A Cluster Analysis of Neuropsychological Impairment in Borderline Personality Disorder: Identifying a Neurocognitive Subtype Linked to Attention Deficit Hyperactivity Disorder.

INTRODUCTION: Cognitive impairment associated with borderline personality disorder (BPD) has been consistently demonstrated. However, a specific neuropsychological profile has not yet been established for this disorder, maybe due to the heterogeneity of BPD. The aim of this work is the search for distinct neuropsychological subtypes among patients with BPD and for the association of neuropsychological subgroups with specific clinical characteristics. METHODOLOGY: One hundred fifteen patients with BPD diagnosis received an extensive neuropsychological evaluation assessing attentional, memory and executive functions indexes. For subtyping strategies, a cluster analysis of neuropsychological BPD distribution was performed. Central clinical dimensions of BPD were measured and analysed in relation with the obtained neuropsychological clusters. RESULTS: Two clusters were found: Cluster 1 showed a significantly lower score on the working memory index, and Cluster 2 had significantly worse overall executive performance, response inhibition and planning abilities. Patients in the neurocognitive Cluster 2 showed significantly higher clinical deficits of attention as measured with subscales of the CAARS attention deficit hyperactivity disorder (ADHD) index (F = 2.549, p < 0.005, d = 11.49). CONCLUSIONS: Two neuropsychological clusters of patients were found in the BPD sample: Cluster 1 patients showed greater impairment in working memory, while Cluster 2 patients had greater deficits of executive functioning, particularly for response inhibition and planning. In addition, BPD patients with greater executive deficits presented greater levels of ADHD clinical features. These findings might also facilitate earlier diagnosis of severe BPD patient profiles and to establish more personalized treatment based on neurocognitive stimulation.

The mediating role of reflective functioning in the association between childhood trauma and suicide attempt.

BACKGROUND: Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. OBJECTIVE: We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. METHOD: We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. RESULTS: Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. CONCLUSION: This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.

Transdiagnostic inflammatory and oxidative biomarkers with predictive capacity of self-injurious behavior in impulsive and unstable disorders.

INTRODUCTION: Alterations in inflammatory processes have previously been reported in impulsive and unstable disorders, as well as in other psychiatric conditions. In order to investigate transdiagnostic biomarkers associated with various phenotypic features of these disorders, this study is designed to identify biomarkers of inflammatory and oxidative endophenotypes related to autolytic behavior. METHODS: Peripheral blood mononuclear cells were collected from 35 patients with borderline personality disorder (BPD), 29 patients with restrictive eating disorder (rED), 21 patients with purging eating disorder (pED) and 23 control subjects. Plasma levels of different inflammatory and oxidative factors were measured by ELISA and the expression of selected proteins was by Western Blot. Principal component analysis (PCA) was performed to categorize the different inflammatory factors. Additionally, Ancova was performed to observe the differences in the principal components among the different groups and logistic regression analysis was conducted to assess the predictive capacity of these components for autolytic behaviors. RESULTS: We found two inflammatory/oxidative components were associated with BPD, characterized by high levels of JNK and ERK and low levels of GPx, SOD and Keap1; and two other inflammatory/oxidative components were linked to pED, associated with more JNK, TBARS and TNF-α and less GPx and SOD. Two components, with more JNK and ERK and less GPx, SOD and Keap1, predicted non-suicidal self-injury and three components, with higher JNK, TBARS and TNF-α levels and lower GPx, SOD and iNOS levels, predicted suicide attempts. CONCLUSIONS: These results strongly support the endophenotypic characterization of impulsivity and the identification of transdiagnostic inflammatory/oxidative biomarkers relevant to autolytic behavior in impulsive and unstable disorders. These dates lay the groundwork for developing of screening tests for these biomarker components to rapidly detect biological risk factors for specific impulse control disorders and future self-injurious behaviors.

Decreased oxytocin plasma levels and oxytocin receptor expression associated with aggressive behavior in aggressive-impulsive disorders.

INTRODUCTION: This study aims to enhance the understanding of the association between the phenotypic and endophenotypic characteristics of impulsive-aggressive disorders, through the study of plasma oxytocin (OXT) and oxytocin receptor (OXTR) levels in patients with borderline personality disorder (BPD) and patients with eating disorders (ED), as well as to examine the relationship of OXT system with aggressive behavior in these disorders. METHODS: 68 patients with BPD, 67 patients with ED and 57 healthy control subjects were examined for plasma oxytocin levels and protein expression of OXTR in blood mononuclear cells. Aggressive behavior was assessed using the State-Trait Anger Expression Inventory (STAXI-2). Other self and hetero-aggressive behaviors were also evaluated through interviews. RESULTS: BPD and ED patients exhibited significantly lower plasma oxytocin levels than control subjects. Furthermore, BPD patients demonstrated significantly reduced expression of OXTR compared to controls. Plasma oxytocin levels negatively correlated with verbal aggression, while OXTR expression was inversely associated with the STAXI trait subscale. CONCLUSIONS: The findings validate the existence of oxytocin system dysfunction in impulsive-aggressive disorders. They also support the link between low OXT levels in plasma and OXTR expression and the impulsive-aggressive behavior that characterizes these patients in both state and trait situations.

Inflammatory and oxidative endophenotypes in borderline personality disorder: A biomarker cluster analysis.

OBJECTIVES: This study is designed to search for aggrupation of inflammatory/oxidative biomarker alterations in borderline personality disorder (BPD) and their association with phenotypic features. METHODOLOGY: Inflammatory/nitrosative proteins were measures in plasma and peripheral blood mononuclear cells obtained from BPD patients. Patients were assessed on different clinical dimensions of BPD. Oxidative damage was tested by measuring TBARS, nitrites, catalase, GPx and SOD. Protein expression of IκBα, NFκB, iNOS, COX-2, PPARγ, Keap1, NQO1, Nrf2 and α7nAChR was also determined. Western blot and ELISA were used for measurements and a cluster analysis of inflammatory/oxidative biomarkers alterations was performed to investigate subgroups of patients with similar alterations and its relationship with clinical features of BPD. RESULTS: 69 patients were included in the study. Two inflammatory/nitrosative clusters of patients were found: Cluster 1 patients showed significantly higher levels of GPx, IκBα, keap1, NQO1, PPARγ, α7nAChR and Nrf2 than cluster 2 patients. These patients had significantly longer duration of illness, milder anxiety symptoms and lower prescription of antipsychotic drugs than cluster 2. CONCLUSIONS: Two clusters of BPD patients according to the inflammatory/nitrosative profiles were identified. Cluster 1 had increased antioxidant and anti-inflammatory biomarkers and was characterised by greater chronicity of illness but less acute symptomatic severity.

Decreased oxytocin plasma levels and oxytocin receptor expression in borderline personality disorder.

INTRODUCTION: Borderline personality disorder (BPD) is characterized by intense affective reactions with underlying social and interpersonal cognitive deficits. Oxytocin has largely been associated with both stress regulation and social cognition in psychiatric patients and in non-clinical populations in previous studies. Finally, abnormal oxytocin levels have been preliminary reported in BPD patients. METHODS: 53 patients with moderate-severe BPD and 31 healthy control subjects were investigated for plasma levels of oxytocin and protein expression of oxytocin receptor in blood mononuclear cells. Clinical assessments were made for severity, functionality, and comorbidity with axis I and II conditions. RESULTS: Oxytocin plasma levels were significantly lower in BPD patients compared with controls. In addition, protein expression of oxytocin receptor was significantly reduced in the BPD group. A positive correlation was found between plasma oxytocin levels and the activity index score of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Oxytocin receptor protein expression, on the contrary, had a negative correlation with the ZKPQ sociability index score. CONCLUSIONS: Results support the evidence of a dysfunction of the oxytocin system in borderline personality disorder, which could be involved in emotional dysregulation and interpersonal disturbances in these patients.

Depressive-type emotional response pattern in impulsive-aggressive patients with borderline personality disorder.

INTRODUCTION: Borderline personality disorder (BPD) is typically characterized by severe affective dysregulation leading to impulsive behaviors. Accordingly, preliminary data suggest the hypothesis that BPD patients could have a specific and altered pattern of subjective emotional response to stimuli. The nature of the emotional response in BPD can be compared with other affective disorders and provide further insight on the nosological proximity with other psychiatric disorders. METHODS: Subjective emotional response was investigated in 19 patients with DSM-IV BPD with no current depressive episode and in 19 healthy control subjects by using the International Affective Picture System (IAPS). The intensity of arousal, valence and dominance was rated in response to 60 images categorized as pleasant, unpleasant and neutral by using a self-assessment instrument. ANOVA of multiple factors was used for between-groups comparisons. RESULTS: The obtained pattern showed that BPD patients considered the unpleasant and neutral images as less aversive than controls, but the activation that these images induced was higher. Patients showed significantly greater arousal than controls for unpleasant and neutral images (p<0.05) but presented greater valence (more positive emotion) for these images (p<0.05). In addition, BPD patients showed lower dominance (greater insecurity and dyscomfort) for positive images (p<0.05). CONCLUSIONS: The subjective emotional response pattern of BPD patients suggests a trait of vulnerability to pleasant stimuli and is similar to the pattern found in depressive patients in previous studies. This supports the evidence that BPD could in part be related with the spectrum of the affective temperament and affective disorders.

Orbitofrontal dysfunction related to depressive symptomatology in subjects with borderline personality disorder.

OBJECTIVE: In order to explore the relationships of fronto-limbic dysfunction with the clinical features of borderline personality disorder (BPD), the authors investigated brain electrophysiological activity in BPD patients following stimulation with emotionally arousing images. METHODS: Seventeen non-medicated patients with borderline personality disorder were studied with magneto-encephalography. Regional cortical activities were obtained by minimum norm estimate (MNE) of steady-state visual evoked fields (ssVEFs). Linear regression models were conducted to explore clinical correlates of brain activity. RESULTS: Although no interaction group × picture category × brain region was found, a significant interaction group × brain region appeared for orbito-frontal cortex (OFC). BPD patients showed significantly reduced magnetocortical activity in left OFC across all picture categories (F = 26.4; p<.05; F = 31.4). Left OFC activity was inversely correlated with depression score in the BDI (r: -0.48, p < 0.05), with score in the Cornell Dysthymia rating scale (r: -0.52, p < 0.05) and with the number of criteria met for depressive personality disorder (r: -0.44, p < 0.05). Left orbitofrontal activity was also inversely correlated with the global score in the GAF (r-0.63, p < 0.01). No correlations were found between OFC activity and impulsivity or global severity of BPD symptoms. CONCLUSIONS: Abnormal functioning at orbitofrontal areas in BPD could be related to the presence of affective symptomatology and is associated with greater functional deterioration of patients.

Diagnostic features of the cycloid psychoses in a first psychotic episode sample.

INTRODUCTION: The cycloid psychoses have not been included in the modern classifications-what makes scientific research difficult. The aim of the present study is to investigate the presence and specific characteristics of the cycloid psychoses in a broad sample of first psychotic episodes. METHODS: Seventy patients diagnosed with one-year first schizophrenia episode, schizophreniform disorder, or schizoaffective disorder were studied (mean age, 27.9 years old; SD±6.34). The detection of the possible cases of cycloid psychosis was done according to the Perris and Brockington operational criteria. Two groups of "cycloid" (n=11) and "non cycloid" (n=59) patients were compared according to demographic and clinical variables, and possible diagnostic variables were evaluated by the ROC curves. RESULTS: Significant differences were found between cycloid and non cycloid groups for a number of clinical variables: prodromic symptoms (p<0.001), PANSS total score (p=0.003), PANSS-P (p=0.009), PANSS-GP (p=0.001), total score for mania by EVMAC (p=0.001), and CDSS for depression (p=0.004). ROC curves were significant for PANSS-GP (AUC=0.791, p=0.002), EVMAC (AUC=0.938, p=0.001), and CDSS (AUC=0.770, p=0.005). A sensitivity/specificity study demonstrated a negative predictive value for PANSS-GP (93.88%), EVMAC (96.30%), and CDSS (93.88%). CONCLUSIONS: According to these results, cycloid psychoses might represent differentiated and well-defined clinical entity.

Functional magnetic resonance studies in eating behavior disorders.

Eating behavior disorders (EBD) constitute a serious somatic and psychiatric condition that occurs mainly in adolescent and young adult women and is characterized by a persistent desire to be extremely thin, pathologic fear of gaining weight and distortion of body perception. From a neurobiological vantage point, it has been suggested that alterations in some neural systems of these patients may exist, either as a cause or effect of their condition. In recent years various research studies have been conducted with the aim of identifying underlying brain disorders in EBD. The purpose of this article was to review the main findings obtained in neuroimaging studies, including PET, SPECT, magnetic resonance spectroscopy (MRS), focusing mainly on functional magnetic resonance imaging (fMRI). Some alterations and changes in metabolism and blood perfusion that accompany the neuroimaging findings will be reviewed, as well as studies designed to determine whether these alterations persist after recovery from the disease.

[Neuropsychological dysfunctions in personality borderline disorder: detection strategies]. / Alteraciones neuropsicológicas en el trastorno límite de la personalidad: estrategias de detección.

INTRODUCTION: Borderline personality disorder (BPD) is characterized by emotional instability and impulsivity. However, there is evidence that neurocognitive alterations have a relevant role in the clinical features of these patients. The present study investigates cognitive function in BPD in order to search for a specific profile of neuropsychological alterations. METHODS: Based on previous research and cognitive complaints reported by patients, a neuropsychological assessment protocol focused on prefrontal functioning was applied. The applied neuropsychological battery included tests assessing the following cognitive domains: memory (fixation, consolidation and recovery processes) categorical evocation, cognitive flexibility, sustained attention, processing rate, inhibitory control and working memory. The patient sample was recruited from an outpatient BPD unit and was composed by 26 patients (14 women, 12 men) diagnosed of BPD. RESULTS: In comparison to the normative values, BPD patients have a deficit in the execution of most of the neuropsychological tests. This deficit was especially present in the following: recovery processes of the immediate and differed memory, working memory, sustained attention and processing rate, verbal fluency, impulse control, cognitive flexibility, abstraction and planning. CONCLUSIONS: BPD patients could present a pattern of neurocognitive alterations that suggests a specific impairment of the prefrontal areas and requires a more detailed study. The neuropsychological dysfunctions could partially explain the behavioral alterations in BPD patients.

[Neuropsychological rehabilitation in patients with borderline personality disorder: a case series]. / Rehabilitación neuropsicológica en pacientes con trastorno límite de personalidad: una serie de casos.

Recent research studies have been confirming the evidence that patients with personality borderline disorder (BPD) suffer significant neuropsychological disorders. Neurocognitive dysfunction of BPD seems to mainly affect the functions characteristic of the prefrontal areas that participate in information processing and management and in the regulation of complex behavioral responses. Neuropsychological disorders not only are seen in the specific tests but are also reflected and could play an important role in the clinical manifestations of borderline disorder, such as emotional dysregulation and impulsive behaviors. Neurocognitive rehabilitation therapy has been used successfully in psychiatric disorders such as schizophrenia, also characterized by the presence of neuropsychological dysfunctions. Thus, it can be expected that rehabilitation of the neurocognitive functions affected in BPD contributes to the patient's functional improvement. The present work describes a series of five patients with BPD who presented important neuropsychological dysfunctions and who were treated successfully with a specific program of neurocognitive rehabilitation. The results observed justify the performance of controlled clinical studies on the efficacy of this technique in the treatment of BPD.

[Neuroimaging studies in borderline personality disorder]. / Estudios de neuroimagen en el trastorno límite de la personalidad.

DSM-IV defines Borderline personality disorder (BPD) as a personality disorder that can be primarily characterized by emotional instability, extremely polarized thought and chaotic interpersonal relations. It is the most common personality disorder. Its prevalence is estimated to be from 0.2% to 1.8% of the general population, and the 76% of them are women. However, despite these data and the different biologic findings, there are few publications on neuroimage about this nosologic entity. Recent studies suggest that a dual cerebral disorder, including frontal and limbic circuits, could be present in characterize BPD. These cerebral areas would also be involved in the serotonergic dysfunction that seems to be related to the impulse dyscontrol and self-aggressive behaviour, characteristic of these patients. Most authors point out the importance of traumatic precedents in the BPD genesis, with a direct relation between stress and the neurobiological findings observed, including the neuroimage changes. The aim of this article is to make a revision of the main neuroimage data found in BPD, including the new techniques such as functional MRI, diffusion tensor MRI and spectroscopy.

Schizophrenia treatment. Critical review on the drugs and mechanisms of action of antipsychotics.

Schizophrenic treatment was developed during the second half of the last century, mainly within the context of the development of antipsychotic drugs. Even though there has been significant progress due to the availability and use of multiple drugs, these can still be classified into three basic groups of antipsychotic drugs (atypical antipsychotics, typical antipsychotics and dopamine partial agonist antipsychotics). Their primary antipsychotic mechanism is still the action on the dopamine systems. Many of the second-generation antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the drug properties that provide the different therapeutic effects from those of the first generation are not clear and some adverse effects may still affect the patient's health and quality of life. Furthermore, the efficacy of the antipsychotics is limited. This has led to the use of adjuvant medications to strengthen the treatment effects. On the other hand, work is being done on the development of new research lines to develop new non-dopaminergic antipsychotic drugs, with not very successful results. The aim of this paper is to make a brief review on the current therapeutic armamentarium for schizophrenia, the strategies to develop drugs, and theories of mechanisms of action of antipsychotics. Emphasis is placed on the new therapeutic targets for the development of future treatments.

[The use of the International Affective Picture System for the study of affective dysregulation in mental disorders]. / Aplicaciones del International Affective Picture System en el estudiode la regulacion emocional en los trastornos mentales.

INTRODUCTION: The International Affective Picture System (IAPS) uses a series of emotional, normative and internationally accessible pictorial stimuli and is considered to be the most reliable and valid system in the experimental study of emotions. The IAPS has been used in research on mental disorders such as schizophrenia, major depression, anxiety or psychopathic personality traits. Furthermore, it is frequently used as independent variable in neuroimaging studies. Some of the approaches to borderline personality disorder consider that the fundamental psychopathological element in these subjects is affective dysregulation, from which the principal symptoms such as intolerance to frustration, reactivity or dysphoria are derived. This review paper has aimed to gather and analyze the information on the study of emotional regulation and the use of the IAPS in the different mental disorders. METHODS: A review is made of the different data bases of the studies published in the general population and in the clinical populations as well as of the internal characteristics of the test. RESULTS: In agreement with the results described in the studies reviewed, the IAPS seems capable of defining specific responses to stimuli in different mental disorders, including mood disorders and schizophrenia. CONCLUSIONS: In conclusion, the use of the IAPS in the study of borderline personality disorder could be of interest for the understanding and treatment of borderline personality disorder in which emotional dysregulation is a principal factor.

Psychopharmacological treatment in borderline personality disorder.

Borderline personality disorder is a disorder with important social and clinical repercussions, which has been treated mainly by psychotherapy. In recent years, the syndromic analysis of this disorder has allowed us to identify different symptoms capable of being improved with psychopharmacology treatment. Thus, its complex symptomatology could be included in four clinical dimensions: impulsive-aggressive, affective instability, cognitive- perceptive and anxiety-inhibition. Antidepressants, mood stabilizers, antipsychotics, anxiolytics, or more recently omega-3 fatty acids have shown efficacy in the treatment of symptomatic dimensions of this disease. We have reviewed scientific articles (reviews, clinical trials or clinical guidelines) published over the last ten years and have proposed therapeutic algorithms for psychopharmacology management in these patients.

[Long-acting injectable risperidone in treatment resistant borderline personality disorder. A small series report]. / Risperidona intramuscular de acción prolongada en el trastorno límite de la personalidad resistente al tratamiento.Un estudio piloto.

INTRODUCTION: Borderline personality disorder (BPD) is usually treated with a combination of antipsychotic and anticonvulsant drugs although only limited efficacy is obtained in many patients. A major problem in the treatment of BPD is the lack of compliance derived form the pathological impulsivity of BPD patients. METHODS: Twelve severe BPD patients refractory to previous treatment with drug combinations for three months were treated with intramuscular long-acting risperidone for a six-month period. Clinical changes were rated with the Clinical Global Impression (CGI), the Brief Psychiatric Rating Scale, anxiety and aggression scales. Functional improvement was evaluated with the Global Assessment of Functioning (GAF). RESULTS: Six-month treatment with IM risperidone was associated with significant improvement of CGI (t: 5.7 - 4.0; p<0.01) and of GAF (t: -4.5; gl: 10; p<0.01). Clinical improvement was robust after the first month of treatment. No relevant extrapiramidal side effects were reported with the exception of mild psychomotor slowing which requires dose adjustments in four patients. CONCLUSIONS: Treatment with i.m. long acting risperidone during six months was associated with significant clinical and functional improvement and excellent tolerability in a group of BPD patients refractory to previous treatment. The results indicate that the effect of IM risperidone in BPD should be further investigated in large placebo-controlled trials.

[Acute tryptophan depletion in eating disorders]. / Depleción aguda de triptófano en trastornos de la conducta alimentaria.

INTRODUCTION: This work describes the rational bases justifying the use of acute tryptophan depletion technique in eating disorders (ED) and the methods and design used in our studies. Tryptophan depletion technique has been described and used in previous studies safely and makes it possible to evaluate the brain serotonin activity. Therefore it is used in the investigation of hypotheses on serotonergic deficiency in eating disorders. Furthermore, and given the relationship of the dysfunctions of serotonin activity with impulsive symptoms, the technique may be useful in biological differentiation of different subtypes, that is restrictive and bulimic, of ED. METHODS: 57 female patients with DSM-IV eating disorders and 20 female controls were investigated with the tryptophan depletion test. A tryptophan-free amino acid solution was administered orally after a two-day low tryptophan diet to patients and controls. Free plasma tryptophan was measured at two and five hours following administration of the drink. Eating and emotional responses were measured with specific scales for five hours following the depletion. A study of the basic characteristics of the personality and impulsivity traits was also done. Relationship of the response to the test with the different clinical subtypes and with the temperamental and impulsive characteristics of the patients was studied. RESULTS: The test was effective in considerably reducing plasma tryptophan in five hours from baseline levels (76%) in the global sample. The test was well tolerated and no severe adverse effects were reported. Two patients withdrew from the test due to gastric intolerance. CONCLUSIONS: The tryptophan depletion test could be of value to study involvement of serotonin deficits in the symptomatology and pathophysiology of eating disorders.

[Historical review of the borderline personality disorder concept]. / Revisión histórica del concepto de trastorno limítrofe de la personalidad (borderline).

INTRODUCTION: The concept of borderline syndrome is the subject of current debate because of its ambiguity and lack of homogeneity. Furthermore, the concept is rejected by many authors as a common category for atypical and non-specific disorders that cannot be classified elsewhere. The current use of the term borderline seems to be more a consequence of its historic use than its true clinical meaning. There is discrepancy on whether this term determines a level of severity, an organization of personality or a defined syndromic entity. In 1938, Stern was the first author to use the term borderline, and it was not introduced in the DSM III until 1980. OBJECTIVE: This work makes a historical review of the use of the term borderline and also of those terms that have been used to define patients with the same characteristics. CONCLUSION: The different schools (psychoanalytic, biological, eclectic and biosocial) have different concepts on the term borderline. There is still no concise and exact definition for the diagnostic criteria of borderline and it is even possible the best term for this group of patients has still not been determined. It will be important to consider the contributions of the DSM V or ICD 11 in the next years.

[Effects of venlafaxine extended release formulation on the clinical management of patients]. / Repercusión de la formulación retard de venlafaxina en el manejo clínico de los pacientes.

One of the issues related with antidepressant drug use is to improve patient compliance. Investigations have searched for simplified administration schedules that focus on having a significant impact on the management of depressive patients. This article has reviewed the extended release formulation characteristics and its effect on the drug pharmacokinetics and clinical assessments of depressive patients. The conclusion of this review is that venlafaxine extended release formulation represents an innovation in the treatment of depression. This formulation provides the same total exposure to venlafaxine with a once-daily dose as the immediate release formulation with several doses, slower gastrointestinal release and smaller fluctuations between maximum and minimal plasma concentrations. These differential characteristics result in a potential improved efficacy and a better tolerability profile. The increased compliance observed with venlafaxine extended release formulation could improve the appropriate management of depressive patients.