Teprotumumab for Thyroid-Associated Ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).

Comparison of self-rated and clinician-rated measures of depressive symptoms: a naturalistic study.

In order to assess the concordance between self-rating and clinician's assessment tools of depression, as well as factors involved in the differences between auto and hetero evaluation, 198 depressed in-patients were assessed at admission and at discharge using the Montgomery Asberg Depression Rating Scale (10-item version, MADRS) and the self-rating scale Symptoms CheckList (90-item version, SCL-90). We found that about 18% of patients overestimated and about 15% underestimated their depressive symptomatology (SCL-90 depression subscale) relative to the psychiatrist's assessment. Logistic regression analysis showed that the presence of personality disorders and previous history of psychiatric disorders predicted the overestimating group. Discriminant analysis showed that approximately 75% of participants were correctly classified when previous history of psychiatric disorders, presence of personality disorders and age were entered separately into the equation.

Depression in inpatients: bipolar vs unipolar.

162 depressed inpatients were divided into three diagnostic groups to compare patterns of sociodemographic characteristics, psychopathology, and psychosocial: 35 had a single episode of major depression, 96 had recurrent major depression, and 31 had a bipolar disorder. Psychopathology and psychosocial functioning were measured by clinician-rated scales, Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, Clinical Global Impression, and self-rating scales, Symptom Checklist-90, Social Support Questionnaire, Social Adjustment Scale. The three groups were comparable on sociodemographic variables, with the exception of education. Univariate analyses showed a similar social impairment as measured by Social Support Questionnaire, Social Adjustment Scale, and no significant differences were recorded for the psychopathology when the total test scores (Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, Clinical Global Index, Symptom Checklist-90) were evaluated. Some differences emerged for single items in the Montgomery-Asberg Depression Rating Scale and Symptom Checklist-90. These findings suggest a substantial similarity among the three groups. Results are discussed in terms of the clinical similarities between unipolar and bipolar patients during a depressive episode as well as the limitations of cross-sectional study implies.

Social adjustment in in-patients with affective disorders: predictive factors.

We assessed social adjustment in 145 depressed in-patients using the self-reporting Social Adjustment Scale (42-item version) to evaluate the contribution of demographic and clinical variables and examine social functioning at different levels of depression. Our results indicate that the presence of a psychopathology in association with interpersonal sensitivity, hostility and perceived social support aspects -- and not the severity of current depressive symptoms -- were the most important factors affecting social adjustment. As expected, social disturbances are more pronounced in severe depressives who experience difficulties in all areas: by contrast, patients with low depressive symptom levels do not appear to be maladjusted, by comparison with a community sample.

Chronic musculoskeletal pain and depressive symptoms in the National Health and Nutrition Examination. I. Epidemiologic follow-up study.

We report here follow-up data on subjects who were examined in two surveys conducted by the United States Center for Health Statistics at an interval of 8 years. The first survey was the 1st National Health and Nutrition Examination Survey (NHANES-1), and the second conducted 8 years later was the National Health and Nutrition Epidemiologic Follow-up Study (NHEFS). From an original sample of 3023 subjects, 153 were known to be deceased, leaving a potential sample of 2870 cases, of whom 2341 were ultimately examined in the NHEFS. The definition of pain used in the NHANES-1 survey identified 15% of the subjects as suffering from persistent pain. Using a different pain definition, in the NHEFS, the frequency of subjects with chronic pain was 32.8%. Applying this second definition, the percentage of subjects with chronic pain in the NHANES-1 had risen from 15 to 20.2. Some subjects (32.5%) who originally had chronic pain were free from pain at the time of follow-up; 59% of the subjects with chronic pain on follow-up did not have it initially. As found originally in the NHANES-1, the group with chronic pain at the NHEFS comprised significantly more females, older people, and people with lower income. On logistic regression analysis the strongest relationship found at the NHEFS between the variables examined was between chronic pain and depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressive and distress symptoms as predictors of low back pain, neck-shoulder pain, and other musculoskeletal morbidity: a 10-year follow-up of metal industry employees.

Six-hundred-seven employees in 3 metal industry plants were studied for depressive and distress symptoms, musculoskeletal symptoms, and findings in the musculo-skeletal system made by a physiotherapist. Measurements were made 3 times at 5-year intervals. The mean distress and depressive symptom scores of the first 2 examinations predicted the change in several musculo-skeletal symptom measures during the second 5-year period, when the effects of age and occupational class were accounted for in multiple regression analysis. They also predicted the development in clinical musculoskeletal findings in men. The proportions of variance explained by the depressive and distress symptoms were modest in magnitude. Analogous analyses were made with reference to the reverse temporal sequence: musculoskeletal disorders were considered as predating the development in depressive and distress symptoms. The musculoskeletal symptom scores were associated with the change in the stress symptoms in men, as did the clinical findings in the neck-shoulder and low back regions. None of the musculoskeletal morbidity scores predicted the change in the depressive symptoms in either sex. We conclude that depressive symptoms predict future musculoskeletal disorders, but not vice versa, whereas the association of stress symptoms and musculoskeletal disorders is reciprocal.

Chronic musculoskeletal pain and depressive symptoms in the general population. An analysis of the 1st National Health and Nutrition Examination Survey data.

Chronic pain and depression frequently occur together. A selection bias afflicts all hospital clinic and family practice populations in which this relationship has been examined. We report here some of the results from civilian populations outside institutions, examined in the United States in national surveys. The findings are based upon the recollection of individuals with respect to the period of 12 months prior to interview and upon the occurrence of depression in the previous week as indicated by the answers to the Depression Scale of the Centre for Epidemiologic Studies (CES-D). They indicate that 14.4% of the United States population between the ages of 25-74 suffer from definite chronic pain related to the joints and musculoskeletal system. Another 7.4% have some pain of uncertain duration. Eighty-three percent of the definite pain group received treatment. Chronic pain subjects scored significantly higher than normals on the CES-D (10.68 +/- S.E.M. 0.76 vs. 8.05 +/- 0.23, P less than 0.01) with subjects with pain of uncertain duration scoring similar to the definite chronic pain population (11.13 +/- 0.76). Using a high cut-off score for depression. 18% of the population with chronic pain were found to have depression. This is in contrast to 8% of the population who did not have chronic pain.

On the relationship between chronic pain and depression when there is no organic lesion.

Patients suffering from pain without evidence of either depression or organic lesions, or of any pathophysiological process to which the pain might be attributed, may be diagnosed as suffering from 'indeterminate pain.' The evidence in the literature which suggests that some of these cases might be due to a 'depressive equivalent' is examined. It is suggested that it is difficult, if not impossible, to formulate a diagnosis of depressive illness in patients who do not have clear symptoms of depression. However, there is evidence in the literature that a relatively high percentage of patients with chronic indeterminate pain appear to have a family history of depression and depressive spectrum disorders. Biological markers of depression also give some indication that certain of these patients may have a link with depressive illness as well as with pain. It is suggested that there is a need to explore the existence of a sub-group of patients with indeterminate pain in whom the mechanism of the pain may be related to the mechanism of depressive illness even though formal depressive symptoms are not found.

Modifications of [3H]imipramine binding sites in platelets of chronic pain patients treated with mianserin.

Tritiated imipramine binding to whole platelets was measured in 16 chronic pain patients who were free from major depression, and in a control group. The maximum binding was significantly lower in chronic pain patients than in the control group, whereas the binding affinity was not significantly different. Twelve patients were treated with mianserin for 21 days; this produced a significant improvement in the mean scores for pain (evaluated with the McGill Questionnaire) and depressive symptoms (assessed with the Zung Self-Rating Scale). The improvement in both types of symptom was accompanied by a significant mean increase in the density of the [3H]imipramine binding sites without modifications in the values of the constant of affinity. All the patients who responded well to treatment (N = 8) had a family history of depressive spectrum disorders (DSD), while none of those who failed to respond had a first degree relative with DSD.

A simple examination of the relationships between pain, organic lesions and psychiatric illness.

It is often assumed that pain can be caused by psychological illness and also that severely painful organic lesions may cause emotional change. If these assumptions are correct, pain in the absence of lesions should be associated with a very high rate of psychiatric diagnosis; pain with lesions should occur with psychological illness more often than by chance but less often than in the group without lesions. To test these hypotheses two groups have been compared, one with pain and no evidence of organic lesions, the other with pain proportionate to organic lesions. Ninety-seven per cent of the first group and 39% of the second group were found to have psychiatric conditions (P less than 0.001).

Antidepressants in the treatment of cancer pain. A survey in Italy.

The authors sent a questionnaire to 79 Italian oncological centres to investigate the use of antidepressants in the treatment of cancer pain. Thirty-five centres (44.3%) responded; twenty-two of these used antidepressants. About 43% of the subjects treated for cancer-related pain received antidepressants. The drug most frequently used was amitriptyline, followed by imipramine, clomipramine and trazodone. The dosages were relatively varied, in some cases under the minimum normally used in antidepressant therapy. Good or fair results were reported in 51% of the patients; the inclusion of all worthwhile responses raised the proportion with benefit to 98%. The majority of the centres stated that a depressive disorder or depressive symptoms were not a necessary precondition for the prescription of antidepressants. The occurrence of side-effects seems to be higher in cancer patients than in depressed subjects; this may be partly related to the fact that in nearly all cases, antidepressants are used in association with other drugs, typically opiates and peripheral analgesics.