Introduction: Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.

Methods: Patients (N=1, 147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2–20 mg/day). Primary outcome was the mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).

Results: Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (−10.1) than placebo (−6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).

Conclusion: For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196).

Introduction: Concomitant psychotropic medication (CPM) treatment is common in persons with major depression (MDD). However, relationships with patient characteristics and response to treatment are unclear.

Methods: Participants with nonpsychotic MDD (N=2682) were treated with citalopram, 20–60 mg/day. Sociodemographic, clinical, and treatment outcome characteristics were compared between those using CPMs at study entry or during up to 14 weeks of citalopram treatment, and non-users.

Results: About 35% of participants used a CPM. Insomnia was the predominant indication (70.3%). CPM users were more likely to be seen in primary care settings (69.3% versus 30.7%), be white, of non-Hispanic ethnicity, married, and have a higher income, private insurance, and certain comorbid disorders. CPM users had greater depressive severity, poorer physical and mental functioning, and poorer quality of life than non-users. Response and remission rates were also lower. CPM users were more likely to achieve ≥50 mg/day of citalopram, to report greater side effect intensity, and to have serious adverse events, but less likely to be intolerant of citalopram.

Conclusion: CPMs are associated with greater illness burden, more Axis I comorbidities (especially anxiety disorders), and lower treatment effectiveness. This suggests that CPM use may identify a more difficult to treat population that needs more aggressive treatment.

The cause of anorexia nervosa (AN) is unclear, but is likely multifactorial, including psychological, familial, environmental, societal, genetic, and other biological factors. This case report of identical 12-year-old female triplets simultaneously concordant for AN illustrates the importance of addressing all these components in evaluation and treatment, and the difficulty of determining the relative importance of each factor in the cause of an individual's eating disorder. An overly close relationship and competitiveness between the girls, treated at times as a triplet group rather than as individuals, as well as stressful family dynamics, were probably important antecedents to the girls' AN. The girls encouraged each other and competed to lose weight. Brief individual and family psychotherapy, parent counseling, nutritional counseling, and psychoeducation led to successful treatment. The triplets were encouraged in treatment to compete with and encourage each other to obtain treatment goals, including eating more healthily and achieving healthy weights. A literature review of AN twins studies is also presented, as these studies add to our understanding of the relative importance of shared genes and shared environment in the development of AN. These studies also add insight into treating individuals from families with multiple affected relatives.

Introduction: Recent data suggest that escitalopram may be more effective in severe depression than other selective serotonin reuptake inhibitors.

Methods: Individual patient data from four randomized, double-blind comparative trials of escitalopram versus a serotonin/norepinephrine reuptake inhibitor (SNRI) (two trials with duloxetine and two with venlafaxine extended release) in outpatients (18–85 years of age) with moderate-to-severe major depressive disorder were pooled. The primary efficacy parameter in all four trials was mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) score.

Results: Significantly fewer escitalopram (82/524) than SNRI (114/527) patients prematurely withdrew from treatment due to all causes (15.6% vs. 21.6%, Fisher Exact: P=.014) and adverse events (5.3% vs. 12.0%, Fisher Exact: P <.0001). Mean reduction in MADRS score from baseline to Week 8 was significantly greater for the escitalopram group versus the SNRI group using the last observation carried forward (LOCF) approach [mean treatment difference at Week 8 of 1.7 points (P <.01)]. Similar results were observed in the severely depressed (baseline MADRS score ≥30) patient subset (mean treatment difference at Week 8 of 2.9 points [P <.001, LOCF]). Observed cases analyses yielded no significant differences in efficacy parameters.

Conclusion: This pooled analysis indicates that escitalopram is at least as effective as the SNRIs (venlafaxine XR and duloxetine), even in severe depression, and escitalopram treatment was better tolerated.

Introduction: Excessive Internet use (EIU), also described as Internet addiction or pathological Internet use, has already become a serious social problem around the world. Some researchers consider EIU as a kind of behavioral addiction. However, there are few experimental studies on the cognitive functions of excessive Internet users (EIUers) and limited data are available to compare EIU with other addictive behaviors, such as drug abuse and pathological gambling.

Methods: In this study, we examined EIUers' functions of decision-making and prepotent response inhibition. Two groups of participants, EIUers and controls, were compared on these two functions by using a Gambling Task and a Go/no-go Task, respectively.

Results: Compared with controls, EIUers selected significantly less net decks in the Gambling Task (P =.007). Furthermore, the EIUers made progress in selecting strategy, but more slowly than did the control group (EIUers, chunk 3 > chunk 1, P<.001; controls, chunk 2 > chunk P<.001; controls, chunk 2 > chunk 1, P<.001). Interestingly, EIUers' accuracy during the no-go condition was significantly higher than that of controls (P=.018).

Conclusion: These results showed some similarities and dissimilarities between EIU and other addictive behaviors such as drug abuse and pathological gambling. The findings from the Gambling Task indicated that EIUers have deficits in decision-making function, which are characterized by a strategy learning lag rather than an inability to learn from task contingencies. EIUers' better performance in the Go/no-go Task suggested some dissociation between mechanisms of decision-making and those of prepotent response inhibition. However, EIUers could hardly suppress their excessive online behaviors in real life. Their ability of inhibition still needs to be further studied with more specific assessments.

Introduction: Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations.

Objective: The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated.

Methods: Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the “early onset” group (EOG): before 11 years of age, 75 patients had

Results: The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the “aggression/violence” and “miscellaneous” dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the “contamination/cleaning” dimension.

Conclusion: The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

This case report describes the use of transcranial magnetic theta burst stimulation (TBS) in the treatment of incapacitating tinnitus accompanied by symptoms of severe depression. Tinnitus is known to be associated with hyperactivity and maladaptive cortical reorganization of the central auditory system. Combined with anxiety and depression, it can occasionally constitute a psychiatric emergency. Recently, it has been demonstrated that tinnitus can be temporarily suppressed by non-invasive transcranial magnetic stimulation. TBS is a newly developed technique for rapid and lasting modulation of cortical excitability. Herein, we present a case of a 54-year-old woman with incapacitating tinnitus that has significantly decreased after three cycles of 1-week treatment with continuous TBS to the temporo-parietal auditory association cortex. According to the Tinnitus Questionnaire, tinnitus intensity decreased from 84 points before to 59 points after treatment. Hamilton Rating Scale for Depression score dropped from 44 to 23 points. TBS showed to be efficient, well-tolerated, and practical in the management of distressing tinnitus accompanied by symptoms of severe depression.

Introduction: The characteristics of Asian American and white problem gamblers using a gambling helpline were examined to identify race-related differences.

Methods: Logistic regression analyses were conducted on data obtained from callers to a gambling helpline serving southern New England in 2000–2003, inclusive.

Results: Of the 144 phone calls used in the analyses, 72 were from Asian American callers and 72 were from white callers who were matched on gender, education, income, marital/cohabitation status, and age. Race-related differences were observed in forms of gambling problems, psychiatric problems secondary to gambling, substance use problems, and family history. Asian American gamblers were more likely to report suicide attempts related to gambling and problems with non-strategic gambling. White gamblers were more likely to report both casino and non-casino gambling problems and personal and familial alcohol use problems. High proportions of both groups reported problems with strategic gambling, gambling-related anxiety, family and financial problems secondary to gambling, financial debt, daily tobacco use, and a family history of problem gambling.

Conclusion: Race-related differences should be considered in optimizing prevention and treatment strategies related to problem gambling.

Introduction: High frequency repetitive transcranial magnetic stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) might be a promising strategy to treat depression, but not all patients show a positive outcome.

Objective: In this open study, we evaluate whether a favorable HF-rTMS treatment outcome could be predicted by baseline prefrontal brain glucose metabolism (CMRglc), measured by 18fluorodeoxyglucose positron emission tomography (18FDG-PET).

Methods: A sample of 21 antidepressant-free, treatment-resistant depression (TRD) patients of the melancholic subtype received 10 sessions of HF-rTMS delivered on the left DLPFC. Patients underwent a static 18FDG-PET before and after HF-rTMS treatment.

Results: Forty-three percent of the patients showed a reduction of at least 50% on their Hamilton Rating Scale for Depression scores. Higher baseline metabolic activities in the DLPFC and the anterior cingulate cortex (ACC) were associated with better clinical outcome. Successful HF-rTMS treatment was related to metabolic changes in subdivisions of the ACC (Brodmann areas 24 and 32).

Conclusion: This biological impact of HF-rTMS on regional brain CMRglc explains to some extent how HF-rTMS may improve moods in TRD patients. Larger sham-controlled HF-rTMS treatment studies are needed to confirm these results.