Pulse-Loaded Intravenous Clomipramine in Treatment-Resistant Obsessive-Compulsive Disorder

Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 03/2006; 26(1):79-83. DOI: 10.1097/
Source: PubMed


Small studies have suggested that intravenous clomipramine (CMI) may be more effective and induce faster improvement in obsessive-compulsive disorder than do orally administered serotonin reuptake inhibitors.
To test these hypotheses, we conducted a randomized, double-blind, double-dummy study of pulse-loaded intravenous versus oral CMI, followed by open-label oral CMI for 12 weeks.
We enrolled a volunteer and referred group of 34 adults with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition obsessive-compulsive disorder of > or =1-year duration and Yale-Brown Obsessive Scale score of > or =20. Eligible subjects had failed > or =2 adequate serotonin reuptake inhibitor trials. Subjects received pulse loaded CMI 150 mg by vein or by mouth on day 1 and 200 mg on day 2. Oral CMI began on day 6 at 200 mg/d and was increased by 25 mg every 4 days to 250 mg/d, as tolerated, for 12 weeks.
Adverse events led to one withdrawal during oral pulse loading and 5 during open-label oral treatment. Intravenous pulse loading did not induce a more rapid or greater Yale-Brown Obsessive Scale score decrease than oral pulse loading at day 6 or by week 12. Day 6 and week 12 improvement were unrelated to plasma drug or metabolite concentrations. Pulse loading itself seemed to induce more rapid and greater improvement than expected in treatment-resistant obsessive-compulsive disorder.
Further investigation of oral pulse-loading regimens in treatment-resistant obsessive-compulsive disorder is warranted.

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Available from: Lorrin M Koran, Oct 29, 2015
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    • "In our study, we did not measure blood levels of clomipramine to correlate the concentration with the clinical response. However, other studies did not find any correlation between peak plasma CMI levels and a clinical response (Koran et al., 1997Koran et al., , 2006) Negative predictors of response have been identified: earlier onset, comorbid disorders (such as tic disorder), social phobia, schizotypal personality disorder, obsessive compulsive personality disorder, presence of hoarding obsessions, and a higher baseline severity of OCD symptoms (Erzegovesi et al., 2001). One study (Mundo et al., 1997) suggested that female subjects show a better anti-obsessional response, especially when treated with CMI. "
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    ABSTRACT: This open-trial was done to evaluate the effectiveness of intravenous (i.v) clomipramine (CMI), in refractory obsessive compulsive disorder (OCD). Thirty OCD poor responders to previous multiple trials of anti-obsessive medications were selected and admitted to the hospital. Severity of the illness and response to treatment were primarily assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). CMI was gradually administered intravenously for one week. All patients were thereafter switched to oral CMI with a maximum dose of 225 mg/day. Y-B OCS total score mean at admission was in the severe range (24-31), and dropped on discharge and follow-ups to moderate range (16-23).At discharge, 23 patients (76.7%) had a decrease in Y-B OCS ≥ 25% and were considered responders while only 18 (60%) were still responders at 24 weeks. No relevant persistent side-effects were reported. IV clomipramine could be of benefit for severe OCD that has not adequately responded to several therapies including oral clomipramine. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    Preview · Article · Jul 2015 · The International Journal of Neuropsychopharmacology
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    • "Intravenous (IV) CMI has been studied in adults, on an investigational basis, typically in inpatients with severe OCD not responsive to multiple prior medication trials, including oral CMI.82–84 IV CMI may be better tolerated than the oral form and it provides 4- to 14-fold higher peak plasma concentrations.83 Response rates in this highly refractory population have been low; for instance, in one placebo-controlled study of 46 patients, 21% of treated patients versus 0% of controls were responders after 2 weeks of daily infusions, with 58% maintaining responder status on oral CMI 1 month later.85 "
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    ABSTRACT: Obsessive-compulsive disorder (OCD) is a chronic anxiety disorder. While medication and psychotherapy advances have been very helpful to patients, many patients do not respond adequately to initial trials of serotonergic medication or cognitive-behavioral therapy (CBT) and require multiple treatment trials or combination therapies. Comorbidity may also influence treatment response. The role of streptococcal infections in pediatric OCD has become an area of intense scrutiny and controversy. In this article, current treatment methods for OCD will be reviewed, with special attention to strategies for treating OCD in children and in patients with comorbid tic disorders. Alternative psychotherapy strategies for patients who are highly anxious about starting CBT, such as cognitive therapy or augmentation with D-cycloserine, will be reviewed. Newer issues regarding use of antibiotics, neuroleptics, and glutamate modulators in OCD treatment will also be explored.
    Preview · Article · Aug 2011 · Neuropsychiatric Disease and Treatment
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    • "However , high dosages of sertraline and possibly citalopram can generate the same phenomenon (Preskorn, et al., 2007; Gillman, 2007; Mandrioli, et al., 2006). Still, no consistent relationship between magnitude or probability of therapeutic response in OCD and plasma concentrations of clomipramine or its metabolite or their sum has been found (Koran, et al., 2006). "
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    ABSTRACT: After 12 weeks of selective serotonin reuptake inhibitor (SSRI) monotherapy with inadequate response, 10 patients received clomipramine and 11 received quetiapine as augmentation agents of the SSRI. The primary outcome measure was the difference between initial and final scores of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), rated in a blinded fashion, and the score of clinical global improvement (CGI-I). Statistical analyses were performed using nonparametric tests to evaluate treatment efficacy and the difference between treatment groups. Percentile plots were constructed with YBOCS scores from the clomipramine and quetiapine groups. Considering response a >or=35% reduction in the initial Y-BOCS score plus a rating of 'much improved' or 'very much improved' on CGI-I, four of eleven quetiapine patients and one out of ten clomipramine patients were classified as responders. The mean final Y-BOCS score was significantly lower than baseline in the quetiapine augmentation group (P = 0.023), but not in the clomipramine augmentation group (P = 0.503). The difference between groups showed a trend towards significance only at week 4, the mean Y-BOCS score being lower for those receiving quetiapine (P = 0.052). A difference between groups was also observed at week 4 according to percentile plots. These results corroborate previous findings of quetiapine augmentation efficacy in obsessive-compulsive disorder (OCD). Clomipramine augmentation did not produce a significant reduction in Y-BOCS scores. Higher target maximum dosages might have yielded different results.
    Full-text · Article · Mar 2009 · Journal of Psychopharmacology
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