Treatment outcomes of depression: the pharmacogenomic research network antidepressant medication pharmacogenomic study.

BACKGROUND: The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder (MDD) is controversial. AIMS: The clinical outcomes of subjects with nonpsychotic MDD were reported and compared with the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study outcomes to provide guidance on the effectiveness of SSRIs. METHODS: Subjects were treated with citalopram/escitalopram for up to 8 weeks. Depression was measured using the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) and the 17-item Hamilton Depression Rating Scale. RESULTS: The group of subjects with at least 1 follow-up visit had a remission (QIDS-C16 ≤ 5) rate of 45.8% as well as a response (50% reduction in QIDS-C16) rate of 64.8%, and 79.9% achieved an improvement of 5 points or higher in QIDS-C16 score. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study subjects were more likely to achieve a response than STAR*D study subjects. After adjustment for demographic factors, the response rates were not significantly different. When reporting the adverse effect burden, 60.5% of the subjects reported no impairment, 31.7% reported a minimal-to-mild impairment, and 7.8% reported a moderate-to-severe burden at the 4-week visit. CONCLUSIONS: Patients contemplating initiating an SSRI to treat their MDD can anticipate a high probability of symptom improvement (79.9%) with a low probability that their symptoms will become worse. Patients with lower baseline severity have a higher probability of achieving remission. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study replicates many findings of the first phase of the STAR*D study after controlling for the differences between the studies.

The use of slow-frequency prefrontal repetitive transcranial magnetic stimulation in refractory neuropathic pain.

OBJECTIVE: A number of antidepressant medications, as well as electroconvulsive therapy, have been shown to reduce chronic pain. Slow-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex has also been shown to have an antidepressant effect. Given the high degree of suffering experienced by subjects with chronic neuropathic pain and the treatment resistance noted in this population, the use of slow-frequency rTMS as adjuvant therapy may be of significant clinical benefit. METHODS: Fifteen sessions of 1-Hz rTMS (1600 stimulations/session) were applied to the right dorsolateral prefrontal cortex as adjuvant treatment in 9 subjects with refractory neuropathic pain over 3 weeks. Pain and depression ratings were performed at baseline, weekly during rTMS treatment, and monthly for up to 3 months after treatment. RESULTS: Five males and 4 females participated, and all had longstanding refractory neuropathic pain (range, 1-19 years), with an average baseline pain rating of 7.3 and no depression (Hamilton Rating Scale for Depression average, 3.6; range, 0-8). Three subjects had a greater than 50% decline in pain ratings by the completion of rTMS treatments, and 1 subject responded more slowly with greater than 50% improvement in pain by the end of the 3-month follow-up. An improvement in pain ratings was noted in responders within the first week. CONCLUSIONS: Although these are preliminary findings in an open treatment trial, the subjects in this trial are among the least likely to have a placebo response. Given that rTMS is a well-tolerated and noninvasive intervention, any sustained improvement in neuropathic pain with rTMS is encouraging.

Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine.

This study examines the relationship between blood concentrations of venlafaxine and its active metabolite, O-desmethyl venlafaxine (ODV), and genetic variants of the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human subjects. Trough blood concentrations were measured at steady state in patients treated with venlafaxine extended release in a clinical practice setting. CYP2D6 and CYP2C19 genotypes were converted to activity scores based on known activity levels of the two alleles comprising a genotype. After adjusting for drug dose and gender effects, higher CYP2D6 and CYP2C19 activity scores were significantly associated with lower venlafaxine concentrations (P < 0.001 for each). Only CYP2D6 was associated with the concentration of ODV (P < 0.001), in which genotypes with more active alleles were associated with higher ODV concentrations. The sum of venlafaxine plus ODV concentration showed the same pattern as venlafaxine concentrations with CYP2D6 and CYP2C19 genotypes with higher activity scores being associated with a lower venlafaxine plus ODV concentration (2D6 P = 0.01; 2C19 P < 0.001). Because allelic variants in both CYP2D6 and CYP2C19 influence the total concentration of the active compounds venlafaxine and ODV, both CYP2D6 and CYP2C19 genotypes should be considered when using pharmacogenomic information for venlafaxine dose alterations.

Bariatric surgery: a primer for eating disorder professionals.

Obesity is a public health epidemic with medical, psychological and economic consequences. It continues to increase globally in prevalence and severity. Despite numerous behaviourally, medically or pharmacologically guided treatments, an effective non-surgical long-term treatment approach has not been identified. Bariatric surgery has surfaced as a viable option for a subset of individuals with medically complicated obesity who have failed non-surgical approaches. Pre-operative evaluation followed by post-operative, longitudinal follow-up by a multidisciplinary team specializing in surgery, medicine, psychiatry/psychology, exercise science and nutrition constitutes recognized and necessary standard of care for these complex patients. More information is needed regarding factors that interfere with successful outcomes and mechanisms of optimal follow-up for bariatric surgery patients to prevent and detect post-operative medical, psychological and social difficulties. We will review these issues with a focus on issues relevant to eating disorders professionals.

Identification and treatment of eating disorders in the primary care setting.

Eating disorders, which are associated with a host of adverse medical morbidities, negative psychological sequelae, and considerable reductions in quality of life, should be diagnosed and treated promptly. However, primary care physicians may find it uniquely challenging to detect eating disorders in their early stages, before obvious physical problems arise and while psychological symptoms are subtle. Although psychological symptoms may dominate the presentation, the physician is an integral member of the treatment team and is in a unique role to diagnose and treat eating disorders. This clinical review surveys the eating disorders literature, identified by searching MEDLINE and PubMed for articles published from January 1, 1983, to September 30, 2009, using the following keywords: anorexia nervosa, bulimia nervosa, eating disorders, eating disorders NOS, binge eating, binge eating disorder, and night eating syndrome. This review also focuses on practical issues faced by primary care physicians in the management of these conditions and other issues central to the care of these complex patients with medical and psychiatric comorbid conditions.

Eating disorders in the elderly.

BACKGROUND: Eating disorders in the elderly are often overlooked. When they occur, significant morbidity and mortality result. In this study we review all existing literature on eating disorders in the elderly and provide practical guidelines for clinicians in recognizing and managing eating disorders in the elderly. METHODS: A literature search using Medline, PubMed, Web of Knowledge, and PsychINFO revealed 48 published cases of eating disorders in people over the age of 50 years. RESULTS: The mean age was 68.6 years (range 50-94), and the majority (88%) of cases were females. The majority (81%) of cases had anorexia nervosa, and 10% had bulimia nervosa. Late onset eating disorders were more common (69%) than early onset. Comorbid psychiatric conditions existed in 60%, most commonly major depression. Management with a combination of behavioral and pharmacologic interventions was most successful, although only 42% were treated successfully. Mortality was high (21%) secondary to the eating disorder and its complications. CONCLUSION: Eating disorders do occur in the elderly and should be included in the differential diagnosis of unexplained weight loss in the elderly.

Measurement of daily activity in restrictive type anorexia nervosa.

OBJECTIVE: The assessment of daily activity in patients with restrictive type anorexia nervosa is limited by an absence of accurate and precise technology. We wanted to test a daily activity detecting device named, the physical activity monitoring system (PAMS). METHOD: Women participants with restrictive type anorexia nervosa (n = 8, 36 +/- 11 years, 17 +/- 2 kg/m(2)) and healthy women participants (n = 8, 30 +/- 11 years, 27 +/- 7 kg/m(2)) were asked to lie, sit, and stand motionless, and walk at 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mph while wearing PAMS. RESULTS: For all restrictive type anorexia nervosa and healthy participants, body posture was correctly detected for all measurements (300/300). There was excellent correlation of an individual's body acceleration with walking velocity and walking energy expenditure (r(2) > .99). CONCLUSION: The PAMS technology could serve as a tool for lending insight into the pathophysiology of restrictive type anorexia nervosa; and potentially measuring compliance with activity recommendations for medical professionals treating individuals with restrictive type anorexia nervosa.

Cytochrome P450 2D6 genotype variation and venlafaxine dosage.

OBJECTIVE: To determine whether the presence or absence of a fully functioning cytochrome P450 2D6 allele was associated with the dosage of the antidepressant drug venlafaxine in patients who had either adverse effects or absence of a therapeutic response to treatment with the immediate release or extended release form of venlafaxine. PATIENTS AND METHODS: We reviewed the electronic medical records of 199 patients enrolled in a previous pharmacogenomic study (June 1, 2002 through April 30, 2004) who had either adverse effects or the absence of a therapeutic response to treatment with psychotropic medications. This review identified 38 patients previously treated with venlafaxine immediate release or extended release and subsequently genotyped for the 2D6 gene with a commercial genotyping assay. Their dosage was examined along with their 2D6 genotype to determine whether the presence or absence of a fully functioning 2D6 allele was associated with their venlafaxine dosage. RESULTS: Of the 38 patients, 5 had a 2D6 genotype that consisted of 1 inactive allele and 1 allele associated with decreased activity. None of these 5 patients were able to tolerate treatment with more than 75 mg/d of venlafaxine. The remaining 33 patients had at least 1 fully active 2D6 allele, 26 of whom had been able to tolerate treatment with 150 mg/d or more of venlafaxine (P less than .002). CONCLUSION: Genetic variations of the P450 2D6 gene may contribute to patient-specific variation in response to treatment with venlafaxine. Physicians should be alert to the possibility that an adverse reaction may indicate a slow metabolizer and consider genotyping such patients.

Sexual abuse survivors and psychiatric hospitalization after bariatric surgery.

BACKGROUND: Some investigators have postulated that a history of being the victim of childhood sexual abuse may impact outcome of bariatric surgery. METHODS: In this retrospective chart review, we examined the electronic medical records of 152 adults with morbid obesity who underwent Roux-en-Y gastric bypass and who had a weight recorded in their medical record or reported in a follow-up surgery at 2 years after the RYGBP. The purpose of this retrospective chart review was to examine the relationship between psychosocial factors assessed preoperatively and the percent of excess weight lost (%EWL) at 2 years after bariatric surgery. RESULTS: We found a high prevalence of being the victim of childhood sexual abuse (27%), adult sexual trauma (9%), and/or physical abuse (19%) at the initial evaluation. There was no association between these factors and %EWL at 2 years. However, when we examined participants' medical records for post-operative psychiatric hospitalizations at our medical center, 8 of 11 hospitalized patients reported a history of childhood sexual abuse (73%). CONCLUSIONS: History of being the victim of childhood sexual abuse is reported frequently by patients seeking bariatric surgery. Our finding that having been the victim of childhood sexual abuse may be associated with increased risk of psychiatric hospitalization after RYGBP has several clinical implications. First, we recommend that clinicians assess carefully for a history of sexual or physical abuse, and secondly, abuse survivors may need to be told that there is an increased risk of psychiatric morbidity after bariatric surgery. Finally, perhaps close monitoring of these patients may prevent psychiatric difficulties after surgery. Further research to verify these preliminary findings is clearly needed.

Assessment and preparation of patients for bariatric surgery.

The number of bariatric surgical procedures performed in the United States has increased steadily during the past decade. Currently accepted criteria for consideration of bariatric surgery include a body mass index (calculated as weight in kilograms divided by the square of height in meters) of 40 kg/m2 or greater (or >35 kg/m2 with obesity-related comorbidities), documented or high probability of failure of nonsurgical weight loss treatments, and assurance that the patient is well informed, motivated, and compliant. Appropriate patient selection is important in achieving optimal outcomes after bariatric surgery. In this article, we review our approach to the medical and psychological assessment of patients who want to undergo bariatric surgery. The medical evaluation is designed to identify and optimally treat medical comorbidities that may affect perioperative risks and long-term outcomes. The psychiatric and psychological assessment identifies factors that may influence long-term success in maintaining weight loss and prepares the patient for the lifestyle changes needed both before and after surgery.

Survey of regional health care providers on selection of treatment for bulimia nervosa.

OBJECTIVE: To determine which treatments clinicians currently recommend for patients with bulimia nervosa (BN), to find out if they recommended evidence-based treatments, and to assess availability and clinician satisfaction with treatment options. METHODS: Surveys were sent to 1,263 health care providers in Minnesota, Iowa, and Wisconsin who were likely to encounter patients with BN. These health care providers comprised all primary care clinicians, physician assistants, advanced practice nurses, and all mental health/chemical dependency clinicians (MDs, Clinical Nurse Specialist (CNS), social workers, doctoral and masters-level therapists, and chemical dependency (CD) counselors) affiliated with the Mayo Clinic in Rochester, Minnesota. RESULTS: Evidence-based treatments for BN are recommended consistently and are generally perceived to be available, at least to practitioners affiliated with a large medical center in the Midwest. Clinician satisfaction with treatment options is modest. DISCUSSION: Clinicians are recommending evidence-based treatments for BN patients and find them to be generally available. Modest satisfaction with available treatments may reflect a realistic understanding of treatment options, which need further development.

Anorexia nervosa: manifestations and management for the gastroenterologist.

Anorexia nervosa is a complex psychiatric disorder with significant morbidity and mortality. It is important for gastroenterologists to be aware of the physiological effects and potential complications of anorexia nervosa, as they are frequently involved in treating patients with this disorder. We review the classic, GI, and neuroendocrinological features of anorexia nervosa. We also discuss gender differences and treatment options in anorexia nervosa. Further studies of GI physiology and pharmacology are needed to determine whether any disturbances may be amenable to therapeutic intervention. Future treatments directed at improving GI sensorimotor function and neurohormonal abnormalities in patients with anorexia nervosa may impact their nutritional rehabilitation and may have important health economic implications as patients avoid hospitalization and are restored to full activities in society. The current team approach, which incorporates psychiatrists, psychologists, nutritionists, pediatricians, internists, and gastroenterologists in the treatment of patients with anorexia nervosa, will continue to be essential.