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Objective: Although there are some randomized controlled trials that highlight the positive role of family-focused treatment added to pharmacotherapy in bipolar disorder, no trials using contemporary methodologies have analyzed the specific effect of working with caregiver-only groups. The aim of this study was to assess the efficacy of a psychoeducational group intervention focused on caregivers of euthymic bipolar patients., Method: A total of 113 medicated euthymic bipolar outpatients who lived with their caregivers were randomized into an experimental and a control group. Caregivers in the experimental group received twelve 90-min group psychoeducation sessions focused on knowledge of bipolar disorder and training in coping skills. The patients did not attend the groups. Caregivers assigned to the control group did not receive any specific intervention. Patients were assessed monthly during both the intervention and the 12 months of follow-up. The primary outcome was time to any mood recurrence., Results: Psychoeducation group intervention focused on the caregivers of bipolar patients carried a reduction of the percentage of patients with any mood recurrence (chi2 = 6.53; p = 0.011) and longer relapse-free intervals (log-rank chi(2) = 4.04; p = 0.044). When different types of episodes were analyzed separately, the effect was significant for both the number of patients who experienced a hypomanic/manic recurrence (chi2 = 5.65; p = 0.017) and the time to such an episode (log-rank chi2 = 5.84; p = 0.015). The differences in preventing depressive and mixed episodes were not significant., Conclusions: A psychoeducation group intervention for the caregivers of bipolar patients is a useful adjunct to usual treatment for the patients in reducing the risk of recurrences, particularly mania and hypomania, in bipolar disorder.

Background: To evaluate the 12-week outcomes (effectiveness, tolerability, and patterns of medication use) of olanzapine (either in antimanic monotherapy or in combination with other antipsychotics, anticonvulsants, and/or lithium) in patients with bipolar mania or mixed mania., Method: EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 24-month prospective observational study of in- and outpatients with acute mania/mixed mania conducted in 14 European countries. Primary outcome measures included Clinical Global Impressions-Bipolar Disorder scale (overall, mania, and depression); 5-item Hamilton Depression Rating Scale; and Young Mania Rating Scale. Tolerability measures included a questionnaire to assess patients' symptomatic complaints., Results: Overall, 2004 patients received olanzapine (olanzapine monotherapy, n=673; olanzapine combination, n=1331). Concomitant therapy with antidepressants and/or anxiolytics was possible in both groups. The countries significantly differed in the use of olanzapine monotherapy versus olanzapine combination (p<.0001). Baseline-to-endpoint changes on the CGI-BP subscales, YMRS, and HAMD-5 were significant within both treatment groups (p<.0001). Olanzapine monotherapy was generally better tolerated than olanzapine combination, particularly with regard to sedation (12% vs 17%; p<.001), tremor (2% vs 5%; p<.001), and akathisia (3% vs 6%; p<.001)., Discussion: The acute-phase EMBLEM results suggest that in naturalistic settings, olanzapine (both as monotherapy and combination) may be effective in treating patients with bipolar mania. The use of olanzapine monotherapy or combination varies significantly across countries, but combination is generally the rule, rather than the exception.

Dual-function hybrid material U1 was designed for simultaneous chromofluorogenic detection and removal of Hg(2+) in an aqueous environment. Mesoporous material UVM-7 (MCM41 type) with homogeneously distributed pores of about 2-3 nm in size, a large specific surface area exceeding 1000 m(2) g(-1), and nanoscale particles was used as an inorganic support. The mesoporous solid is decorated with thiol groups that were treated with squaraine dye III to give a 2,4-bis(4-dialkylaminophenyl)-3-hydroxy-4-alkylsulfanylcyclobut-2-enone (APC) derivative that is covalently anchored to the inorganic silica matrix. The solid was characterised by various techniques including X-ray diffraction, transmission electron microscopy, Raman spectroscopy, and nitrogen adsorption. This hybrid solid is the chemodosimeter for Hg(2+) detection. Hg(2+) reacts with the APC fragment in U1 with release of the squaraine dye into the solution, which turns deep blue and fluoresces strongly. Naked-eye Hg(2+) detection is thus accomplished in an easy-to-use procedure. In contrast, U1 remains silent in the presence of other thiophilic transition metal ions, alkali and alkaline earth metal ions, or anions ubiquitously present in water such as chloride, carbonate, sulfate, and phosphate. Material U1 acts not only as chemodosimeter that signals the presence of Hg(2+) down to parts-per-billion concentrations, but at the same time is also an excellent adsorbent for the removal of mercury cations from aqueous solutions. The amount of adsorbed mercury ranges from 0.7 to 1.7 mmol g(-1), depending on the degree of functionalisation. In addition, hybrid material U1 can be regenerated for both sensing and removal purposes. As far as we know, U1 is the first example of a promising new class of polyfunctional hybrid supports that can be used as both remediation and alarm systems by selective signalling and removal of target species of environmental importance. Model compounds based on silica gel (G1), fumed silica (F1), and micrometre-sized MCM-41 scaffolds (M1) were also prepared and studied for comparative purposes.

Background: Numerous studies have documented high rates of functional impairment among bipolar disorder (BD) patients, even during phases of remission. However, the majority of the available instruments used to assess functioning have focused on global measures of functional recovery rather than specific domains of psychosocial functioning. In this context, the Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the main functioning problems experienced by psychiatric patients, particularly bipolar patients. It comprises 24 items that assess impairment or disability in six specific areas of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time., Methods: 101 patients with DSM-IV TR bipolar disorder and 61 healthy controls were assessed in the Bipolar Disorder Program, Hospital Clinic of Barcelona. The psychometric properties of FAST (feasibility, internal consistency, concurrent validity, discriminant validity (euthymic vs acute patients), factorial analyses, and test-retest reliability) were analysed., Results: The internal consistency obtained was very high with a Cronbach's alpha of 0.909. A highly significant negative correlation with GAF was obtained (r = -0.903; p < 0.001) pointing to a reasonable degree of concurrent validity. Test-retest reliability analysis showed a strong correlation between the two measures carried out one week apart (ICC = 0.98; p < 0.001). The total FAST scores were lower in euthymic (18.55 +/- 13.19; F = 35.43; p < 0.001) patients, as compared with manic (40.44 +/- 9.15) and depressive patients (43.21 +/- 13.34)., Conclusion: The FAST showed strong psychometrics properties and was able to detect differences between euthymic and acute BD patients. In addition, it is a short (6 minutes) simple interview-administered instrument, which is easy to apply and requires only a short period of time for its application.

Rationale: There are very few data as to the social and occupational adaptation of patients with bipolar disorder in Spain and even less is known about the resource use they generate., Objective: To determine the functional status and healthcare resource use of the Spanish sample of the pan European EMBLEM (European Mania in Bipolar Longotudinal Evaluation of Medication) study of bipolar patients in manic or mixed phase., Method: The EMBLEM study recruited 3536 patients, 312 of whom (8.82%) were enrolled in Spain. Patients had to be adults with a diagnosis of bipolar disorder who were initiating at the discretion of their treating psychiatrist oral treatment for an acute manic phase. They were evaluated using the Spanish versions of rating scales for the severity of mania (Young Mania Rating Scale), bipolar disorder (CGI BD) for mania, depression and hallucinations delusions, and depression (HAMD 5 item version of the Hamilton Scale); the Life Chart Method (LCM) and 2 items of the SLICE of LIFE were used to evaluate functioning. Information was collected on healthcare resource utilization during the preceding year., Results: Sixty three percent of the patients presented with moderate to very severe work related difficulties in the year preceding his her manic episode. Forty percent of the patients failed to comply either totally or partly with their prescribed treatment. Subjects required an average of 1.5 hospitalizations during the year prior to enrollment, with a mean stay of approximately 10 days, and between 7 and 8 outpatient visits per year.

Background: Persistent impairments in neurocognitive function have been described in bipolar disorder., Aims: To compare the cognitive performance of patients with bipolar II disorder with that of patients with bipolar I disorder and a healthy control group., Method: The study included 71 euthymic patients with bipolar disorder (38 bipolar I, 33 bipolar II), who were compared on clinical and neuropsychological variables (e.g. executive function, attention, verbal and visual memory) and contrasted with 35 healthy controls on cognitive performance., Results: Compared with controls, both bipolar groups showed significant deficits in most cognitive tasks including working memory (DigitSpan Backwards, P=0.002) and attention (DigitSpan Forwards, P=0.005; Trail Making Test, P=0.001). Those with type II disorders had an intermediate level of performance between the bipolar I group and the control group in verbal memory (P<0.005) and executive functions (Stroop interference task, P=0.020)., Conclusions: Cognitive impairment exists in both subtypes of bipolar disorder, although more so in the bipolar I group. The best predictors of poor psychosocial functioning in bipolar II disorder were subclinical depressive symptoms, early onset of illness and poor performance on a measure related to executive function.

Pyrylium-containing mesoporous materials have been used for the chromo-fluorogenic sensing of biogenic amines in an aqueous environment.

Despite the increasing use of lamotrigine (LTG) in bipolar disorder, little is known about its impact on cognition in bipolar patients. Therefore, we have evaluated 33 bipolar I and II patients on cognitive measures (verbal memory, attention, executive functions) while receiving either LTG (n = 15) or another anticonvulsant (carbamazepine or valproate; n = 18). Patients receiving LTG were generally diagnosed as having bipolar II disorder, had experienced more depressive episodes but a lesser number of hospitalizations, and had better performance than the patients receiving carbamazepine or valproate on the verbal fluency task. A moderate effect size also suggests that both groups may differ on the immediate verbal memory test (California Verbal Learning Test). These preliminary results suggest a safer neurocognitive profile of LTG on bipolar patients, as compared with other anticonvulsants.

A versatile procedure for anchoring dyes into the pores of multidimensional zeolites by including organic dye precursors in the synthesis gel has been developed. To prove the concept, an aniline-functionalised zeolite Beta was obtained by reaction of triethylorthosilicate (TEOS), tetraethylammonium hydroxide, and N-methyl,N-(propyl-3-trimethoxysilyl)aniline (MPTMSA) in the presence of HF. Further extraction of the structure-directing agents resulted in a highly crystalline, white, functionalised zeolite Beta containing anchored aniline groups. Similar organic functionalised molecular sieves (OFMS) have been explored as novel catalysts, but, as far as we know, OFMS have never been used as precursors for dye-immobilisation or to design new solid-based host systems for selective molecular sensing processes as is reported here. In a second step the solids containing dyes were prepared by reaction of the hybrid material with the appropriate reactives to obtain tricyanovinylbenzene, triphenylpyrylium, azoic, and squaraine derivatives. All these reactions are straightforward and involve electrophilic aromatic substitution or diazotisation reactions at the electron-rich aniline ring. The final dye-functionalised solid materials were isolated by simple filtration and washing procedures and have been characterised by a number of techniques. In all cases the Beta structure of the solid remains unaltered. Among the large number of areas where dye-containing zeolites might be of importance, we were interested in testing their unconventional use as heterosupramolecular hosts in chromogenic protocols. To check their potential use as chemosensors, microporous solids with anchored triphenylpyrilium and squaraine dyes were selected and used as sensors for the chromogenic discrimination of amines. It was found that the response of both solids to amines was basically governed by the three-dimensional (3D) solid architecture that tuned the intrinsic unselective reactivity of the pyrylium dye. By using new solid-state supramolecular chemistry protocols we believe that these, and similar future dye-zeolite hosts, might be promising new sensor materials allowing the visible discrimination of selected target guests by size and/or polarity within families or closely related molecules.

Objective: To conduct the first randomized, controlled trial assessing the prophylactic efficacy of gabapentin in bipolar disorder., Method: We conducted a 1-year, double-blind, randomized, comparative, placebo-controlled, parallel-group, multicenter study. As this was a pure prophylactic trial, only euthymic bipolar I and II patients (DSM-IV) were randomly assigned in a 1:1 ratio to gabapentin (N = 13) or placebo (N = 12) added to the current treatment (lithium, valproate, carbamazepine, or any combination but not antipsychotics or antidepressants). Subjects participated in the study for 12 months. The primary efficacy parameter was the Clinical Global Impressions scale for Bipolar Illness, Modified (CGI-BP-M), which was assessed at all visits. Other assessments were the Young Mania Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Pittsburgh Sleep Quality Index (PSQI), and the systematic collection of reported adverse events. Data were collected from May 1999 to February 2004., Results: The change from baseline to month 12 in mean CGI-BP-M scores between groups was statistically significant (p = .0046). Mean score change from baseline to endpoint in the gabapentin group was -2.1, and the mean score change in the placebo group was -0.6. No emerging manic or depressive symptoms were seen in either group as measured with the YMRS, HAM-D, HAM-A, and PSQI. In the PSQI-6 subscale (use of sleeping medication), the mean score change at month 12 in the gabapentin group was 0.9, and the mean score change in the placebo group was 0.05 (p = .0267). Overall, gabapentin was well tolerated., Conclusion: This small, randomized clinical trial comparing the prophylactic efficacy of adjunctive gabapentin to placebo suggests that, despite lack of acute efficacy, treatment with gabapentin might provide some benefit on the long-term outcome of bipolar disorder.

Background: Amisulpride is a selective D(2)-D(3) antagonist that has been reported to be effective in the treatment of schizophrenia and major depressive disorder. However, no prospective study to date has assessed the effectiveness and tolerability of this compound in mania., Method: Twenty DSM-IV-defined acutely ill manic bipolar patients with a Young Mania Rating Scale (YMRS) score of 20 or more entered this open, prospective, 6-week study. Assessments included the YMRS, the Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions Scale for Bipolar Disorder, Modified (CGI-BP-M), and the systematic report of adverse events. Amisulpride was added to other medications, but other antipsychotics were not allowed., Results: Fourteen patients (70%) completed the study. Using last-observation-carried-forward (LOCF) analyses, amisulpride produced significant improvements on the YMRS (p = .0001), the HAM-D (p < .0141), and the overall (p = .0003), mania (p = .0001), and depression (p = .0268) subscales of the CGI-BP-M. The most common side effect was sedation (N = 5, 25%), but there were also some extrapyramidal symptoms, galactorrhea, insomnia, and agitation. The mean amisulpride dose was 680 mg/day (LOCF) and 786 mg/day in completers., Conclusions: This first prospective study on amisulpride in the treatment of mania suggests that, despite the limitations of the open, observational design and small sample size, amisulpride may be effective and reasonably safe in the treatment of bipolar mania. D(2) and D(3) antagonism may be involved in the mechanisms of the therapeutic response to antipsychotics in mania.

Background: The co-occurrence of personality and bipolar disorders is quite common. Bipolar patients with personality disorders have been described as having poorer outcome than 'pure' bipolar patients. However, from a combined-approach point of view, a little has been done to improve the course of these patients. Psychoeducation has shown its efficacy in the prevention of relapses in the bipolar population but, to date, no data is available on its efficacy in the management of bipolar patients with personality disorders., Method: The present study shows a subanalysis from a single-blind randomized prospective clinical trial on the efficacy of group psychoeducation in bipolar I patients. Bipolar patients fulfilling DSM-IV criteria for any personality disorder were randomized to either psychoeducational treatment or a non-structured intervention. There were 22 patients in the control group and 15 in the psychoeducation group. All patients received naturalistic pharmacological treatment as well. The follow-up phase comprised 2 years where all patients continued receiving naturalistic treatment without psychological intervention and were assessed monthly for several outcome measures., Results: At the end of the follow-up phase (2 years), a 100% of control group patients fulfilled criteria for recurrence versus a 67% in the psychoeducation group (p < 0.005). Patients included in the psychoeducation group had a higher time-to-relapse and a significantly lower mean number of total, manic and depressive relapses. No significant differences regarding the number of patients who required hospitalization were found but the mean duration of days spent in the hospitalization room was significantly higher for the patients included in the control group., Conclusion: Psychoeducation may be a useful intervention for bipolar patients with comorbid personality disorders. Further studies should address the efficacy of specifically tailored interventions for this common type of patients.

Olanzapine is an effective drug for the long-term treatment of bipolar disorder but is associated with burdensome weight gain. Topiramate is a novel anticonvulsant that may induce weight loss in some patients. This is the first study to address the long-term efficacy and impact on weight of the combination of olanzapine and topiramate in bipolar patients. Twenty-six Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar spectrum patients received olanzapine plus topiramate cotherapy for treatment of their manic (n = 14), hypomanic (n = 6), depressive (n = 2), and mixed (n = 1) symptoms for 1 year. Three rapid cycling patients were also enrolled despite being euthymic. Efficacy was assessed with the Young Mania Rating Scale, the Hamilton Depression Rating Scale, and the Modified Clinical Global Impressions for Bipolar Disorder. Weight, body mass index, and side effects were collected at every visit. Thirteen (50%) patients completed the 1-year follow-up. By intent-to-treat, patients significantly improved from baseline in Young Mania Rating Scale scores (P < 0.0001), Hamilton Depression Rating Scale (P < 0.05), and Modified Clinical Global Impressions for Bipolar Disorder subscales (mania P < 0.0001, depression P < 0.05, overall P < 0.0001). Most patients gained weight during the first month of combined treatment (mean weight gain 0.7 +/- 0.6 kg), but at the 12-month endpoint, the mean weight change was -0.5 +/- 1.1 kg. The combination of olanzapine and topiramate was efficacious for the long-term treatment of bipolar patients and appeared to carry some benefits for controlling weight gain. Given the limitations of the open, uncontrolled design, further trials are warranted with this combination., (Copyright 2004 Lippincott Williams and Wilkins)

Objective: The study aims were to address neuropsychological functioning across different states of bipolar illness and to determine relationships among clinical features, neuropsychological performance, and psychosocial functioning., Method: Several domains of cognitive function were examined in 30 depressed bipolar patients (DSM-IV criteria for major depression, Hamilton Depression Rating Scale score > or = 17), 34 manic or hypomanic bipolar patients (DSM-IV criteria for manic or hypomanic episode, Young Mania Rating Scale score > or = 12), and 44 euthymic bipolar patients (6 months of remission, Hamilton depression scale score < or = 8, and Young Mania Rating Scale score < or = 6). The comparison group consisted of 30 healthy subjects without history of neurological or psychiatric disorders. A neuropsychological battery assessed executive function, attention, and verbal and visual memory., Results: The three groups showed cognitive dysfunction in verbal memory and frontal executive tasks in relation to the comparison group. Low neuropsychological performance was associated with poor functional outcome. Impairment of verbal memory was related to the duration of illness and the numbers of previous manic episodes, hospitalizations, and suicide attempts., Conclusions: A poorer performance was observed in all bipolar groups regarding executive function and verbal memory in relation to the healthy comparison subjects. These cognitive difficulties, especially related to verbal memory, may help explain the impairment regarding daily functioning, even during remission. Further studies should focus on testing, whether optimizing prophylactic pharmacological treatment and psychoeducation might reduce cognitive impairment, and whether bipolar patients would benefit from neuropsychological rehabilitation in order to reduce the impact of cognitive impairment in their overall functioning.

Background: The aim of this study was to assess the effectiveness and safety of risperidone monotherapy for acute and continuation treatment of mania., Method: Ninety-six DSM-IV acutely manic bipolar patients with a Young mania rating score (YMRS) of 20 or more entered this open, multicentre, 6-month study. Efficacy was assessed with the YMRS, the positive and negative syndrome scale (PANSS) and the clinical global impressions scale (CGI). Safety was assessed with the UKU side effect rating scale and with the Hamilton depression rating scale, for the assessment of a switch to depression., Results: 80 patients (83.3%) completed the study. Using the last-observation-carried-forward analysis, risperidone produced highly significant improvements (p<0.0001) on the all efficacy measures from weeks 1 (YMRS) and 4 (PANSS and CGI) onwards, for a 6-month period. There was a significant increase in extrapyramidal side-effects by week 4 (p=0.015) and a significant decrease at the 6-month endpoint (p=0.027). Risperidone did not induce depressive symptoms, as mean HDRS scores actually improved (p<0.0001), and exacerbation of mania was rare (n=4, 4.2%). The mean dose of risperidone was 4.2 mg/day., Conclusion: Monotherapy with risperidone is effective and well tolerated in acute and continuation treatment of mania. The results should be confirmed in randomized, double-blind clinical trials., (Copyright 2004 John Wiley & Sons, Ltd.)

We evaluated the efficacy and safety of adjunctive topiramate in bipolar II patients who were either treatment-resistant to or unable to tolerate lithium, carbamazepine or valproate. Nineteen DSM-IV bipolar II patients received increasing doses of open-label topiramate as adjunctive therapy for their hypomanic (n=15) or depressive (n=4) symptoms. Sixteen patients completed the 12-week follow-up. There were highly significant improvements in YMRS, HDRS and CGI-BP-M scores (p=0.0001). Of the fifteen hypomanic patients, eight (53%) were rated as responders to topiramate (50% reduction in YMRS scores), and five (33%) met criteria for remission (YMRS score pound 8). Two of the four patients with a depressive episode at study entry (50%) were rated as responders (50% reduction in HDRS score), and one (25%) achieved remission (HDRS score pound 6). Topiramate was generally well tolerated. One third of the patients experienced weight loss. These preliminary results suggest that adjunctive topiramate may be useful in treating bipolar II disorder.

Background: The safety and efficacy of the combination of risperidone and topiramate in the long-term treatment of mania were assessed in a 12-month, multicenter open study., Method: Subjects (N = 58) who met DSM-IV criteria for bipolar disorder and for a manic episode received both risperidone and topiramate for the treatment of their manic symptoms. Patients with mixed episodes were excluded. Risperidone could be discontinued at any point, but patients had to be on topiramate therapy for at least 12 months to be considered completers. Efficacy was assessed with the Young Mania Rating Scale (YMRS) and a modified version of the Clinical Global Impressions for Bipolar Disorder (CGI-BP-M). Safety was assessed with systematic collection of side effect data, weight, and the Hamilton Rating Scale for Depression (HAM-D) scores, to address the risk of switch into depression., Results: 41 patients (70.7%) completed the study. There was a significant improvement on the YMRS (p <.001) and the CGI-BP-M subscales for manic symptoms (p <.005) and long-term outcome (p <.005) from week 2 onward. Relapse rates were significantly lower during the 12-month study period compared to the precedent year (p <.0001). There was no increase in depressive symptoms as measured by the HAM-D. 37 patients (63.8 %) experienced at least 1 adverse event, the most frequent of which was somnolence (N = 7, 12.1%). At endpoint, the patients' mean weight had decreased an average of 1.1 +/- 0.4 kg., Conclusion: Despite the limitations inherent to the open design, this naturalistic study suggests that the combination of risperidone and topiramate may be a valuable option for the short- and long-term treatment of mania.

Background: Studies on individual psychotherapy indicate that some interventions may reduce the number of recurrences in bipolar patients. However, there has been a lack of structured, well-designed, blinded, controlled studies demonstrating the efficacy of group psychoeducation to prevent recurrences in patients with bipolar I and II disorder., Methods: One hundred twenty bipolar I and II outpatients in remission (Young Mania Rating Scale score <6, Hamilton Depression Rating Scale-17 score <8) for at least 6 months prior to inclusion in the study, who were receiving standard pharmacologic treatment, were included in a controlled trial. Subjects were matched for age and sex and randomized to receive, in addition to standard psychiatric care, 21 sessions of group psychoeducation or 21 sessions of nonstructured group meetings. Subjects were assessed monthly during the 21-week treatment period and throughout the 2-year follow-up., Results: Group psychoeducation significantly reduced the number of relapsed patients and the number of recurrences per patient, and increased the time to depressive, manic, hypomanic, and mixed recurrences. The number and length of hospitalizations per patient were also lower in patients who received psychoeducation., Conclusion: Group psychoeducation is an efficacious intervention to prevent recurrence in pharmacologically treated patients with bipolar I and II disorder.

Introduction: This study analyzes the effectiveness and safety of lamotrigine in the treatment of bipolar II disorder. Patients and methods. Seventeen patients with DSM-IV bipolar II disorder with a history of poor response to lithium or other mood-stabilizers gave their consent to be treated with lamotrigine. Th ey we re followed-up for 6 months and assessed with the Young Mania Scale (YMRS), Hamilton Depression Rating Scale (HDRS-17) and the modified version of the Global Clinic Impresion Scale for Bipolar Disorder ( CG I-BP-M)., Results: Twelve patients completed the study. Three patients dropped out due to side effects (two because of mild rash, which vanished after treatment was discontinued and one because of vomiting) and two due to lack of efficacy. The mean dose of lamotrigine for patients completing the study was 202.1 64.4 mg/day. There was a significant improvement in HDRS-17 scores (p= 0.004) and the depressive (p=0.002) and overall (p= 0.002) subscales of the CGI-BP-M., Conclusions: This study confirms previous findings concerning the antidepressant profile of lamotrigine and its potential effectiveness in bipolar II disorder.

Objectives: The aim of this study was to assess the prevalence of infection by HCV, HBV, HDV and HIV and their biological and histopathological patterns in 104 intravenous drug users., Methods and Results: Seventy-five patients (72%) had anti-HCV antibodies. Transmission was rapid because 33% of those who had been drug users for 6 months or less had anti-HCV antibodies. The contamination rate was very high because 90% of those who had been drug users for 2 years or less had anti-HCV antibodies. Thirty-four (33%) had an HBV marker, and 6 were HBs Ag carriers. None of the patients had anti-HDV antibodies. Only one patient had anti-HIV antibodies. Twenty-five anti-HCV antibody positive drug users underwent liver biopsy. Seven (28%) had normal ALAT levels and 18 (72%) had permanently or intermittently elevated ALAT levels. The mean histological activity on the Knodell index was 4.1 (range: 1-8)., Conclusions: This study indicates that contamination by HCV is almost inevitable after 2 years of intravenous drug use. The low prevalence of HBV, HDV, and HIV infection might be explained by a low endemic state of these viruses in our area.