Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).

Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing.

Human leukocyte antigen B (HLA-B) is a gene that encodes a cell surface protein involved in presenting antigens to the immune system. The variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in response to carbamazepine treatment. We summarize evidence from the published literature supporting this association and provide recommendations for the use of carbamazepine based on HLA-B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this article is to provide information to allow the interpretation of clinical HLA-B*15:02 genotype tests so that the results can be used to guide the use of carbamazepine. The guideline provides recommendations for the use of carbamazepine when HLA-B*15:02 genotype results are available. Detailed guidelines regarding the selection of alternative therapies, the use of phenotypic tests, when to conduct genotype testing, and cost-effectiveness analyses are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on the PharmGKB website at (http://www.pharmgkb.org).

Accuracy of body image perception and preferred weight loss strategies in schizophrenia: a controlled pilot study.

OBJECTIVE: Obesity in severely mentally ill (SMI) populations is an increasing problem, but there is no controlled data regarding the relationship between SMI and weight perception. METHOD: Fifty patients with schizophrenia and 50 demographically matched control participants were recruited. Weight, height, and body image accuracy were assessed for all participants, and assessments of mood, psychotic symptom severity and anxiety, and preferred modes of weight loss were assessed for the schizophrenia sample. RESULTS: Patients with schizophrenia were significantly more likely to be obese than controls (46% vs. 18%, P < 0.005), and most patients expressed an interest in losing weight. Obese participants with schizophrenia underestimated their body size (11.0%) more than controls (4.9%) (P < 0.05). CONCLUSION: Patients with schizophrenia are more likely to underestimate their body size, independent of the effects of obesity. However, they also express concern about weight issues and willingness to participate in psychoeducational groups targeted at weight loss.

Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain.

BACKGROUND: Reports of gabapentin use in diabetic peripheral neuropathy pain stimulate a need for controlled trials to determine its comparative efficacy to the therapeutic standard of amitriptyline hydrochloride. OBJECTIVE: To determine the efficacy of gabapentin compared with amitriptyline in treating diabetic peripheral neuropathy pain. DESIGN: Prospective, randomized, double-blind, double-dummy, crossover study. SETTING: Veterans Affairs San Diego Healthcare System, Ambulatory Care Clinic. PATIENTS: Twenty-eight veterans were referred by their primary care providers. Two patients withdrew before randomization because of no neuropathic pain after washout; a third withdrew for unexpected surgery that required analgesics. Three patients withdrew because of adverse effects and 1 for protocol violation. INTERVENTIONS: Patients with stable glycemic control and neuropathic pain randomized to 6 weeks of therapy with gabapentin, 900 to 1800 mg/d, or amitriptyline hydrochloride, 25 to 75 mg/d, with a 1-week washout before crossover. MAIN OUTCOME MEASURES: Pain relief measured by pain scale with verbal descriptors and global pain score assessment at treatment end. RESULTS: Participants and investigators were blinded throughout. Mean dosages were of gabapentin, 1565 mg/d, and of amitriptyline hydrochloride, 59 mg/d. Sixty-five percent of patients reached maximum dose with gabapentin and 54% with amitriptyline. Mean score diary analysis showed pain relief with gabapentin and amitriptyline was not significantly different (P = .26). Global data were obtained from 21 of 25 enrolled patients who completed the study. Moderate or greater pain relief was experienced in 11 (52%) of 21 patients with gabapentin and 14 (67%) of 21 patients with amitriptyline. There were no significant period or carry-over effects (P = .35). CONCLUSIONS: Although both drugs provide pain relief, mean pain score and global pain score data indicate no significant difference between gabapentin and amitriptyline. Gabapentin may be an alternative for treating diabetic peripheral neuropathy pain, yet does not appear to offer considerable advantage over amitriptyline and is more expensive. Larger trials are necessary to define gabapentin's place in treating diabetic peripheral neuropathy pain.