Vagus nerve stimulation for treatment-resistant mood disorders: a long-term naturalistic study.

BACKGROUND: Limited therapeutic options are available for patients with treatment-refractory major depression who do not respond to routinely available therapies. Vagus nerve stimulation showed adjunctive antidepressant effect in chronic treatment resistant depression, even though available studies rarely exceed 2-year follow up. We report a naturalistic 5-year follow up of five patients who received VNS implant for resistant depression (3 patients with major depressive disorder and 2 with bipolar disorder). METHODS: Response was defined as a reduction of the 17-item HDRS total score ≥50% with respect to baseline, remission as a score ≤7. RESULTS: Response and remission rates were both 40% (2/5) after 1 year, and 60% (3/5) at 5 years. Two patients withdrew from the study because of side effects or inefficacy of stimulation. CONCLUSIONS: Our case series showed that long-term VNS may be effective in reducing severity of depression in a small but significant minority of patients, although two patients had stimulation terminated because of adverse effects and/or refusal to continue the study.

Recurrence rates of bipolar disorder during the postpartum period: a study on 276 medication-free Italian women.

The postpartum period is considered a time of heightened vulnerability to bipolar disorder. The primary goal of this study was to examine the frequency and the polarity of postpartum episodes in a clinical sample of women with bipolar disorder who were medication-free during their pregnancies. In addition, we sought to examine whether there are differences in terms of clinical features of bipolar disorder between women with and without postpartum episodes. Lastly, we analyzed the potential relationship between polarity of the postpartum episodes and clinical features of bipolar disorder. The presence/absence of postpartum episodes and their characteristics were obtained from medical records of 276 women with bipolar disorder who were medication-free during their pregnancies. Two hundred seven women (75.0 %) had a history of one or more postpartum mood episodes: depressive (79.7 %), (hypo)manic (16.4 %), or mixed episodes (3.9 %). Psychotic symptoms during postpartum episodes were associated with depression in 37 (22.4 %) patients, with mania in 19 (67.8 %) patients, and with mixed episodes in 7 (87.5 %) patients. Postpartum manic and mixed episodes were significantly associated with type I disorder and with psychotic features. Our findings indicate high risk of clinically ascertained mood episodes during postpartum period in bipolar women who are not treated during pregnancy.

Insight in stable schizophrenia: relations with psychopathology and cognition.

OBJECTIVE: This study evaluated the relationship among insight, sociodemographic and clinical variables, symptoms and cognitive functions in a population of outpatients with stable schizophrenia, in order to identify possible contributing factors to awareness. METHOD: Two-hundred and seventy-six consecutive outpatients with stable schizophrenia were enrolled in a cross-sectional study. All subjects were assessed by psychiatric scales and interview, and a wide neuropsychological battery. A factor analysis was performed to identify cognitive factors and multiple regression analyses were executed to test the contribution of variables considered to insight. RESULTS: Our results showed that positive and negative symptoms, executive functions, verbal memory-learning were contributors of awareness of mental illness; positive and negative symptoms explained variability in awareness of the need for treatment; positive symptoms and executive functions contributed to awareness of the social consequences of disorder. CONCLUSIONS: These results suggested that insight was partially influenced by positive and negative symptoms and by cognitive functions. A complex system of overlapping variables may underlie impaired insight, contributing to a different extent to specific dimensions of poor insight in patients with stable schizophrenia.

Stressful life events and obsessive-compulsive disorder: clinical features and symptom dimensions.

The potential role of stressful life events (SLEs) in the genesis of obsessive-compulsive disorder (OCD) has been suggested by several authors, but whether the number or the severity or the type of SLEs preceding the onset of OCD has a triggering effect is unclear. Further, sociodemographic and clinical features of OCD preceded by SLEs, and the relationship between type of SLEs and type of obsessive-compulsive symptomatology remain mainly unexplored. The aims of this study were to compare the clinical features of OCD with and without SLEs preceding it and to examine the relationship between type of SLEs and OCD symptom dimensions. The number and type of SLEs which occurred before the onset of OCD were determined in 329 patients: the raters had to decide whether an occurrence 12 months before the onset of OCD would fit any of the 61 items on Paykel's list, and each event reported was carefully investigated in order to determine the exact time of occurrence. At least one event preceded the onset of OCD in 200 patients (60.8%), and this was significantly associated with female gender, abrupt onset of the disorder and somatic obsessions. Moreover, LogReg Analysis identified three specific traumatic events ("hospitalization of a family member", "major personal physical illness", "loss of personally valuable object") significantly associated with a symptom dimension (symmetry obsessions, repeating, ordering/arranging, counting, and checking compulsions). Additional evidence regarding the association among SLE-preceded OCD, female gender, somatic obsessions and symmetry/ordering symptoms should be obtained to advance the understanding of OCD.

[OCD during pregnancy and post partum]. / La paziente con DOC in gravidanza e nel post partum.

AIM: Obsessive-compulsive disorder (OCD) can occur with specific characteristics during the pregnancy/postpartum period. The presence of OCD in a such delicate period in a woman's life can lead to severe suffering of the patient herself, of her relatives and the newborn. The purpose of this article is to offer a comprehensive review of scientific literature concerning the relationship between OCD and pregnancy/post partum. METHODS: Literature was identified by searching in Medline (Medical Literature Analysis and Retrieval System On-line), using the PubMed search engine. The keywords used were "obsessive-compulsive disorder", "pregnancy", "post partum period", "perinatal period". RESULTS: The last trimester of pregnancy and the post partum period are at increased risk of onset of OCD, especially in susceptible individuals. During pregnancy/post partum, OCD is characterized by typical clinical features: obsessions (in particular aggressive and/or contamination) are more frequent than compulsions (checking and/or washing); further, if untreated, the symptomatology tends to persist and/or recur during any subsequent pregnancies. DISCUSSION: From the literature it appears that the diagnosis of OCD during pregnancy/post partum should be performed as soon as possible, both to ensure the correct patient and family psychoeducation, and timely access to psychopharmacological treatment and/or psychotherapy.

[Combined treatments in obsessive-compulsive disorder: current knowledge and future prospects]. / L'integrazione dei trattamenti nel disturbo ossessivo-compulsivo: conoscenze attuali e prospettive future.

AIM: Serotonin reuptake inhibitors (SRIs) and/or cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). The study discuss whether: a) combining both treatments ab initio is more effective than either monotherapy alone; and b) a sequential treatment is effective both in responder and non responder patients. METHODS: Have been carried out a search on Medline/PubMed database, selecting clinical randomized controlled studies in English. Have been examined 9 randomized controlled studies where combined treatment ab initio was compared to CBT alone, and 6 where combination treatment was compared to SRI alone. No controlled studies were found for sequential treatments in OCD. Have been then examined naturalistic studies, 2 including responder patients and 7 including non responder patients. RESULTS: Of the 9 studies, 7 didn't find any additional benefit of combining treatments as compared to CBT alone; in 1 study the combination strategy resulted more effective than CBT alone in children and adolescents, and in another in severely depressed adult patients with OCD. As compared to SRIs alone, combining treatments was not more effective in 4 studies, while in 2 studies it was more effective. All studies concerning sequential treatments found evidence of efficacy of this strategy. DISCUSSION: Combining ab initio CBT and SRI has not been found to be clearly superior of either therapy alone, except for patients with severe depression and for children and adolescents. On the contrary, a sequential strategy may be used successfully both to treat residual symptoms in responders and to determine clinical response in resistant patients.

Age-specific prevalence of metabolic syndrome in Italian patients with bipolar disorder.

AIM: Metabolic syndrome (MetS) is highly prevalent in patients with bipolar disorder (BD). Little research has evaluated the risk profile of MetS and cardiovascular disease in different gender and age groups in these patients. Our aim is to evaluate the prevalence of MetS in Italian patients with BD stratified by gender and age, and to determine the correlates of MetS. METHODS: Subjects with BD were included and stratified by sex and age according to the following age groups: <30; 30-39; 40-49; 50-59; ≥ 60 years. Socio-demographic and clinical characteristics, lifestyle information, and comorbidity for cardiovascular diseases and diabetes were collected. MetS was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. RESULTS: MetS was evaluated in 200 patients, with a prevalence of 26.5%. Men had higher rates of hypertension and hypertriglyceridemia, women had more abdominal obesity. Women had a peak of prevalence in the ≥ 60 years group, while men displayed high rates even in the young age groups. In young patients, MetS was associated with Cluster B personality disorders and less physical exercise. CONCLUSION: Our paper highlights the importance of evaluating MetS even in young patients with bipolar disorder, especially males. The strong association with lack of physical exercise suggests that the implementation of healthy behaviors might be relevant in order to prevent MetS and future adverse cardiovascular outcomes.

[Lithium and anticonvulsants in the treatment of mania and in the prophylaxis of recurrences]. / Litio e anticonvulsivanti nel trattamento della mania e nella profilassi delle ricorrenze.

INTRODUCTION: A mood stabilizer is an agent effective in treating both poles of the illness and at the same time being able to prevent both manic and depressive episodes in bipolar disorder. According to a broader definition, a mood stabilizer should be effective in decreasing the frequency or severity of any type of episode in bipolar disorder, without worsening the frequency or severity of episodes of opposite polarity. According to this, anticonvulsants and atypical antipsychotics can be considered as mood stabilizers. AIM AND METHODS: In this paper we review the use of lithium and other anticonvulsants that have proved effective in randomized controlled trials of the treatment of manic episodes and prevention of recurrences of bipolar disorder. RESULTS: Lithium and valproate are considered as first-line treatment options for acute mania while evidence regarding carbamazepine is insufficient to consider it as a first-line agent. Patients who fail to respond to first-line treatments may benefit from the adjunct of an atypical antipsychotic such as olanzapine, quetiapine, risperidone or aripiprazole. Lithium retains the strongest evidence of efficacy in the prophylaxis of manic episodes, lamotrigine in the prevention of depressive episodes. Valproate and carbamazepine have no indication for long-term treatment of bipolar disorder. DISCUSSION: Lithium can still be considered a gold standard in the treatment of manic episodes as well as in the prophylaxis of recurrences. Other anticonvulsants should be employed in particular situations, such as valproic acid in the treatment of mania and lamotrigine in the prevention of depressive recurrences.

Investigation of CNR1 and FAAH endocannabinoid gene polymorphisms in bipolar disorder and major depression.

Experimental data suggest that the endogenous cannabinoid system is involved in mood regulation, but no study has been performed so far to investigate the role of endocannabinoid genes in the susceptibility to major depression (MD) and/or bipolar disorder (BD). We assessed the CB1 receptor gene (CNR1) single nucleotide polymorphism (SNP) rs1049353 (1359 G/A) and the fatty acid amide hydrolase (FAAH) gene rs324420 SNP (cDNA 385C to A) for their associations with MD and/or BD in 83 Caucasian patients with recurrent MD, 134 Caucasian individuals with BD, and 117 Caucasian healthy subjects. The distribution of the CNR1 1359 G/A genotypes and alleles significantly differed among the groups (chi(2)=12.595; df=4, P=0.01 for genotypes; chi(2)=13.773; df=2, P=0.001 for alleles) with MD patients showing a higher frequency of both AG, GG genotypes and A allele as compared to healthy controls. The distribution of the FAAH cDNA 385C to A genotypes, according to the CC dominant model (AA+AC vs. CC), significantly differed among the groups (chi(2)=6.626; df=2, P=0.04), with both BD patients and MD patients showing a non-significant slightly higher frequency of the AC genotype. These findings, although preliminary, suggest that the CNR1 1359 G/A and the FAAH cDNA 385C to A gene variants may contribute to the susceptibility to mood disorders.

No effect of adding brief dynamic therapy to pharmacotherapy in the treatment of obsessive-compulsive disorder with concurrent major depression.

BACKGROUND: Until now no studies have investigated the benefits of adding brief dynamic therapy (BDT) to medication in obsessive-compulsive disorder (OCD), while a number of recent investigations have demonstrated the efficacy of supplemental BDT among patients with major depressive disorders (MDD). The objective of the present study was to explore the efficacy of BDT combined with pharmacotherapy in comparison with pharmacotherapy alone in the treatment of OCD with concurrent MDD. METHODS: A 12-month randomized clinical trial compared a standard selective serotonin reuptake inhibitor treatment with (n = 27) or without (n = 30) supplemental BDT in patients with OCD and concurrent MDD. Supplemental BDT was added during the first 16-week trial; all patients continued to be treated with only pharmacotherapy in the following continuation phase. The primary efficacy assessments were the Yale-Brown Obsessive Compulsive Scale and the 17-item Hamilton Rating Scale for Depression; the secondary efficacy measures included the Clinical Global Impression scale and the Global Assessment of Functioning. The data analysis was conducted on the 'intent-to-treat (ITT) efficacy patient sample'. RESULTS: Fifty patients completed the study. No difference between the 2 treatment groups was found at any point by any assessment method in the ITT study sample. CONCLUSIONS: Supplemental BDT in the treatment of patients with OCD with concurrent MDD who are receiving effective medication has no significant clinical effect on both obsessive and depressive symptoms.

Neuropsychiatric symptoms underlying caregiver stress and insight in Alzheimer's disease.

OBJECTIVE: Cluster analysis based on Alzheimer's disease (AD) neuropsychiatric profile demonstrated validity on caregiver burden, nursing-home placement and survival. The aims of our study were to explore the validity of this approach on caregiver burden, lack of insight and cognitive impairment and to examine the impact of neuropsychiatric profiles on these variables. METHOD: A data-driven approach (two-step cluster analysis) identified groups of patients based on similarities of their neuropsychiatric symptom profile, as assessed by the Neuropsychiatric Inventory (NPI). ANOVAs and chi(2) tests were used to compare groups with regard to continuous and categorical variables. Linear regressions tested the relationships between NPI and clinical variables. RESULTS: Psychotic/behavioral, depressive and minimally symptomatic clusters differed for caregiver burden and lack of insight. Patients in the minimally symptomatic cluster showed better insight than those in the depressive cluster. Caregivers of the psychotic/behavioral cluster experienced the highest burden. We found positive relationships between NPI and lack of insight in the depressive and minimally symptomatic clusters and between NPI and caregiver burden in all three clusters. Caregiver burden was influenced by the type of symptoms. CONCLUSIONS: The cluster analysis was valid for lack of insight and caregiver burden. Symptoms predominant on caregiver burden could become targets for therapy.

Relative contributions of psychotic symptoms and insight to quality of life in stable schizophrenia.

The purpose of this study was to examine the relative contributions of psychotic symptomatology such as delusions and hallucinations, and insight to quality of life (QOL) in a sample of outpatients with stable schizophrenia. Eighty-three consecutive outpatients with stable schizophrenia were enrolled in a cross-sectional study. We performed a path analysis using a multiple regression technique to assess the specific effect of psychotic symptomatology on QOL and the possible mediating role of insight. Our findings suggested that (i) psychotic symptomatology was negatively correlated to both QOL and the two dimensions of insight we considered (awareness of symptoms and attribution of symptoms); (ii) the impact of insight on QOL was not uniform as attribution of symptoms positively predicted QOL, while the effect of symptom awareness was negative; (iii) when the mediation effect of insight was taken into account, psychotic symptomatology was no longer a significant predictor of QOL on its own. These results suggested a complex pattern of relationships between different dimensions of insight, QOL and psychotic symptomatology. Different dimensions of insight could be related to different aspects of outcome, and this would need to be reflected in rehabilitation programs.

Family accommodation in obsessive-compulsive disorder: Relation to symptom dimensions, clinical and family characteristics.

Family accommodation is the term used to indicate the process whereby family members of patients with obsessive-compulsive disorder (OCD) assist or participate in the patients' rituals. Family accommodation is a relatively under-researched phenomenon in OCD but an important one because it may be predictive of poor treatment outcome. This study systematically examined several socio-demographic and clinical variables that are associated with family accommodation in a well-characterized sample of adult patients and their healthy family members. Experienced clinicians administered the Family Accommodation Scale (FAS) to 141 psychopathology-free family members cohabiting with 97 patients with OCD. The items of the FAS were first subjected to principal component analysis (PCA) and the resulting domains of family accommodation (Participation, Modification, and Distress and Consequences) introduced as dependent variables in a series of multiple regression models assessing the relationship between family accommodation domains and a wide range of clinical variables, including Axis I and II psychopathology and symptom dimensions derived from the Yale-Brown Obsessive-Compulsive Scale (YBOCS) Symptom Checklist. The results showed that family accommodation was common, with the provision of reassurance, participation in rituals and assisting the patient in avoidance being the most frequent practices (occurring on a daily basis in 47%, 35%, and 43% of family members, respectively). The PCA of the YBOCS Symptom Checklist yielded four symptom dimensions, which were identical to those previously identified in the international literature. Multiple linear regression analyses showed that a higher score on the contamination/washing symptom dimension and a positive family history for an anxiety disorder other than OCD (referring to a family member other than the participant in this study) predicted greater scores on several domains of family accommodation. Our study confirms that family accommodation is frequent and distressing in psychopathology-free family members cohabiting with adult OCD patients. Family accommodation is particularly frequent and distressing when the patient has prominent contamination/washing symptoms and/or when another family member has a history of an anxiety disorder. Such families may be more likely to benefit from family-based interventions but this remains to be tested in controlled trials.

Clinical predictors of health-related quality of life in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a serious mental disorder that has severe impact on a person's quality of life and those living with a person with OCD. This study systematically examined the clinical variables that are predictive of several domains of quality of life in a large, well-characterized sample of patients attending a specialized treatment unit in Italy. METHODS: The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was administered to 151 patients with OCD and their scores were compared to published Italian norms. A principal component analysis was performed on the 13 major categories of the Yale-Brown Obsessive-Compulsive Scale (YBOCS) Symptom Checklist to derive symptom dimension scores. The association between various domains of quality of life and a wide range of clinical variables, including symptom dimension scores, was examined using multiple regression models. RESULTS: Compared to published Italian norms, patients with OCD showed impairment in most domains of quality of life, particularly social functioning. The principal component analysis of the YBOCS Symptom Checklist yielded 5 symptom dimensions that were identical to those previously identified in the international literature. Fewer years of education, higher depression scores (Hamilton Rating Scale for Depression), higher YBOCS obsessions scores, and higher scores on the contamination/washing symptom dimension independently predicted a poorer score on the physical health component of the SF-36. Higher YBOCS compulsions scores, the presence of a current mood disorder, and higher anxiety scores (Hamilton Rating Scale for Anxiety) predicted a poorer score on the mental health component of the SF-36. CONCLUSIONS: Our study confirms that quality of life is severely impaired in patients with OCD. The identification of predictors of quality of life in OCD can help clinicians to adapt their treatment protocols to cater for the individual needs of their patients.

Adaptation of interpersonal psychotherapy to borderline personality disorder: a comparison of combined therapy and single pharmacotherapy.

OBJECTIVE: Combined treatment with interpersonal psychotherapy (IPT) and antidepressants (ADs) has been found more effective than single pharmacotherapy in patients with major depression and concomitant borderline personality disorder (BPD). The aim of our study is to investigate whether combined treatment with a modified version of IPT is still superior to ADs when treating patients with a single diagnosis of BPD. METHOD: Fifty-five consecutive outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnosis of BPD were enrolled. They were randomly assigned to 2 treatment arms for 32 weeks: fluoxetine 20 to 40 mg per day plus clinical management; and fluoxetine 20 to 40 mg per day plus IPT adapted to BPD (IPT-BPD). Eleven patients (20%) discontinued treatment owing to noncompliance. Forty-four patients completed the treatment period. They were assessed at baseline, and at week 16 and 32 with: a semi-structured interview for demographic and clinical variables; Clinical Global Impression Scale (CGI-S); Hamilton Depression Rating Scale (HDRS); Hamilton Anxiety Rating Scale (HARS); Social and Occupational Functioning Assessment Scale (SOFAS); BPD Severity Index (BPD-SI); and a questionnaire for quality of life (Satisfaction Profile [SAT-P]). A univariate general linear model was performed with 2 factors: duration and type of treatment. P values of less than 0.05 were considered significant. RESULTS: Remission rates did not differ significantly between subgroups. Duration, but not type of treatment, had a significant effect on CGI-S, HDRS, SOFAS, and total BPD-SI score changes. Combined therapy was more effective on the HARS; the items: interpersonal relationships, affective instability, and impulsivity of BPD-SI; and the factors: psychological functioning and social functioning of SAT-P. CONCLUSIONS: Combined therapy with adapted IPT was superior to fluoxetine alone in BPD patients, concerning a few core symptoms of the disorder, anxiety, and quality of life.

[Bipolar disorders and metabolic syndrome: a clinical study in 185 patients]. / Disturbi bipolari e sindrome metabolica: studio clinico in un campione di 185 pazienti.

AIMS: This study aimed to evaluate the prevalence of metabolic syndrome (MetS) in Italian patients with bipolar disorder (BD) and to determine the sociodemographic and clinical correlates of MetS in this patient population. METHODS: 185 subjects with BD I, II, NAS, cyclothymic disorder and schizoaffective disorder, bipolar subtype were included. Sociodemographic and clinical characteristics, lifestyle information (alcohol and smoking habits and rate of physical exercise) and comorbidity for cardiovascular diseases and diabetes were collected. Patients were assessed for MetS according to American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) criteria. RESULTS: MetS was present in 27.9% of the sample. Abdominal obesity was present in 48.9%, hypertension in 53.8%, high triglycerides in 36.6%, low HDL-C levels in 33.3% and fasting hyperglycemia in 11.5% of the sample. Of the investigated variables, age, duration of illness, rate of obesity and cardiovascular disease were higher in patients with MetS. MetS was also associated with the absence of physical activity. CONCLUSIONS: MetS is highly prevalent in Italian patients with BD. Our 27.9% prevalence rate is similar to the rates reported in other European studies and lower than that in US studies. Elderly and obese patients with BD are at particularly high risk for MetS. The absence of physical exercise is also associated to MetS.

Relative contribution of antipsychotics, negative symptoms and executive functions to social functioning in stable schizophrenia.

The purpose of this study was to examine the relative contributions of antipsychotic medication, negative symptoms and executive functions to impairment in social functioning in a sample of outpatients with stable schizophrenia. One-hundred and sixty-eight consecutive outpatients with stable schizophrenia were enrolled in a cross-sectional study. We performed a path analysis using multiple regression technique in order to assess the specific effect of antipsychotic type (first-generation antipsychotics versus second-generation antipsychotics) on social functioning and the possible mediating role of executive functions and negative symptoms. Our findings suggested that (i) second generation antipsychotics (SGAs) use predicted better social functioning (Beta=.24, p=.003) and better executive functions (Beta=.25, p=.003); conversely SGAs use was not associated with lesser negative symptoms (Beta=.00, p=.981); (ii) impaired executive functions and severity of negative symptoms were associated with worse social functioning (Beta=.19, p=.016; Beta=.28, p=.001); (iii) when we inserted in the model Positive and Negative Syndrome Scale - Negative Symptom subscale (PANSS-N) and Wisconsin Card Sorting Test - number of achieved sorting categories (WCST-cat), the former failed to show a mediation effect, while the latter seemed to mediate partially the effect of SGAs on social functioning. Taken together, the present results suggest that it is critical to examine individually executive functions and negative symptoms because they seem to relate to social functioning in different and independent ways and thus might represent separable treatment targets. Furthermore, social functioning appears a complex outcome multiply determined with no single predictor variable explaining a sufficient amount of variance.

Quality of life and psychopathology during the course of schizophrenia.

OBJECTIVE: This study evaluated a population of outpatients with stable schizophrenia to analyze if relationships between patterns of symptomatology and quality of life (QOL) change during the time course of illness. METHODS: We recruited 168 outpatients with stable schizophrenia, and we further divided our sample into 3 groups of patients (72 months of illness). Psychiatric assessment included the Quality of Life Scale, the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Clinical Global Impression-Severity Scale. All clinical variables significantly related to Quality of Life Scale scores were subsequently analyzed using a multiple stepwise regression to assess their independent contribution to QOL in the 3 patient groups. RESULTS: Quality of life and symptoms profiles were similar among patient groups. After controlling for potentially confounding variables, multiple regression revealed that depressive symptoms appeared to have a stronger relationship with QOL during the early 3-year course of the illness. In the period between 4 and 6 years of illness, negative symptoms were the most reliable predictors of QOL. After the 6-year course of illness, negative symptoms remained the most reliable predictors of QOL, together with severity of illness, whereas positive and depressive symptoms had a minor role. CONCLUSIONS: Despite similar QOL and symptoms profiles, these findings suggested that relationships among patterns of symptomatology and QOL change during the course of schizophrenia.

Efficacy and tolerability of pharmacotherapies for borderline personality disorder.

Borderline personality disorder is a pervasive pattern of instability of interpersonal relationships, affects and self-image, as well as marked impulsivity. Although psychotherapy is needed to attain lasting improvements in a patient's personality and overall functioning, practice guidelines state that pharmacotherapy is indicated to manage state symptoms and trait vulnerabilities. Three psychopathological dimensions are the main targets for pharmacotherapy of borderline personality disorder: affective dysregulation, impulsive-behavioural dyscontrol and cognitive-perceptual symptoms. Guidelines recommend the use of antidepressant agents and mood stabilizers for affective dysregulation and impulsive-behavioural dyscontrol, and antipsychotics for cognitive-perceptual symptoms. This review aims to report and discuss data from clinical trials, reviews and meta-analyses concerning drug efficacy and tolerability in the treatment of borderline personality disorder. Investigations that considered antidepressant agents mainly focused on SSRIs, which are recommended as first-line treatments for affective instability and impulse dyscontrol. Both open-label and randomized controlled studies have been performed, predominantly concerning the efficacy of fluoxetine and fluvoxamine. Other classes of antidepressants, such as TCAs and MAOIs, were investigated as alternative treatments for borderline personality disorder, but the risk of adverse effects and toxicity is a limitation to their use in clinical practice. Increasing amounts of data have recently been collected on the use of mood stabilizers to control mood instability and impulsivity in patients with borderline personality disorder. More substantial data were derived from controlled trials of valproate semisodium, although other drugs such as lithium, carbamazepine, oxcarbazepine and lamotrigine were tested with promising results. Several first-generation antipsychotics were studied in open-label and controlled trials, with good effects on behavioural dyscontrol and psychotic-like symptoms. Selection biases and heterogeneity of drugs and methods somewhat limited the value of these results. More recent investigations have examined atypical antipsychotics, with most of these studies being open-label trials with small sample sizes; however, a few controlled studies have been performed using olanzapine, showing improvements in impulsivity, anger and hostility. In conclusion, a large number of different drugs have been evaluated in the treatment of patients with borderline personality disorder. Initial findings are encouraging for many of these drugs. However, data need to be replicated in further controlled studies with head-to-head comparisons and long-term follow-ups. Many questions remain to be answered.