[Treatment of obsessive-compulsive disorder: drugs, psychotherapy or combined treatments?]. / Il trattamento del disturbo ossessivo-compulsivo: farmaci, psicoterapia o trattamento integrato?

Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, little is known concerning whether combining both treatments ab initio is more effective than either monotherapy alone. A review of the available literature, which is poor, shows that combining ab initio CBT and SRI has not been found to be clearly superior of either therapy alone, except for patients with severe depression (who could be treated effectively with pharmacotherapy alone) and for children and adolescents. Another promising area of research is combined sequential treatment, that is the addition of CBT in subjects not responding to SRIs alone. More research is clearly needed in order to achieve a personalized treatment plan for every OCD patient.

Effects of maintenance lithium treatment on serum parathyroid hormone and calcium levels: a retrospective longitudinal naturalistic study.

OBJECTIVE: The aim of this retrospective longitudinal naturalistic study was to evaluate the effects of maintenance lithium treatment on parathyroid hormone (PTH) and calcium levels. METHODS: A retrospective longitudinal naturalistic study design was used. Data were collected from the database of a tertiary psychiatric center covering the years 2010-2014. Included were bipolar patients who had never been exposed to lithium and had lithium started, and who had PTH, and total and ionized calcium levels available before and during lithium treatment. Paired t-tests were used to analyze changes in PTH and calcium levels. Linear regressions were performed, with mean lithium level and duration of lithium exposure as independent variables and change in PTH levels as dependent variable. RESULTS: A total 31 patients were included. The mean duration of lithium treatment was 18.6±11.4 months. PTH levels significantly increased during lithium treatment (+13.55±14.20 pg/mL); the rate of hyperparathyroidism was 12.9%. Neither total nor ionized calcium increased from baseline to follow-up; none of our patients developed hypercalcemia. Linear regressions analyses did not show an effect of duration of lithium exposure or mean lithium level on PTH levels. CONCLUSION: Lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation, calcium and PTH should be added.

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.

Combined treatment of borderline personality disorder with interpersonal psychotherapy and pharmacotherapy: predictors of response.

Borderline personality disorder (BPD) is characterized by affective instability, impulsive behaviors, and disturbed interpersonal relationships. A previous study of our group found that combined therapy with interpersonal psychotherapy adapted to BPD (IPT-BPD) and fluoxetine was superior to single pharmacotherapy in BPD patients. The aim of the present study was to examine what clinical factors predicted response to combined therapy in patients evaluated in the previous efficacy study. The subgroup of 27 patients allocated to combined therapy was analyzed. Patients were treated for 32 weeks with fluoxetine 20-40 mg/day plus IPT-BPD. Patients were assessed at baseline and week 32 with an interview for demographic and clinical variables, CGI-S, HDRS, HARS, SOFAS, BPDSI, and SAT-P. Statistical analysis was performed with multiple regression. The difference of CGI-S score between baseline and week 32 (∆CGI-S) was the dependent variable. Factors significantly and independently related to ∆CGI-S were the BPDSI total score and the items abandonment, affective instability, and identity. Patients with more severe BPD psychopathology and with a higher degree of core symptoms such as fear of abandonment, affective instability, and identity disturbance have a better chance to improve with combined therapy with fluoxetine and IPT-BPD.

Increased uric acid levels in bipolar disorder subjects during different phases of illness.

BACKGROUND: Recent evidence indicates the possible involvement of adenosine and the purinergic system in the pathophysiology of bipolar disorder (BD). The aim of this study is to compare serum uric acid (UA) levels in a large group of BD patients (in mania, depression and euthymia) vs. a control group of patients with different psychiatric disorders. METHODS: 150 BD (SCID-I; DSM-IV) patients were compared to 150 age- and gender-matched subjects with MDD, OCD, or Schizophrenia. Mean serum UA values were compared with the ANOVA, with Bonferroni's post-hoc tests. RESULTS: Mean serum UA levels (5.06 ± 1.45 vs. 4.17 ± 1.05 mg/dL) and rates of hyperuricaemia (30.7% vs. 6.7%) were significantly higher in the bipolar than in the control group. No differences were detected between bipolars in different phases of illness, with all three groups (manic, depressive and euthymic bipolars) showing significantly higher UA levels as compared to controls. No correlations were found between UA levels and YMRS or HAM-D scores. Mean UA levels were also higher in bipolars never exposed to mood stabilizers vs. controls (5.08 ± 1.43 vs. 4.17 ± 1.05 mg/dL), with no differences compared to other bipolars. LIMITATIONS: Our study suffers from the lack of a healthy comparison group; moreover, longitudinal data are missing. CONCLUSIONS: Our study provides further evidence of a purinergic dysfunction associated with BD, in all phases of the illness. It is possible that increased UA levels are a trait marker of higher vulnerability to bipolar disorder, and are even more increased during mania (mostly in the first manic episode of drug-naïve patients).

[Interpersonal psychotherapy: a model of intervention for borderline personality disorder]. / La psicoterapia interpersonale: un modello di intervento per il disturbo borderline di personalità

Interpersonal psychotherapy (IPT) was proposed in 1984 by Klerman and colleagues. It is a time-limited psychotherapy (12-16 sessions), diagnosis-focused, based on a medical model. Psychiatric symptoms develop in an interpersonal context. Acting on this context, it is possible to induce remission and prevent subsequent recurrences. IPT is aimed at the resolution of the interpersonal crisis, improving social functioning and psychiatric symptoms. At first, it was addressed to treat major depression, not psychotic or bipolar. Later IPT has been applied to a growing number of psychiatric disorders, because of their frequent and remarkable interpersonal dimension. However, specific adaptations of IPT have been required to consider the different clinical characteristics of these disorders. To date, among Axis II disorders, only borderline personality disorder (BPD) has been a target of IPT. The frequent comorbidity with mood disorders and the relational problems due to BPD core symptoms are the main reasons for the proposal of an adapted model of IPT: the IPT-BPD. This model has a longer duration (34 sessions), and is designed to deal with chronicity of BPD, poor therapeutic alliance and the high risk of suicide and self-harm of these patients. Although studies aimed to test the efficacy of IPT in borderline patients were performed with promising results, replication of findings in larger samples is required.

Negative symptoms and everyday functioning in schizophrenia: a cross-sectional study in a real world-setting.

Negative symptoms have been suggested to have a greater impact on real-world functioning in schizophrenia than other symptoms. We aimed to examine the relationship of specific negative symptoms components ("expressive deficits" - DE - which include alogia and blunted affect, and "avolition" - AA - which includes amotivation, anhedonia, and asociality), with separate domains of real-world outcomes (the Personal and Social Performance Scale - PSP - and selected items of the Heinrichs Quality of Life Scale - QLS - that did not overlap with negative symptoms) and two functional milestones (recent employment and marriage). Regression analyses were performed to identify the determinants of QLS and PSP scores and of the two milestones, in 92 consecutive outpatients with stable schizophrenia. AA was the strongest predictor of QLS interpersonal relations and social network (IRSN), PSP total score and the first three PSP domains. The variance explained ranged from 36% for PSP self care to 54% for the PSP personal and social relationships. Moreover, higher scores in AA were significant predictors of the single status. DE does not appear to have an impact at real-world functional performance. Taken together, our analysis indicates a relatively specific set of relationships between the AA subdomain and aspects of real-world functioning in schizophrenia. These findings, if confirmed, could have important implications for research, diagnostics and treatment: in fact our results would suggest that AA and DE should be analyzed as separate and distinct domains to be rated and treated individually.

[Lithium treatment and potential long-term side effects: a systematic review of the literature]. / Trattamento con litio e potenziali effetti collaterali a lungo termine: una revisione sistematica della letteratura.

INTRODUCTION AND AIM: Lithium is recommended by all treatment guidelines for bipolar disorder (BD) as a first-line maintenance treatment. However, the potential side effects and risks associated with long-term lithium use may at times make the implementation of these recommendations in daily practice challenging. The aim of the study is to review available literature on potential long-term side effects of lithium. MATERIALS AND METHODS: A PubMed/Medline search was performed on papers dealing with long-term treatment with lithium and side effects. Articles published from January 1980 to February 2013 were selected. RESULTS: Long-term lithium treatment is associated with a reduced urinary concentrating ability, with subsequent polyuria and polidypsia and nephrogenic diabetes insipidus (in 10-40% of patients). Lithium also reduces glomerular filtration rate, and increases risk of renal failure, although the absolute risk is small (0.5% of patients). Lithium treatment is associated with significant higher TSH levels, with a 6-fold greater risk of hypothyroidism in lithium-treated than in control subjects. Less known is the increase of PTH and calcium levels induced by lithium. An exacerbation of psoriasis is also frequently associated with lithium treatment. CONCLUSIONS: Lithium remains a fundamental tool for the treatment of BD. Clinicians should know potential side effects (renal, endocrine and dermatological) associated with long-term treatment with lithium, for a correct management of the patient. A specialist referral is often necessary; the question is how to deal with long-term side effects more than whether or not withdrawing lithium. This decision should remain a psychiatrist's competence.

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.

Efficacy of omega-3 fatty acids in the treatment of borderline personality disorder: a study of the association with valproic acid.

Omega-3 fatty acids have received increasing interest due to their effects in stabilizing plasmatic membranes and regulating cell signaling. The efficacy of omega-3 fatty acids in psychiatric disorders, in particular mood disorders, has been studied. There have been two trials on eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) in the treatment of borderline personality disorder (BPD). The present 12-week controlled trial aimed to assess the efficacy of the association of EPA and DHA with valproic acid, compared to single valproic acid, in 43 consecutive BPD outpatients. Participants were evaluated at baseline and after 12 weeks with: Clinical Global Impression - Severity (CGI-S), Hamilton Scales for depression and anxiety (HAM-D, HAM-A), Social and Occupational Functioning Assessment Scale (SOFAS), borderline personality disorder severity index (BPDSI), Barratt Impulsiveness Scale - version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self-Harm Inventory (SHI) and Dosage Record Treatment Emergent Symptom Scale (DOTES).

Lithium-associated hyperparathyroidism and hypercalcaemia: a case-control cross-sectional study.

BACKGROUND: Lithium is recommended as a first-line treatment for Bipolar Disorder (BD). Thyroid and renal alterations are well known lithium side-effects, while effects on parathyroids are less studied. The aim of this case-control cross-sectional study is to compare parathyroid hormone (PTH) and calcium levels in lithium-exposed bipolar patients and in subjects who had never been exposed to lithium. METHODS: 112 BD patients were enrolled, 58 on lithium since at least 1 month (mean exposure 60.8 ± 74.8 months) and 54 in the control group. Blood exams included complete blood count, PTH, total and ionized calcium, TSH, T3 and T4, creatinine, urea, sodium and potassium, and lithium serum levels. The Student's t-test and the Pearson's Chi-square test were used for bivariate analyses. A linear regression model was used to analyze the relationship between the duration of exposure to lithium and PTH and calcium levels. RESULTS: PTH and ionized calcium levels were significantly higher in lithium-exposed patients; the proportions of subjects with hyperparathyroidism (8.6%) and hypercalcaemia (24.1%) were significantly greater in lithium-exposed patients. The linear regression analyses showed a significant effect of exposure to lithium in months on ionized calcium levels but not on PTH levels. LIMITATIONS: Given the cross-sectional design of the study we could not identify the exact time of occurrence of hyperparathyroidism. CONCLUSIONS: Our results indicate that lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation and during long-term lithium maintenance, calcium (and eventually PTH) should be added.

[Brain stimulation therapies for treatment-resistant depression]. / Tecniche di stimolazione cerebrale nel trattamento della depressione resistente.

Treatment-resistant depression (TRD) is a major public health problem, affecting patients, their close relatives, and the society as a whole. Despite recent developments in psychopharmacotherapy, more than 50% of depressed patients fail to reach complete remission even when adequately treated. Neurostimulation therapies are an open field in research for the treatment of TRD, involving the delivery of physical interventions either through electric current or a magnetic field to target selective or generalized brain regions. In this paper we review evidences for four brain-stimulation therapies, i.e. electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS), and we enlighten several new approaches regarding ECT, rTMS and epidural cortical stimulation (EpCS). ECT is the form of neurostimulation with the most extensive evidence, rTMS and VNS have a much smaller evidence base. There is emerging evidence that DBS is effective for otherwise TRD, but this is still an investigational approach. Other approaches are anecdotal reports. ECT and rTMS can be considered as a first-line treatment under specific circumstances. Evidence supporting VNS is less consistent and DBS remains an investigational treatment. Other techniques are promising, but double-blind studies are warranted to evaluate these new approaches to TRD.

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.

Prosody recognition and audiovisual emotion matching in schizophrenia: the contribution of cognition and psychopathology.

This study aimed to evaluate the ability to decode emotion in the auditory and audiovisual modality in a group of patients with schizophrenia, and to explore the role of cognition and psychopathology in affecting these emotion recognition abilities. Ninety-four outpatients in a stable phase and 51 healthy subjects were recruited. Patients were assessed through a psychiatric evaluation and a wide neuropsychological battery. All subjects completed the comprehensive affect testing system (CATS), a group of computerized tests designed to evaluate emotion perception abilities. With respect to the controls, patients were not impaired in the CATS tasks involving discrimination of nonemotional prosody, naming of emotional stimuli expressed by voice and judging the emotional content of a sentence, whereas they showed a specific impairment in decoding emotion in a conflicting auditory condition and in the multichannel modality. Prosody impairment was affected by executive functions, attention and negative symptoms, while deficit in multisensory emotion recognition was affected by executive functions and negative symptoms. These emotion recognition deficits, rather than being associated purely with emotion perception disturbances in schizophrenia, are affected by core symptoms of the illness.

Metabolic syndrome and obsessive-compulsive disorder: a naturalistic Italian study.

OBJECTIVE: The increased risk for metabolic syndrome (MetS) in individuals with schizophrenia and bipolar disorder has been documented. No study examined MetS in patients with obsessive-compulsive disorder (OCD), despite the fact that a great proportion of them are treated with antipsychotic addition. The aim of our study was to investigate the prevalence and the sociodemographic and clinical correlates of MetS in an Italian sample of patients with OCD. METHOD: Subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, OCD and a Yale-Brown Obsessive-Compulsive Scale score ≥ 16 were included. Sociodemographic and clinical characteristics, current and lifetime pharmacological treatments, lifestyle information, and comorbidity for cardiovascular diseases and diabetes were collected. MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III modified criteria. RESULTS: We enrolled 104 patients with OCD. MetS was present in 21.2% (95% confidence interval: 13.7%-30.3%) of the sample. Abdominal obesity was present in 36.5%, hypertension in 42.3%, high triglycerides in 23.1%, low high-density lipoprotein cholesterol levels in 22.1% and fasting hyperglycemia in 4.8% of the sample. MetS was associated with cigarette smoking (duration of cigarette smoking), absence of physical activity, a higher body mass index and a greater proportion of obesity. Among pharmacological treatments, MetS was associated with the duration of the exposure (lifetime) to antipsychotics. CONCLUSIONS: This is the first study that examined the prevalence and correlates of MetS in a sample of patients with OCD. Our cross-sectional evaluation found a prevalence of MetS higher than those reported in the Italian general population, although the confidence interval encompasses the general population estimate reported. Patients with OCD on antipsychotic treatment are particularly at risk for MetS and should be carefully monitored for metabolic abnormalities and cardiovascular complications.

[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.

Rethinking the role of long-acting atypical antipsychotics in the community setting.

Schizophrenia is a relapsing and evolving condition, which requires treatment continuity. Increasing evidence shows that antipsychotic discontinuation is associated with relapse in most patients, and that early interventions have a positive impact on long-term outcomes. Poor adherence to antipsychotics is a major factor in the treatment of schizophrenia and a relevant risk factor for relapse. Considerable effort has been made toward improving adherence, including the development of long-acting injectable (LAI) antipsychotics. LAIs have traditionally been reserved for patients with repeated nonadherence; currently, several misconceptions prevent their more widespread use. The recent introduction of LAI formulations of atypical antipsychotics and the encouraging results in terms of the reduction in relapse rates and avoidance of hospitalization warrant a reassessment of the role of LAIs in the management of schizophrenia. This paper presents the position of a panel of nine Italian schizophrenia experts on the use of novel LAI medications, with a focus on community-based services, the prevailing setting of schizophrenia treatment in Italy. The need to change the attitude toward LAIs--no longer a treatment of last resort, but a component of multimodal strategies leading patients to remission and rehabilitation--is emphasized. The paper also presents recommendations for LAI atypical antipsychotic use in the community setting.

[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.