Non-remitted Patients Research Articles

Cost Effectiveness of Long-Term Treatment with Eszopiclone for Primary Insomnia in Adults

Although the clinical benefits of pharmacological treatments for insomnia have been studied, no systematic assessment of their economic value has been reported. This analysis assessed, from a broad payer and societal perspective, the cost effectiveness of long-term treatment with eszopiclone (LUNESTA, Sepracor Inc., [Marlborough, MA, USA]) for chronic primary insomnia in adults in the US. A decision analytical model was developed based on the reanalysis of a 6-month placebo-controlled trial, which demonstrated that eszopiclone 3mg significantly improved sleep and daytime function measures versus placebo in adults with primary insomnia. Patients were classified as either having remitted or not remitted from insomnia based upon a composite index of eight sleep and daytime function measures collected during the trial. These data were supplemented with quality-of-life and healthcare and lost productivity cost data from the published literature and medical and absenteeism claims databases. Compared with non-remitted patients, patients classified as remitted had lower monthly healthcare and productivity costs (in 2006 dollars) [a reduction of $US242 and $US182, respectively] and higher quality-adjusted life-year (QALY) weight (a net gain of 0.0810 on a scale ranging from 0 to 1). During the study, eszopiclone-treated patients were about 2.5 times more likely to have remitted than placebo-treated patients. Six months of eszopiclone treatment reduced direct (healthcare) and indirect (productivity) costs by an estimated $US245.13 and $US184.19 per patient, respectively. Eszopiclone use was associated with a cost of $US497.15 per patient over 6 months (including drug cost, dispensing fee, physician visit and time loss to receive care). Thus, after considering the above savings and the costs associated with eszopiclone treatment over 6 months, cost increased by $US252.02 (excluding productivity gains) and $US67.83 (including productivity gains) per person. However, eszopiclone treatment was also associated with a net QALY gain of 0.006831 per patient over the same period. Consequently, the incremental cost per QALY gained associated with eszopiclone was approximately $US9930 (including productivity gains [i.e. $US67.83 / 0.006831]) and $US36 894 (excluding productivity gains [i.e. $US252.02 / 0.006831]). Sensitivity analyses using a variety of scenarios suggested that eszopiclone is generally cost effective. This analysis suggested that long-term eszopiclone treatment was cost effective over the 6-month study period, particularly when the impact on productivity costs is considered. Given the increasing interest in new pharmacological interventions to manage insomnia, payers and clinicians alike should carefully consider the balance of health and economic benefits that these interventions offer. Accordingly, additional research in this area is warranted.

Does adding psychotherapy to pharmacotherapy improve social functioning in the treatment of outpatient depression?

The existence of an overall association between severity of depression and level of social functioning is well documented. To increase the probability of a long-term recovery, a normal level of social functioning is essential. It is currently unknown whether combined therapy has a better outcome than pharmacotherapy with regard to social functioning. In a 6-month randomized clinical trial in outpatients with major depression, all patients studied had a baseline score of at least 14 points on the 17-item Hamilton Depression Rating Scale (HDRS). The two conditions consist of pharmacotherapy (PhT) (N=84) and combined therapy (CoT), pharmacotherapy plus 16 sessions of short psychodynamic supportive psychotherapy (N=83). Efficacy was assessed using the 17-item HDRS, the Clinical Global Impression (CGI) Severity and Improvement scales, the Depression subscale of the Symptom Checklist-90 (SCL-90), the Quality of Life Depression Scale (QLDS), more the Groningen Social Disability Schedule (GSDS). Severity of depression decreased significantly (on the SCL-90 Depression subscale and the QLDS) more in the CoT condition. A larger improvement in social functioning was demonstrated for remitted patients than for nonremitted patients. The number of dimensions of social functioning that had improved significantly was higher in CoT than in PhT. There was a moderate advantage of the CoT condition on both depressive symptoms and level of social functioning in comparison with PhT. We also found a positive association between depression severity and level of social functioning.

Remission in early psychosis: Rates, predictors, and clinical and functional outcome correlates

Background Recently, the “Remission in Schizophrenia Working Group” proposed remission criteria consisting of a reduction to mild levels on key symptoms for at least 6 months. Aims This study applied these remission criteria to a large first-episode psychosis sample in order to (1) determine the rates of remission; (2) explore predictors of remission; and (3) test the external validity of these criteria. Methods We analyzed data from 462 subjects with a first-episode of psychosis who participated in a long-term, multinational, randomized, double-blinded trial of risperidone and haloperidol over 2 to 4 years. Results At some time point in the study 323 (70%) of the 462 subjects had a reduction to mild levels on the key symptoms as measured by the PANSS although only 109 (23.6%) maintained this level for at least 6 months thereby meeting remission criteria. The two strongest predictors of remission were shorter duration of untreated psychosis ( p = 0.01) and treatment response at 6 weeks ( p = 0.001). Compared to non-remitted patients, those in remission experienced greater improvement on all PANSS subscales ( p < .0001), CGI-S ( p < .0001), better quality of life ( p = 0.006), fewer relapses ( p < .0001), displayed a more favorable attitude towards their medication ( p = .002), had lower EPS levels according to the ESRS ( p = < .0001) and received lower doses of antipsychotic medication ( p = 0.003). The remission and non-remission groups did not differ significantly regarding composite cognitive scores, suicidality and body mass index. Conclusions The results suggest that the remission criteria, although based solely on core symptom improvement, can effectively identify patients who have a more favorable overall outcome.

0428 EFFECTIVENESS OF ANTIPSYCHOTIC TREATMENT IN NEVER TREATED PATIENTS WITH SCHIZOPHRENIA: 36-MONTH RESULTS FROM THE SCHIZOPHRENIA OUTPATIENTS HEALTH OUTCOMES (SOHO) STUDY

Recently, the “Remission in Schizophrenia Working Group” proposed remission criteria consisting of a reduction to mild levels on key symptoms for at least 6 months.This study applied these remission criteria to a large first-episode psychosis sample in order to (1) determine the rates of remission; (2) explore predictors of remission; and (3) test the external validity of these criteria.We analyzed data from 462 subjects with a first-episode of psychosis who participated in a long-term, multinational, randomized, double-blinded trial of risperidone and haloperidol over 2 to 4 years.At some time point in the study 323 (70%) of the 462 subjects had a reduction to mild levels on the key symptoms as measured by the PANSS although only 109 (23.6%) maintained this level for at least 6 months thereby meeting remission criteria. The two strongest predictors of remission were shorter duration of untreated psychosis (p = 0.01) and treatment response at 6 weeks (p = 0.001). Compared to non-remitted patients, those in remission experienced greater improvement on all PANSS subscales (p < .0001), CGI-S (p < .0001), better quality of life (p = 0.006), fewer relapses (p < .0001), displayed a more favorable attitude towards their medication (p = .002), had lower EPS levels according to the ESRS (p = < .0001) and received lower doses of antipsychotic medication (p = 0.003). The remission and non-remission groups did not differ significantly regarding composite cognitive scores, suicidality and body mass index.The results suggest that the remission criteria, although based solely on core symptom improvement, can effectively identify patients who have a more favorable overall outcome.

The effect of temperament and character on response to selective serotonin reuptake inhibitors in panic disorder

In this prospective study, temperament and character were evaluated in patients with panic disorder (PD), before 1 year of medication therapy, to verify whether these factors influenced the outcome of treatment. Seventy-one PD patients were evaluated with the SCID-IV, the Temperament and Character Inventory (TCI), the SCL-90, the Ham-A and the Ham-D. Patients were treated with pharmacotherapy and were evaluated monthly over 1 year. Before treatment, non-remitted patients showed higher levels of harm avoidance (HA) and lower levels of persistence (P), self-directedness (SD) and cooperativeness (C), whereas remitted patients showed only higher levels of HA. After controlling the effect of the confounding variables, the likelihood to achieve remission was positively related to SD score (OR = 1.12; P = 0.002), particularly 'self-acceptance' SD dimension (OR = 1.30; P = 0.02). Our data suggest that in PD: i) the evaluation of personality, using the Cloninger's model, confirms the presence of personality pathology as one predictor of non-response to treatment; ii) in patients with low SD a combination of medication and cognitive-behaviour therapy should be the most effective treatment.

The effect of pharmacotherapy on personality disorders in panic disorder: A one year naturalistic study

Background In this prospective study, Personality Disorders (PersD) were evaluated in patients with Panic Disorder (PD), before and after one year of pharmacotherapy to verify whether personality characteristics changed after treatment. Method Sixty PD patients and 60 sex and age-matched normal controls participated in the study. All subjects were evaluated with the SCID-IV, the Structured Interview for DSM-IV Personality Disorders (SIDP), the SCL-90, the Ham-A and the Ham-D. Patients were treated with paroxetine or citalopram and were evaluated monthly for one year to assess the remission of symptoms. The SIDP was re-administered to the patients at the end of the study. Results Before treatment, PD patients showed a higher prevalence (60%) of PersD than normal subjects (8%). After treatment, PersD rate decreased (43%) due to the reduction of the rate of paranoid, avoidant and dependent PersD. When the effect of the treatment on personality traits was evaluated, we found that avoidant traits decreased only in remitted patients, paranoid traits decreased both in remitted and in non-remitted patients, and dependent traits decreased only in patients with major depression comorbidity. Limitations The small sample size and the short length of the follow-up period of our study suggest caution in the generalization of our results. Conclusions In our PD patients, an improvement of symptoms was associated with a reduction of paranoid, avoidant and dependent traits, with a normalization of paranoid traits and a persistence of avoidant and dependent characteristics. Therefore, our data suggest that in PD patients not only paranoid traits but also avoidant and dependent traits show, at least in part, a state phenomenon.

Remission in schizophrenia: Results from a 1-year study of long-acting risperidone injection

Purpose Although treatment advances have improved outcomes in schizophrenia, definitions of remission and recovery are still evolving. Recently proposed criteria for remission (mild or less on multiple core-symptom ratings for at least 6 months) have been applied to a 1-year study of long-acting risperidone injection. Methods In a 50-week, open-label trial, stable patients with schizophrenia or schizoaffective disorder who received long-acting risperidone injection every 2 weeks were assessed using the Positive and Negative Syndrome Scale (PANSS). Remission criteria for the PANSS were applied; global illness severity (Clinical Global Impressions) and patient-rated health status (36-Item Short-form Health Survey) were measured. Results Groups were identified by initial remission status (excluding the time component). Although considered clinically “stable,” 68.2% (394 / 578) did not meet the symptom-severity component of remission criteria at baseline. Following long-acting, injectable risperidone treatment, 20.8% (82) of nonremitted patients achieved symptom remission for at least 6 months, with significant decreases in mean PANSS total and cluster scores ( P < 0.0001) and significantly improved patient-rated health status ( P < 0.0001). Percentages rated as not ill, very mild, or mild increased from 39% to 88%. Among 31.8% (184 / 578) of patients meeting the symptom-severity component of remission criteria at baseline, 84.8% (156) maintained these criteria at endpoint. Conclusions Among previously “stable,” nonremitted patients, many achieved symptom remission after long-acting, injectable risperidone treatment, with significant improvements in multiple symptom domains and patient-rated health status. These results warrant further study as these remission criteria may represent a meaningful clinical endpoint and an important step towards functional recovery.

Determinants of subjective quality of life in depressed patients: The role of self-esteem, response styles, and social support

Background We aimed to assess the subjective quality of life (QOL) in depressed patients after discharge from inpatient treatment and to investigate the net impact of self-related constructs (self-esteem, response styles to depressed mood) and of social support on specific subjective QOL domains. Method Four weeks after discharge from inpatient treatment, 89 unipolar depressed patients were assessed with a comprehensive battery of psychopathology and psychosocial measures. Subjective QOL was assessed using the World Health Organization Quality of Life Scale (WHOQOL-BREF). Analyses included hierarchical regressions. Results Non-remitted patients reported poorer subjective QOL than fully and partially remitted patients regarding physical and psychological health, and overall QOL. After adjusting for demographic and clinical history variables, interviewer-rated severity of depression accounted for 4% to 36% of the variance in individual QOL domain scores. Self-esteem, rumination, distraction and the existence of a partnership added further increments to the explained variance of the psychological QOL domain. Rumination, partnership, and network size of family members providing psychological crisis support also predicted subjective QOL on the social relations domain. Conclusion Our results suggest that self-esteem, response styles to depressed mood, and social support characteristics contribute substantially to the psychological and social domains of subjective QOL in depressed patients. These associations are not attributable to concurrent symptom severity. Therapy with depressed patients should not only focus on symptom reduction but should help the patients to establish and maintain supportive relationships and to enhance self-appreciation and skills to cope with negative mood in order to improve psychological well-being and health-related quality of life.

Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder.

Hypothalamic-pituitary-adrenal (HPA) axis function, as variously measured by the responses to the combined dexamethasone/corticotrophin-releasing hormone (dex/CRH) test, the dexamethasone suppression test (DST) and basal cortisol levels, has been reported to be abnormal in bipolar disorder. To test the hypothesis that HPA axis dysfunction persists in patients in remission from bipolar disorder. Salivary cortisol levels and the plasma cortisol response to the DST and dex/CRH test were examined in 53 patients with bipolar disorder, 27 of whom fulfilled stringent criteria for remission, and in 28 healthy controls. Serum dexamethasone levels were measured. Patients with bipolar disorder demonstrated an enhanced cortisol response to the dex/CRH test compared with controls (P=0.001). This response did not differ significantly between remitted and non-remitted patients. These findings were present after the potentially confounding effects of dexamethasone levels were accounted for. The dex/CRH test is abnormal in both remitted and non-remitted patients with bipolar disorder. This measure of HPA axis dysfunction is a potential trait marker in bipolar disorder and thus possibly indicative of the core pathophysiological process in this illness.

Hippocampal and Amygdala Changes in Patients With Major Depressive Disorder and Healthy Controls During a 1-Year Follow-Up

Although the hippocampus has been found to be smaller in patients with depression, prospective longitudinal in vivo studies are necessary to investigate whether depression can result in a further diminution of hippocampal volumes or whether a smaller hippocampal volume predisposes an individual to the development of depression. Thirty patients with DSM-IV major depressive disorder as well as 30 healthy control subjects matched for age, gender, and handedness were examined at admission to the hospital and 1 year later using a documentation of the medical history and high-resolution magnetic resonance imaging (MRI) for the presence of depression and to determine changes in hippocampal as well as amygdala volumes. Patients were enrolled from March 2000 to August 2002. No significant hippocampal and amygdala volume changes were observed in patients or controls between baseline and 1-year follow-up investigations. However, the subgroup of patients who were nonremitted at the time of the follow-up investigation showed significantly reduced left and right hippocampal volumes at both baseline and the 1-year follow-up compared with remitted patients. Moreover, the right hippocampal volumes of nonremitted patients were significantly smaller compared with matched healthy controls. These results do not support the hypothesis that hippocampal volumes diminish during the 1-year follow-up period. However, smaller hippocampal volumes may be related to a poor clinical outcome after 1 year.

Residual cognitive impairment in late-life depression after a 12-month period follow-up.

This study investigated cognitive impairment in late-life depression in a follow-up design. The main objective was to assess the most important cognitive domains implicated in late-life depression, in patients who underwent pharmacological treatment, in the acute phase and twelve months after. Neuropsychological and clinical data were used from the baseline of patients and controls, to determine the cognitive impairment in the acute phase. Patients repeated the neuropsychological assessment at twelve months. There were significant differences between patients and controls at baseline. But in the patients there was no change over twelve months. There were no differences between remitted and non-remitted patients on neuropsychological scores. The cognitive impairment seen in the elderly depressed patients seems to be a trait characteristic of this mental disease, even when the depressive episode has remitted.

Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients

Background: Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. Methods: TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n=30) and nonremitted patients (NRP; n=28). Baseline results of these two groups were compared with each other and 30 healthy controls. Results: Basal levels of total T 3 (T 3T) and free T 3 (T 3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. Conclusions: The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T 3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics.

Psychosocial and clinical predictors of unipolar depression outcome in older adults.

This study examined psychosocial and clinical predictors of depression non-remittance among a sample of initially clinically depressed elders. Incident and prevalent unipolar depression cases (n = 166) were enrolled into the MHCRC for the Study of Depression in Late Life and followed for 12 months while undergoing treatment using a standardized algorithm. The outcome was remission vs non-remission (<6 vs > 7 on the Montgomery-Asberg Depression Rating Scale (MADRS)) at one-year follow-up. Baseline predictor variables included psychosocial factors, such as four domains of social support, basic and instrumental activities of daily living (ADLs), and clinical factors, which included use of ECT, past history of depression, comorbidities, and antidepressant treatment. At one-year follow-up, 45% of the sample was in remission based upon MADRS scores. In bivariate analyses, non-remitted patients were more likely at baseline to use benzodiazepines, anxiolytic/sedatives, and/or MAO inhibitors than patients in remission, and have more depressive episodes. Among psychosocial factors, non-remitted patients had at baseline, more ADL and IADL problems and decreased subjective social support as compared to patients in remission. In logistic regression analyses more depression episodes, using anxiolytic/sedatives, more IADL problems and decreased subjective social support predicted poor depression outcome after one-year. While clinical and diagnostic variables were related to improvement, baseline psychosocial factors were also important.

Family and extrafamily resources and the 10-year course of treated depression.

A group of 313 depressed patients and 284 controls was assessed at baseline (treatment intake for the patients) and at 1-year, 4-year, and 10-year follow-ups. Stably remitted patients achieved levels of family and extrafamily resources that were comparable with those of the controls. Although partially remitted and nonremitted patients' social resources improved, they continued to show deficits in these areas relative to controls and stably remitted patients. Several indexes of social resources predicted stable remission: more family independence, fewer family arguments and less conflict, and more helpful friends and activities with friends. Assessment of social resources at treatment intake and short-term follow-ups can help identify and provide intervention foci for patients at risk for nonremission of depression.

Functioning and life context among spouses of remitted and nonremitted depressed patients.

Functioning and life context among spouses of remitted and nonremitted depressed patients.

Anterior pituitary function in patients with advanced breast cancer in reference to bilateral total adrenalectomy and oophorectomy

For decades it has been postulated that hormonal inbalance is a major factor in tumorigenesis in the target organ. The regression of breast cancer induced by oophorectomy has been attributed to the removal of ovarian hormones in which estrogens play a important role. It is also known that the adrenal cortex secrete an amount of estrogen. These findings led to the conclusion that oophorectomy and adrenalectomy should be recommended for advanced breast cancer in man. In addition, there are extensive experimental data suggesting that pituitary hormones also lead to mammary tumors.Recently, it has been established that adrenalectomy and oophorectomy, or hypophysectomy can induce prolonged regression of advanced breast cancer in 50 percent of patients. About 50 patients with advanced breast cancer received bilateral total adrenalectomy and oophorectomy in our clinic, 50 per-cent of these patients had remissions during more than 1 month and 40 per cent during more than 6 months. The average period of remission was 13.4 months. This operative procedure was effective because the mean survival time of remitted patients was 20.3 months compared with 2.3 months in non-remitted patients. Nearly half of the patients thus treated were benefited however, the rest had no remission.If the effectiveness of this procedure could be predicted for each patient, unncessary major surgery would be avoided for those patients who obtained no remission. Moreover, even among remitted patients who had a relapse after one year or so, the exact mechanism of the relapse remains obscure.The purpose of this paper is to put forward a working hypothesis in the hope that further investigation may lead to an anticipation of the effectiveness of surgery and an understanding of the exact mechanism of relapse. Several anterior pituitary functions before and after bilateral total adrenalectomy and oophorectomy were studied.Urinary excretion of prolactin was determined by pigeon crop-sac method, urinary excretion of gonadotrophin was determined by chemical assay and bio-assay (mouse uterine weight method), serum sulfation factor was determined by ALMQVIST's method, and blood ACTH activity was estimated by adrenal ascorbic acid depletion method in hypophysectomized rat.The summary of results was as followed : 1) No increase of excretion of prolactin, gonadotrophin and growth hormone was observed in patients with breast cancer. 2) No excess excretion of ACTH was observed in the adrectomized and oophorectomized patients with advanced breast cancer when they were maintained with adequate administration of steroid. No increase of excretion of prolactin, gonadotrophin and growth hormone was also observed in these patients.3) There was no correlation between efficiency of surgery and the urinary excretion of prolactin and gonadotrophin. Therefore, it was impossible to anticipate the response of adrenalectomy and oophorectomy.4) No increase of excretion of prolactin, gonadotrophin and ACTH was observed in the relapsed patients who previously had remissions after adrenalectomy and oophorectomy. It may be concluded that there are some other factors influencing the relapse besides pituitary hormones.