If you've tried everything else, here's a lead your doctor can check out. Although it's more dangerous for the average person with OCD to take street drugs, according to the following article there's a small percentage of patients that benefit from a low dose of morphine every 5 to 8 days. Some also benefit from narcotic antagonists like naltrexone. OCD, trichotillomania, self-injury, and compulsive picking are also discussed. The article was copied from the alt.support.ocd newsgroup on 02-23-99. ________________________________________________________________________ A Possible New Treatment Approach to Obsessive-Compulsive Disorder Dear Sir: I would like to report on a possible new treatment approach to obsessive-compulsive disorder (OCD). The use of narcotic antagonists and agonists has been of great benefit in a small number of treatment- resistant cases of OCD and OCD-spectrum disorders that have presented to the anxiety disorders clinic where I work. Two cases will be briefly discussed and the rationale for the use of narcotic agonists/antagonists also briefly reviewed. Case I is a 55-year-old, divorced, unemployed female who had severe OCD since early adolescence. Her main symptoms consisted of cleaning, checking, and preoccupation with detail that resulted in extreme slowness. Her illness waxed and waned but had become progressively worse over the years. Response to the usual antiobsessional medication was minimal. Under the care of a previous psychiatrist, she had received bilateral cingulotomies (he amputated parts of her brain) with no benefit. Under my care for the last 6 years, the patient showed no response to trials of all of the selective serotonin reuptake inhibitors (SSRIs), alone or in combination, or to a course of intravenous clomipramine infusions. Electroconvulsive therapy relieved her comorbid depression only for a short period of time. Cognitive- behavioural therapy provided by an experienced behavioural therapist was of limited benefit. A further psychosurgical procedure of bilateral anterior capsulotomy provided only temporary modification of symptoms. Over the last 2 years she developed a new symptom of compulsive picking that has become so severe that on admission to hospital, her face, breasts, and abdomen were severely excoriated. Demoralized, with few remaining family supports, she was being assessed for a nursing home placement because she no longer was able to cope on her own. On the basis of reports in the veterinary literature of narcotic antagonists being effective in compulsive behaviours in animals, as well as on the proven safety of naltrexone in the treatment of drug and alcohol addiction, I decided to try this approach in this patient. Naltrexone 50 mg/day was given initially and then increased to 100 mg/day. Within a few days, the compulsive picking dramatically decreased, although the patient continued to be very dysphoric. At this point, based on anecdotal report from another patient with severe OCD that her symptoms had dramatically remissed for up to a week when given morphine following surgery, I elected to try a narcotic agonist in this particular case. After a suitable washout period for the naltrexone, morphine sulphate was given subcutaneously a dose of 10 mg . The response was dramatic. Twenty-four hours later, the patient remained mildly euphoric and free of all OCD symptoms. This state lasted for several days. Oral morphine was then tried, and after some adjustment, a dose of 30 mg was found to be effective for 6 to 7 days, particularly diminishing the compulsive picking and the dysphoria. Other narcotic agonists such as propoxyphene and pentazocine, had no effect. The patient continued to do well on the oral morphine and entered a rehabilitation program, where the morphine was discontinued. She suffered a relapse, but now she remains much improved after the morphine was restarted at a dose of 30 mg every 5 to 6 days. Case 2 was a 35-year-old single female who was unemployed but trained as an accountant. She had severe trichotillomania, (compulsively plucked on her hair) which began in her early 20s; she had received extensive treatment for this condition, but all of the SSRIs including clomipramine, had been ineffective. She had no other symptoms of OCD or depression. The trichotillomania worsened under stress and was confined to her head and eyebrows. She wore a wig because of large areas of baldness. Her life had become very restricted because of the time spent in hair- pulling activity and the embarrassment of her being bald. Repeated trials of SSRIs with augmentation remained ineffective. A trial of naltrexone was undertaken at 100 mg/day. After 2 to 3 weeks, the trichotillomania dramatically decreased, and her hair started growing back. Unfortunately she could not afford the cost of the medication and discontinued it with a return of symptoms. Since these 2 cases were treated, 4 other end-stage cases of OCD (the only other option was psychosurgery) have been successfully treated with oral morphine, the dose ranging from 20 to 40 mg given every 5 to 8 days. Three cases of OCD-spectrum disorder (2 with trichotillomania, one with compulsive gambling) have been treated with naltrexone with marked improvement. The use of narcotic antagonists has been undertaken before for various impulse-control disorders in humans, as well as for stereotypical behaviour in animals. Repetitive, self-injurious behaviour in humans is a complex phenomenon to understand and to treat. Narcotic antagonists such as naltrexone or naloxone have been shown to diminish such behaviours in humans for several days following the administration of a single dose. This approach has been tried in mentally challenged adults who repeatedly injure themselves and in compulsive wrist cutters (1-4). A similar positive effect is seen in stereotypical behaviours in animals such as acral lick, flank sucking, tail chasing in dogs, crib biting, flank biting in horses, and repetitive chewing behaviours in pigs, to name a few. In animals, narcotic antagonists such as naltrexone, Nalmefene, and naloxone have been effective for several days after a single dose (5-8). The narcotic antagonist naltrexone has also been successfully used for the treatment of alcohol and drug addiction (9,10), although its mechanism of action is not clear. It is postulated that the opiate receptor system functions as part of the positive reinforcement or reward system of the brain. Painful stimulation has been demonstrated to produce an increase of endorphin release leading to pain relief. A model has been developed in which pain-inducing behavior such as wrist cutting is postulated to result in endorphin release leading to relief of pain and tension, which then reinforces the original behaviours (1,11). In alcoholism, narcotic antagonists are postulated to block this pleasure or reward system, which leads to cessation of the drinking behaviour (12). The opioid receptor system in the brain is complex, and although some of the effects of morphine have been known for hundreds of years, it was only in 1973 that opiate-binding sites were discovered in the central nervous system of mammals and not until 1976 that the first endogenous opioids were discovered (13,14). Further to this, several classes of opiate receptors have been delineated, the main ones being mu, delta, and kappa, although there are others (15). Morphine works primarily on the mu receptor with analgesia and/or euphoria being the result, but it has an effect on the other receptors as well. Subtypes of each receptor have also been identified, and of possible relevance to OCD is the concentration of opioid receptors found in the striatal system, particularly the caudate nuclei (16,17), which appear to be an important region in the pathogenesis of OCD (18,19). In the cases in which morphine was useful, it is puzzling why the effect lasted for at least 5 days following a single oral dose. None of the patients reported a euphoric response beyond what could be expected as a result of symptom relief. This suggests the involvement of opioid receptors other than the mu receptor. The risk of addiction, if this is true, should be very low, if it exists at all. The cases discussed are being followed very closely from this perspective, but there has been no evidence of dose escalation. The response to narcotic agonists or antagonists in a few cases is similar to that reported in the veterinary literature and reinforces the concept of a neuroethological approach to the understanding of OCD, with a possible common pathogenesis for stereotypies in animals, such as the acral lick syndrome in dogs, and similar repetitive motor behaviours in humans, such as compulsive picking or hair pulling (20,21). Although there are many useful treatment approaches for OCD, about 30% of patients do not respond to traditional therapy and continue to remain very chronically ill. The last-resort treatment is often psychosurgery, a procedure not readily available for most (22). It is hoped that this letter may stimulate other thoughts on this subject. Clearly, there is a need for research. Of interest, a recent television documentary on medical advances had a short section in OCD. A psychiatrist from Baylor Medical College in Texas was interviewed and made a brief comment about the successful use of morphine in a few cases of otherwise intractable OCD. I am in the process of trying to find the name of this individual. Lorne Warneke, BSc, MD, FRCPC Edmonton, Alberta References 1. Richardson IS. Zaleski W. Naloxone and self-mutilation. Biol Psychiatry 1983:18:99-101. 2. Hennan B. et al. Naltrexone decreases self-injurious behaviour. Ann Neurol 1987:22:550-2. 3. Davidson W, et al. Effects of naloxone on self-injurious behaviour. Research in Mental Retardation 1993:4;1-4. 4. Lienemann J, I Walter F. Reversal or self-abusive behaviour with naltrexone (letter]. J Clin Psychopharmacol 1989:9:448-9. 5. Kiley-Worthington M. Stereotypes in horses. Equine Pract 1983:5:34-40. 6. Brown S. Crowell-Davia 5, Malcolm T. Edwards P. Naloxone-response compulsive tail chasing in a dog. JAMA 1987;190:8844. 7. White S. Naltrexone for treatment of acral lick dermatitis in dogs. JAMA 1990; 1996: 1073-6 8. Dodman N. et al. Use of narcotic antagonists to modify stereotypic self-licking, self-chewing and scratching behaviour in dogs. JAMA 1988;193:815-9. 9. Volpicelli S et al. O'Brien C. Effect of naltrexone on alcohol 'high' in alcoholics. Am J Psych 1995:152:613-5. 10. O'Malley SS. Naltrexone and coping skills therapy for alcohol dependency. Arch Gen Psychiatry 1991:49:1181-7. 11. Winchal FL Stanley M. Self-injurious behaviour a review of the behaviour and biology of self-mutilation. Am J Psych 1991:1411;306-17. 12. Bozuth M. Opiate reinforcernent processes: reasssembling multiple mechanisms. Addiction 1994:89:1425-34. 13. Pert CB. Snyder SH. Opiate receptor: demonstration in nervous issue. Science 1973:179:1011-4. 14. Hughes J et al. Identification o two related pentapeptides from the brain with potent opiate agonist activity. Nature 1975:258:577-9. 15. Unterwald EM. Zukin RS. The endogenous opioidergic system. In: Reid D. editor Opioids, bulimia and alcohol abuse and alcoholism. Anne Arbor (MI):Springer-Verlag: 1990. p. 49-72. 16. Murin LC et al. Striatal opiate receptors: pre- and post- synaptic localization Life Sci 1980:27:1175-83. 17. Woo SK. et al. Specific opioid-amphetamine interactions in the caudate putamen. Psychopharmacology 1985:85:271-6. 18. Baxter L, Schwartrr S. Bergnsann K. Caudate glucose metabolic rate changes with both drug and behaviour therapy for obsessive-compulsive disorder. Arch Gen Psych 1992:49:681-9. 19. Swedo S. et al. Cerebral glucose metabolism in childhood-onset obsessive- compulsive disorder: revisualization during pharmacotherapy. Arch Gen Psychiatry 1992:49:690-4. 20. Stein DJ. et al. The neuroethological method of obsessive-compulsive disorder. Compr Psychiatry 1992:33:274-81. 21. Hollander E. Behavioural disorders in veterinary practice: relevance to psychiatry. Comp Psychiatry 1994:35:275-85. 22. Jenike M. Pharmacologic treatment of obsessive compulsive disorder. Psychiatr Clin North Am 1992:15:895-919. Posted in accordance for educational purposes as allowed for by the fair use doctrine. Commercial use is prohibited. ___________________________________________________________________ This page is hosted by GEOCITIES Get your own Free Home Page at http://www.geocities.com