AbstractThe overallobjective of this study is to test if the drugs clomipramineor D-cycloserine can enhance the relative, combined efficacy ofExposure-Response Prevention Therapy (ERP) in treating Obsessive–Compulsivedisordered adult patients (Storch et al., 2007). Obsessive–compulsivedisorder is a prevalent, persistent and immobilizing life disorder. There aretwo confirmed first-line therapies for treatment of OCD; Serotonin reuptakeinhibitors (SRIs), an antidepressant drug and Exposure-ResponsePrevention Therapy (ERP) which is a type of Cognitive Behavior Therapy(CBT) (Storch et al., 2007). Even though, ERP and SRIs are said to be the bestavailable treatments for OCD some patients after the interventions don’texperience a complete symptom resolution (Foa et al.
, 2005). Clomipramine,a tricyclic antidepressant, and D-cycloserine, an antibiotic was researched andrevealed to help enhance ERP effects in OCD. However, there are still gaps inthe studies that have yet to disclose if there is a direct link in Clomipramineor D-cycloserine medications and an increase in efficacy of ERP. 60 adultparticipants with OCD are randomized, double-blinded into 2 placebo-controlledtrials 1. ERP + DCS versus ERP + Clomipramine versus ERP + placebo 2.
DCSversus Clomipramine versus placebo. Predicted results are patients who receivethe treatment combination of a drug and ERP Therapy will have a higher successrate of the extinction of OCD rather than patients who only receive ERP Therapyor only a drug.Can Certain Drugs Enhance the Effectsof Exposure-Response Prevention Therapy in Adult Obsessive-CompulsiveDisordered patients?As humans we all differ in personalities, characteristics and behaviorslike the little mannerisms we do or the weird pet peeves we might have.However, there is a point in which a small recurring compulsive act or behaviorcan become an obsession and take toll on one’s everyday life. OCD (Obsessive-compulsive disorder) is amental illness described as having recurrent obsessive images, thoughts, orimpulses eliciting anxiety and causing one to act in compulsive behaviors ormental acts to reduce distress (Foa et al.
, 2005). OCD was viewed as acondition with an unfavorable prognosis, predominantly in individual patientspresenting severe symptoms, slow onset, and non-episodic progression (Slater& Roth, 1969). It is a common and chronic disorder which can affect peopleof all ages and is characteristically a very disabling life disorder. Asix-month prevalence is estimated at 1%–2% (Myers et al., 1984) while a lifetimeprevalence is at 2%–3% (Karno et al., 1988, Robins et al.
, 1984). The quitehigh prevalence, the usually long gap between onset and treatment, and therelated omnipresent dysfunctions emphasize the significance for developing andallocating effective treatments for OCD diagnosed patients (Foa et al., 2005).This study seeks to advance further research in the approaches taken fortreating people suffering from OCD.Exposure-Response Prevention TherapyExposure-Response Prevention Therapy (ERP) is a type of CognitiveBehavior Therapy (CBT), which is currently stated to be the superior type ofpsychotherapy for treatment of Obsessive-CompulsiveDisorder (March et al.
, 1997). ERP therapy works by promoting fearextinction by unlearning fears through long orderly sessions of exposure tostimuli that is anxiety eliciting and prevention from fear reducing actions andbehaviors like avoidance and rituals (Chasson et al., 2010).
Sinceits first debut in 1966 by Victor Meyer, many patients have been treated byvariations of the procedure (Boulougouris& Bassiakos. 1973; Catts & McConaghy, 1975; Emmelkamp & Kraanen,1977; Foa & Goldstein, 1978; Marks, Hodgson, & Rachman, 1975). About10 to 20 sessions are linked with reduction of OCD symptoms in approximately85% of patients and 55% stating a significant improvement” (Chasson et al.,2010) . Although, there is an issue in which the success rates don’t take intoaccount of the high 25% patient refusal or dropout rates (Schruers et al.
,2005). As well, ERP therapy doesn’t help all diagnosed patients and individualswho do benefit incompletion of the interventions often remain somewhatsymptomatic. Alternative methods are needed such as serotonergic medicationsspecifically Serotonin Reuptake Inhibitors (SRIs), an antidepressantdrug which is the second of the only 2 first-line established treatments forOCD (EPR therapy being the first). Although, SRIs have moderate efficiency andare typically coupled with unwanted side effects (Storch et al.
, 2007). Therefore,further investigation in the methodologies that may enhance the treatment efficacyof ERP therapy are necessary. ClomipramineA deeper exploration of different types of pharmacotherapies arerequisite for OCD treatment. Clomipramine is a tricyclic antidepressant thoughtto help enhance the effects of ERP therapy. While limitations of side effectsomit clomipramine from being used as a first-line treatment it still residesboth the most efficacious and best studied drug for OCD(Foa et al., 2005). It was originally acknowledged by clinicalresponse (Capstick& Seldrup, 1973; Marshall & Micev, 1975; Van Renynghe de Voxvrie, 1968)and was subsequently proved through placebo-controlled trials (Thoren, Asberg,Cronholm, Jomestedt, & Traskman, 1980). Marks et al.
(1988),compared the effects of clomipramine and placebo over 4 weeks, followed by anadditional 3 weeks of ERP or relaxation (Foa et al., 2005). In the study’sresults the combination of ERP therapy with administered clomipramine had an acute progressiveadded effect in comparision to the ERPplacebo combination (Marks et al., 1988). In addition, anotherstudy, the Christensen et. al (1987) study, which investigated many otherapproaches for OCD treatment found that the characteristic of reducingobsession ability was stated to be connected with clomipramine drug.
However,both studies did not for a direct comparisonof ERP and clomipramine alone, there is an absence of a major, randomized,controlled trial comparing these two treatments (Christensen et al., 1987). the sufficiency ofantidepressant treatment on patients with the absence of depression is still unclear,where related studies contrast in conclusions. Some authors like Markset al. (1983), have contented to the statement that in obsessive compulsives,antidepressants are only effective if there was an initial presence ofdepression (Christensenet al., 1987), while others like (Insel et. al, 1983), have contested that theclomipramine drug has a certain therapeutic effect on obsessive-compulsivesymptoms (Christensen et al., 1987).
D-cycloserineConsidering different types of medication other than antidepressantsas a source for treating OCD is seen in some research studies. Perviousevidence advocates that the antibioticD-cycloserine (DCS), initially approved by the Food and Drug Administration(FDA) to treat tuberculosis, Alzheimer’s disease negative symptoms inschizophrenia (Storch et al., 2007), effectively increases the therapeuticeffects of Exposure and Response Prevention therapy for Obsessive–CompulsiveDisorder (Chasson et al., 2010). Research focused studies on the neuralcircuitry lead to DCS being used as an adjunctive pharmacological approach aswhen paired with ERP it supposedly aids in the underlying extinction of fear throughenhancing associative learning by operating as a partial agonist atN-methyl-d-aspartate (NMDA) receptors in the amygdala of the brain (Storch et al., 2007) and thus, used as a technique to enhance ERP results. Conversely,many receptor agonists ofNMDA are connected to substantialneurotoxicity, signifying that these partial agonists are more beneficial to notexpose patients to this serious health risk (Storch et al., 2007).
Additionally, data advocates that the effects of D-cycloserine disappear midwaythrough the treatment process, but it is unknown as to what extent. (Chasson etal., 2010).The Present StudyA vital query concerns the combined and relative efficacy of thementioned treatments. In the treatment of OCD patients, research supports theidea that additional medications other than SRIs can be used to enhance theefficiency of ERP therapy. Though, in terms of the two pharmaceuticaltreatments (Clomipramine and D-cycloserine), research seems to suggest resultsof enhancing ERP but all such studies lack the ability to come to one unitedconclusion in which these drugs actually benefit the OCD patient by reducingthe obsessive-compulsive symptoms and directly facilitating the efficacy ofERP. In the present study, the researcher will manipulate the type of druggiven to each participant in combination with ERP therapy vs its controls foreach to clearly view if there is a direct effect of each type of drug on OCDthrough enhancing ERP. The researcher predicts that the Obsessive CompulsiveDisordered patients who receive the treatment combination of a drug andExposure-Response Prevention Therapy will have a higher success rate of theextinction of OCD rather than patients who only receive ERP Therapy or only adrug.
The researcher also hypothesizes that patients receiving Clomipramine astheir drug treatment (with or without out ERP) will have more success intreating OCD symptoms than those receiving D-cycloserine.MethodParticipants In this study, the participants include 60 adult patients with aObsessive Compulsive Disorder as a primary diagnosis. They recruited from localpsycratic hosipitals. Aged 20-40 years with no comorbidity of other diagnoses(psychosis, autism, bipolar disorder, or substance dependence or abuse). Nosite differences across baseline demographics (range in ethnicity and race) orclinical characteristics (Storchet al., 2010). Participants cannot be pregnant or be having unprotectedsex (for females), have epilepsy, primary hoarding symptoms, renalinsufficiency, or generally poor physical health (Storch et al.
, 2010).MaterialsDiagnosis of OCDestablished with a Structured Clinical Interview for DSM-IV Axis I disorders,Patient Edition (SCID-I/P; First, Spitzer, Gibbon, & Williams, 1995).”The SCID is a widely used semi-structured, clinician-administeredinterview designed to establish psychiatric diagnoses based on criteria fromthe Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (APA,2000)”(Chassonet al., 2010, p. 677). “Yale-Brown obsessive–compulsivescale-self-report (Baer et al., 1993; Steketee et al., 1996)” (Chasson etal.
, 2010, p. 677). “The Y-BOCS-SR originated from theclinician-administered version (Goodman et al., 1989a, 1989b), which is said tobe the best standard evaluation of OCD severity (Grabill et al., 2008)” (Chasson etal.
, 2010, p. 677). The assessment contains 10 severity measuring itemsfor “obsessions and compulsions using a five-point scale (higher scorescorrelate to more severityz)” (Chasson et al.
, 2010, p. 677). “The Y-BOCS-SR hasproved to posse exceptional validity and reliability (Steketee et al.
,1996)” (Chassonet al., 2010, p. 677).Design This experimentconsists of 2 double-blinded, randomized Placebo-controlled trial. 6 groupswith 10 patients per group. 1.
ERP + DCS versus ERP + Clomipramine versus ERP +placebo 2. DCS versus Clomipramine versus placebo. Those patients who receiveERP get ten exposure and response prevention sessions paired with DCS orClomipramine or placebo taken 1 hour before sessions (Storch et al., 2010).Those patients who don’t receive ERP get DCS or Clomipramine or placebo at thesame time the other patients receiving ERP sessions take theirs. ProcedureFully informedeach participant of the purpose and procedures of the study then obtain writtenconsent.
At pretreatment participants received an assessment, after the tenth session,posttreatment, and one month after treatment termination (Chassonet al., 2010). At pretreatment, participants complete study measures(OCD diagnosis determined by structured clinical interview for DSM-IV and SCID),physical examinations and determination if DCS and Clomipramine is contraindicatingwith study physicians (SCID; Miller and Rollnick 2002). A computer-generatedprogram randomizes participants in a double-blinded fashion to ERP + DCS or ERP+ Clomipramine or ERP + placebo or DCS or Clomipramine or placebo (Chasson etal., 2010). The participants receiving ERP therapy receive 10 twice-weekly,60-min ERP sessions administered by licensed clinical psychologists.
One hourbefore each session, participants received either a 100 mg pill of DCS or Clomipramineor placebo. At this time, participants not receiving ERP receive their pill aswell and is administered in a double-blind fashion. Participants also completeda self-report version of the Yale-Brown Obsessive–Compulsive Scale (Baer etal., 1993; Steketee et al., 1996) before each session/before pill is taken (Chasson etal.
, 2010). Participants were administered the Y–BOCS-SR every twosessions/pill taken to assess rate of change (Storch et al., 2007)