Naltrexone augmentation in OCD: a double-blind placebo-controlled cross-over study
Amiaz R, Fostick L, Gershon A, Zohar J;
Commented by , 30 Jun 2008
Aim
To determine if naltrexone augmentation relieves symptoms in obsessive compulsive disorder (OCD) sufferers who have failed to respond to 2 adequate trials of first-line medication.
Hypothesis
Naltrexone augmentation will improve symptoms of OCD compared to placebo augmentation of standard first-line medication to which there has been no initial response.
Method
10 OCD sufferers who had failed to respond to 2 or more adequate trials of standard pharmacological treatments were randomized into a double-blind crossover study. Each treatment was given for 5 weeks with a single week taper in between in conjunction with the patient's current treatment.
Two arms were used: 50mg of naltrexone, increasing to 100mg after one week, and placebo. Outcomes were measured at weekly intervals for the duration of the study, these included: OCD symptoms (Yale-Brown Obsessive compulsive scale, Y-BOCS), mood (Montgomery-Asberg Depression Rating Scale, MADRS), anxiety (Hamilton anxiety scale, HAM-A) and clinical impression (clinical global impression-improvement, CGI-I).
Results
When receiving naltrexone patients had significantly worse CGI-I and MADRS scores. HAM-A was worse in the naltrexone group when assessed on a drug x week ANOVA, but had no significant differences at any individual week. There were no significant differences in the Y-BOCS score between groups.
Dr Christmas', Dr Hood's and Prof Nutt's comments
With planning of a new Diagnostics and Statistics Manual (DSM-V) already underway, there is currently much debate over the reclassification of the anxiety disorders. One possibility being considered is the removal of OCD from the anxiety disorder group and into a group of "obsessive compulsive spectrum disorders" (OCSD).
This group has been proposed to include a wide spectrum of disorders such as: OCD, obsessive compulsive (or anankastic) personality disorder, trichotillomania, body dysmorphic disorder, eating disorders, impulse control disorders (such as pyromania, kleptomania, pathological gambling, and intermittent explosive disorder) and substance abuse disorders (ref. 1).
The primary arguments for moving OCD together with this new category of disorders include: the disorders share a core feature of repetitive thoughts and behaviours, high levels of comorbidity of OCSDs, shared familial/genetic factors, neurocircuitry abnormalities (fronto-striatal alterations) and a similar response to treatment (eg: treatment response to selective serotonin reuptake inhibitors) (ref. 1).
Many of these observations are contentious and none of them encompass the entirety of the disorders proposed to be included in the group. This has resulted in some very eloquent rebuttals of the proposal (ref. 2, ref. 3).
This debate has energised research in this field. A key issue is whether or not these disorders have fundamental biological similarities. Unfortunately, it is likely that DSM-V will be published before this issue has a chance to be resolved. One possible beneficial outcome from this debate in general is a greater determination to examine the biological characteristics of previously neglected areas of psychiatry.
The study reported here was essentially trying to find a link in treatment response between OCD and other members of the proposed OCSD group. Naltrexone is best known as an effective treatment in substance abuse disorders (ref. 4), but it also has some evidence of efficacy in other OCSDs: pathological gambling (ref. 5, ref. 6), kleptomania (ref. 7), compulsive sexual behaviour (ref. 8) and impulse control disorders (ref. 9).
Therefore, a positive result in this trial would have provided a tentative link between these disorders via a common response to opioid antagonists. Sadly, the authors repeat the unfortunate practice of using means and fractional integer values to describe the central tendency of the ordinal measure CGI-I, which should be discouraged.
Additionally, the study's other limitations of small sample size, augmentation rather than primary treatment design (especially given the heterogeneous primary medicines and) and use of treatment resistant patients (who are less likely to respond to any intervention), make the results far from definitive.
References
1. Hollander E, Braun A, Simeon D. Should OCD leave the anxiety disorders in DSM-V? The case for obsessive compulsive-related disorders. Depression and Anxiety 2008; 25 (4); 317-329
2. Storch EA, Abramowitz J, Goodman WK. Where does obsessive-compulsive disorder belong in DSM-V? Depression and Anxiety 2008; 25 (4); 336-347
3. Mataix-Cols D, Pertusa A, Leckman JF. Issues for DSM-V: how should obsessive-compulsive and related disorders be classified? American Journal of Psychiatry 2007; 164 (9); 1313-1314. (Free full text article)
4. Chick J, Anton R, Checinski K, Croop R, Drummond DC, Farmer R, et al. A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Alcohol and Alcoholism 2000; 35 (6); 587-593
5. Kim SW, Grant JE, Adson DE, Shin YC. Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling. Biological Psychiatry 2001; 49 (11); 914-921
6. Kim SW, Grant JE. An open naltrexone treatment study in pathological gambling disorder. International Clinical Psychopharmacology 2001; 16 (5); 285-289
7. Kim SW, Grant JE. An open-label study of naltrexone in the treatment of kleptomania. Journal of Clinical Psychiatry 2002; 63 (4); 349-356
8. Raymond NC, Grant JE, Kim SW, Coleman E. Treatment of compulsive sexual behaviour with naltrexone and serotonin reuptake inhibitors: two case studies. International Clinical Psychopharmacology 2002; 17 (4); 201-205
9. Kim SW. Opioid antagonists in the treatment of impulse-control disorders. Journal of Clinical Psychiatry 1998; 59 (4); 159-164