Jerónimo Saiz

Double-blind comparison of fluoxetine versus clomipramine in the treatment of obsessive compulsive disorder

There is evidence of the clinical efficacy and safety of clomipramine and the newer selective serotonin reuptake inhibitors (SSRIs) for the treatment of obsessive-compulsive disorder (OCD). In the present study, we have compared the efficacy and safety of 40 mg/day of fluoxetine and 150 mg/day of clomipramine in patients with OCD, diagnosed according to DSM-IIIR. A total of 55 patients entered this 8-week, double-blind controlled study. Efficacy for both drugs was comparable. The primary efficacy criterion, the Y-BOCS Total score, did not show any significant differences between treatment arms. Response rate was higher with clomipramine, using a 25% decrease in Y-BOCS Total score as response threshold, but there were no significant differences between treatment arms using a 35% threshold. Overall safety and tolerability were good for both drugs, being slightly better for fluoxetine.

Enhanced cortisol suppression in eating disorders with impulsive personality features

Evidence of both blunted and enhanced cortisol suppression with the dexamethasone test (DST) is available in eating disorders (ED), suggesting that different subtypes of ED might be characterized by distinct neurobiological stress response dysfunctions. Other evidence indicates that ED patients with impulsive clinical features might have enhanced cortisol suppression similar to patients with impulsive personality disorders. A group of 52 patients with restrictive anorexia, binge eating-purging anorexia and bulimia nervosa were studied with a very low dose (0.25 mg) dexamethasone test and measures of phenomenology, personality and impulsivity. Patients with bulimic symptoms had significantly higher rates of cortisol suppression than controls and than restrictive anorectic patients. Percent cortisol suppression showed a strong and significant correlation with the patients score on the Barratt Impulsiveness Scale. A hypersensitive cortisol response to dexamethasone, which might reflect hypothalamic-pituitary-adrenal axis dysfunctions might be specifically associated with impulsive subtypes of eating disorders.

The course of negative symptoms in first-episode schizophrenia and its predictors: A prospective two-year follow-up study

AIMS This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. METHODS In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. RESULTS There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1>Time 2>Time 3); F(2,151)=20.45, p<0.001. Poorer premorbid adjustment (p=0.01) and higher negative symptoms at baseline (p<0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R2=0.21, p<0.001). CONCLUSIONS We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome.

Informe del 3.er Foro sobre Políticas de Actuación del Consejo Europeo del Cerebro

a Área de Psiquiatría, Universidad de Oviedo, CIBERSAM, Oviedo, Spain b Universidad Autónoma de Madrid, Madrid, Spain c Clínica Universitaria de Navarra, Pamplona, Spain d Fundación Mundo Bipolar, Madrid, Spain e Hospital Nisa Pardo, Aravaca, Madrid, Spain f Hospital Ramón y Cajal, Universidad de Alcalá de Henares, CIBERSAM, Madrid, Spain g Federación Española de Parkinson h Medtronic Iberia, Madrid, Spain i Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, CIBERSAM, Madrid, Spain j Consejo Español del Cerebro, Madrid, Spain

Psychobiology of borderline personality traits related to subtypes of eating disorders: A study of platelet MAO activity

Increased and decreased levers of platelet monoamine oxidase (MAO) activity have been reported in patients with eating disorders, indicating abnormalities of the serotonin turnover. However, whether these findings are related to eating disorders or are rather reflecting the pathophysiology of borderline personality traits in these patients is still unknown. Platelet MAO activity and comorbid personality disorders were investigated in 72 patients with different subtypes of eating disorders (ED) and in a group of 28 healthy controls. ED patients comprised the following subtypes: 25 anorexia nervosa (AN) restrictive, 14 AN binge eating-purging (AN b-p), 3 anorexia nervosa not otherwise specified (AN NOS) and 30 bulimia nervosa (BN). Personality disorders and traits were assessed with the Structured Interview for Personality Disorders (SCID-II), the Zanarini Rating Scale for Borderline Personality Disorder, and the Barrat Impulsiveness Scale. Platelet MAO activity was significantly lower in ED patients with comorbid borderline personality disorder (BPD) than in ED without Borderline personality disorder (BDP). Platelet MAO activity was significantly and inversely correlated with the number and severity of BPD clinical features. In the subsample of patients with binge eating-purging symptoms (AN b-p, AN NOS and BN), platelet MAO activity was significantly lower in binge-purge patients with comorbid BPD than in binge-purge patients without BPD. The whole group of eating disorders had a significantly reduced lever of platelet MAO activity compared with the control group. The results suggest that low platelet MAO activity might characterize eating disorders with comorbid borderline personality traits, reflecting greater serotonin dysfunction in these patients. The role of decreased platelet MAO as an endophenotype with specific clinical manifestations should be explored in future studies.

Pharmacogenomic Information In The Treatment Of Major Depression: Results From A Randomized Clinical Trial

Abstract Mental disorders are one of the leading causes of disability globally. Inherited genetic variation in pharmacokinetic (PK) and pharmacodynamic (PD) genes may contribute to the observed interindividual differences in clinical efficacy and tolerability of psychopharmaceuticals. Therefore, strategies for improving effectiveness of pharmacological treatments translating pharmacogenomic information from bench to clinic have been recently attempted. However, effectiveness of available psychiatric pharmacogenomic tools in ameliorating clinical symptoms has not been analyzed in populations of suitable size by means of adequately powered multicentric randomized clinical trials. The Neuropharmagen personalized medicine platform integrates pharmacogenomic data from the analysis of PK and PD genes to provide actionable recommendations for psychoactive drugs, including genotype-specific dose adjustments and the risk of specific adverse effects based on FDA-approved drug labelling, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, and meta-analyses of clinical studies. Moreover, within the Neuropharmagen platform, pharmacogenomic recommendations can be complemented combined with alerts on drug-drug, drug-clinical condition and drug-environmental factor interactions. Notably, the later can be updated by the doctor whenever there are changes in the condition of the patient or the pharmacological treatment. Clinical efficacy of the Neuropharmagen test has been evaluated in two multicentric clinical studies totaling 462 patients analyzed for the primary outcome at study endpoint. A retrospective study evaluating patients with different psychiatric diagnoses and at least 1 treatment failure found that patients whose treatment followed the pharmacogenetic (PGx) test recommendations had odds of improvement about 4 times higher than patients whose treatment did not (adjusted OR = 3.86, 95%CI 1.36–10.95; p = 0.011). Recently, we have completed a prospective randomized clinical trial conducted in 316 patients with major depressive disorder with a wide range of depression severities and number of treatment failures. In this talk, I will describe the main results of both studies, with a major focus in those obtained in the multicentric randomized clinical trial. Overall, the combined results of studies conducted with Neuropharmagen show that PGx-guided treatment constitutes a significant tool to improve clinical response and medication tolerability, especially in subjects with moderate to severe depression and in those with previous failed drug trials.

Impulsivity in everyday life: the role of platelet MAO

Arato, M., Banki, C.M., Bissette, G. and Nemeroff, C.B. (1989) Elevated CSF CRF in suicide victims. Biol. Psychiatry 25, 355 359. Banki, C.M., Bissette, G., Nemeroff, C.B. and Arato, M. (1988) Corticotropin-releasing factor in depression and suicide. In: M611er, J.H., Schmidtke, A. and Welz, R. (Eds.), Current Issues of Suicidology. Springer, Berlin, pp. 247 251. Charlton, B.G., Wright, C., Leake, A., Ferrier, I.N., Cheetham, S.C. and Katona, C.L.E. (1988) Somatostatin immunoreactivity in postmortem brain from depressed suicides. Arch. Gen. Psychiatry 45, 597 597. Nemeroff, C.B. (1989) Clinical significance of psychoneuroendocrinology in psychiatry: focus on the thyroid and adrenal. J. Clin. Psychiatry 50 (Suppl.), 13 20. Norman, W.H., Brown, W.A., Miller, l.W., Keitner, G.I. and Overholser, J.C. (1990) The dexamethasone suppression test and completed suicide. Acta Psychiatr. Scand. 81, 120 125. Tr/iskman-Bendz, L., Ekman, R., Regnell, G. and Ohmann, R. (1992) HPA-related CSF neuropeptides in suicide attempters. Eur. Neuropsychopharmacol. 2, 99 106.