[Opicapone for the treatment of Parkinson's disease: real-life data in Spain]. / Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.

Opicapone is a catechol-O-methyl-transferase (iCOMT) inhibitor authorized in Europe in 2016 and indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. The efficacy of opicapone in these patients has been demonstrated in two pivotal randomized clinical trials, BIPARK I and BIPARK II, in which it has demonstrated its superiority versus placebo and non-inferiority versus entacapone. Although they constitute the gold standard for the evaluation of interventions, randomized clinical trials present limitations of external validity due to the use of strict eligibility criteria. Therefore, it is considered necessary to have a more comprehensive evaluation of the efficacy of the drug, complementing the information obtained from randomized clinical trials with that of "real world or real clinical practice" studies. The objective of this review has been to collect and put into perspective the information available on opicapone coming from real clinical practice studies in Spain. The data from Spain with opicapone in 18 series with more than 1,000 patients in total, confirm the safety and efficacy previously reported with this iCOMT. Furthermore, they show that opicapone is especially useful in patients with a less advanced stage of the disease and mild motor fluctuations, which would suggest that the earlier its introduction in the therapeutic scheme for the management of motor fluctuations, the better is the benefit-risk ratio for the drug.

TITLE: Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.Resumen. La opicapona es un inhibidor de la catecol-O-metiltransferasa (iCOMT) autorizado en Europa en 2016 como terapia adyuvante a las preparaciones de levodopa/inhibidores de la dopa descarboxilasa en pacientes adultos con enfermedad de Parkinson y fluctuaciones motoras de final de dosis que no puedan ser estabilizados con esas combinaciones. La eficacia de la opicapona en estos pacientes ha sido demostrada en dos ensayos clínicos pivotales, BIPARK I y BIPARK II, en los que se ha demostrado la superioridad frente al placebo y la no inferioridad frente a la entacapona. A pesar de que constituyen el estándar para la evaluación de intervenciones, los ensayos clínicos aleatorizados presentan limitaciones de validez externa debidas a la utilización de criterios estrictos de elegibilidad. Por tanto, se considera necesario disponer de una evaluación más amplia de la eficacia general del fármaco, complementando la información de los ensayos clínicos aleatorizados con estudios de 'vida real o práctica clínica real'. El objetivo de esta revisión ha sido recopilar y poner en perspectiva la información disponible sobre los resultados de la opicapona en estudios de práctica clínica real en España. Los datos acumulados en España con opicapona en 18 series con más de 1.000 pacientes confirman la seguridad y la eficacia de este iCOMT comunicadas previamente. Además, muestran que la opicapona es especialmente útil en pacientes en un estadio de la enfermedad menos avanzado y fluctuaciones motores leves, lo que sugeriría una mejor relación beneficio-riesgo cuanto más temprana sea su introducción en el esquema terapéutico para el tratamiento de las fluctuaciones motoras.

Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España / Opicapone for the treatment of Parkinson's disease: real-life data in Spain

La opicapona es un inhibidor de la catecol-O-metiltransferasa (iCOMT) autorizado en Europa en 2016 como terapia adyuvante a las preparaciones de levodopa/inhibidores de la dopa descarboxilasa en pacientes adultos con enfermedad de Parkinson y fluctuaciones motoras de final de dosis que no puedan ser estabilizados con esas combinaciones. La eficacia de la opicapona en estos pacientes ha sido demostrada en dos ensayos clínicos pivotales, BIPARK I y BIPARK II, en los que se ha demostrado la superioridad frente al placebo y la no inferioridad frente a la entacapona. A pesar de que constituyen el estándar para la evaluación de intervenciones, los ensayos clínicos aleatorizados presentan limitaciones de validez externa debidas a la utilización de criterios estrictos de elegibilidad. Por tanto, se considera necesario disponer de una evaluación más amplia de la eficacia general del fármaco, complementando la información de los ensayos clínicos aleatorizados con estudios de ‘vida real o práctica clínica real’. El objetivo de esta revisión ha sido recopilar y poner en perspectiva la información disponible sobre los resultados de la opicapona en estudios de práctica clínica real en España. Los datos acumulados en España con opicapona en 18 series con más de 1.000 pacientes confirman la seguridad y la eficacia de este iCOMT comunicadas previamente. Además, muestran que la opicapona es especialmente útil en pacientes en un estadio de la enfermedad menos avanzado y fluctuaciones motores leves, lo que sugeriría una mejor relación beneficio-riesgo cuanto más temprana sea su introducción en el esquema terapéutico para el tratamiento de las fluctuaciones motoras.(AU)

Opicapone is a catechol-O-methyl-transferase (iCOMT) inhibitor authorized in Europe in 2016 and indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors in adult patients with Parkinson’s disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. The efficacy of opicapone in these patients has been demonstrated in two pivotal randomized clinical trials, BIPARK I and BIPARK II, in which it has demonstrated its superiority versus placebo and non-inferiority versus entacapone. Although they constitute the gold standard for the evaluation of interventions, randomized clinical trials present limitations of external validity due to the use of strict eligibility criteria. Therefore, it is considered necessary to have a more comprehensive evaluation of the efficacy of the drug, complementing the information obtained from randomized clinical trials with that of “real world or real clinical practice” studies. The objective of this review has been to collect and put into perspective the information available on opicapone coming from real clinical practice studies in Spain. The data from Spain with opicapone in 18 series with more than 1,000 patients in total, confirm the safety and efficacy previously reported with this iCOMT. Furthermore, they show that opicapone is especially useful in patients with a less advanced stage of the disease and mild motor fluctuations, which would suggest that the earlier its introduction in the therapeutic scheme for the management of motor fluctuations, the better is the benefit-risk ratio for the drug.(AU)

Current status of atypical antipsychotics for the treatment of fibromyalgia.

The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.

Agomelatine for the treatment of patients with fibromyalgia and depressive symptomatology: an uncontrolled, 12-week, pilot study.

INTRODUCTION: Agomelatine, a melatonin agonist and selective 5-HT2C antagonist, is a novel antidepressant with sleep-enhancing properties. The purpose of this study was to assess the efficacy and tolerability of agomelatine among patients with fibromyalgia and depression. METHODS: 23 patients with fibromyalgia and depressive symptomatology received 25-50 mg of agomelatine daily for 12 weeks. The primary outcome measure was the change of the Beck depression inventory score. Secondary outcome measures included the hospital anxiety and depression scale, Pittsburgh sleep quality index, Fibromyalgia Impact Questionnaire, short-form health survey, brief pain inventory and patient's global impression scale. RESULTS: Agomelatine significantly improved depression, global fibromyalgia severity and pain intensity but effect sizes were small. No improvement was seen in sleep quality. Patients categorized as responders to treatment had milder disease severity than non-responders. Agomelatine therapy was well tolerated and patients only reported mild and transient side effects. DISCUSSION: Agomelatine slightly improved depressive and fibromyalgia symptomatology but did not improve sleep quality. Our data do not support agomelatine as a first-line treatment option for the treatment of fibromyalgia and depression.

An open-label study of levopromazine (methotrimeprazine) as an add-on therapy in fibromyalgia management.

OBJECTIVES: To assess the potential efficacy and tolerability of levopromazine(methotrimeprazine) in the treatment of fibromyalgia. METHODS: Unicentre, open-label study conducted in thirty-five outpatients, aged 18 years or older, who met the ACR criteria for fibromyalgia and had not satisfactorily responded to previous fibromyalgia treatment. Levopromazine, flexibly dosed (12.5-100 mg/d), was added to the outpatients' original treatment regimens for 12 weeks. The primary outcome measure was the mean change from baseline to endpoint in the Fibromyalgia Impact Questionnaire (FIQ) total score in the intent-to-treat sample. Secondary outcomes included the Clinical Global Impression (CGI) of Severity scale, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory, State-Trait Anxiety Inventory, 12-Item Short Form Health Survey, and individual items of the FIQ. RESULTS: The mean FIQ total score did not decrease significantly at the study endpoint (63.37 SD 11.32 vs. 61.19 SD 9.32, p=0.73). Pain intensity, as evaluated by the Visual Analogue Scale, remained unchanged at study endpoint (8.5 SD 1.6 vs. 8.2 SD 1.2, p=0.49). A statistically significant reduction was observed in the PSQI score (15.65 SD 3.33 vs. 12.23 SD 3.79, p<0.001, effect size: 1.03) and the CGI-severity score (4.71 SD 0.64 vs. 4.03 SD 1.01, p<0.002, effect size: 1.06). No significant or relevant changes were seen in the remaining fibromyalgia symptoms, psychopathological scales or quality-of-life. The drug was well tolerated. CONCLUSIONS: Despite its efficacy in improving sleep quality, levopromazine does not appear to be a useful alternative treatment for fibromyalgia.

Effects of pool-based exercise in fibromyalgia symptomatology and sleep quality: a prospective randomised comparison between stretching and Ai Chi.

OBJECTIVE: To evaluate the effectiveness and tolerability of two pool-based physical therapies, stretching and Ai Chi, in fibromyalgia symptomatology and sleep quality. METHODS: Eighty-one patients, randomly assigned to stretching (n=39) or Ai Chi (n=42), received 18 physiotherapy sessions and were evaluated at baseline, at treatment termination, and after 4 and 12 weeks of follow-up. Main outcome measures were the Fibromyalgia Impact Questionnaire (FIQ) and the Pittsburgh Sleep Quality Index (PSQI). Secondary outcome measures included the Beck Depression Inventory (BDI), the State and Trait Anxiety Inventory (STAI), and the SF-12 Health Survey (SF-12). Data analysis was done with repeated measures ANOVA and effect size estimation. RESULTS: No differences were found between groups but significant reduction in the FIQ and the PSQI scores were observed in Ai Chi but not in stretching group, with larger effect sizes and longer effect duration on sleep measures. BDI scores decreased in stretching but not in Ai Chi group with small effect sizes. Trait-anxiety scores decreased in both groups also with small effect sizes. The mental component summary of the SF-12 increased only in stretching group with effect sizes moderate to large. CONCLUSIONS: Although no global differences were found between groups, Ai Chi significantly improved fibromyalgia symptomatology and sleep quality, whereas stretching only improved subjects' psychological well-being.

Pregabalin augmentation of quetiapine therapy in the treatment of fibromyalgia: an open-label, prospective trial.

INTRODUCTION: Quetiapine has been shown to improve fibromyalgia symptoms, especially sleep disturbance, fatigue, morning stiffness, and mental well-being, but lacks an effect on pain. The purpose of this study was to evaluate if pregabalin, which has shown antialgic activity in fibromyalgia, added to quetiapine treatment additionally improved fibromyalgia symptomatology. METHODS: This was an open-label, 12-week study. Pregabalin was administered to 19 female fibromyalgia patients at a starting dose of 75 mg/day subsequently adjusted in according to the drug's efficacy and tolerability. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, the State and Trait Anxiety Inventory, and the SF-12 Health Survey. RESULTS: Data analysis was done on the Intention-To-Treat sample which included 18 patients. Pregabalin significantly improved the pain and tiredness after awakening subscales of the FIQ as well as the physical component of the SF-12. Six patients withdrew from the study, 3 because of side effects. CONCLUSIONS: Our results suggest that the use of pregabalin can be a useful augmentation strategy in fibromyalgia patients partially responding to quetiapine.

Trigger point evaluation in migraine patients: an indication of peripheral sensitization linked to migraine predisposition?

Although migraine is a neurovascular disorder, both scalp tenderness and referred pain have been observed in migraine patients. The present study was carried out to investigate the presence of trigger points eliciting referred pain in 98 migraine patients and in 32 healthy subjects. Trigger points were found in 92 (93.9%) migraineurs and in nine (29%) controls (P < 0.0001). The number of individual migraine trigger points varied from zero to 14 (modal number: 4), and was found to be related to both the frequency of migraine attacks (P < 0.0001), and the duration of the disease (P = 0.017). About 74% of the total detected trigger points were found in temporal and/or suboccipital areas; other locations were mainly found in patients showing more than four trigger points. Trigger point palpation provoked a migraine attack in 30 (30.6%) patients. Pericraneal allodynia was found in 15 (15.3%) patients. These data indicate that nociceptive peripheral sensitization is a usual finding in migraine, and that central sensitization can develop in patients with frequent attacks and long-lasting disease. Trigger points' detection in migraine patients could be useful when applying therapies like acupuncture, needling or botulinum toxin injections directed to reduce peripheral sensitization.

Psychometric properties of the Spanish version of the screening scale for DSM-IV Generalized Anxiety Disorder of Carroll and Davidson.

INTRODUCTION: The aim was to validate the Spanish version of the screening scale for DSM-IV General Anxiety Disorder of Carroll and Davidson for use in research and clinical practice in Spain for screening and assessing specific anxiety symptoms of patients with Generalized Anxiety Disorder (GAD). METHODS: Observational, prospective, multisite, study comparing between patients with DSM-IV diagnosis of GAD (group A), starting or switching treatment (group A1) or stable patients (group A2), followed-up for 6 months (group A1) or 2 weeks (group A2) versus healthy control subjects (group B), assessed in a single visit. RESULTS: Among 223 valuable subjects the scale showed: a) adequate feasibility with a mean time of administration: 6.53 and 4.49 min (TD: 5.48 and 3.56) in groups A and B, and percentage of patients without response <5 %; b) adequate reliability (Kuder-Richardson coefficient: 0.85 and 0.79 in groups A1 and A2, and CCI coefficient: 0.89 in group A2); c) adequate validity, showing capability for discriminating between patients and controls, with area under curve AUC: 0.9713 (IC 95 %: 0.9510-0.9917), and obtaining a high correlation with HARS (r=0.88) and CGI-G (r=0.87) scales, y d) adequate sensitivity to clinical changes from start and end of treatment (SES: -1.6, -3.1 and -3.8 after 1, 3 and 6 months), spite of the high percentage of patients with highest score in group A1 (38.6 %). CONCLUSION: The Spanish version of the screening scale for DSM-IV GAD showed adequate psychometric properties for use in research and clinical practice in Spain as well as an screening as evaluative measure for patients with GAD, spite of the ceiling effect showed in severe patients.

Propiedades psicométricas de la versión española de la Escala de Detección del Trastorno de Ansiedad Generalizada según DSM-IV de Carroll y Davidson / Psychometric Properties of the Spanish Version of the Screening Scale for DSM-IV Generalized Anxiety Disorder of Carroll and Davidson

Introducción. El objetivo era validar en español la Escala del trastorno de ansiedad generalizada (TAG) de Carroll y Davidson para su uso en la práctica e investigación clínica en España para detectar y evaluar los síntomas específicos de ansiedad de los pacientes con TAG. Métodos. Estudio observacional, prospectivo, multicéntrico, comparativo entre pacientes con diagnóstico DSM-IV de TAG (grupo A) que iniciaron o cambiaron de tratamiento (grupo A1) o estables (grupo A2), seguidos durante 6 meses (grupo A1) o 2 semanas (grupo A2), frente a controles sanos (grupo B) evaluados en una ocasión. Resultados. La escala mostró en 223 sujetos valorables: a) adecuada factibilidad con tiempo de administración medio: 6,53 y 4,49 min (DT: 5,48 y 3,56) en grupos A y B, y porcentaje de pacientes sin respuesta<5%; b) adecuada fiabilidad (coeficientes Kuder-Richardson: 0,85 y 0,79 en grupos A1 y A2, y CCI: 0,89 en grupo A2); c) adecuada validez, confirmándose su capacidad discriminante entre pacientes y controles, con área bajo la curva AUC: 0,9713 (IC 95 %: 0,9510-0,9917), y su alta correlación con escalas HARS (r=0,88) y CGI-G (r=0,87), y d) adecuada sensibilidad para detectar cambios clínicos entre antes y después del tratamiento (SES: -1,6, -3,1 y -3,8 en meses 1, 3 y 6) pese al elevado porcentaje de pacientes con puntuación máxima en grupo A1 (38,6 %). Conclusiones. La Escala del TAG posee adecuadas propiedades psicométricas para su uso en la práctica e investigación clínica en España como instrumento de cribado y evaluativo con pacientes con TAG pese al efecto techo que presenta en pacientes graves

Introduction. The aim was to validate the Spanish version of the screening scale for DSM-IV General Anxiety Disorder of Carroll and Davidson for use in research and clinical practice in Spain for screening and assessing specific anxiety symptoms of patients with Generalized Anxiety Disorder (GAD). Methods. Observational, prospective, multisite, study comparing between patients with DSM-IV diagnosis of GAD (group A), starting or switching treatment (group A1) or stable patients (group A2), followed-up for 6 months (group A1) or 2 weeks (group A2) versus healthy control subjects (group B), assessed in a single visit. Results. Among 223 valuable subjects the scale showed: a) adequate feasibility with a mean time of administration: 6,53 and 4,49 min (TD: 5.48 and 3.56) in groups A and B, and percentage of patients without response < 5 %; b) adequate reliability (Kuder-Richardson coefficient: 0.85 and 0.79 in groups A1 and A2, and CCI coefficient: 0.89 in group A2); c) adequate validity, showing capability for discriminating between patients and controls, with area under curve AUC: 0.9713 (IC 95 %: 0.9510-0.9917), and obtaining a high correlation with HARS (r=0.88) and CGI-G (r=0.87) scales, y d) adequate sensitivity to clinical changes from start and end of treatment (SES: -1.6, -3.1 and -3.8 after 1, 3 and 6 months), spite of the high percentage of patients with highest score in group A1 (38.6 %). Conclusion. The Spanish version of the screening scale for DSM-IV GAD showed adequate psychometric properties for use in research and clinical practice in Spain as well as an screening as evaluative measure for patients with GAD, spite of the ceiling effect showed in severe patients

A 6-month prospective observational study on the effects of quetiapine on sexual functioning.

OBJECTIVE: The aim of this study was to assess the long-term impact of quetiapine on sexual functioning of patients with schizophrenia treated in a real practice setting. METHODS: This was a multicenter, noncomparative, open-label, and naturalistic study conducted in outpatients with a diagnosis of schizophrenia or schizophreniform disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Patients were evaluated at baseline, day 15, and at the end of months 1, 3, and 6 using the Brief Psychiatry Rating Scale, the Clinical Global Impression Severity and Improvement Scales, and the Psychotropic-Related Sexual Dysfunction Questionnaire. All primary effectiveness analyses were based on the intent-to-treat sample and consisted primarily of last-observation-carried-forward analysis of Psychotropic-Related Sexual Dysfunction Questionnaire, Brief Psychiatry Rating Scale, and Clinical Global Impression Improvement of Illness Scale. RESULTS: Eighty-six patients were recruited by 19 investigators, and 82 patients were included in the intent-to-treat sample. Psychotropic-Related Sexual Dysfunction Questionnaire total scores for the patients decreased progressively and significantly from baseline to the study end point. When only patients who initiated quetiapine treatment without being switched from another antipsychotic (n = 28) were included in the intent-to-treat analysis, Psychotropic-Related Sexual Dysfunction Questionnaire scores remained almost unchanged throughout the study. Sexual dysfunction rates, defined as a change in the score of any item greater than 0, were 3.7%, 2.4%, 2.4%, and 4.9% for decreased libido, delayed ejaculation/orgasm, lack of ejaculation/orgasm, and difficulties with erection/lubrication, respectively. Overall, quetiapine was efficacious and well tolerated. CONCLUSION: Despite the limitations of the design, our results suggest that quetiapine shows a low frequency of sexual dysfunction during long-term treatment of patients with schizophrenia or schizophreniform disorder in the clinical practice setting.

Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiapine or haloperidol: results of the EIRE study.

OBJECTIVES: The aim of this cross-sectional study, the EIRE study, was to assess the frequency of several side effects with antipsychotics in the clinical setting. This paper addresses the adverse effect of weight gain. METHOD: Outpatients diagnosed of schizophrenia according to DSM-IV criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. Data were collected in a single visit, including data on demographic, clinical and treatment characteristics. Mean weight change was evaluated retrospectively by means of clinical charts and the weight at the time of the visit; in addition, the corresponding item of a modified version of the UKU, a Scandinavian side-effect rating scale, was used. Chi-squared test and logistic regression methods were used to analyze frequency of weight gain between treatments. RESULTS: Out of 669 recruited, 636 evaluable patients were assessed. The treatment with the highest number of patients with weight gain as an adverse reaction on the UKU scale was olanzapine (74.5%), followed by risperidone (53.4%) and haloperidol (40.0%). The proportion of patients with clinically relevant weight gain (>or=7% increase versus initial weight) was also higher with olanzapine (45.7%) than with risperidone (30.6%) and haloperidol (22.4%). Five patients (13.5%) treated with quetiapine had some degree of weight gain according to the UKU scale, although no patient showed a clinically relevant weight gain (>or=7%). Treatment with olanzapine and risperidone were identified as risk factors of weight gain versus haloperidol. The risk of weight gain was higher in women (OR: 4.4), overweight patients (OR: 3.0) and in patients with

Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.

Frequency of Extrapyramidal Adverse Reactions in Schizophrenic Outpatients Treated with Risperidone, Olanzapine, Quetiapine or Haloperidol : Results of the EIRE Study.

OBJECTIVE: The EIRE (Estudio de Investigaciön de Resultados en Esquizofrenia - Outcomes Research Study in Schizophrenia) study was initiated in order to assess the frequency of adverse reactions [extrapyramidal symptoms (EPS), hyperprolactinaemia, sexual dysfunction and weight gain] caused by atypical antipsychotics and haloperidol in patients with schizophrenia during routine treatment in clinical practice. This paper presents the results of the assessment of extrapyramidal adverse reactions. PATIENTS AND STUDY DESIGN: Outpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV), criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. In this cross-sectional and non-interventional study data were collected in a single visit; this included demographic and clinical characteristics, current antipsychotic and concomitant treatment, and data on several adverse effects listed in a modified version of the UKU (Udvalg for Kliniske Undersogelser - Committee on Clinical Investigations) scale. For paired comparisons of the frequency of adverse reactions between treatments the Chi-squared (χ2) test was used. For estimation of the risk of a given adverse reaction with a given treatment a logistic regression method was used. RESULTS: 636 evaluable patients (of 669 recruited) were assessed. The frequency of EPS with haloperidol (78.3% of the cases) was higher than with risperidone (55.1%), quetiapine (39.5%) and olanzapine (35.8%) [χ2: p < 0.05], and the difference between risperidone and olanzapine was also statistically significant (χ2: p < 0.05). Very similar results were obtained in the individualised analysis of the items as regards the occurrence of akathisia, which was also more frequent in the haloperidol (36.8%) and risperidone (19.7%) groups than in the olanzapine (11.4%) and quetiapine (2.6%) groups (χ2: p < 0.05). Olanzapine, quetiapine and risperidone also showed a lower risk of EPS than haloperidol when adjusting by dose. CONCLUSION: Our results suggest that the atypical antipsychotics studied are less likely to induce extrapyramidal adverse reactions compared with haloperidol in stabilised patients, although these reactions are still common.

Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction.

BACKGROUND: Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and clomipramine, are frequently associated with sexual dysfunction. Other antidepressants (nefazodone, mirtazapine, bupropion, amineptine, and moclobemide) with different mechanisms of action seem to have fewer sexual side effects. The incidence of sexual dysfunction is underestimated, and the use of a specific questionnaire is needed. METHOD: The authors analyzed the incidence of antidepressant-related sexual dysfunction in a multicenter, prospective, open-label study carried out by the Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. The group collected data from April 1995 to February 2000 on patients with previously normal sexual function who were being treated with antidepressants alone or antidepressants plus benzodiazepines. One thousand twenty-two outpatients (610 women, 412 men; mean age = 39.8 +/- 11.3 years) were interviewed using the Psychotropic-Related Sexual Dysfunction Questionnaire, which includes questions about libido, orgasm, ejaculation, erectile function, and general sexual satisfaction. RESULTS: The overall incidence of sexual dysfunction was 59.1% (604/1022) when all antidepressants were considered as a whole. There were relevant differences when the incidence of any type of sexual dysfunction was compared among different drugs: fluoxetine, 57.7% (161/279); sertraline, 62.9% (100/159); fluvoxamine, 62.3% (48/77); paroxetine, 70.7% (147/208); citalopram, 72.7% (48/66); venlafaxine, 67.3% (37/55); mirtazapine, 24.4% (12/49); nefazodone, 8% (4/50); amineptine, 6.9% (2/29); and moclobemide, 3.9% (1/26). Men had a higher frequency of sexual dysfunction (62.4%) than women (56.9%), although women had higher severity. About 40% of patients showed low tolerance of their sexual dysfunction. CONCLUSION: The incidence of sexual dysfunction with SSRIs and venlafaxine is high, ranging from 58% to 73%, as compared with serotonin-2 (5-HT2) blockers (nefazodone and mirtazapine), moclobemide, and amineptine.

[Evaluation of the psychometric properties of the Spanish version of 5 questionnaires for the evaluation of post-traumatic stress syndrome]. / Evaluación de las propiedades psicométricas de la versión española de cinco cuestionarios para la evaluación del trastorno de estrés postraumático.

AIM: To determine the psychometric properties of the Spanish versions of the following scales for assessing PTSD patients: TQ, CAPS-DX, DTS, TOP-8, and DGRP. METHODS: Data from 63 PTSD patients and 23 healthy subjects were analysed. Internal consistency and test-retest reliability (after 15 days) were calculated. Convergent validity was analysed by correlating subjects' scores with the number of symptoms (DSM-IV) and scores on the CGI scale. Discriminative capability was analysed by comparing TQ, CAPS-DX, DTS, TOP-8, and DGRP patients' scores with scores from healthy subjects, and between patients' subgroups according to the presence or absence of psychiatric comorbidity and to the degree of severity as determined by the CGI-S. RESULTS: CAPS-DX, DTS, TOP-8, and DGRP showed an adequate internal consistency (Cronbach alpha: 0.74-0.91) and all of them obtained ICC between 0.77 and 0.93. The five questionnaires were able to discriminate between patients and healty subjects, and between the patients' subgroups. CONCLUSIONS: The Spanish versions of the TQ, CAPS-DX, DTS, TOP-8, and DGRP have shown adequate reliability and validity for assessing PTSD patients in daily clinical practice. CAPS-DX seems to be more adequate a diagnostic and DTS a severity rating scale.

[Psychometric characteristics of the psychotropic-related sexual dysfunction questionnaire. Spanish work group for the study of psychotropic-related sexual dysfunctions]. / Propiedades psicométricas del Cuestionario de Disfunción Sexual Secundaria a Psicofármacos. Grupo Español de Trabajo Para El Estudio de las Disfunciones Sexuales Secundarias a Psicofármacos.

BACKGROUND: The presence of sexual function impairment in patients with psychiatric disorders is very common and could be an effect of the medication (mainly antidepressant and neuroleptics). The patient frequently has difficulties to communicate this adverse effect and the assessment of these changes by the physician should be encouraged. The real SD incidence is underestimated and the use of a specific questionnaire is needed. METHODS: The authors analyse psychometric characteristics of the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ) that includes questions about libido, orgasm, ejaculation, erectile function and general sexual satisfaction. The questionnaire was applied to 62 patients who were taking nefazodone "de novo" (n = 18) or were switched to nefazodone (n = 44) due to bad tolerated sexual dysfunction secondary to other antidepressant. RESULTS: The PRSexDQ has shown an excellent feasibility with nil percentage of patients with missing responses on all items except on items 1 and 2 (1.7% and 15.5% of patients with missing response). Cronbach's alpha value was 0.93, which indicates adequate reliability. The PRSexDQ also showed adequate construct validity. As it may be expected, the PRSexDQ showed a high correlation with a Clinical Global Impression scores on Sexual Dysfunction (r = 0.79) and moderate correlation with Hamilton Depression scores (r = 0.63). PRSexDQ also showed good discrimination between naive and pretreated depressed or dysthymic patients, with statistically significant differences between those groups of patients. Finally, the instrument showed adequate sensitivity for detecting clinical changes on sexual dysfunction with greater changes in the patients treated previously with antidepressants and who were switched to nefazodone than in naive patients (SES = -3.77 in patients switching to nefazodone; SES = -0.64 in naive patients).

Evaluación de las propiedades psicométricas de la versión española de cinco cuestionarios para la evaluación del trastorno de estrés postraumático / Evaluation of the psychometric properties of the Spanish version of five questionnaires for the assessment of post-traumatic stress disorders

Objetivo: Evaluar las propiedades psicométricas de la versión española de los instrumentos de medida TQ, CAPSDX, DTS, TOP-8 y DGRP para su uso en la investigación y la práctica asistencial con pacientes que padecen trastorno de estrés postraumático (TEPT). Métodos: 63 pacientes diagnosticados de TEPT y 23 individuos sanos fueron reclutados y valorados. Se analizó la fiabilidad en términos de consistencia interna y test-retest (a los 15 días). La validez concurrente se analizó mediante análisis correlacionales con el número de síntomas según criterios DSM-IV y la escala CGI. La validez discriminante se evaluó comparando la puntuación obtenida en los cuestionarios de evaluación de TEPT entre pacientes y controles y entre subgrupos de pacientes según presencia de trastornos psiquiátricos concomitantes y el estado de salud en la escala CGI. Resultados: Todas las subescalas de los cinco cuestionarios mostraron una adecuada consistencia interna (alfa de Cronbach: 0,74-0,91), excepto el cuestionario TQ y los criterios B y C del cuestionario TOP-8. Además, todas mostraron adecuada fiabilidad test-retest (CCI= 0,77-093), excepto la subescala del criterio D del cuestionario TOP-8. Los cinco cuestionarios discriminaron entre pacientes y controles y entre subgrupos de pacientes según comorbilidad y el nivel de gravedad medido mediante la escala CGI. Conclusiones: La versión española de los cuestionarios TQ, CAPS-DX, DTS, TOP-8 y DGRP ha mostrado poseer adecuada fiabilidad y validez en la evaluación de pacientes con TEPT, aunque la entrevista CAPS-DX parece ser más adecuada para ayuda diagnóstica y el cuestionario DTS para la evaluación en la práctica asistencial habitual. (AU)

Propiedades psicométricas del Cuestionario de Disfunción Sexual Secundaria a Psicofármacos / Psychometric characteristics of the Psychotropic-Related Sexual Dysfunction Questionnaire

El empeoramiento en la función sexual en pacientes con trastornos psiquiátricos es muy frecuente y con frecuencia es secundario a la medicación (fundamentalmente antidepresivos y neurolépticos). Los pacientes tienen dificultad para comunicar este efecto adverso y debe alentarse la evaluación de estos cambios por el médico. Estudios anteriores demuestran que se necesitan cuestionarios específicos para medir este efecto adverso, ya que la incidencia real de disfunción sexual suele estar subestimada. Material y métodos: Los autores analizan las propiedades psicométricas del Cuestionario de Disfunción Sexual Secundaria a Psicofármacos que incluye preguntas acerca de la líbido, orgasmo, eyaculación, función eréctil (lubrificación vaginal en mujeres) y satisfacción sexual general. El cuestionario fue aplicado en 62 pacientes que tomaron nefazodona de novo (n= 18) o que fueron cambiados a nefazodona (n= 44) debido a disfunción sexual mal tolerada secundaria a otro antidepresivo. Resultados: El cuestionario mostró excelente factibilidad con un porcentaje nulo de pacientes sin respuesta excepto en los ítems 1 y 2 (1,7 por ciento y 15,5 por ciento de pacientes sin respuesta respectivamente). El valor * de Cronbach fue de 0,93, indicando adecuada fiabilidad. El cuestionario también mostró una adecuada validez de constructo. Tal y como se esperaba, existió una alta correlación con las puntuaciones de la impresión clínica global de disfunción sexual (r= 0,79) y moderada correlación con las puntuaciones de la escala de Hamilton de depresión (r= 0,63). También discriminó adecuadamente entre los pacientes nuevos y pretratados diagnosticados de depresión o distimia con diferencias significativas entre estos grupos. Finalmente el instrumento mostró adecuada sensibilidad para detectar cambios clínicos en la función sexual con cambios más grandes en el grupo tratado previamente con antidepresivos comparado con los pacientes que iniciaron tratamiento de novo (SES= 3,77 en pacientes cambiados a nefazodona; SES= 0,64 en pacientes nuevos). (AU)