usual-maximal dosage of sertraline, switching to fluvoxamine, switching to venlafaxine, augmentation with memantine, and augmentation with aripiprazole.
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.
