Dopamine partial agonism in antipsychotic-induced sexual dysfunction.

INTRODUCTION: Sexual dysfunction is a frequent side effect associated with antipsychotic treatment. It is known to be caused by the hyperprolactinemia that results from the D2 receptor blockade that is characteristic of antipsychotic drugs. The D2 partial dopaminergic agonism of aripiprazole could explain why its use does not usually cause this side effect, and may even revert it when added to another antipsychotic. CASE REPORTS: We present the cases of two patients treated with D2 dopaminergic antagonists for a first episode of psychosis, who complained of amenorrhea and erectile dysfunction during follow-up. After the addition of aripiprazole to their previous antipsychotic treatment, these side effects reverted without a negative impact on treatment adherence or therapeutic efficacy. CONCLUSIONS: Pharmacological treatments with the potential of reverting sexual dysfunction secondary to antipsychotic treatment can improve compliance and quality of life of our patients, especially in those who are younger and are being treated for a first psychotic episode. In the cases reported here, the use of aripiprazole as an adjunctive treatment resulted in the disappearance of the undesirable effects without affecting the efficacy already achieved with the previous antipsychotic treatment.

From dopaminergic genes to psychiatric disorders.

Individual vulnerability to develop neurological and psychiatric disorders is associated with both genetic and environmental factors. Association studies in patients have explored the contribution of gene variants in the dopaminergic system in these disorders. This system is involved in motor control, endocrinological function, the reward system and cognition. The diverse physiological functions of dopamine are mediated by five different dopamine receptors, encoded by the genes DRD1, DRD2, DRD3, DRD4 and DRD5. These genes have various types of polymorphisms that can produce changes in the genetic product or expression levels. In recent years, the development of new technologies for genetic analysis, and a wider comprehension of the genetic sequences of these genes have increased our understanding of the implications of the dopaminergic system in both health and pathological states. It has also allowed the identification of genetic variants that may represent risk or protection factors for a variety of psychiatric disorders.

Association in alcoholic patients between psychopathic traits and the additive effect of allelic forms of the CNR1 and FAAH endocannabinoid genes, and the 3' region of the DRD2 gene.

Little is known about the genetic factors that underlie the comorbidity between alcohol use disorder and antisocial personality disorder. Previous studies have associated both, dopaminergic and endocannabinoid systems to severe alcoholism with non-adaptive disrupted behaviours. In this work we have examined some gene variants involved in such systems in a sample of alcoholic patients to test whether there is a relationship with antisocial traits. The genetic analysis involved the genotyping of the single nucleotide polymorphism (SNP) TaqIA located nearby the DRD2 gene, the 10-repeat allele of a variable number tandem repeats (VNTR) of the SLC6A3 gene, the C385A FAAH SNP and the 3'-UTR microsatellite of CNR1 gene. The clinical study was performed in 137 Spanish alcohol dependent males. Antisocial Personality Disorder (DSM-IV) diagnosis was made by applying the International Personality Disorder Examination, and psychopathic traits were evaluated by the Hare's Psychopathy Checklist revised (PCL-R). The genotype distribution indicates there is a relationship between the TaqIA SNP, CNR1 and FAAH genes and PCL-R's Factor 1 in alcoholic patients. This relationship seems to be additive and independent and might be responsible for 11.4% of the variance in this PCL-R subscale. Our results suggest the implication of the dopaminergic and endocannabinoid systems in those processes leading to the comorbidity of alcoholism and antisocial behaviour.

Naltrexone improves outcome of a controlled drinking program.

Naltrexone is widely used in therapeutic programs with abstinence as a goal. However, it has been used in only a few studies aimed at reducing alcohol consumption. The purpose of this study was to evaluate the efficacy of naltrexone as an adjunct in controlled drinking programs. This was an open randomized study of 12 weeks duration that compared two therapeutic strategies: use of naltrexone in a controlled drinking program (NTX+CD) and the controlled drinking program alone (CD), without NTX. Each group comprised 30 male patients with mild alcohol dependence. During treatment, there were no differences between groups in drinking behavior, though the NTX+CD group showed significantly less craving. In the 12-month follow-up period, the NTX+CD group showed significantly fewer drinking days and heavy drinking days and less craving than the CD group. The results of this study suggest a role for naltrexone in controlled drinking programs.

Detection of subclinical depression in bipolar disorder: a cross-sectional, 4-month prospective follow-up study at community mental health services (SIN-DEPRES).

OBJECTIVE: The aim of this study was to assess the prevalence and the impact of depressive symptoms on the functional outcome of bipolar disorder outpatients in remission. METHOD: A cross-sectional, prospective 16-week study of a cohort of 739 euthymic bipolar disorder patients (DSM-IV-TR criteria) recruited by 94 investigators was conducted. Clinical stability was assessed at baseline and at week 16 with the modified Clinical Global Impressions Scale-Bipolar Version, and depressive symptoms were assessed at baseline with the 17-item Hamilton Depression Rating Scale (HDRS-17 [primary endpoint measure]), the Montgomery-Asberg Depression Rating Scale (MADRS), and the self-applied Center for Epidemiologic Studies-Depression Scale (CES-D). Functional status was evaluated with the Social and Occupational Functioning Assessment Scale (SOFAS) and Social Adaptation Self-evaluation Scale (SASS). The study was conducted from April 2006 to March 2007. RESULTS: Subclinical depressive symptoms (SDS) were detected on the HDRS-17 in 16.9% of the sample. In symptom-free patients, the incidence of new SDS after 16 weeks was 20% (MADRS score > 7). At baseline, SDS patients compared to non-SDS patients presented with poorer social-occupational performance (SOFAS score mean difference, -11.9; 95% CI, -14.2 to -9.6) and poorer social adjustment (SASS score mean difference, -5.6; 95% CI, -7.1 to -4.1). Depressive symptoms were inversely related to functional status and social adjustment: MADRS-SOFAS correlation coefficients, r = -0.54 (P < .0001), and MADRS-SASS correlation coefficients, r = -0.42 (P < .0001). The self-applied survey identified additional cases with depressive symptoms, showing an SDS total prevalence of 44.9%. CONCLUSIONS: Depressive symptoms in apparently remitted bipolar disorder outpatients are not rare and result in a decline in occupational outcome and social maladjustment.

Effects of zonisamide in the treatment of alcohol dependence.

OBJECTIVE: Anticonvulsant drugs have been used in the treatment of alcohol dependence. The purpose of the present study was to evaluate tolerance and safety of zonisamide in a sample of patients presenting alcohol dependence. METHODS: Open-label zonisamide was examined in 22 outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence. Zonisamide was started at a dose of 50 mg/d and titrated to a maximun dose of 300 mg/d. Subjects received a baseline evaluation including Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and the Severity of Alcohol Dependence Scale. Alcohol craving and alcohol consumption were assessed at weeks 2, 4, 6, 8, 10, and 12. The concentration of γ-glutamyltransferase was used as an indirect measure of alcohol consumption. RESULTS: Significant improvement was observed in visual analog scale for craving severity scores, weekly drink consumption, and γ-glutamyltransferase. Zonisamide was well tolerated, with only a dropout due to adverse events. CONCLUSIONS: Zonisamide is safe and well tolerated in this sample and associated with improvement in alcohol craving and alcohol consumption. A placebo-controlled study would be of interest.

Use of cocaine by heavy drinkers increases vulnerability to developing alcohol dependence: a 4-year follow-up study.

OBJECTIVE: The development of alcohol dependence is associated with specific individual personality traits and previous consumption of other drugs of abuse. However, there is little information on these risk factors in heavy drinkers before and after they meet the criteria for alcohol dependence. This study examined the influence of cocaine use and the role of impulsivity in the development of DSM-IV alcohol dependence in nondependent drinkers in a 4-year follow-up study. METHOD: A prospective cohort study was conducted to establish the risk factors associated with DSM-IV alcohol dependence. Four hundred seventy-one (nondependent) heavy drinkers were enrolled in a prospective study. At baseline, 280 were classified as heavy drinkers (HD) and 191 as heavy drinkers who also used cocaine (HD + Co). Clinical variables related to alcohol and cocaine use were assessed at 2 years and at the end of the 4-year follow-up period. The study was conducted from September 2001 until September 2006 in Madrid, Spain. RESULTS: At the 4-year follow-up assessment, 67.9% of the HD + Co group met DSM-IV criteria for alcohol dependence compared to 13.6% of the HD group. Odds ratios for alcohol dependence were 12.3 and 7.0 for male and female cocaine users, respectively. Clinical and psychological variables related to impulsivity were associated with the development of alcohol dependence. The amount of cocaine used during follow-up was associated with a more rapid progression to alcohol dependence. CONCLUSIONS: This study revealed that cocaine use or an impulsive personality in heavy drinkers increased the risk of developing DSM-IV alcohol dependence by 3.8 and 12.6 times, respectively. These results may be useful in designing new strategies for preventing the development of alcohol dependence.

Patterns of mental health service utilization in a general hospital and outpatient mental health facilities: analysis of 365,262 psychiatric consultations.

PURPOSE: Mental health is one of the priorities of the European Commission. Studies of the use and cost of mental health facilities are needed in order to improve the planning and efficiey of mental health resources. We analyze the patterns of mental health service use in multiple clinical settings to identify factors associated with high cost. SUBJECTS AND METHODS: 22,859 patients received psychiatric care in the catchment area of a Spanish hospital (2000-2004). They had 365,262 psychiatric consultations in multiple settings. Two groups were selected that generated 80% of total costs: the medium cost group (N = 4,212; 50% of costs), and the high cost group (N = 236; 30% of costs). Statistical analyses were performed using univariate and multivariate techniques. Significant variables in univariate analyses were introduced as independent variables in a logistic regression analysis using "high cost" (>7,263$) as dependent variable. RESULTS: Costs were not evenly distributed throughout the sample. 19.4% of patients generated 80% of costs. The variables associated with high cost were: age group 1 (0-14 years) at the first evaluation, permanent disability, and ICD-10 diagnoses: Organic, including symptomatic, mental disorders; Mental and behavioural disorders due to psychoactive substance use; Schizophrenia, schizotypal and delusional disorders; Behavioural syndromes associated with physiological disturbances and physical factors; External causes of morbidity and mortality; and Factors influencing health status and contact with health services. DISCUSSION: Mental healthcare costs were not evenly distributed throughout the patient population. The highest costs are associated with early onset of the mental disorder, permanent disability, organic mental disorders, substance-related disorders, psychotic disorders, and external factors that influence the health status and contact with health services or cause morbidity and mortality. CONCLUSION: Variables related to psychiatric diagnoses and sociodemographic factors have influence on the cost of mental healthcare.

Diagnostic stability of psychiatric disorders in clinical practice.

BACKGROUND: Psychiatric disorders are among the top causes worldwide of disease burden and disability. A major criterion for validating diagnoses is stability over time. AIMS: To evaluate the long-term stability of the most prevalent psychiatric diagnoses in a variety of clinical settings. METHOD: A total of 34 368 patients received psychiatric care in the catchment area of one Spanish hospital (1992-2004). This study is based on 10 025 adult patients who were assessed on at least ten occasions (360 899 psychiatric consultations) in three settings: in-patient unit, 2000-2004 (n=546); psychiatric emergency room, 2000-2004 (n=1408); and out-patient psychiatric facilities, 1992-2004 (n=10 016). Prospective consistency, retrospective consistency and the proportion of patients who received each diagnosis in at least 75% of the evaluations were calculated for each diagnosis in each setting and across settings. RESULTS: The temporal consistency of mental disorders was poor, ranging from 29% for specific personality disorders to 70% for schizophrenia, with stability greatest for in-patient diagnoses and least for out-patient diagnoses. CONCLUSIONS: The findings are an indictment of our current psychiatric diagnostic practice.

Agonismo parcial dopaminérgico en la disfunción sexual secundaria a antipsicóticos / Dopamine partial agonism in antipsychoticinduced sexual dysfunction

Introducción. La disfunción sexual es un efecto secundario frecuente de los antipsicóticos. Ha sido relacionada con la hiperprolactinemia producida por el antagonismo dopaminérgico D2 propio de los fármacos antipsicóticos. El agonismo parcial dopaminérgico D2 del aripiprazol podría explicar por qué su utilización no suele producir ese efecto secundario y que incluso lo revierta al añadirse aripiprazol al tratamiento con otros antipsicóticos. Casos clínicos. Se presentan dos casos clínicos con un primer episodio psicótico en tratamiento con antagonistas dopaminérgicos D2, que desarrollan amenorrea y disfunción eréctil respectivamente. Tras añadir aripiprazol a su tratamiento antipsicótico previo remiten estos efectos secundarios manteniendo adherencia y eficacia terapéutica. Conclusiones. Los fármacos que pueden disminuir los efectos secundarios en la esfera sexual pueden mejorar la aceptación al tratamiento y la calidad de vida, especialmente en pacientes jóvenes con primeros episodios psicóticos. En los casos presentados, el uso de aripiprazol como fármaco adyuvante, se tradujo en una mejoría en los efectos secundarios de la esfera sexual, sin comprometer la eficacia terapéutica (AU)

Introduction. Sexual dysfunction is a frequent side effect associated with antipsychotic treatment. It is known to be caused by the hyperprolactinemia that results from the D2 receptor blockade that is characteristic of antipsychotic drugs. The D2 partial dopaminergic agonism of aripiprazole could explain why its use does not usually cause this side effect, and may even revert it when added to another antipsychotic. Case reports. We present the cases of two patients treated with D2 dopaminergic antagonists for a first episode of psychosis, who complained of amenorrhea and erectile dysfunction during follow-up. After the addition of aripiprazole to their previous antipsychotic treatment, these side effects reverted without a negative impact on treatment adherence or therapeutic efficacy. Conclusions. Pharmacological treatments with the potential of reverting sexual dysfunction secondary to antipsychotic treatment can improve compliance and quality of life of our patients, especially in those who are younger and are being treated for a first psychotic episode. In the cases reported here, the use of aripiprazole as an adjunctive treatment resulted in the disappearance of the undesirable effects without affecting the efficacy already achieved with the previous antipsychotic treatment (AU)