Excoriation (skin-picking) disorder in adults: a cross-cultural survey of Israeli Jewish and Arab samples.

OBJECTIVE: We sought to estimate the lifetime prevalence of Excoriation (Skin-Picking) Disorder (SPD) in the Israeli adult population as a whole and compare SPD prevalence in the Jewish and Arab communities. We also explored demographic, medical and psychological correlates of SPD diagnosis. METHODS: Questionnaires and scales screening for SPD, and assessing the severity of perceived stress, depression, obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), alcohol use, illicit drug use, and medical disorders were completed in a sample of 2145 adults attending medical settings. RESULTS: The lifetime prevalence of SPD was 5.4% in the total sample; it did not differ between genders or within Jewish and Arab subsamples. Severity of depression (p<0.001), OCD (p<0.001) and perceived stress (p=<0.001) were greater in the SPD positive sample. Similarly, diagnoses of BDD (p=0.02) and generalized anxiety (p=0.03) were significantly more common in the SPD-positive respondents. Alcohol use and illicit substance use were significantly more common among SPD positive respondents in the total sample (both p's=0.01) and the Jewish subsample (p=0.03 and p=0.02, respectively). Hypothyroidism was more prevalent in the SPD-positive Jewish subsample (p=0.02). In the total sample, diabetes mellitus was more common in women than in men (p=0.04). CONCLUSION: Lifetime SPD appears to be relatively common in Israeli adults and associated with other mental disorders. Differences in the self-reported medical and psychiatric comorbidities between the Jewish and Arab subsamples suggest the possibility of cross-cultural variation in the correlates of this disorder.

Obsessive-compulsive symptoms in schizophrenia: implications for future psychiatric classifications.

Although obsessive-compulsive symptoms are not considered primary features, they are prevalent, independent of psychosis, and substantially modify clinical characteristics, course, treatment and prognosis of schizophrenia. The authors highlight the clinical significance of obsessive-compulsive symptoms in schizophrenia, provide diagnostic criteria for "schizo-obsessive" patients and address future directions for research.

Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI.

Despite the impressive safety of gadolinium (Gd)-based contrast agents (GBCAs), a small number of patients report the onset of new, severe, ongoing symptoms after even a single exposure-a syndrome termed Gadolinium Deposition Disease (GDD). Mitochondrial dysfunction and oxidative stress have been repeatedly implicated by animal and in vitro studies as mechanisms of Gd/GBCA-related toxicity, and as pathogenic in other diseases with similarities in presentation. Here, we aimed to molecularly characterize and explore potential metabolic associations with GDD symptoms. Detailed clinical phenotypes were systematically obtained for a small cohort of individuals (n = 15) with persistent symptoms attributed to a GBCA-enhanced MRI and consistent with provisional diagnostic criteria for GDD. Global untargeted mass spectroscopy-based metabolomics analyses were performed on plasma samples and examined for relevance with both single marker and pathways approaches. In addition to GDD criteria, frequently reported symptoms resembled those of patients with known mitochondrial-related diseases. Plasma differences compared to a healthy, asymptomatic reference cohort were suggested for 45 of 813 biochemicals. A notable proportion of these are associated with mitochondrial function and related disorders, including nucleotide and energy superpathways, which were over-represented. Although early evidence, coincident clinical and biochemical indications of potential mitochondrial involvement in GDD are remarkable in light of preclinical models showing adverse Gd/GBCA effects on multiple aspects of mitochondrial function. Further research on the potential contributory role of these markers and pathways in persistent symptoms attributed to GBCA exposure is recommended.

Dynamic Serial Cytokine Measurements During Intravenous Ca-DTPA Chelation in Gadolinium Deposition Disease and Gadolinium Storage Condition: A Pilot Study.

PURPOSE: The aim of this study was to investigate the feasibility of measuring early changes in serum cytokine levels after intravenous diethylenetriaminepentaacetic acid (Ca-DTPA) chelation in patients manifesting either gadolinium deposition disease (GDD) or gadolinium storage condition (GSC) and the possible usefulness of this method in further research. METHODS: Four patients with recent-onset GDD (≤1 year) and 2 patients with long-standing GSC (4 and 9 years) underwent chelation with intravenous bolus administration of Ca-DTPA. Multiple blood draws were performed to measure serum cytokines: at T = 0 (before Ca-DTPA injection) and 1, 5, 10, 30, 60 minutes, and 24 hours after Ca-DTPA injection. Patients rated the severity of GDD symptom flare at 24 hours. The 24-hour urine Gd amounts were measured prechelation and for the 24 hours after chelation. Serum samples were analyzed blind to whether patients had GDD or GSC but with knowledge of the time points characterizing each sample. RESULTS: Urine samples for both GDD and GSC patients showed increases in Gd postchelation. All GDD patients experienced flare reactions postchelation; the 2 GSC patients did not. Two cytokines, EGF and sCD40L, peaked at 30 minutes postchelation in at least 4 of the 6 participants. Three cytokines, ENA78/CXCL5, EOTAXIN/CCL11, and LEPTIN, peaked at 24 hours in at least 4 of the 6 participants. Two participants were high outliers for a large number of cytokines across time points. No clear distinction between GDD and GSC was apparent from the cytokine patterns, although differences were present. CONCLUSIONS: This pilot study describes precise temporal resolution (in the range of minutes) after a cytokine-inciting event. Select cytokines exhibited peak values at different time points. At this preliminary stage of investigation, peak cytokine release seems to reflect the amount of Gd mobilized rather than the severity of the patient symptomatic reaction. Too few subjects were studied to support statistical analysis between GDD and GSC groups, although differences were observed through visual data analysis.

Open-label trial of aripiprazole in the treatment of trichotillomania.

BACKGROUND: Serotonin reuptake inhibitors have been disappointing in the treatment of trichotillomania (TTM). Recent evidence suggests that medications that modulate dopamine may be helpful in this disorder. OBJECTIVE: To determine if the D2 partial agonist aripiprazole would be effective in the treatment of TTM. METHODS: Twelve subjects participated in an 8-week, open-label, flexible-dose study of aripiprazole treatment of TTM. Primary end points were reduction in the Massachusetts General Hospital Hair Pulling Scale (MGHHPS) and MGHHPS Actual Pulling Subscale (MGHHPS-APS). Secondary end points were the Clinical Global Impressions-Improvement Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Beck Depression Inventory, and Beck Anxiety Inventory. RESULTS: Eleven of 12 subjects had 2 or more assessments; one subject dropped out during the first week. For subjects with 2 or more assessments, there was a significant mean reduction in both primary end points, the MGHHPS score (mean change, 7.8; SD, ± 7.8; P ≤ 0.01) and the MGHHPS-APS score (mean change, 3.9; SD, ± 4.1; P ≤ 0.02). Seven subjects had a greater than 50% reduction in MGHHPS; 7 subjects had an exit Clinical Global Impressions-Improvement Scale of 2 or lower, and 5 participants had absolute exit scores of 3 or lower on the MGHHPS and 1 or lower on the MGHHPS-APS. There were no significant changes in mood-related secondary end points. The mean aripiprazole dose for all completers (N = 11) was 7.5 mg/d (± 3.4 mg/d). CONCLUSIONS: This small open-label study suggests that aripiprazole is a promising treatment for the treatment of trichotillomania. Larger double-blind, placebo-controlled studies are needed to follow up on these findings.

Psychiatric complications of treatment with corticosteroids: review with case report.

Corticosteroids are widely used in modern medicine but can result in troubling psychiatric side-effects. Physicians and other medical professionals should be aware of the potential for these side-effects, possible means of prevention, and efficacious treatments. Herein, we review adult case report data published during the past quarter-century on adverse corticosteroid-induced psychiatric effects, and present a case of corticosteroid-induced psychotic depression. PubMed and PsychLit databases were searched using the terms 'corticosteroids', 'steroids', and the generic names of corticosteroid medications with terms for psychiatric symptoms or syndromes, including psychosis, mania, hypomania, depression, apathy, anxiety, panic, depersonalization, delirium, confusion, hallucinations, delusions, paranoia, cognitive impairment and dementia. Fifty-five cases and a number of clinical trials investigating the incidence and treatment of these psychiatric symptoms and syndromes were identified. Data on incidence, drug dose, risk factors, course of illness and treatment (when present) were tabulated. We conclude that the cumulative data indicate that psychiatric complications of corticosteroid treatment are not rare and range from clinically significant anxiety and insomnia, to severe mood and psychotic disorders, delirium and dementia. While tapering or discontinuation of the corticosteroid treatment may remedy these adverse side-effects, psychotropic medications are often required because of the medical necessity of the corticosteroid or the severity of the psychiatric symptom. Further studies are needed to better understand the deleterious psychiatric effects associated with corticosteroids.

Altered Functional Mitochondrial Protein Levels in Plasma Neuron-Derived Extracellular Vesicles of Patients With Gadolinium Deposition.

The retention of the heavy metal, gadolinium, after a Gadolinium-Based Contrast Agent-assisted MRI may lead to a symptom cluster termed Gadolinium Deposition Disease. Little is known of the disorder's underlying pathophysiology, but a recent study reported abnormally elevated serum levels of pro-inflammatory cytokines compared to normal controls. As a calcium channel blocker in cellular plasma and mitochondrial membranes, gadolinium also interferes with mitochondrial function. We applied to sera from nine Gadolinium Deposition Disease and two Gadolinium Storage Condition patients newly developed methods allowing isolation of plasma neuron-derived extracellular vesicles that contain reproducibly quantifiable levels of mitochondrial proteins of all major classes. Patients' levels of five mitochondrial functional proteins were statistically significantly lower and of two significantly higher than the levels in normal controls. The patterns of differences between study patients and controls for mitochondrial dynamics and mitochondrial proteins encompassing neuronal energy generation, metabolic regulation, ion fluxes, and survival differed from those seen for patients with first episode psychosis and those with Major Depressive Disorder compared to their controls. These findings suggest that mitochondrial dysfunction due to retained gadolinium may play a role in causing Gadolinium Deposition Disease. Larger samples of both GDD and GSC patients are needed to allow not only testing the repeatability of our findings, but also investigation of relationships of specific mitochondrial protein deficiencies or excesses and concurrent cytokine, genetic, or other factors to GDD's neurological and cognitive symptoms. Studies of neuronal mitochondrial proteins as diagnostic markers or indicators of treatment effectiveness are also warranted.

Acute Chelation Therapy-Associated Changes in Urine Gadolinium, Self-reported Flare Severity, and Serum Cytokines in Gadolinium Deposition Disease.

OBJECTIVES: The aim of this study was to determine the following in patients who have undergone magnetic resonance imaging with gadolinium-based contrast agents (GBCAs) and meet the proposed diagnostic criteria for gadolinium deposition disease (GDD): (1) the effectiveness of chelation therapy (CT) with intravenous Ca-diethylenetriaminepentaacetic acid in removing retained gadolinium (Gd) and factors affecting the amount removed; (2) the frequency of CT-induced Flare, that is, GDD diagnostic symptom worsening, and factors affecting Flare intensity; (3) whether, as reported in a separate cohort, GDD patients' serum cytokine levels differ significantly from those in healthy normal controls and change significantly in response to CT; and (4) whether urine Gd, Flare reaction, and serum cytokine findings in GDD patients are mimicked in non-ill patients described as having gadolinium storage condition (GSC). MATERIALS AND METHODS: Twenty-one GDD subjects and 3 GSC subjects underwent CT. Patients provided pre-CT and post-CT 24-hour urine samples for Gd content determination along with pre-CT and 24-hour post-CT serum samples for cytokine analysis. Patients rated potential Flare 24 hours after CT. Pre-CT and post-CT 24-hour urine Gd analyses and Luminex serum cytokine assays were performed blind to patients' GDD and GSC status and all other data except age and sex. Serum cytokine levels in a healthy normal control group of age- and sex-matched subjects drawn from Stanford influenza vaccination studies were measured once, contemporaneously with those of GDD and GSC patients, using the same Luminex assay. RESULTS: Urine Gd amounts increased post-CT by 4 times or more after 87% of the 30 CT sessions. The most important factors appeared to be the time since the last GBCA dose and the cumulative dose received. Urine Gd amounts for GDD and GSC patients fell in the same ranges. All GDD patients, and no GSC patient, reported a Flare 24 hours post-CT. Linear regression found that Flare intensity was significantly predicted by a model including pre- and post-CT Gd amounts and the number of GBCA-enhanced magnetic resonance imaging. Post-CT, multiple cytokines showed strong positive relationships with GDD patients' Flare intensity in multivariable models. The pre-CT serum levels of 12 cytokines were significantly different in GDD patients compared with healthy flu vaccine controls. The small number of GSC patients precluded analogous statistical testing. Post-CT, GDD patients' serum levels of 20 cytokines were significantly decreased, and 2 cytokines significantly increased. These cytokines did not exhibit the same change pattern in the 3 GSC patients. The small number of GSC patients precluded statistical comparisons of GSC to GDD patients' results. CONCLUSIONS: In this preliminary study, 24-hour urine Gd content increased markedly and similarly in GDD and GSC patients after Ca-diethylenetriaminepentaacetic acid CT. Post-CT Flare reaction developed only in GDD patients. The current study is the second finding significantly different serum cytokine levels in GDD patients compared with healthy normal controls. These differences and the difference between GDD and GSC patients' Flare and cytokine responses to CT suggest some inflammatory, immunologic, or other physiological differences in patients with GDD. Further research into the treatment and physiological underpinnings of GDD is warranted.

Body dysmorphic disorder: some key issues for DSM-V.

Body dysmorphic disorder (BDD), a distressing or impairing preoccupation with an imagined or slight defect in appearance, has been described for more than a century and increasingly studied over the past several decades. This article provides a focused review of issues pertaining to BDD that are relevant to DSM-V. The review presents a number of options and preliminary recommendations to be considered for DSM-V: (1) Criterion A may benefit from some rewording, without changing its focus or meaning; (2) There are both advantages and disadvantages to adding a new criterion to reflect compulsive BDD behaviors; this possible addition requires further consideration; (3) A clinical significance criterion seems necessary for BDD to differentiate it from normal appearance concerns; (4) BDD and eating disorders have some overlapping features and need to be differentiated; some minor changes to DSM-IV's criterion C are suggested; (5) BDD should not be broadened to include body integrity identity disorder (apotemnophilia) or olfactory reference syndrome; (6) There is no compelling evidence for including diagnostic features or subtypes that are specific to gender-related, age-related, or cultural manifestations of BDD; (7) Adding muscle dysmorphia as a specifier may have clinical utility; and (8) The ICD-10 criteria for hypochondriacal disorder are not suitable for BDD, and there is no empirical evidence that BDD and hypochondriasis are the same disorder. The issue of how BDD's delusional variant should be classified in DSM-V is briefly discussed and will be addressed more extensively in a separate article.

The prevalence of pathologic skin picking in US adults.

OBJECTIVE: Despite increasing recognition of the potentially severe medical and psychosocial costs of pathologic skin picking (PSP), no large-sample, randomized investigation of its prevalence in a national population has been conducted. METHOD: Two thousand five hundred and thirteen US adults were interviewed during the spring and summer of 2004 in a random-sample, national household computer-assisted phone survey of PSP phenomenology and associated functional impairment. Respondents were classified for subsequent analysis according to proposed diagnostic criteria. RESULTS: Of all respondents, 16.6% endorsed lifetime PSP with noticeable skin damage; 60.3% of these denied picking secondary to an inflammation or itch from a medical condition. One fifth to one quarter of those with lifetime PSP not related to a medical condition endorsed tension or nervousness before picking, tension or nervousness when attempting to resist picking, and pleasure or relief during or after picking. A total of 1.4% of our entire sample satisfied our criteria of picking with noticeable skin damage not attributable to another condition and with associated distress or psychosocial impairment. Pickers satisfying these latter criteria differed from other respondents in demographics (age, marital status) and both picking phenomenology and frequency.

Extended-release fluvoxamine and improvements in quality of life in patients with obsessive-compulsive disorder.

OBJECTIVE: We hypothesized that subjects with obsessive-compulsive disorder (OCD) who received extended-release fluvoxamine (fluvoxamine ER) in a 12-week placebo-controlled trial would exhibit improvements in psychosocial domains of health-related quality of life (HRQOL) and that additional improvements would occur after a 40-week open-label extension trial. We also hypothesized that greater OCD symptom improvement in the first 12 weeks of treatment would be associated with greater HRQOL improvement after 52 weeks of treatment. METHODS: In the 12-week placebo-controlled trial, subjects were randomized to receive placebo or 100 mg/d of fluvoxamine ER and then titrated in weekly 50 mg increments to a final dose of 100 to 300 mg/d. All subjects enrolled in the 40-week extension trial followed a similar titration, during which they were maintained on their highest well-tolerated dose. RESULTS: After 12 weeks of treatment, fluvoxamine ER subjects experienced significantly greater decreases than placebo subjects in Yale-Brown Obsessive-Compulsive Scale scores (P = .001). Both the active drug and placebo groups exhibited significant improvements in psychosocial domains of HRQOL; further improvement occurred after 40 weeks of open-label treatment with active drug. The greater the improvement in OCD severity at 12 weeks, the greater the improvement at 52 weeks in the psychosocial domains (Social Functioning r = -0.39, P = .027; Emotional Problems r = -0.37, P = .037; Mental Health r = -0.49, P = .004). CONCLUSION: Improvement in Yale-Brown Obsessive-Compulsive Scale severity scores during treatment with fluvoxamine ER was associated with improvements in psychosocial aspects of HRQOL that increased over an extended period of treatment.

An initial investigation of serum cytokine levels in patients with gadolinium retention.

OBJECTIVE: To determine whether individuals with proposed gadolinium deposition disease (GDD) have elevated serum levels of pro-inflammatory and pro-fibrotic cytokines, and whether specific cytokines are correlated with certain symptoms. MATERIALS AND METHODS: Twenty-four participants recruited between May 2016 and June 2017 met GDD diagnostic criteria. The 64 control subjects provided serum samples before prophylactic flu vaccination. Serum cytokine levels were obtained with Luminex serum cytokine assay using eBiosciences/Affymetrix human 62-plex kits. Wilcoxon rank-sum tests were performed to assess the difference between the median fluorescence intensity values for the participants and the control group. Generalized linear models were built to evaluate the association between each cytokine of interest and selected participant symptoms. RESULTS: Serum levels of 14 cytokines, including nine pro-inflammatory cytokines, were statistically significantly elevated compared to controls (p ≤ 0.05). Hypotheses regarding pro-fibrotic cytokines and cytokine links to specific symptoms' intensity were not confirmed. CONCLUSION: The statistically significantly elevated cytokines may be markers of susceptibility to GDD or agents of symptom induction. These findings suggest that individuals developing symptoms characteristic of GDD after a contrast-assisted magnetic resonance imaging should be studied to investigate whether gadolinium retention and elevated cytokines may be related to their symptoms.

OBJETIVO: Determinar se indivíduos com doença de deposição de gadolínio (DDG) apresentam níveis séricos elevados de citocinas pró-inflamatórias e pró-fibróticas e se citocinas específicas estão correlacionadas com determinados sintomas. MATERIAIS E MÉTODOS: Vinte e quatro participantes recrutados entre maio/2016 e junho/2017 cumpriram os critérios de diagnóstico de DDG. Amostras de soro de 64 indivíduos controles foram obtidas antes de vacinação profilática contra a gripe. Os níveis de citocinas séricas foram mensurados com o ensaio Luminex usando kits 62-plex humanos. Foram realizados testes de Wilcoxon para avaliar a diferença dos valores médios de intensidade de fluorescência entre os participantes e o grupo controle. Foram construídos modelos lineares generalizados para avaliar a associação entre cada citocina de interesse e os sintomas dos participantes selecionados. RESULTADOS: Níveis séricos de 14 citocinas, incluindo 9 citocinas pró-inflamatórias, foram estatisticamente significantes em comparação aos controles (p ≤ 0,05). Hipóteses sobre as citocinas pró-fibróticas e associação das citocinas com a intensidade de sintomas específicos não foram confirmadas. CONCLUSÃO: Citocinas estatisticamente elevadas podem ser marcadores de suscetibilidade para DDG ou agentes de indução de sintomas. Esses achados sugerem que indivíduos que desenvolvem sintomas da DDG após ressonância magnética com contraste devem ser estudados para investigar se a retenção de gadolínio e citocinas elevadas podem estar relacionadas aos seus sintomas.

Adequacy of pharmacotherapy among medicaid-enrolled patients newly diagnosed with obsessive-compulsive disorder.

OBJECTIVE: To determine the adequacy of pharmacotherapy received by patients with newly-diagnosed obsessive-compulsive disorder (OCD), based on current practice guidelines. METHODS: A 9 year (1997-2006) retrospective claims analysis of adults enrolled in Florida Medicaid for at least 3 continuous years was conducted to determine the percentage who received both a minimally effective duration (> 8 continuous weeks) and dose of first-line OCD pharmacotherapy during the year following their first ("index") OCD diagnosis. RESULTS: Among 2,960,421 adult (> 18 years of age) enrollees, 2,921 (0.1%) were diagnosed with OCD. Among the 2,825 OCD patients without comorbid Asperger syndrome or autism, 843 had newly-diagnosed OCD and at least 12 months of follow-up data after their index diagnosis. Among these 843 patients, 588 (69.7%) received first-line OCD pharmacotherapy but only 323 (38.3%) received a minimally effective pharmacotherapy trial in the year following their index diagnosis. CONCLUSIONS: Among clinically-diagnosed persons with OCD (<10% of those with the disorder), a minority of newly-diagnosed patients receive a minimally effective pharmacotherapy trial consistent with current standards of care. Reasons such as limited patient adherence and/or physician awareness of guidelines must be identified and redressed to ameliorate the patient, healthcare system, and economic burdens associated with OCD.

The prevalence of body dysmorphic disorder in the United States adult population.

OBJECTIVE: In clinical samples, body dysmorphic disorder (BDD) is associated with substantial suffering and reduced quality of life. Limited surveys report widely varying prevalence estimates. To better establish the prevalence of BDD, we conducted a United States nationwide prevalence survey. METHOD: We conducted a random sample national household telephone survey in the spring and summer of 2004 and interviewed 2,513 adults, of whom 2,048 qualified for the BDD-module administration. The computer-assisted, structured interviews, conducted by trained lay interviewers, addressed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BDD, along with information regarding several impulse-control disorders and the respondents' financial and demographic data. RESULTS: The rate of response was 56.3%, which compared favorably with rates in federal national health surveys. The cooperation rate was 97.6%. Respondents included a higher percentage of women and people >55 years of age than in the US adult population, and a lower percentage of Hispanics. The estimated point prevalence of DSM-IV BDD among respondents was 2.4% (49/2,048) (by gender: 2.5% for women, 2.2% for men), exceeding the prevalence of schizophrenia and bipolar disorder type I and about that of generalized anxiety disorder. BDD prevalence decreased after 44 years of age, and a larger proportion of BDD respondents were never married. Of those meeting DSM-IV criteria for BDD, 90% (45/49) met the DSM-IV distress criterion, and 51% (25/49) met the interference-with-functioning criterion. CONCLUSION: A study using clinically valid interviews is needed to evaluate these results. Such studies could inform treatment by documenting rates of seeking treatment from various sources, suicide attempt rates, and the prevalence of comorbid conditions.

Estimated prevalence of compulsive buying behavior in the United States.

OBJECTIVE: Compulsive buying (uncontrolled urges to buy, with resulting significant adverse consequences) has been estimated to affect from 1.8% to 16% of the adult U.S. population. To the authors' knowledge, no study has used a large general population sample to estimate its prevalence. METHOD: The authors conducted a random sample, national household telephone survey in the spring and summer of 2004 and interviewed 2,513 adults. The interviews addressed buying attitudes and behaviors, their consequences, and the respondents' financial and demographic data. The authors used a clinically validated screening instrument, the Compulsive Buying Scale, to classify respondents as either compulsive buyers or not. RESULTS: The rate of response was 56.3%, which compares favorably with rates in federal national health surveys. The cooperation rate was 97.6%. Respondents included a higher percentage of women and people ages 55 and older than the U.S. adult population. The estimated point prevalence of compulsive buying among respondents was 5.8% (by gender: 6.0% for women, 5.5% for men). The gender-adjusted prevalence rate was 5.8%. Compared with other respondents, compulsive buyers were younger, and a greater proportion reported incomes under 50,000 US dollars. They exhibited more maladaptive responses on most consumer behavior measures and were more than four times less likely to pay off credit card balances in full. CONCLUSIONS: A study using clinically valid interviews is needed to evaluate these results. The emotional and functional toll of compulsive buying and the frequency of comorbid psychiatric disorders suggests that studies of treatments and social interventions are warranted.

High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial.

OBJECTIVE: To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment. METHOD: Sixty-six nonresponders to 16 weeks of sertraline treatment who met DSM-III-R criteria for current OCD were randomly assigned, in a double-blind continuation phase of a multicenter trial, either to continue on 200 mg/day of sertraline or to increase their dose to between 250 and 400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were collected from July 26, 1994, to October 26, 1995. RESULTS: The high-dose (250-400 mg/day, mean final dose = 357, SD = 60, N = 30) group showed significantly greater symptom improvement than the 200-mg/day group (N = 36) as measured by the YBOCS (p = .033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011). Responder rates (decrease in YBOCS score of > or = 25% and a CGI-I rating < or = 3) were not significantly different for the 200-mg/day versus the high-dose sertraline group, either on completer analysis, 34% versus 52%, or on endpoint analysis, 33% versus 40%. Both treatments showed similar adverse event rates. CONCLUSION: Greater symptom improvement was seen in the high-dose sertraline group compared to the 200-mg/day dose group during continuation treatment. Both dosages yielded similar safety profiles. Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment.

Potential markers for problematic internet use: a telephone survey of 2,513 adults.

OBJECTIVE: The Internet has positively altered many aspects of life. However, for a subset of users, the medium may have become a consuming problem that exhibits features of impulse control disorders recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. METHOD: This is the first large-scale epidemiological study of problematic Internet use through a random-digit-dial telephone survey of 2,513 adults in the United States. Given the lack of validated criteria, survey questions were extrapolated from established diagnostic criteria for impulse control disorders, obsessive-compulsive disorder, and substance abuse. Four possible diagnostic criteria sets were generated. The least restrictive set required the respondent to report an unsuccessful effort to reduce Internet use or a history of remaining online longer than intended, Internet use interfering with relationships, and a preoccupation with Internet use when offline. RESULTS: The response rate was 56.3%. Interviews averaged 11.3 minutes in duration. From 3.7% to 13% of respondents endorsed > or =1 markers consistent with problematic Internet use. The least restrictive proposed diagnostic criteria set yielded a prevalence of problematic Internet use of 0.7%. CONCLUSION: Potential markers of problematic Internet use seem present in a sizeable proportion of adults. Future studies should delineate whether problematic Internet use constitutes a pathological behavior that meets criteria for an independent disorder, or represents a symptom of other psychopathologies.

Quetiapine augmentation in obsessive-compulsive disorder resistant to serotonin reuptake inhibitors: an open-label study.

BACKGROUND: The response of obsessive-compulsive disorder (OCD) to serotonin reuptake inhibitors (SRIs) is often inadequate. Case series reporting successful augmentation with risperidone and olanzapine led us to investigate quetiapine in OCD that was resistant to SRI treatment. METHOD: In this 8-week, 2-site (S1, S2), open-label trial, 30 adults (16 at S1 and 14 at S2) with a DSM-IV diagnosis of OCD, SRI-resistant, received augmentation with quetiapine, with the dose doubled every 2 weeks from 25 mg to 200 mg/day. Primary outcome was measured with the Yale-Brown Obsessive Compulsive Scale (YBOCS). A response was defined as a > or = 25% decrease from the baseline YBOCS score. RESULTS: Significant differences between the sites in patient characteristics (7/14 at S2 were hoarders, i.e., more treatment resistant, vs. 1/16 at S1; p = .01) and in quetiapine treatment (mean +/- SD dose of 116 +/- 72 mg/day at S2 vs. 169 +/- 57 mg/day at S1; p = .039) necessitated separate analysis of results. At S1, the mean +/- SD YBOCS score fell significantly from 27.7 +/- 7.0 to 23.3 +/- 8.4 (t = 2.96, df = 15, p = .01), and the responder rate was 31% (5/16). At S2, the mean YBOCS score did not decrease significantly, and the responder rate was 14% (2/14). Most adverse medication events were mild or moderate. Two subjects (13%) at S1 and 3 (21%) at S2 withdrew due to adverse events. CONCLUSION: The results at S1 resemble those reported with other atypical antipsychotics and suggest that quetiapine augmentation may benefit treatment-resistant OCD. The poorer results at S2 may reflect the large proportion of hoarders or the less intense treatment. Longer, higher dose, large, double-blind, placebo-controlled comparison trials of atypical antipsychotics are needed.

Double-blind treatment with oral morphine in treatment-resistant obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) often responds inadequately to serotonin reuptake inhibitors (SRIs). A case series reported substantial response to once-weekly oral morphine. We conducted a placebo-controlled, double-blind trial to investigate whether once-weekly oral morphine is effective in SRI-resistant OCD. METHOD: Subjects with DSM-IV-defined OCD for > or =3 years who had failed > or =2 adequate SRI trials and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of > or =20 were recruited. Current medications were continued. Subjects were randomly assigned to random-order, 2-week blocks of once-weekly morphine, lorazepam, and placebo. Week 2 dosage was increased, decreased, or maintained depending on response and side effects. RESULTS: We enrolled 23 subjects, who had failed 2 to 6 SRI trials. The median screening Y-BOCS score was 29. The median Y-BOCS score after morphine (highest dose) was 25 (median decrease = 13%). Seven subjects (30%) were responders (Y-BOCS decreases > or =25%). The median Y-BOCS score after lorazepam (highest dose) was 27 (median decrease = 6%). Four subjects (17%) responded to lorazepam; 1 was a morphine responder. The median Y-BOCS score after placebo (highest dose) was 27 (median decrease = 7%), and no subject responded. Responses differed significantly among the 3 conditions (Friedman 2-way analysis of variance, chir(2) = 13.92, df = 2, p = .01). Wilcoxon matched-pairs signed-rank tests (T = 56.5, p = .05) showed significance for morphine versus placebo but not lorazepam versus placebo. CONCLUSION: Our results support the hypothesis that once-weekly oral morphine can reduce symptoms in some treatment-resistant OCD patients. The mechanism of action is unknown. Further studies of mu-agonists and glutamate antagonists are warranted.

Mirtazapine for obsessive-compulsive disorder: an open trial followed by double-blind discontinuation.

BACKGROUND: Many patients with obsessive-compulsive disorder (OCD) experience little response to standard treatment with serotonin reuptake inhibitors. Mirtazapine enhances serotonergic function by a mechanism distinct from reuptake inhibition. Because a pilot study suggested effectiveness of mirtazapine in OCD, we conducted a controlled trial. METHOD: We recruited 30 subjects, 15 treatmentnaive and 15 treatment-experienced, with DSM-IV OCD of > or =1 year's duration and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of > or =20. In the 12-week, open-label phase, subjects received mirtazapine starting at 30 mg/day and titrated over 2 weeks as tolerated to 60 mg/day. At week 12, responders (YBOCS score decrease > 25%) were randomly assigned, double-blind, to continue mirtazapine or switch to placebo for 8 weeks, including a 1-week, double-blind taper week for placebo subjects. RESULTS: In the open-label phase, the mean +/-SD YBOCS score fell from 28.3 +/-3.7 to 20.3 +/-8.5 (paired samples t = 4.81, p < .0001). Four subjects (13.3%) discontinued for side effects. Sixteen subjects (53.3%) (8 treatmentnaive, 8 treatment-experienced) were responders and 15 agreed to randomization. Response was independent of comorbid mood disorders. In the 8-week, double-blind, placebo-controlled discontinuation phase, the mirtazapine group's mean YBOCS score fell a mean +/-SD of 2.6 +/-8.7 points while the placebo group's mean score rose a mean +/-SD of 9.1 +/-7.5 points (Mann Whitney U = 6.5, p = .005, 1-tailed). All other outcome measures were consistent with mirtazapine's superiority versus placebo. CONCLUSION: Mirtazapine may be an effective pharmacotherapy for OCD. If our results are replicated, larger double-blind studies would be indicated.