Medication discontinuation with depot and oral antipsychotics in outpatients with schizophrenia: comparison of matched cohorts from a 12-month observational study.

AIMS: This study compared all-cause medication discontinuation (any switch, augmentation or medication discontinuation) in matched cohorts of patients with schizophrenia who were initiated on depot or oral antipsychotics. Other objectives included between-group comparisons of resource use, and clinical and functional outcomes. METHODS: This post hoc analysis of a one-year, multicentre, prospective, observational study included outpatients with schizophrenia who required a change in their antipsychotic medication because of a physician-perceived risk of medication non-adherence. Patients were matched 1 : 1 using an optimal algorithm with rank-based Mahalanobis distances. All-cause medication discontinuation was compared using the Klein and Moeschberger test for survival and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a Cox proportional hazards model, stratifying on matched pairs. RESULTS: Forty patients who initiated a depot antipsychotic could be matched to patients who initiated an oral antipsychotic. Fewer depot-treated patients discontinued their antipsychotic medication at least once compared with oral-treated patients [20% (8/40) vs. 40% (16/40)]. Depot-treated patients discontinued their medication later (Klein and Moeschberger test p = 0.025) and were less likely to discontinue their initial antipsychotic medication [HR = 0.33 (95% CI, 0.12-0.92), p = 0.033] than oral-treated patients. There were few differences in resource use and no differences in clinical and functional outcomes between cohorts. CONCLUSION: In this matched-cohort analysis, patients with schizophrenia who were considered to be non-adherent with their prior oral antipsychotics were less likely to discontinue their medication for any cause if they were initiated on depot compared with oral antipsychotics.

Duloxetine 60 mg/day for the prevention of depressive recurrences: post hoc analyses from a recurrence prevention study.

OBJECTIVE: To assess the efficacy of duloxetine 60 mg/day in the prevention of depressive recurrence in patients with major depressive disorder (MDD). METHODS: Patients having at least three episodes of MDD in the past 5 years received open-label (OL) duloxetine 60-120 mg/day for up to 34 weeks. Patients meeting response criteria were then randomised to either duloxetine or placebo for up to 52 weeks of double-blind maintenance treatment. Only patients taking duloxetine 60 mg/day during the OL phase, and randomised to either duloxetine (remained on 60 mg/day dose) or placebo, were included in this post hoc analysis. The primary outcome measure was time to recurrence of a major depressive episode. The 17-item Hamilton Rating Scale for Depression (HAMD(17)) was used to evaluate depressive symptomatology. Global and physical functioning and pain were also assessed. Safety and tolerability were assessed via analysis of treatment-emergent adverse events (TEAEs), vital signs and weight. RESULTS: A total of 124 patients were randomised to duloxetine 60 mg/day (n = 64) or placebo (n = 60). Time to depressive recurrence was significantly longer in duloxetine-treated patients compared with placebo-treated patients (p = 0.001). During the double-blind maintenance phase, 31.7% of placebo-treated patients experienced a depressive recurrence compared with 12.5% of duloxetine-treated patients (p = 0.004). The HAMD(17) total score and most of its subscales as well as the Clinical Global Impression of Severity (CGI-S), significantly worsened in the placebo group compared with the duloxetine 60 mg/day group. There were no significant differences between treatment groups in TEAEs, discontinuations because of adverse events, vital signs or weight. CONCLUSIONS: Treatment with duloxetine 60 mg/day was associated with a longer time to depressive recurrence and a significantly lower recurrence rate compared with placebo.

History of illness prior to a diagnosis of bipolar disorder or schizoaffective disorder.

BACKGROUND: There are obstacles to early identification of bipolar disorder. Identifying and treating illness early in its time course may be associated with a better prognosis. METHODS: A questionnaire was administered at interview, when the participant was euthymic, to participants (n=240) enrolled in the Bipolar Comprehensive Outcomes Study (BCOS). Information was collected about the sequential timeline of specific symptoms of mental illness up to when they first received a diagnosis of Bipolar Disorder or Schizoaffective Disorder. RESULTS: Any symptoms of mental illness were first experienced at 17.5 years (median; Inter Quartile Range (IQR) 13.8-24.3; n=216) and mood swings at 18.0 years (IQR 14-25; n=197). Symptoms of depression were experienced at 18.0 years (IQR 14-25; n=197), a full episode of depression at 21.2 years (IQR 17-28.5; n=200), symptoms of mania at 21.0 years (IQR 16.8-29.5; n=212) and a full episode of mania at 24.1 years (IQR 19-30.5; n=205). Medical treatment was sought at 24.0 years (IQR 19-31.5; n=217). Participants received a diagnosis of Bipolar Disorder or Schizoaffective Disorder at 30.0 years (IQR 23-37.3; n=215). Having had a previous diagnosis other than Bipolar Disorder or Schizoaffective Disorder was reported by 120 of 216 participants who answered this question, most commonly unipolar depression (26.6%). Diagnostic delay was greater in individuals with early onset disorder. CONCLUSIONS: Participants typically experience a long sequential course of symptoms, episodes, treatments and diagnosis. The polarity of onset is most commonly depressive, and subthreshold symptoms tend to precede threshold symptoms of both polarities. LIMITATIONS: Data were collected retrospectively.

Axis I and axis II comorbidity in panic/agoraphobic patients with and without suicidal ideation.

In view of the controversial relationship between certain aspects of panic disorder with agoraphobia (PDA), suicidal ideation and comorbidity, the purposes of this study were to compare severity of PDA and Axis I and Axis II comorbidity in PDA patients with and without suicidal ideation, and to examine predictors of suicidal ideation in these patients. Eighty-eight consecutive outpatients with PDA were administered structured diagnostic interviews for the DSM-IV Axis I and Axis II disorders (SCID-I and SCID-II), while the severity of PDA was assessed by means of the Panic Disorder Severity Scale. Of the patients, 25 (28.4%) reported suicidal ideation in past years ('ideators'). The severity of PDA was greater among ideators, and they were significantly more likely to have a personality disorder and more than one comorbid Axis I and Axis II disorder. There were no ideators without either Axis I or Axis II comorbidity. Univariate logistic regression identified several predictors of suicidal ideation: any DSM-IV Cluster C personality disorder, any DSM-IV Cluster B personality disorder, any comorbid mood disorder, and severity of PDA. With multivariate logistic regression, a combination of any Cluster C personality disorder and severity of PDA emerged as the most significant predictor of suicidal ideation. These findings have implications for clinical practice in that PDA patients should be carefully assessed for the severity of their illness and presence of certain personality disorders and comorbid mood disorders, because they may all increase the risk for suicidal ideation.

Characteristics of neurasthenia: examination and cross-cultural applicability of ICD-10 Diagnostic Criteria for Research.

The purpose of this study was to examine characteristics of Yugoslav patients with neurasthenia diagnosed according to the ICD-10 Diagnostic Criteria for Research (ICD-10-DCR), and to examine the ICD-10-DCR symptoms of neurasthenia and applicability of the corresponding diagnostic criteria to Yugoslav patients with this condition. Thirty-four patients with the ICD-10-DCR neurasthenia and 31 patients with mixed anxiety and depressive disorder were compared in terms of demographic variables, results of several questionnaires, symptom profiles and comorbidity with other mental disorders. Patients with neurasthenia were less educated and more often held jobs as unskilled and semiskilled workers; they had a more chronic course of illness, tended to report more symptoms, manifested more hostility, somatization and hypochondriacal tendencies and received a comorbid diagnosis of hypochondriasis more frequently. In addition to exhaustion and weakness, the most prominent features of neurasthenia were irritability, anger, nervousness, various somatic symptoms and tension. An ICD-10-DCR diagnosis of neurasthenia could not be made in slightly over one-third of patients who would have otherwise met criteria for this diagnosis because of the imposed diagnostic hierarchy, ie, due to current comorbidity with affective disorders and generalized anxiety disorder in such patients. It is concluded that the ICD-10-DCR concept of neurasthenia is generally suitable for Yugoslav patients, except for the diagnostic hierarchy requirement. The diagnostic criteria therefore require revision in order to reflect more accurately the variability in clinical presentation of neurasthenia in different countries.

A prospective study of the impact of subthreshold mixed states on the 24-month clinical outcomes of bipolar I disorder or schizoaffective disorder.

OBJECTIVES: The clinical significance of subthreshold mixed states is unclear. This study investigated the clinical outcomes in participants with bipolar I disorder or schizoaffective disorder, using the Cassidy and Benazzi criteria for manic and depressive mixed states, respectively. METHODS: Participants (N=239) in a prospective observational study of treatment and outcomes in bipolar I or schizoaffective disorder, bipolar type, were grouped based on study entry clinical presentation as having pure depression (n=63) if they satisfied DSM-IV-TR criteria for a Major Depressive Episode (MDE), depressive mixed state if they also had at least three concurrent hypomanic symptoms (n=33), or not depressed (n=143) if they did not satisfy the criteria for MDE. Participants were similarly grouped as having pure mania (n=3) if they satisfied DSM-IV criteria for a Manic Episode, manic mixed state if they also had at least two concurrent depressive symptoms (n=33), or not manic (n=203). Clinical data were collected by interview every 3 months over a 24-month period. RESULTS: Measures of quality of life, mental and physical health over the 24-month period were significantly worse for participants who were classified as having mixed states at study entry on most outcome measures compared to participants who were not in an illness episode at study entry. A depressive mixed state was predictive of greater manic symptomatology over the 24 months compared to participants with pure depression. CONCLUSION: In participants with a current episode of mood disorder, the presence of subthreshold symptoms of opposite polarity was associated with poorer clinical outcomes over a 24-month period.

Diagnostic agreement between the DSM-IV and ICD-10-DCR personality disorders.

The SCID-II Personality Questionnaire, modified for DSM-IV and ICD-10 Diagnostic Criteria for Research (ICD-10-DCR), was administered to 58 consecutive patients with agoraphobia with panic disorder in order to screen for personality disorders (PDs) and assess diagnostic agreement between DSM-IV and ICD-10-DCR. The diagnostic agreement, as expressed by kappa values, was 0.78 for the presence of any personality disorder (PD), but it ranged from 0.51 for schizoid PD to 0.83 for dependent PD. There was a tendency for ICD-10-DCR to overdiagnose PDs, except for borderline and dependent PDs. The sources of disagreement can be traced to differences in the conceptualization of some PDs and differences in diagnostic criteria and diagnostic thresholds; these are further examined in an effort to improve diagnostic criteria and attain greater compatibility between the two diagnostic systems.

The outcome of sex reassignment surgery in Belgrade: 32 patients of both sexes.

Several aspects of the quality of life after sex reassignment surgery in 32 transsexuals of both sexes (22 men, 10 women) were examined. The Belgrade Team for Gender Identity Disorders designed a standardized questionnaire for this purpose. The follow-up period after operation was from 6 months to 4 years, and four aspects of the quality of life were examined: attitude towards the patients' own body, relationships with other people, sexual activity, and occupational functioning. In most transsexuals, the quality of life was improved after surgery inasmuch as these four aspects are concerned. Only a few transsexuals were not satisfied with their life after surgery.