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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.

Abbreviated Summary The open-label trial of Williams, Sudheimer, Cole, et al., suggests safety, feasibility, and high efficacy for treatment-refractory OCD of an accelerated, fMRI-guided, high-dose, cTBSmod protocol targeting the right frontal pole. Larger, randomized, controlled trials are needed to test the promising results of this pilot study. Clinicaltrials.gov Registry Numbers NCT03404609.

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.

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. Resumo 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.

Many patients with OCD respond partially or not at all to standard medications and cognitive behavioral therapy approaches, making alternate treatments necessary. We review the preliminary evidence that exists in support of the use of stimulants, high-dose caffeine, opiates, memantine, ondansetron, ketamine, and transcranial magnetic stimulation in some patients with OCD. Although limited by small or modest sample sizes, open-label study designs, and brief follow-up periods, studies suggest that each of these strategies can help some patients who have inadequately responded to first-line treatments. The existing data and the unmet needs of OCD patients justify research attention to further test these treatments’ safety and efficacy. Previously untested drugs also deserve attention, especially as recent research has suggested new possible contributors to OCD pathophysiology. Similarly, psychotherapeutic interventions beyond CBT should be investigated, and treatments with preliminary evidence in OCD, including Acceptance Commitment Therapy, Danger Ideation Reduction Therapy, and technology-enabled interventions like computerized CBT and Virtual Reality Exposure Therapy, should be carefully tested.

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

Based on the available evidence, we would offer a Compulsive Buying Disorder (CBD) patient the choice of a 12-session trial of Cognitive Behavioral Therapy (CBT) targeting CBD, or a seven-week trial of pharmacotherapy with citalopram. We would treat any co-morbid psychiatric disorder with appropriate psychotherapy or pharmacotherapy, and evaluate the need for couples or family therapy, and for inpatient treatment of suicidality, or comorbid conditions. We would also encourage the use of educational self-help materials. Patients preferring pharmacotherapy would be encouraged to take steps to help control CBD behaviors, e.g., identify the needs over-shopping is meeting and design more rational ways to meet them; find other ways to experience pleasure; take a “truly needed” shopping list along and purchase only these items; leave credit cards at home; avoid shopping alone—a friend may curtail compulsive buying; avoid shopping malls or other personally tempting venues; resist the convenience of online shopping and don’t allow websites to store credit card information, as this makes transactions even speedier and thus more dangerous; keep a daily journal of purchases and expenditures and of the irrational thoughts and feelings driving compulsive buying, and use self-help materials to combat them; reward yourself for exerting control. During medication visits, we would inquire regarding any difficulties in implementing these behavioral changes, and help problem-solve these difficulties. If an adequate CBT trial were ineffective, we would recommend a pharmacotherapy trial. If an adequate pharmacotherapy trial (with or without the informal behavioral therapy approaches listed) were ineffective, we would recommend a formal CBT trial. If this trial also failed, we would offer the patient sequential trials of emerging drug therapies (e.g., naltrexone and memantine). We would encourage patients to continue an effective treatment for a year (i.e., with “booster sessions” of CBT or continued drug therapy), to firmly establish the new shopping habits.

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.

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.

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.

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.

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 (

Impulse-control disorders (ICDs) constitute a heterogeneous group of conditions linked diagnostically by difficulties in resisting "the impulse, drive, or temptation to perform an act that is harmful to the person or to others." Specific ICDs share clinical, phenomenological and biological features with obsessive-compulsive disorder (OCD) that have suggested that these disorders might be categorized together. However, other data suggest significant differences between OCD and ICDs. In this article, clinical, phenomenological and biological features of the formal ICDs are reviewed and compared and contrasted with those of OCD. Available data indicate substantial differences between ICDs and OCD that suggest independent categorizations. Existing research gaps are identified and avenues for future research suggested.

Introduction Two small, double-blind, placebo-controlled, single-dose, crossover studies found dextroamphetamine (d-amphetamine) 30 mg clearly superior to placebo in relieving symptoms of obsessive-compulsive disorder (OCD). We conducted a 5-week, double-blind, caffeine-controlled study to test the hypothesis that d-amphetamine, added after an adequate selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) trial, would be more effective than caffeine in reducing residual OCD symptoms of moderate or greater severity. Method Between August 2006 and February 2008, we enrolled adults with DSM-IV OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of >or= 20 after >or= 12 weeks of adequate treatment with an SSRI or SNRI. Subjects were randomly assigned to double-blind d-amphetamine 30 mg/d or caffeine 300 mg/d added to their SSRI/SNRI and other medications. Responders (first week mean Y-BOCS score decrease of >or= 20%) entered the study's 4-week double-blind extension phase. Results We enrolled 24 subjects, 11 women and 13 men, with a mean (SD) age of 40 (13.2) years and mean baseline Y-BOCS scores of 26.5 (4.1) for the d-amphetamine group (n = 12) and 29.1 (4.0) for the caffeine group (n = 12). At the end of week 1, 6 of 12 d-amphetamine subjects (50%) and 7 of 12 caffeine subjects (58%) were responders. At week 5, the responders' mean Y-BOCS score decreases were, for the d-amphetamine group (last observation carried forward), 48% (range, 20%-80%); and, for the caffeine group, 55% (range, 27%-89%). Obsessive-compulsive disorder and depression improvement were independent. The double-blind remained intact. No subject discontinued the study due to side effects. Conclusions Larger, double-blind, placebo-controlled trials of both d-amphetamine and caffeine augmentation are needed in OCD subjects inadequately responsive to adequate doses of an SSRI or SNRI. Trial registration clinicaltrials.gov Identifier: NCT00363298.

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 ≥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.

Obsessive-compulsive symptoms (OCS) are clinically important phenomena in schizophrenia patients. Lamotrigine has a modulating effect on glutamatergic neurotransmission relevant to pathophysiology of both schizophrenia and OCD. Efficacy and tolerability of lamotrigine in schizophrenia and schizoaffective patients with comorbid OCS were evaluated. In an 8-week, open-label trial, lamotrigine (25 mg/day for 1 week, 50 mg for 2 weeks, 100 mg for 2 weeks, 200 mg for 3 weeks) was added to ongoing psychotropic drug regimens in schizophrenia (N = 5) and schizoaffective disorder (N = 6) patients with clinically significant OCS [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score > 16]. The Y-BOCS score for nine completers decreased significantly from baseline to week 8 (22.9 ± 6.1 vs 17.4 ± 3.6; t = 2.33, df = 1, P = 0.033). Five patients, all with schizoaffective disorder, were responders (≥35% decrease in Y-BOCS score). No significant changes were detected in schizophrenia symptom severity. Depressive symptoms, assessed with the Calgary Depression Rating Scale, improved significantly (6.4 ± 1.5 vs 4.0 ± 2.5; t = 3.19, df = 1, P = 0.013); this change positively correlated with OCS improvement (r = 0.69, P = 0.04). Lamotrigine was safe and well tolerated. Explicit evaluation of therapeutic efficacy of adjunctive lamotrigine in schizoaffective disorder patients with comorbid OCS merits further investigation.

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.

BACKGROUND Although not as common as major depressive disorder, dysthymia is not rare and is associated with substantial impairment. Antidepressants and some psychotherapies are often effective. We explored the efficacy of the antidepressant duloxetine, a serotonin and norepinephrine reuptake inhibitor. METHOD Between February 2005 and April 2006, we recruited 24 adults with DSM-IV dysthymia or dysthymia and concurrent major depression ("double depression") who had an entry score of > or = 17 on the clinician-rated Inventory for Depressive Symptomatology (IDS-C). We excluded subjects with significant medical illnesses and those requiring other psychotropic agents or undergoing psychotherapy. Subjects received duloxetine 60 mg/day for 6 weeks, increased as tolerated to 120 mg/day for the remainder of the 12-week trial for those with an inadequate treatment response. RESULTS The subjects' mean +/- SD IDS-C scores decreased significantly from baseline (27.3 +/- 6.3) to endpoint (7.8 +/- 7.4, Student t = 12.38, df = 23, p < or = .001). The IDS-C response rate (intent-to-treat [ITT]) was 83% (20/24); the remission rate (ITT) was 79% (19/24). Among study completers, these rates were 89% (17/19) and 84% (16/19). Five subjects (21%) discontinued for side effects. CONCLUSION Duloxetine appears to be an effective and well-tolerated treatment for dysthymia and double depression. A double-blind, placebo-controlled study is under way. If duloxetine is found to be effective, studies powered to detect potential, clinically important differences between duloxetine and other antidepressants will be needed. CLINICAL TRIALS REGISTRATION ClinicalTrials.gov identifier NCT00185575.

BACKGROUND: Kleptomania has no definitive treatment. Mixed reports of benefit from openly prescribed selective serotonin reuptake inhibitors led us to design a double-blind, placebo-controlled discontinuation trial of escitalopram. METHOD: Between December 2002 and March 2005, we recruited 24 subjects aged >or=20 years with DSM-IV kleptomania of >or=1 year's duration. We excluded subjects with organic mental disorders, psychoses, substance or alcohol abuse, suicidal risk, bipolar I or II disorder, anorexia nervosa, or antisocial personality disorder and subjects requiring other psychotropic medications. Our primary outcome measure was theft episodes per week. A responder was defined as a subject having a > 50% decrease in theft episodes per week and a Clinical Global Impressions-Improvement scale score of "much improved" or "very much improved." Escitalopram was started at 10 mg/day and increased as necessary and tolerated after week 4 to 20 mg/day. At the end of week 7, responders were randomly assigned to a 1-week taper followed by 16 weeks of placebo or to continuation of treatment for 17 weeks at their week 7 escitalopram dose. RESULTS: Nineteen subjects (79%) were week 7 responders and 15 were randomly assigned. Five subjects (4 responders) withdrew early: 1 for unrelated illness, 1 for protocol deviation, 2 for side effects, and 1 for withdrawn consent. Three (43%) of 7 escitalopram subjects relapsed compared with 4 (50%) of 8 placebo subjects (Fisher exact test p = .38). CONCLUSION: The high response rate during open-label escitalopram treatment was not better maintained by double-blind escitalopram than by placebo. Kleptomania may be a heterogeneous pathological behavior better treated with pharma-cotherapy in some cases and psychologically or with combined treatment in others.

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. 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.

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, obsessivecompulsive 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 ≥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.

Neurological soft-sign abnormalities have been implicated in obsessive-compulsive disorder (OCD). This first comprehensive data analysis evaluated the association between baseline neurological soft signs and treatment response in 117 OCD patients treated with controlled-release fluvoxamine in a double-blind placebo-controlled trial. Total and right-sided soft signs for the responders and the nonresponders did not differ significantly. Left-sided visuospatial soft signs were significantly increased in treatment nonresponders compared to responders. These subtle neurological abnormalities may implicate a potential subgroup of OCD patients with poorer treatment response. This may have treatment implications and therefore serve as a screening tool in OCD.

Although schizophrenia and obsessive-compulsive disorder (OCD) are distinct diagnostic entities, there are substantial areas of overlap between the two disorders in clinical characteristics, affected brain areas and pharmacotherapy. Though OCD patients apparently do not have increased risk for developing schizophrenia, schizotypal personality disorder has consistently been found in OCD patients. Compelling evidence also points to an increased rate of OCD in schizophrenia patients. Accurate diagnosis of both disorders in their "pure" and overlapping forms is necessary in order to evaluate etiological mechanisms underlying schizophrenia and OCD, and to provide adequate treatment and prognosis. In this review, we address some aspects of the current status of research pertinent to the OCD-schizophrenia interface and suggest further steps towards the clinical and etiological identification of homogeneous subgroups on the putative OCD-schizophrenia axis.

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.

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.

BACKGROUND Compulsive shopping disorder is increasingly recognized as a treatable impulse-control disorder. We report the first long-term, naturalistic follow-up of patients with compulsive shopping disorder, which examined the course of illness over 1 year in a cohort that had completed up to 3 months of open-label treatment with citalopram, 20 mg/day to 60 mg/day. In that trial, 17 (71%) of 24 subjects who met McElroy and colleagues' diagnostic criteria for compulsive shopping disorder were responders (Clinical Global Impressions-Improvement scale rating of much or very much improved and Yale-Brown Obsessive Compulsive Scale-Shopping Version score decrease of >/= 50%). METHOD Follow-up interviews occurred 3, 6, 9, and 12 months after study end. Data gathered included comorbid conditions, estimated total debt, 2-week spending, whether the patient was taking citalopram, and illness versus remission status. Remission was defined as no longer meeting diagnostic criteria for compulsive shopping disorder. Data were gathered between March 2000 and January 2002. RESULTS Of responders at trial end, 81% (13/16), 71% (10/14), 71% (10/14), and 73% (11/15) were in remission at 3, 6, 9, and 12 months. Mean 2-week compulsive shopping expenditures decreased from 773 US dollars (median = 500 US dollars) at baseline to 351 US dollars (median = 0 US dollars) at month 12, and mean total debt decreased from 17,833 US dollars (median = 20,000 US dollars) to 16,752 US dollars (median = 14,000 US dollars). No clear association was seen between taking citalopram and remission status (p =.55, p =.08, p =.58, and p =.60 at 3, 6, 9, and 12 months, respectively; Fisher exact test). The majority of trial nonresponders remained ill at each follow-up point. CONCLUSION An acute response to citalopram predicts a greater likelihood of continued remission over 1 year, although the mechanisms that maintain remission require further investigation.

Background: Open-label trials suggested that fluvoxamine and citalopram may be effective for compulsive shopping disorder, but 2 double-blind fluvoxamine trials failed to confirm this. To test the hypothesis that citalopram is a safe, effective treatment for this disorder, we conducted a 7-week, open-label trial followed by a 9-week, double-blind, placebo-controlled discontinuation trial. Method: From Jan. 2001 to Jan. 2002, we enrolled adult outpatients meeting diagnostic criteria suggested in a prior study for compulsive shopping disorder and having a score of ≥ 17 on the Yale-Brown Obsessive Compulsive Scale-Shopping Version (YBOCS-SV). Open-label citalopram was started at 20 mg/day and increased, absent marked response and limiting side effects, to 60 mg/day. Responders (subjects rated much improved or very much improved on the Clinical Global Impressions-Improvement scale [CGI-I] and having a ≥ 50% decrease in YBOCS-SV score) were randomized to double-blind citalopram treatment at the week 7 dose or placebo for 9 weeks. Results: We enrolled 24 subjects (23 women and 1 man). Mean ± SD YBOCS-SV scores decreased significantly from 24.3 ± 4.6 at baseline to 8.2 ± 8.1 at week 7 (Wilcoxon signed rank: z = 4.20, p

OBJECTIVE: The aim of this 12-week, double-blind, flexible-dose, placebo-controlled, parallel-arm, multicenter trial was to determine the safety and efficacy of fluvoxamine in a controlled-release (CR) formulation in adult outpatients with obsessive-compulsive disorder (OCD). METHOD: 253 adult outpatients with DSM-IV OCD were randomly assigned to receive 100 to 300 mg of fluvoxamine CR (N = 127) or placebo (N = 126) once daily for 12 weeks. Intent-to-treat analyses of efficacy assessments with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I) were conducted. RESULTS: Fluvoxamine CR was significantly (p

Background While selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of obsessive-compulsive disorder (OCD), approximately 40% of patients fail to respond to SSRIs. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that might be effective in the treatment of OCD, even among those who have failed previous SSRI trials. Method Thirty-nine patients who met DSM-IV criteria for OCD, including 29 who were resistant to prior SRI treatment trials, were treated with venlafaxine in an open, naturalistic fashion. Improvement was assessed using the Clinical Global Impressions-Improvement scale. Results Of 39 patients treated with venlafaxine, 27 (69.2%) were rated as sustained treatment responders. Of the 29 patients who did not respond to 1 or more previous SRI trials, 22 (75.9%) were rated as having sustained response to treatment. Mean dose of venlafaxine was 232.2 mg/day (range, 37.5-375 mg/day), and it was generally well tolerated. Conclusion Venlafaxine may be beneficial to individuals with OCD, including those who have not responded to prior SSRI trials. However, these findings must be interpreted with caution, as the study is limited by its open, retrospective nature and its inclusion of patients with comorbid diagnoses and patients on concomitant medications. Prospective, controlled trials with a more homogeneous patient population are needed to replicate these preliminary findings.

BACKGROUND Compulsive shopping, a DSM-IV impulse-control disorder not otherwise specified, is characterized by preoccupation with shopping and inability to resist buying unneeded items, with resulting marked distress, social or occupational impairment, and financial and/or familial problems. Because an open-label trial suggested that fluovaxamine, a selective serotonin reuptake inhibitor (SSRI), is effective for this disorder, we tested the effectiveness of the SSRI citalopram. METHOD We enrolled adults meeting formal diagnostic criteria (as defined by McElroy and colleagues) in a 12-week open-label trial. We excluded subjects with obsessive-compulsive disorder, bipolar disorder, substance abuse or dependence, or psychotic disorders. Citalopram treatment was begun at 20 mg/day and increased every 2 weeks by 20 mg/day, absent marked response and limiting side effects, to 60 mg/day. At endpoint, all subjects were asked to give written informed consent for follow-up telephone interviews at 3-month intervals for 12 months. RESULTS We enrolled 24 subjects, 22 women and 2 men, whose mean +/- SD age was 43.7 +/- 8.1 years; most had been shopping compulsively for 2 decades or more. Citalopram (mean +/- SD endpoint dose = 35.4 +/- 21.4 mg/day) produced rapid, marked, sustained improvements on both the Yale-Brown Obsessive Compulsive Scale-Shopping Version and the Clinical Global Impressions-Improvement (CGI-I) scale in subjects with and without comorbid conditions. Seventeen subjects (71%) were responders, achieving ratings of much or very much improved on the CGI-I, including 2 of the 3 subjects who discontinued for adverse events (sedation or agitation). During a 6-month follow-up period, those continuing citalopram therapy were less likely to relapse than those discontinuing the medication. CONCLUSION Citalopram appears to be a safe and effective treatment for compulsive shopping. Acute and long-term, double-blind, placebo-controlled trials of citalopram and other SSRIs for the treatment of this disorder are indicated.

Obsessive-compulsive disorder (OCD) typically begins early in life and has a chronic course. Despite the need for long-term treatment, the authors found no placebo-controlled studies that have examined the relapse-prevention efficacy of maintenance therapy.Patients who met criteria for response after 16 and 52 weeks of a single-blind trial of sertraline were randomly assigned to a 28-week double-blind trial of 50-200 mg/day of sertraline or placebo. Primary outcomes after the double-blind trial were full relapse, dropout due to relapse or insufficient response, or acute exacerbation of OCD symptoms.Of 649 patients at baseline, 232 completed 52 weeks of the single-blind trial and met response criteria. Among the 223 patients in the double-blind phase of the study, sertraline had significantly greater efficacy than placebo on two of three primary outcomes: dropout due to relapse or insufficient clinical response (9% versus 24%, respectively) and acute exacerbation of symptoms (12% versus 35%). Sertraline resulted in improvement in quality of life during the initial 52-week trial and continued improvement, significantly superior to placebo, during the subsequent 28-week double-blind trial. Long-term treatment with sertraline was well tolerated. Over the entire study period, less than 20% of the patients stopped treatment because of adverse events.Sertraline demonstrated sustained efficacy among patients responding to treatment and was generally well tolerated during the 80-week study. During the study's last 28 weeks, sertraline demonstrated greater efficacy than placebo in preventing dropout due to relapse or insufficient clinical response and acute exacerbation of OCD symptoms.

INTRODUCTION : Compulsive shopping behaviour has recently received long overdue attention as a clinical issue. Curiosity about this condition has led to questions about its identification, characterization as a disorder, and treatment. METHOD : This article presents two case vignettes illustrating diagnostic criteria and points that distinguish this disorder from OCD hoarding or mania. These issues are discussed. RESULTS : The authors present some suggested treatment approaches CONCLUSION : Greater awareness of the prevalence and social consequences of compulsive shopping behaviour highlights the need for treatment and for educational resources for clinicians and the general public. (Int J Psych Clin Pract 2002; 6: 65-68)

Various studies suggest that selective serotonin reuptake inhibitors (SSRIs) may be useful in treating pathologic skin-picking. The authors investigated the effectiveness of fluoxetine in treating this behavior. Fifteen subjects with clinically significant skin-picking were recruited by newspaper advertisement. They received 6 weeks of open-label treatment with fluoxetine. Responders were then randomized to 6 weeks of double-blind fluoxetine or placebo. Treatment effect was assessed with standardized rating scales. All 15 subjects completed open-label treatment, and 8 were responders. Of these eight, the four randomized to double-blind fluoxetine maintained clinically significant improvement. The four randomized to placebo returned to their baseline symptom level. Larger studies are needed to determine which individuals are likely to respond to fluoxetine and the relative effectiveness of fluoxetine, other SSRIs, and other forms of treatment.

Background: After considering the effects of 5-HT receptor agonists with different binding profiles on the symptoms of obsessive-compulsive disorder (OCD), Zohar and Kindler hypothesized that the 5-HT1D receptor was implicated in this disorder’s pathophysiology. Methods: We explored the 5-HT1D hypothesis in a 5-day, random, double-blind, placebo-controlled trial of oral sumatriptan 100 mg/day in medication-free adults with OCD. We hypothesized that sumatriptan, a 5-HT1D agonist, would diminish 5-HT release, thereby worsening OCD symptoms. We further hypothesized that by beginning to desensitize 5-HT1D receptors, sumatriptan pretreatment would promote a faster response or an increased likelihood of response to subsequent treatment with a selective serotonin reuptake inhibitor. Results: The five sumatriptan subjects’ OCD symptom worsening, as measured by the Yale–Brown scale (↑ 17.6% (S.D. 14.6)), was significant when compared to the slight symptom decrease in the five placebo subjects (↓ 5.2% (S.D. 4.9), P

Anxiety commonly complicates the clinical presentation of depression and has been associated with poorer long-term outcome, but little information is available on the clinical correlates, and comparative effect on treatment response, of subsyndromic or secondary anxiety. Patients diagnosed with chronic major or double depression were randomized to 12 weeks of double-blind treatment with either sertraline or imipramine in a 2:1 ratio. A high anxiety subgroup was operationally defined by a HAM-D anxiety/somatization factor score > or = 7. The effect of study treatment was measured utilizing the HAM-D, CGI, HAM-D anxiety/somatization factor, as well as a quality of life measure (Q-LES-Q) and a measure of psychosocial functioning (the MOS-SF-36). Two hundred nine patients were treated with imipramine and 426 patients were treated with sertraline. Thirty-six percent of the total met criteria for the high anxiety subgroup. According to Kaplan-Meier probability estimates, patients with significant concurrent anxiety symptoms were more likely to respond by 12 weeks (66.4%) than those without significant anxiety symptoms (54.2%). There was no significant difference in response rates for sertraline vs. imipramine. Both drugs were effective at treating high baseline levels of anxiety, with 60% of sertraline patients and 58% of imipramine patients having 50% or greater reduction from baseline in HAM-D anxiety/somatization factor scores, and only 4.6% and 9.9%, respectively, reporting treatment-emergent worsening in anxiety at study endpoint. Despite the chronicity of depressive illness, acute treatment with both sertraline and imipramine significantly improved psychosocial and quality of life measures. High baseline levels of anxiety did not reduce overall antidepressant response but did somewhat delay the onset of response to sertraline or imipramine in patients with chronic depression.

Obsessive-compulsive disorder (OCD) is a severe mental disorder with a lifetime prevalence of 1.6{%} in the US population, although the identified obsessive-compulsive spectrum may affect up to 10{%} of the US population. Furthermore, OCD is a chronic, profoundly disabling illness that impacts negatively on the academic, occupational, social and family patients’ functioning as well as on their families’ lives. Indeed, OCD is tenth in the World Bank’s and WHO’s ten leading causes of disability ranking.

The World Health Organization has determined that obsessive-compulsive disorder (OCD) is the 10th leading medical cause of disability across the globe. Unfortunately, a substantial proportion of patients with OCD fail to respond to medication trials. In the pivotal double-blind, placebo-controlled trials that established the efficacy of clomipramine and the selective serotonin reuptake inhibitors (SSRIs), 40% to 60% of patients were nonresponders to a given drug. Moreover, patients who do not respond to their first medication trial may be less likely than treatment-naive patients to respond to subsequent trials. For example, only 33% of patients participating in double-blind trials who had failed trials of one or more serotonin reuptake inhibitors (SRIs) benefited from a subsequent trial of sertra-line, compared with 53% of those who were treatment naive (Rasmussen, Baer, Eisen, and Shera, unpublished data, 15th Annual Meeting, American Psychiatric Association, May 17-22, 1997).At the Fourth International Obsessive-Compulsive Disorder Conference, held in February 2000 in St. Thomas, US Virgin Islands, an afternoon panel was devoted to considering issues and strategies related to treatment-refractory OCD. The panel presentations were divided into three groups: time to response and outcome after long-term followup; pharmacologic strategies for nonresponders; and new data concerning nonpharmacologic interventions.

Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain.We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments.Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and in the psychotherapy group, as compared with 73 percent in the combined-treatment group. (P0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (P0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug (e.g., headache, somnolence, dry mouth, nausea, and dizziness).Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.

ResumenHemos investigado la eficacia comparativa del citalopram frente a citalopram administrado con clomipramina en trastorno obsesivo-compulsivo (OCD) resistente al tratamiento. Dieciséis pacientes ambulatorios adultos participaron en un ensayo abierto distribuido al azar de 90 días. Los pacientes elegibles tenían de 18 a 45 años, OCD del DSM-III-R de moderado a grave de un año o más de duración, una puntuación de línea de base en la escala de Yale-Brown (Y-BOCS) de 25 o más y ningún otro diagnóstico activo del eje I, y habían tenido fracasos en ensayos adecuados de clomipramina y fluoxetina. El grupo de citalopram más clomipramina (n = 9) experimentó una disminución de porcentaje significativamente mayor en la puntuación media de la Y-BOCS para el día 90 que el grupo de citalopram solo (n = 7). Unicamente una paciente de citalopram disminuyó su puntuación en 35% o más, y dos en 25% o más. Los nueve pacientes de citalopram más clomipramina experimentaron disminuciones de 35% o más. Los efectos secundarios fueron de leves a moderados en ambos grupos. También tratamos con citalopram a seis pacientes de OCD que no habían tolerado la fluoxetina y la clomipramina solas; tres lograron disminuciones de la puntuación de la Y-BOCS de 35% o más a los 90 días. Puesto que el citalopram no afecta significativamente al metabolismo de la clomipramina, es poco probable que la mejoría en el grupo de combinación de medicamentos se haya derivado de mayores niveles de clomipramina en plasma. Se precisan ensayos controlados doble ciego de citalopram en OCD y de combinación de citalopram con clomipramina en OCD resistente al tratamiento.

Background Chronic depressions are common, disabling, and undertreated, and prior chronicity predicts future chronicity. However, few studies directly inform the acute or maintenance phase treatments of chronic depressions and even less is known about the effects of treatment on psychosocial functioning. Method We describe the design and rationale for 2 parallel double-blind, randomized, multicenter acute and maintenance phase treatment trials. One focused on DSM-III-R major depression currently in a chronic (> or = 2 years) major depressive episode, the other on DSM-III-R major depression with concurrent DSM-III-R dysthymia ("double depression"). Results Considering the critical knowledge deficits, we designed a 12-week acute phase safety and efficacy trial of sertraline versus imipramine, followed by a 16-week continuation treatment phase for subjects with a satisfactory therapeutic response. Patients receiving sertraline who successfully completed the continuation phase entered a 76-week maintenance trial to compare sertraline with placebo; those taking imipramine continued without a placebo substitution. As part of the acute trial, subjects completing but failing to respond to the initial 12-week acute phase medication were crossed over (double-blind) to the alternative medication for a 12-week acute phase trial. We obtained naturalistic follow-up data (up to 18 months) for subjects exiting the protocol at any time. Conclusion Multiphase protocols for chronic depression can test efficacy by randomized contrasts as well as shed light on key clinical issues such as the degree of response or attrition expected at particular times in a trial or the preferred medication sequence in a potential multistep treatment program.

Background: Challenge with intravenous clomipramine (CMI) is serotonin selective and has been reported to transiently exacerbate symptoms in obsessive-compulsive disorder (OCD) patients, and to predict subsequent response to oral CMI therapy. Methods: We administered CMI (12.5 mg, IV) to medication free OCD patients ( N = 29) and normal controls ( N = 22) to characterize neurohormonal response. A subset of OCD patients (26/29), was then treated with either pulse load IV or oral CMI followed by 8 weeks of oral CMI therapy. Results: In response to CMI challenge, OCD patients exhibit blunted cortisol and exaggerated growth hormone response relative to normal controls. OCD patients differ from controls in "sadness" ratings, with controls exhibiting increased dysphoria in response to CMI. Growth hormone response to CMI challenge predicts treatment response (≥ 25% ↓ YBOCS from baseline) to oral CMI at 8 weeks. Conclusions: Growth hormone abnormalities associated with OCD in response to CMI challenge differentiates nonresponders after 8 weeks of oral CMI treatment from responders.

Objective: We compared gradually increased to pulse loaded doses of open-label, intravenous clomipramine (CMI) in patients with obsessive-compulsive disorder (OCD). Method: We treated adult outpatients with DSM-III-R OCD, who had no prior exposure to effective treatments. Pulse loading patients received 150 mg on day 1; 150 mg or 200 mg on day 2. Gradual dosing patients received 25 mg per day increased to 200 mg per day over 2 weeks and then continued for a mean of 43 days (n=40). After i.v. dosing, all patients received oral CMI; the total treatment period was 6 months. Results: Pulse loading completers (n=7) had a rapid, dramatic response (mean Y-BOCS score decrease of 32% five days after pulse-loading). At this point (day 7), completers in the gradual intravenous group (n=20) exhibited no mean change in Y-BOCS score. The pulse loading group reached both a 25% or greater and a 50% or greater decrease in Y-BOCS score statistically and clinically significantly faster than the gradual group. Conclusions: Pulse-loaded intravenous CMI for the treatment of OCD deserves further study.