High-Dose Sertraline Strategy for Nonresponders to Acute Treatment for Obsessive-Compulsive Disorder: A Multicenter Double-Blind Trial

Rationale:In the rewarded alternation model of obsessive compulsive disorder (OCD), the serotonin agonist m-chlorophenylpiperazine (mCPP) increases persistent behaviour, while chronic pretreatment with selective serotonin reuptake inhibitor (SSRI-fluoxetine) but not benzodiazepine or desipramine abolishes mCPP effects. However, we noted that acute SSRI administration also causes transient persistence increases, counteracted by mCPP pretreatment.Objectives:This studya.further explores the apparent cross-tolerance between fluoxetine and mCPP andb.extends the model by investigating its sensitivity to dopaminergic manipulations (D2,3 agonism - quinpirole).Methods:In both experiments, baseline and drug testing was carried out under daily T-maze alternation training.Exp.1:Matched group (n=8) pairs of rats received one of the following 20-day pretreatments (daily intraperitoneal administration):1.saline,2.low-dose fluoxetine (2.5mg/kg),3.low-dose mCPP (0.5mg/kg) or4.combined fluoxetine+mCPP.One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10mg/kg), the other with high-dose mCPP (2.5mg/kg).Exp.2:One group (n=12) of rats received 20-day treatment with saline, another with quinpirole (0.5 mg/kg).Results:Exp.1:Saline and low-dose mCPP- or fluoxetine-pretreated animals showed significant persistence increases under both challenges, while combined low-dose fluoxetine+mCPP pretreatment afforded full protection from either challenge.Exp.2:Quinpirole significantly increased directional persistence after 13 administration days.Conclusions:These results establish the sensitivity of the rewarded alternation OCD model to D2,3receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.

Download Full-text

Duloxetine augmentation in resistant obsessive compulsive disorder: Surveying a new medication for challenges in treatment of OCD

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.361 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S415-S415

Author(s):

A. Mowla

Keyword(s):

Obsessive Compulsive Disorder ◽

Primary Outcome Measure ◽

Controlled Clinical Trial ◽

Double Blind Study ◽

Obsessive Compulsive ◽

Double Blind ◽

Compulsive Disorder ◽

Significant Difference ◽

Competing Interest ◽

To Receive

IntroductionUp to 50% of patients with OCD have failed to respond in SSRI trials, so looking for pharmacological alternatives in treatment of obsessive compulsive disorder (OCD) seems necessary.ObjectivesSurveying duloxetine augmentation in treatment of resistant OCD.AimsStudy the effects of serotonin-norepinephrine enhancers for treatment of OCD.MethodsThis augmentation trial was designed as an 8-week randomized controlled, double blind study. Forty-six patients suffering from OCD who had failed to respond to at least 12 weeks of treatment with a selective serotonin reuptake inhibitor (fluoxetine, citalopram or fluvoxamine) were randomly allocated to receive duloxetine or sertraline plus their current anti OCD treatment. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the primary outcome measure.ResultsForty-six patients (24 of 30 in duloxetine group and 22 of 27 in sertraline group) completed the trial. Both groups showed improvement over the 8-week study period (mean Y-BOCS total score at week 8 as compared with baseline: P < 0.001 and P < 0.001) without significant difference (P = 0.861). Those receiving duloxetine plus their initial medications experienced a mean decrease of 33.0% in Y-BOCS score and the patients with sertraline added to their initial medication experienced a mean decrease of 34.5% in Y-BOCS.ConclusionsOur double blind controlled clinical trial showed duloxetine to be as effective as sertraline in reducing obsessive and compulsive symptoms in resistant OCD patients. However, it needs to be noted that our study is preliminary and larger double blind placebo controlled studies are necessary to confirm the results.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Download Full-text