Psychopharmacological Treatment of Obsessive-Compulsive Disorder Comorbid With Body Dysmorphic Disorder and Pathological Gambling Disorder

To the Editor: We would like to present a unique report that describes simultaneous treatment of three related disorders in one person, and the first case study of successful use of memantine in pathological gambling disorder (PGD). The concept of obsessive-compulsive–related disorders was introduced by Hollander, then refined to “obsessive-compulsive spectrum disorders” (OCSD); it involves obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), and PGD, among other numerous proposed psychiatric disorders.¹ Frequent comorbidity and treatment response to the serotonin-reuptake inhibitors (SRIs) in OCD, BDD, and PGD, are two facts that support the concept of OCSD. According to a study by Phillips et al.,² OCD, BDD, and comorbid BDD/OCD did not significantly differ in terms of age, marital status, or any patient demographic variable. However, a comorbid group had more severe OCD symptoms than an OCD-only group and more severe BDD symptoms than BDD-only group. The comorbid group was also more likely than subjects with OCD to have any mood disorder. Furthermore, depressive symptoms were significantly more severe in subjects with comorbid BDD/OCD than in those with “pure” OCD or BDD. Moreover, a higher proportion of the comorbid group had experienced suicidal ideation than subjects with OCD, and a higher percentage of the comorbid group had attempted suicide, as compared with both the OCD and BDD groups. Regarding treatment, if BDD is comorbid with OCD, SRIs can be used effectively to treat both disorders. In case a patient does not respond or BDD symptoms persist despite appropriate antidepressant dosing, one of the possible treatment suggestions is augmentation with an antipsychotic.³ As for pathological gambling, it is an impulse-control disorder. With respect to PG comorbidity with OCD, it was found to range from 1% to 20%.⁴ Regarding neurobiology of OCD, there are several lines of evidence that implicate glutamatergic neurotransmission dysfunction. These include genetic, cerebrospinal fluid, animal models, and pharmacological and clinical studies. All of this evidence posits that glutamatergic neurotransmission-based pharmacotherapy for OCD and OCDS deserves considerable attention and investigation. The list of possible candidates, that is, glutamatergic neurotransmission-modulating agents, includes riluzole, topiramate, lamotrigine, N-acetylcisteine, LY354740, memantine, amantadine, dizocilpin, and D-cycloserin.⁵

Considering PGD, specifically, one report, by Grant et al.⁶ emphasizes that modulation of glutamate by N-acetylcistein might be of crucial importance in reward-seeking behavior in PGD. The first basic science report of a memantine antagonism effect on glutamate was published in 1991 by Erdo et al.⁷ on cortical cell cultures, with the most recent spectroscopic study of effects of memantine on glutamate and glutamine concentrations in prefrontal cortex by van Wageningen et al.⁸

Furthermore, an open-label clinical study was conducted with memantine, showing its positive effects on OCD symptoms.⁹ Our patient, “Mr. N,” was a 23-year-old university student who was referred to us because of SRI-resistant OCD. Severe OCD and BDD were diagnosed at initial examination, with a YBOCS score 26 and initial YBOCS-BDD score of 30. Mr. N spent about 6 hours/day in obsessions and compulsive ritualistic behavior. The rituals included “ritual for ears,” which consisted of checking his ears on a bathroom mirror three times in a row. Before going to sleep, he checked his face twice in the mirror, then went twice to the bathroom and once outside to the street. If somebody interrupted him during a meal, he had to go to check his appearance in the bathroom mirror. When getting dressed, he avoided touching a wall; if he did touch it, he had to remove his clothes. When he heard the word “pressure,” he was obliged to leave the apartment. He called various parts of the apartment the “territory” (the living room, corridor, mirror, being separate territories). Nobody could interrupt him when crossing from one territory to another. Treatment with the SRI paroxetine 20 mg/day for 8 weeks was only effective on depressive symptoms (anamnesis data), with no improvement in OCD symptoms. The antipsychotic risperidone was initiated with 3 mg/day of risperidone, which resulted in a major improvement, with more than a 50% decrease in YBOCS score after 1 week (subclinical: 7 points on YBOCS).

At this point, he first mentioned “recreational gambling” (going every other day to bet on football matches). After 8 weeks of continuous combination of risperidone and paroxetine, we saw a remission of BDD, with a YBOCS BDD score of 15. Coincidentally, the pathological gambling symptoms emerged after resolution of OCD and BDD, when DSM-IV PGD was diagnosed, with an initial score on of 35 on the GSAS (severe PGD).¹⁰ Furthermore, his mother complained about his multiple aggressive requests for money in order to bet. Therefore, Mr. N was started on memantine 20 mg/day. After 8 weeks of memantine treatment, we noted a more-than-50% reduction on the GSAS (mild disorder score: 10), with more control over his thoughts about gambling, less anticipatory tension and excitation, and no personal trouble and aggressive acts toward his mother. After 12 weeks of memantine treatment, the same GSAS score was maintained. Placebo-controlled trials are needed to confirm our findings. We also suggest that higher doses of memantine might prove to be more effective than those administered in dementia and in our case study.