Treating patients for comorbid depression, anxiety disorders, and somatic illnesses.

Patients who have comorbid depression and anxiety present primary care physicians a diagnostic as well as a treatment challenge. Identifying these patients is imperative as they have a higher suicide rate than those with depression alone. Patients with major depressive disorder and other psychiatric illness (ie, comorbid generalized anxiety disorder) have a double-fold increase of suicide attempts than patients without comorbid depression. Other medical illnesses may also be comorbid with depression and anxiety. The key to accurate diagnosis is the physician's high index of suspicion, the use of appropriate rating scales for assessment, including patients' self-rating scales, and the team approach. Such scales are also helpful in monitoring progress of treatment and in empowering patients to take an active role in their treatment, which may include pharmacologic or nonpharmacologic treatment options. Patient education in which depression and anxiety are described as biological disorders or medical illnesses averts patients' embarrassment and increases compliance. Referral for psychotherapy also increases compliance. Discussion includes summaries of studies documenting the efficacy, advantages, and disadvantages of medications that have been approved by the US Food and Drug Administration for depression and anxiety. A few medications used off label are mentioned briefly.

The effects of celecoxib augmentation on cytokine levels in schizophrenia.

Celecoxib augmentation therapy has been reported to enhance the rate of clinical response for patients with schizophrenia. This may be due in part to an effect of celecoxib in the immune dysfunction associated with schizophrenia. Given concerns about the safety of COX-2 inhibitors, studies investigating cytokine levels in medicated patients with schizophrenia are of public health importance. Twenty-eight schizophrenia subjects stabilized on olanzapine or risperidone were randomized to receive 8 wk of celecoxib (400 mg/d) or placebo. Serum soluble IL-2 receptor (sIL-2r) and in-vitro PHA-stimulated whole-blood cytokine production levels were measured at baseline, 1 wk, and 8 wk. Celecoxib augmentation did not alter any of the cytokine parameters measured for the overall study group. However, 1 wk of celecoxib augmentation increased TNF-alpha and IL-2 production levels in olanzapine-treated subjects. These elevations did not persist by week 8. Overall, celecoxib does not significantly modify cytokine levels in medicated schizophrenia subjects.

Celecoxib augmentation of continuously ill patients with schizophrenia.

BACKGROUND: Previous reports have demonstrated a beneficial effect of celecoxib adjunctive therapy for patients with an acute exacerbation of schizophrenia. We investigated the effects of celecoxib augmentation of atypical antipsychotic medications for continuously symptomatic outpatient subjects with schizophrenia to further extend these findings. We hypothesized that celecoxib augmentation therapy would improve psychopathology ratings compared with placebo. METHODS: Thirty-eight symptomatic outpatient subjects meeting DSM-IV criteria for schizophrenia and on a stable dose of an atypical antipsychotic medication for at least three months were randomized to receive 8 weeks of double blind placebo or celecoxib (400 mg/day) augmentation. Measures of psychopathology, functional disability, and extrapyramidal side effects were performed throughout the study. RESULTS: The treatment cohorts did not differ on any of the clinical outcome measures. CONCLUSIONS: Celecoxib augmentation of continuously ill outpatient subjects with schizophrenia did not improve clinical symptoms or measures of disability.

Studies characterizing 60 kda autoantibodies in subjects with schizophrenia.

BACKGROUND: Studies suggest that schizophrenic patients have an increased prevalence of serum antibodies to neuroblastoma cell proteins migrating at 60 kilodaltons (kDa). We present work identifying and characterizing 60 kDa antigen-antibody interactions. METHODS: Sera from schizophrenic subjects and normal volunteers were screened by Western blotting. Proteins migrating at 60 kDa were characterized by two-dimensional gel electrophoresis and indirect immunofluorescent staining of human epithelial cell (HEp-2) slides. Human brain and bladder cell complementary deoxyribonucleic acid libraries were screened with immunoaffinity-purified antibodies. Complementary deoxyribonucleic acid clones were sequenced and compared with published databases. Proteins were generated by in vitro transcription/translation and expression in an Escherichia coli BL21 system. Immunoprecipitation and immunohistochemistry studies were performed. RESULTS: Fifteen percent (17/117) of schizophrenic subjects and 3% (2/62) of normal volunteers had autoantibodies that reacted with 60 kDa proteins [chi(2)(1) = 4.4, p =.037]. Five percent of subjects had autoantibodies directed against 60 kDa heat shock protein (HSP60) [chi(2)(1) = 3.3, p =.100). Two-dimensional gel electrophoresis identified 13 different proteins migrating at 60 kDa; 5 were splice variants of HSP60, and 2 corresponded with a protein associated with MYC (PAM). CONCLUSIONS: There is an increased prevalence of autoantibodies that bind to proteins migrating at 60 kDa in subjects with schizophrenia. Potential target antigens include HSP60 and PAM.