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BACKGROUND: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with 'real-world' treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication. METHODS: Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale - Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data. RESULTS: On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts. CONCLUSIONS: Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.
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Trastorno Bipolar/tratamiento farmacológico , Pacientes Ambulatorios/psicología , Pautas de la Práctica en Medicina/estadística & datos numéricos , Trastornos Psicóticos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antidepresivos/administración & dosificación , Antidepresivos/uso terapéutico , Antimaníacos/administración & dosificación , Antimaníacos/uso terapéutico , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Australia , Benzodiazepinas/administración & dosificación , Benzodiazepinas/uso terapéutico , Carbamazepina/administración & dosificación , Carbamazepina/uso terapéutico , Quimioterapia Combinada/psicología , Femenino , Humanos , Carbonato de Litio/administración & dosificación , Carbonato de Litio/uso terapéutico , Masculino , Persona de Mediana Edad , Olanzapina , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Calidad de Vida/psicología , Recurrencia , Ácido Valproico/administración & dosificación , Ácido Valproico/uso terapéuticoRESUMEN
OBJECTIVE: The staging model suggests that early stages of bipolar disorder respond better to treatments and have a more favourable prognosis. This study aims to provide empirical support for the model, and the allied construct of early intervention. METHODS: Pooled data from mania, depression, and maintenance studies of olanzapine were analyzed. Individuals were categorized as having had 0, 1-5, 6-10, or >10 prior episodes of illness, and data were analyzed across these groups. RESULTS: Response rates for the mania and maintenance studies ranged from 52-69% and 10-50%, respectively, for individuals with 1-5 previous episodes, and from 29-59% and 11-40% for individuals with >5 previous episodes. These rates were significantly higher for the 1-5 group on most measures of response with up to a twofold increase in the chance of responding for those with fewer previous episodes. For the depression studies, response rates were significantly higher for the 1-5 group for two measures only. In the maintenance studies, the chance of relapse to either mania or depression was reduced by 40-60% for those who had experienced 1-5 episodes or 6-10 episodes compared to the >10 episode group, respectively. This trend was statistically significant only for relapse into mania for the 1-5 episode group (p=0.005). CONCLUSION: Those individuals at the earliest stages of illness consistently had a more favourable response to treatment. This is consistent with the staging model and underscores the need to support a policy of early intervention.
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Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Modelos Psicológicos , Adulto , Edad de Inicio , Trastorno Bipolar/clasificación , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/psicología , Progresión de la Enfermedad , Método Doble Ciego , Diagnóstico Precoz , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Olanzapina , Pronóstico , Escalas de Valoración Psiquiátrica , Recurrencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Tobacco smoking is more prevalent among people with mental illnesses, including bipolar disorder, than in the general community. Most data are cross-sectional, and there are no prospective trials examining the relationship of smoking to outcome in bipolar disorder. The impact of tobacco smoking on mental health outcomes was investigated in a 24-month, naturalistic, longitudinal study of 240 people with bipolar disorder or schizoaffective disorder. METHOD: Participants were interviewed and data recorded by trained study clinicians at 9 interviews during the study period. RESULTS: Comparisons were made between participants who smoked daily (n = 122) and the remaining study participants (n = 117). During the 24-month study period, the daily smokers had poorer scores on the Clinical Global Impressions-Depression (P = .034) and Clinical Global Impressions-Overall Bipolar (P = .026) scales and had lengthier stays in hospital (P = .012), compared with nonsmokers. LIMITATIONS: Smoking status was determined by self-report. Nicotine dependence was not measured. CONCLUSION: These findings suggest that smoking is associated with poorer mental health outcomes in bipolar and schizoaffective disorder.
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Trastorno Bipolar/terapia , Trastornos Psicóticos/terapia , Fumar/epidemiología , Adulto , Edad de Inicio , Trastorno Bipolar/epidemiología , Estudios de Casos y Controles , Comorbilidad , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Prevalencia , Estudios Prospectivos , Trastornos Psicóticos/epidemiología , Resultado del Tratamiento , Victoria/epidemiologíaRESUMEN
BACKGROUND: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, observational study of participants with bipolar I or schizoaffective disorder examining clinical, functional, and economic outcomes associated with naturalistic treatment. METHODS: Participants prescribed mood stabilisers were assessed using various measures, including the Young Mania Rating Scale (YMRS), 21-item Hamilton Depression Rating scale (HAMD21), Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), and the EuroQol instrument (EQ-5D). RESULTS: 240 participants were recruited from two sites. On average, participants were 41.8+/-12.7 years of age (mean+/-SD), 58.3% were female, and 73.3% had a diagnosis of bipolar I disorder at study entry. The majority of participants were moderately ill, with an average CGI-BP Overall score of 3.8+/-1.3. Most participants had subthreshold mania and depression symptoms, indicated by HAMD21 Total 13.4+/-8.6, CGI-BP Depression 3.2+/-1.3, YMRS Total 8.2+/-8.5 and CGI-BP Mania 3.0+/-1.6 average scores. For bipolar participants, 94.6% of hospitalisations for psychiatric treatment in the past 3 months were single admissions (vs. 65.2% for schizoaffective participants, p=.002). Bipolar participants rated their overall health state higher (EQ-5D scores: 68.2+/-18.8 vs. 61.6+/-22.7, p=.023), had a higher mean weekly wage ($500-$999, 21.3% vs. 6.3%), lower unemployment (22.2% vs. 48.4%), and higher romantic relationship status (47.1% vs. 26.6%). LIMITATIONS: The observational design and small sample size may have limited the causal relationships and generalisability within the current findings. CONCLUSIONS: Participants were characterised by social and occupational dysfunction at entry, but schizoaffective participants appeared to be more severely affected. Effective treatment is required to address both clinical and functional impairment.
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Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/psicología , Adulto , Anciano , Anticonvulsivantes/uso terapéutico , Antipsicóticos/uso terapéutico , Australia , Benzodiazepinas/uso terapéutico , Trastorno Bipolar/diagnóstico , Carbamazepina/uso terapéutico , Estudios de Cohortes , Femenino , Estado de Salud , Humanos , Carbonato de Litio/uso terapéutico , Masculino , Olanzapina , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/psicología , Calidad de Vida , Índice de Severidad de la Enfermedad , Ajuste Social , Resultado del Tratamiento , Ácido Valproico/uso terapéuticoRESUMEN
BACKGROUND: The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. METHOD: This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo-treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. RESULTS: TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. DISCUSSION: In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. CONCLUSIONS: The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation.
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Antidepresivos/uso terapéutico , Ensayos Clínicos Controlados como Asunto/estadística & datos numéricos , Trastorno Depresivo Mayor/tratamiento farmacológico , Tiofenos/uso terapéutico , Relación Dosis-Respuesta a Droga , Clorhidrato de Duloxetina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Efecto Nocebo , Resultado del TratamientoRESUMEN
BACKGROUND: Randomised, placebo-controlled trials of treatments for depression typically collect outcomes data but traditionally only analyse data to demonstrate efficacy and safety. Additional post-hoc statistical techniques may reveal important insights about treatment variables useful when considering inter-individual differences amongst depressed patients. This paper aims to examine the Gradient Boosted Model (GBM), a statistical technique that uses regression tree analyses and can be applied to clinical trial data to identify and measure variables that may influence treatment outcomes. METHODS: GBM was applied to pooled data from 12 randomised clinical trials of 4987 participants experiencing an acute depressive episode who were treated with duloxetine, an SSRI or placebo to predict treatment remission. Additional analyses were conducted on the same dataset using the logistic regression model for comparison between these two methods. RESULTS: With GBM, there were noticeable differences between treatments when identifying which and to what extent variables were associated with remission. A single logistic regression only revealed a decreasing or increasing relationship between predictors and remission while GBM was able to reveal a complex relationship between predictors and remission. LIMITATIONS: These analyses were conducted post-hoc utilising clinical trials databases. The criteria for constructing the analyses data were based on the characteristics of the clinical trials. CONCLUSIONS: GBM can be used to identify and quantify patient variables that predict remission with specific treatments and has greater flexibility than the logistic regression model. GBM may provide new insights into inter-individual differences in treatment response that may be useful for selecting individualised treatments. TRIAL REGISTRATION: IMPACT clinical trial number 3327; IMPACT clinical trial number 4091; IMPACT clinical trial number 4689; IMPACT clinical trial number 4298; NCT00071695; NCT00062673; NCT00036335; NCT00067912; NCT00073411; NCT00489775; NCT00536471; NCT00666757 (note that trials with IMPACT numbers predate mandatory clinical trial registration requirements).
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Depresión/tratamiento farmacológico , Trastorno Depresivo/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tiofenos/uso terapéutico , Adulto , Anciano , Clorhidrato de Duloxetina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Regresión , Resultado del TratamientoRESUMEN
Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness. Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled. There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.
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Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Enfermedad Aguda , Adulto , Citalopram/uso terapéutico , Ciclohexanoles/uso terapéutico , Depresión/psicología , Trastorno Depresivo Mayor/psicología , Clorhidrato de Duloxetina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paroxetina/uso terapéutico , Recurrencia , Tiofenos , Factores de Tiempo , Resultado del Tratamiento , Clorhidrato de VenlafaxinaRESUMEN
OBJECTIVE: We examined whether identification of patients with placebo-remitter characteristics and placebo-nonremitter characteristics enhances the ability to identify drug-placebo treatment differences and, perhaps, differences between agents in major depressive disorder (MDD). We hypothesized: 1) that drug-placebo differences in remission rates would be greater for both duloxetine and selective serotonin reuptake inhibitors (SSRIs) among placebo nonremitters than placebo remitters and: 2) that the difference between active treatments would also be greater in placebo nonremitters than placebo remitters. DATA AND METHODS: Data were obtained from seven randomized, parallel, double-blind MDD studies which compared the effects of duloxetine (N = 795), placebo (N = 510), and SSRIs (N = 551). The 17-item Hamilton depression rating scale (HAMD) was used to assess depression severity. The classification of participants as having placebo-remitter or placebo-nonremitter characteristics was based on age, duration of current MDD episode, HAMD anxiety score, and HAMD core score. Odds ratios (ORs) for remission comparing active treatment and placebo were obtained from logistic regression models. Tests of homogeneity were used for between-group comparisons. RESULTS: For placebo nonremitters, both duloxetine (OR = 3.52 [95% CI: 2.21, 5.62; P < 0.0001]) and SSRIs (OR = 2.38 [95% CI: 1.45, 3.89; P = 0.0006]) showed significantly higher remission rates compared to placebo. Drug-placebo differences in remission were significantly greater for placebo nonremitters than for placebo remitters for both duloxetine (P = 0.02) and SSRIs (P = 0.049). For placebo remitters, remission with duloxetine (OR = 1.83 [95% CI: 1.35, 2.47; P = 0.0001]), but not the SSRIs selected for this study (OR = 1.31 [95% CI: 0.93, 1.84; P = 0.12]), was significantly greater than placebo. Contrary to expectation, the advantage of duloxetine over the SSRIs was not greater in placebo nonremitters. However, the fact that our analysis required patient-level data limited the number of agents studied, compromising generalization. CONCLUSIONS: Our study suggests that drug-placebo differences in remission rates will be greater in subjects with placebo-nonremitter than with placebo-remitter characteristics.
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Trastorno Depresivo Mayor/tratamiento farmacológico , Efecto Placebo , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Clorhidrato de Duloxetina , Humanos , Placebos/uso terapéutico , Inducción de Remisión , Tiofenos/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: In some individuals, recovery from episodes of mental illness may be impeded by maladaptive illness beliefs and behaviors. For individuals with chronic illness, acceptance of its presence and consequences is necessary to seek appropriate treatment, adjust their lifestyle, and adhere to recommended management strategies. Some have difficulty adjusting out of the sick role or develop a degree of illness investment. The Illness Cognitions Scale (ICS) is a 17-item validated scale that measures cognitive factors associated with the sick role. We conducted analyses to test the hypothesis that there may be an association between illness cognitions and clinical and functional measures. METHODS: The ICS was administered to 89 participants at the final study visit of a 24-month observational study involving patients with bipolar I disorder or schizoaffective disorder. RESULTS: Higher scores on the ICS were correlated with more severe depression (p<0.0001), worse general health (p=0.0002), worse functioning (p=0.0001), and worse scores in psychosocial measures including the State Hope Scale (p=0.0082), the Social Provisions Scale (p=0.0054) and the Rosenberg Self-Esteem Scale (p=0.0025). CONCLUSIONS: Illness cognitions and behavior may be a neglected factor that could influence treatment outcomes in bipolar disorder. The ICS might be useful for identifying individuals whose recovery may be facilitated by targeted psychological intervention that addresses these factors.
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Actitud Frente a la Salud , Trastorno Bipolar/psicología , Trastorno Bipolar/terapia , Rol del Enfermo , Adulto , Enfermedad Crónica , Cognición , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/psicología , Trastornos Psicóticos/terapia , Resultado del TratamientoRESUMEN
It is often difficult to determine whether a patient may best benefit by augmenting their current medication or switching them to another. This post-hoc analysis compares patients' clinical and functional profiles at the time their antipsychotic medications were either switched or augmented. Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month international observational study. Clinical and functional measures were assessed at the time of first treatment switch/augmentation (0-14 days prior) and compared between Switched and Augmented patient groups. Due to low numbers of patients providing such data, interpretations are based on effect sizes. Data at the time of change were available for 87 patients: 53 Switched and 34 Augmented. Inadequate response was the primary reason for treatment change in both groups, whereas lack of adherence was more prevalent in the Switched group (26.4% vs 8.8%). Changes in clinical severity from study initiation to medication change were similar, as indicated by Clinical Global Impressions-Severity scores. However, physical and mental component scores of the 12-item Short-Form Health Survey improved in the Augmented group, but worsened in the Switched group. These findings suggest that the patient's worsening or lack of meaningful improvement prompts clinicians to switch antipsychotic medications, whereas when patients show some improvement, clinicians may be more likely to try bolstering the improvements through augmentation. Current findings are consistent with physicians' stated reasons for switching versus augmenting antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research.
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BACKGROUND: This study aimed to improve physicians' understanding of the treatment circumstances and needs of outpatients with schizophrenia at risk of nonadherence, by naturalistically assessing antipsychotic treatment patterns, clinical outcomes, and health care service use in this little-studied patient population. METHODS: In this one-year, prospective, multicenter, noninterventional, observational study, patients considered at risk of nonadherence by their physicians were switched from their primary oral antipsychotic to another oral or a depot antipsychotic at study entry. All cause treatment discontinuation (antipsychotic switch, augmentation, or discontinuation) during the study was assessed using Kaplan-Meier survival analyses and descriptive statistics. Patients' illness severity, quality of life, attitude towards medication, patient-reported adherence, and health care resource utilization were assessed during the study. RESULTS: Of the 406 enrolled patients, 43 (10.6%) were switched to depot and 363 (89.4%) were switched to oral antipsychotics at study entry. During the study, 99 (24.4%) patients switched, augmented, or discontinued their antipsychotic (all cause treatment discontinuation). Of the 99 patients who switched, augmented, or discontinued their antipsychotic, 8 (18.6%) were taking depot and 91 (25.0%) were taking oral antipsychotics. These patients were switched to either depot (n = 15) or oral (n = 78) antipsychotics, or discontinued their antipsychotic medication (n = 6). Inadequate response was the most frequently reported reason for medication discontinuation. During the study, patients' clinical and functional status improved significantly and service use was low. Most patients considered themselves to be adherent at study entry, and this favorable self-perception increased during the study (from 68.5% to 88.1%). CONCLUSION: Although identified as at risk of nonadherence, few patients in this naturalistic study discontinued their prescribed antipsychotic medication during the study. The discrepancy between the physicians' perception of their patient's medication adherence and the patients' self-perceived adherence highlights the need to better understand the underlying reasons for this phenomenon.
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In this year-long, prospective observational study, sociodemographic, clinical, and functional characteristics were assessed in outpatients with schizophrenia from Australia, Mexico, Romania, and Taiwan who were switched from their primary oral antipsychotic to another oral or depot antipsychotic at study entry because of physician-perceived nonadherence risks. Patients (N = 406) rated their quality of life and functioning level as low. Few patients (10.6%, 43/406) were switched to depot antipsychotics, with country-specific differences (P < 0.001). Although illness severity was similar between subgroups, the depot switch subgroup had: a documented history of nonadherence (32.6% versus oral: 4.7%); recent alcohol (48.8% versus 23.2%; P < 0.001) or illicit drug use (16.3% versus 5.0%; P = 0.010); recent depot antipsychotic (20.7% versus 7.5%; P = 0.030) and mood stabilizer use (51.7% versus 26.3%; P = 0.008); poorer attitudes towards medication (P = 0.004); and poorer illness awareness (P = 0.041). Findings indicate that even when a risk of nonadherence has been identified, few patients with schizophrenia receive depot antipsychotics, despite being prime candidates for depot therapy. Findings suggest physicians may select depot therapy based on previous nonadherence, substance use, recent depot antipsychotic and mood stabilizer use, poor attitudes towards medications, and poor illness awareness.
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OBJECTIVES: Recent studies have proposed the existence of three distinct subgroups of bipolar 1 disorder based on age at onset (AAO). The present study aims to investigate potential clinical and functional differences between these subgroups in an Australian sample. METHODS: Participants (n = 239) were enrolled in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal, observational, cross-sectional study. Assessment measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ-5D). Participants were also asked about their age at the first major affective episode. RESULTS: Three AAO groups were compared: early (AAO < 20, mean = 15.5 ± 2.72; 44.4% of the participants); intermediate (AAO 20-39, mean = 26.1 ± 4.8; 48.14% of the participants) and late (AAO > 40, mean = 50.6 ± 9.04; 7.4% of the participants). Higher rates of depression, suicidal ideation and binge drinking were reported by the early AAO group. This group also reported poorer quality of life in a number of areas. The early AAO group had a predominant depressive initial polarity and the intermediate group had a manic predominance. CONCLUSION: Early AAO is associated with an adverse outcome.
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We assessed the impact of real danger on several aspects of the panic disorder (PD) patients' psychopathology and level of disability. At the time of the NATO air strikes on Belgrade, 84 PD patients who were in partial or complete remission were administered the Panic and Agoraphobia Scale (PAS). All had been treated previously, and the majority (58.3%) were taking antipanic medications. The PAS, which was used as part of the regular follow-up assessment battery for PD patients, measures the overall severity of PD and the severity of key aspects and components of PD. Compared to the PAS assessments made before the onset of air strikes, the PAS assessments made at the time of air strikes showed significant differences in terms of decreased overall severity of PD, fewer health concerns, decrease in the level of disability, and greater intensity and frequency of anticipatory anxiety. Differences on the measures of panic attacks and agoraphobic avoidance were negligible. These results suggest that there is no relationship between panic attacks and real danger and lend support to the notion that panic attacks and fear induced by real danger are different phenomena. Contrary to the expectations of many PD patients, the presence of real danger does not seem to be associated with deterioration in their functioning, and PD patients can be reassured that they are not likely to cope worse under conditions of danger.