The impact of depressive symptoms in stability phases on bipolar disorder outpatients’ functional aspects could be important to determine if they are impaired and their treatment requirements. Our aim is to describe functional impact and social adjustment in stable BD, regarding present subclinical depressive symptoms.

Crossectional, prospective, 16-week study of a cohort of 761 BD patients included by 94 investigators. Clinical stability was assessed at baseline and week 16, with the Clinical Global Impression scale for BD (CGI-BP-M), depressive symptoms at baseline with the Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Scale (MADRS) and with the self-applied Center for Epidemiologic Studies-Depression Scale (CES-D). Functional status was evaluated with Social and Occupational Functioning Assessment Scale (SOFAS) and Social Adaptation Self-evaluation Scale (SASS).

Depressive symptoms were detected: mean scores on the HDRS 3.7 (SD 3.1), MADRS 4.9 (SD 4.5) and CES-D 15.2 (SD 9.9) scales. On EEASL mean was 79.5 (SD 12.7), showing a slight decline in social-labour activity and poor social adjustment; SASS mean was 37.5 (SD 7.9). 3.4% of the sample (95%CI 2.0-4.8) presented mild depression with moderate functional impact. The presence of depressive symptoms is related to social-labour functional impact and social maladjustment. The highest correlation coefficients are seen between EEASL and MADRS (r= -0.54, p<0.0001) and between SASS and CES-D (r=-0.47, p<0.0001).

Depressive symptoms on BD outpatients may result in a decline in social-labour functionality and social maladjustment. Self-applied tests performed during follow-up provide important information about patient's functionality.

To examine the long-term efficacy and safety of quetiapine in combination with lithium (Li) or divalproex (DVP) in the prevention of recurrent mood events (manic, mixed, or depressed).

Patients with bipolar I disorder (DSM-IV, most recent episode manic, mixed or depressed) received open-label quetiapine (400–800 mg/day; flexible, divided doses)+Li/DVP (target serum concentrations 0.5–1.2 mEq/L and 50–125 μg/mL) for up to 36 weeks to achieve ≥12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with quetiapine (400–800 mg/day)+Li/DVP or placebo+Li/DVP for up to 104 weeks. Primary endpoint was time to recurrence of any mood event defined by medication initiation, hospitalization, YMRS or MADRS scores ≥20 at two consecutive assessments, or study discontinuation due to a mood event.

1953 patients entered the stabilization phase and 623 were randomized and received ≥1 dose of study medication. Rates of recurrence of a mood event were 20.3% (63/310) vs 52.1% (163/313) for quetiapine and placebo groups, respectively, a risk reduction of 68% (HR 0.32; P<0.0001). Risk reductions were similar for manic and depressed events (HRs 0.30 and 0.33, respectively; P<0.0001). Safety data were consistent with the recognized safety profile of quetiapine. However, a greater incidence of blood glucose ≥126 mg/dL was observed in the quetiapine treatment group.

Maintenance treatment with quetiapine+Li/DVP was significantly more effective than placebo+Li/DVP in increasing the time to recurrence of a mood event in stable patients with bipolar I disorder.

Supported by funding from AstraZeneca Pharmaceuticals LP.

An international, randomized, double-blind, parallel-group study was designed to determine the efficacy and safety of quetiapine+Li/DVP compared with placebo+Li/DVP in the prevention of recurrent mood events (manic, mixed, or depressed) in patients with bipolar I disorder.

Patients with bipolar I disorder (DSM-IV, most recent episode manic, mixed or depressed) received open-label quetiapine (400–800 mg/day; flexible, divided doses) plus Li/DVP (target serum concentrations 0.5–1.2 mEq/L and 50–125 μg/mL, respectively) for up to 36 weeks to achieve at least 12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with quetiapine (400–800 mg/day) plus Li/DVP or placebo+Li/DVP for up to 104 weeks. Primary endpoint was time to recurrence of any mood event defined by medication initiation, hospitalization, YMRS or MADRS score ≥20 at two consecutive assessments or at final assessment if the patient discontinued, or study discontinuation due to a mood event.

1461 patients entered the stabilization phase and 703 (48%) were randomized to double-blind treatment receiving at least one dose of study medication (ITT population). A markedly lower proportion of patients had a mood event in the quetiapine+Li/DVP versus placebo+Li/DVP group (18.5% vs 49.0%, respectively), with a risk reduction of 72% (hazard ratio 0.28; P<0.0001). The incidence of adverse events was similar between the two treatment groups.

Maintenance treatment with quetiapine+Li/DVP significantly increased the time to recurrence of any mood event compared with placebo+LI/DVP. Long-term treatment with quetiapine was generally well-tolerated.

Supported by funding from AstraZeneca Pharmaceuticals LP.

Antidepressants are recommended to be withdrawn during a manic episode. This analysis explored the characteristics of patients receiving antidepressants during an acute manic episode in the context of a large, observational study.

EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year prospective observational study of acute mania/mixed mania. Of 2416 patients, 345 (14%) were taking an antidepressant (AD) and 2071 (86%) were not (NAD) during acute mania. Demographic and clinical variables were collected at baseline and at outpatient visits up to 2 years. Illness severity was measured using Clinical Global Impressions–Bipolar Disorder (CGI-BP), 5-item Hamilton Depression Rating Scale (HAM-D-5), and Young Mania Rating Scale (YMRS). Logistic regression analysis was used to identify variables associated with AD use.

AD use varied across countries (p<0.05), more use with mixed episodes (p<0.001), rapid cyclers (p=0.02), more previous depressive episodes (p<0.001) and higher HAM-D-5 severity at baseline (p<0.001) but less use with higher education (p=0.029), YMRS (p=0.022), CGI-BP overall (p=0.006) severity and inpatients at baseline (p<0.001). There were no differences in alcohol abuse or suicide attempts. Depression recurrence rates were significantly higher with AD (p<0.001).

The EMBLEM study suggests that patients with mania receiving antidepressants are more likely to be outpatients with mixed mania or rapid cycling, and have a higher risk of depressive recurrence during follow-up. Clinicians seem to maintain antidepressants in manic patients to address depressive features during mania and prevent further depressive episodes.

EMBLEM was supported by Eli Lilly and Company.

To evaluate the efficacy, safety and tolerability of aripiprazole plus valproate/lithium in the treatment of patients with bipolar I mania partially non-responsive to lithium or valproate monotherapy.

This multicentre, randomized study included patients with bipolar I disorder (manic/mixed episode, with/without psychotic features). Partial non-responders with therapeutic lithium (0.6–1.0 mmol/l) or valproate (50–125 μg/ml) levels were randomized (2:1) to double-blind combination aripiprazole (aripiprazole [15–30 mg/day] + lithium/valproate; n=253) or placebo + lithium/valproate (n=131). The primary endpoint was mean change from baseline in YMRS Total Score at Week 6 (LOCF).

The aripiprazole combination therapy demonstrated significant improvement from baseline in the YMRS Total score versus placebo + lithium/valproate at Week 1 and all subsequent visits (all p<0.05) up to Week 6 (–13.3 vs. –10.7, p=0.002; LOCF). Significant improvements from baseline to Week 6 were observed with aripiprazole vs. placebo + lithium/valproate in CGI-BP-S (mania) score (–1.9 vs. –1.6; p=0.014; LOCF) and the LIFE-RIFT score (–1.76 vs. –0.99; p=0.046; LOCF). At endpoint, aripiprazole plus lithium/valproate was associated with significantly greater remission rate (YMRS Total score ≤12) and response rate (≥50% improvement from baseline in YMRS Total) than placebo + lithium/valproate. Similar percentages of patients had clinically relevant weight gain (aripiprazole + lithium/valproate vs. placebo + lithium/valproate: 3.0% vs. 3.9%; p=0.718, Week 6, LOCF). Aripiprazole combination therapy was well tolerated.

In patients with bipolar mania, aripiprazole in combination with lithium/valproate is an effective and well-tolerated treatment that improves psychosocial functioning.

Previous studies on the prevalence of metabolic syndrome in patients with bipolar disorder have reported higher rates than in their respective general populations.

This study evaluates the prevalence rate and modal subcomponents of metabolic syndrome in 34 patients treated in University Hospital Centre Zagreb,Croatia.

Naturalistic, cross sectional study. Patients were evaluated for the presence of metabolic syndrome according to NCEP ATP-III criteria.

Mean age was 41.1(SD 12.9). Overall prevalence rate of MetS was 35.3%. Forty seven percent met the criterion for abdominal obesity, 58.8% for hypertrigliceridemia, 23.5 % for low HDL cholesterol, 50.0% for hypertension, and 23.5 for high fasting glucose. There was no diference in the prevalence rate by gender.

Clinical medical monitoring for these parameters is recommended. Psychotropic drugs use may confer differential risk for developing the metabolic syndrome.

Evaluate the efficacy and tolerability of quetiapine and lithium monotherapy for major depressive episodes in bipolar disorder during an acute 8-week period and up to 52-week continuation phase.

802 patients (499 bipolar I, 303 bipolar II) were randomized to quetiapine 300mg/d (n=265), quetiapine 600mg/d (n=268), lithium 600mg/d (n=136), or placebo (n=133) for 8 weeks. Primary endpoint was change from baseline to 8 weeks in MADRS total score. After 8 weeks, patients with MADRS ≤12 and YMRS ≤12 entered a 26- to 52-week continuation phase of quetiapine (300mg/d or 600mg/d) or placebo. Patients on lithium received 300mg/day of quetiapine (results of continuation phase not included here and to be presented separately).

LSM MADRS score change at 8 weeks was -15.36 (quetiapine 300mg/d), -16.10 (quetiapine 600mg/d), -13.60 (lithium), and -11.81 (placebo; P<0.001 for both quetiapine doses, P=0.123 for lithium, versus placebo; LOCF ANCOVA). Quetiapine (both doses)-treated, but not lithium-treated, patients showed significantly greater improvements (P≤0.05) in MADRS response and remission rates, HAM-D, CGI-BP-S, CGI-BP-Change, and HAM-A at Week 8 versus placebo; MADRS item 10 (suicidal thoughts) improved with quetiapine 600mg/d versus placebo (P=0.013). Most common adverse events considered drug-related included somnolence, dry mouth, and dizziness with quetiapine (both doses) and nausea with lithium.

Quetiapine (300mg/d or 600mg/d) was more effective than placebo for the treatment of acute depressive episodes in bipolar I and bipolar II disorder. Quetiapine treatment was generally well tolerated.

Supported by funding from AstraZeneca Pharmaceuticals LP.

Evaluate efficacy and tolerability of quetiapine and paroxetine monotherapy for major depressive episodes in bipolar disorder during an acute 8-week period and up to 52-week continuation phase.

740 patients (478 bipolar I, 262 bipolar II) were randomized to quetiapine 300mg/d (n=245), quetiapine 600mg/d (n=247), paroxetine 20mg/d (n=122), or placebo (n=126) for 8 weeks. Primary endpoint was change from baseline to 8 weeks in MADRS total score. After 8 weeks, patients with MADRS ≤12 and YMRS ≤12 entered a 26- to 52-week continuation phase of quetiapine (300mg/d or 600mg/d) or placebo. Patients on paroxetine received 300mg/d of quetiapine (continuation phase results not included here and to be presented separately).

LSM MADRS score change at 8 weeks was -16.19 (quetiapine 300mg/d),-16.31 (quetiapine 600mg/d), -13.76 (paroxetine), and -12.60 (placebo; P<0.001 for both quetiapine doses, P=0.313 for paroxetine, versus placebo; LOCF ANCOVA). Quetiapine (both doses)-treated patients showed significantly greater improvements (P≤0.05) in MADRS response rate, HAM-D, CGI-BP-S, CGI-BP-Change, HAM-A, and MADRS item 10 (suicidal thoughts) at Week 8 versus placebo; MADRS remission rates improved with quetiapine 600mg/d versus placebo (P=0.012). Paroxetine improved HAM-A scores versus placebo (P=0.033).

Most common adverse events considered drug-related included dry mouth, somnolence, sedation, and dizziness with quetiapine (both doses); dry mouth, sedation, headache, insomnia, and nausea with paroxetine.

Quetiapine (300mg/d or 600mg/d) was more effective than placebo for the treatment of acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated.

Supported by funding from AstraZeneca Pharmaceuticals LP.

Modafinil improves the residual excessive daytime sleepiness (EDS) in patients who remain sleepy despite nCPAP therapy however, its effects on cognitive performance in this group of OSA patients have been equivocal. In the present study we examined the effects of a single modafinil dose on cognitive performance in newly diagnosed OSA patients, prior to the onset of nCPAP therapy.

Twelve unmedicated patients recently diagnosed with Obstructive Sleep Apnea (OSA) following polysomnography, entered into a double-blind, randomized, placebo-controlled crossover study using a single 200 mg dose of modafinil. The Cambridge Neuropsychological Test Automated Battery (CANTAB) and Visual Analogue Scales (VAS) were used.

Consistent with its alerting effects, modafinil increased VAS-rated alertness and improved visual and sustained attention (CANTAB Reaction Time Tests and RVIP). There was a trend for improvement in VAS-rated mood and anxiety. Modafinil improved problem solving performance (CANTAB Stockings of Cambridge) which was accompanied by prolonged thinking times. A similar pattern of improvement with improved recall coupled by prolonged response times was seen in the CANTAB Delayed Matching-To-Sample test of visual memory.

This modafinil-induced alteration in the speed-accuracy trade-off has been previously seen in healthy subjects and adults with ADHD and indicates that modafinil increases the ability to “reflect” on problems coupled with decreased impulsive responding. If these benefits are shown to be maintained with chronic administration, modafinil may have potential as an important therapy for OSA patients with residual EDS following nCPAP therapy.

Cognitive dysfunction is a major component of schizophrenia, with deficits in executive function particularly pertinent to successful daily living and outcome.The objective of this study was to explore the long-time efficacy of Olanzapine in the treatment of cognitive control in schizophrenia.

36 cases of patients maintained treated with Olanzapine and 30 cases of patients treated with chlorpromazine were included in the 6 months follow-up study. Cognitive control was tested with Wisconsin card sorting test (WCST) and Trail Making.

At the time of 6 months，all the scores of total trial, sorts, perseverative errors and random errors on WCST and all target of Trail Making Test were significantly decreased in the two groups of patients (P<0.05 or P<0.01)；but the decreased rate of perseverative errors on WCST of Olanzapine group were significantly higher than that of chlopromazine group(P<0.01).

Olanzapine have a good efficacy in the long-time treatment of cognitive control in schizophrenia.

Several case reports and small, placebo-controlled-trials have reported improvements in cognition and negative symptoms when galantamine has been prescribed adjunctively to patients with schizophrenia. We report our findings from a nine-month, open-label, pilot study to evaluate the long-term efficacy of adjunctive galantamine for the treatment of functional impairments in outpatients with chronic schizophrenia or schizoaffective disorder.

Fourteen outpatients were initiated to open-label treatment with galantamine (8, 12 or 24 mg/day, dependent on tolerance with a target dose of 24 mg/day). The primary outcome measures were competence in activities of daily living as assessed with the Independent Living Scale (ILS), quality of life as assessed with the Quality of Life Scale (QLS), and negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS).

Of the 14 subjects who began treatment, six subjects completed the nine-month study. No significant changes were observed between baseline and either end of study or month 5 on any of the outcome measures. Three subjects withdrew due to an exacerbation of psychotic symptoms and/or a lack of treatment response; one withdrew due to weight gain; and four withdrew for reasons unrelated to the study drug. After a few months treatment, three subjects experienced an overall increase in activation and an associated increase in psychotic and mood symptoms.

Treatment with adjunctive galantamine did not yield functional improvements and may have been associated with agitation and decompensation. Clinical caution and further research are warranted.

Idiopathic basal ganglia calcification (IBGC) is a neuropathological finding known to manifest motor disturbance, cognitive impairment and psychiatric symptoms. Pathophysiology of psychiatric symptoms, however, remains controversial. Previous biochemical study suggests that dopaminergic impairment is involved in IBGC. We therefore performed positron emission tomography (PET) to elucidate the pre- and postsynaptic dopaminergic function and glucose metabolism in two IBGC patients.

Case 1 is a 44 years old woman presented with disorganized thought, echolalia, verbigeration and parkinsonism. She was administered bitemporal electro-convulsive therapy (ECT). Case 2 is a 35 years old woman with persecutory delusion. Computed tomography showed bilateral symmetric calcification of striatum, globus pallidus and dentate nucei. Other causes of intracranial calcification were excluded. PET scans were obtained using [11C]-labeled 2β-carbomethoxy-3β-(4-flurophenyl)-tropane, [11C]-labeled raclopride and [18F] fluorodeoxyglucose.

The decreased binding potential was severe in bilateral head of caudate nuclei and anterior putamen. In case 1, the decline was also found in posterior putamen. There were widespread decreases of glucose uptake in frontal, temporal and parietal cortices bilaterally in case 1. Significant hypometabolism was observed in the right frontal, temporal and parietal cortices. After the ECT session, the previous areas of significant hypometabolism in the right hemisphere had improved. In case 2, there was no significant change of glucose metabolism in cerebral cortex.

The difference in affected region within basal ganglia might be associated with the diverse clinical pictures in IBGC. Particularly, in the psychiatric manifestation, dopaminergic dysfunction in caudate nucleus and anterior putamen could be participated.

The aim of the study is to investigate vegetative reactivity at the different stages of major depressive disorder (MDD).

clinico-psychopathological method, clinico-anamnestic method, the Zung self-rating depression scale, the method of the heart rate variability analysis for assessment of vegetative regulation. The study is conducted from 2000 to 2007. In the first part of the study the assessment of vegetative regulation at the initial stage of MDD is provided (82 patients even 72 healthy persons). In the second part the vegetative regulation is studied at the stages of stabilization and reduction of MDD (76 patients even 66 healthy persons).

The results of investigation are shown reduction in the total heart rate variability, increase in tension level of regulatory systems at the initial stage of MDD. The activity balance of the sympathetic, parasympathetic and suprasegmental mechanisms of autonomic nervous system remains.

At the stage of depression stabilization the disruption of different components of autonomic nervous system balance occurs. The prevalence of the activity of suprasegmental ergotropic systems and the functional decrease of sympathetic mechanisms activity are observed. At the stage of the depression reduction the decrease of the activity of suprasegmental ergotropic systems with the hyper-activation of peripheral sympathoadrenal mechanisms are revealed.

Obtained data could be considered in chose and efficiency rating of therapy at the different stages of MDD.

Bruxism is the most common form of maxillofacial hyperkinesia. Behavioral disorders as well as affective psychological factors, depression and anxiety being one of the most prominent factors, can together with emotional stress, induce bruxism. There has been the correlation between medications and bruxism (for example SSRI's).

We reported a case of a 47-year-old female patient who has been psychiatrically treated for depression since 1988 (F 32.1 by ICD 10). In 2005, she was hospitalised for the second time, this time for depression with psychotic traits (F 33.3 by ICD 10) due to which she was also hospitalised in 2006 and 2007. During 2005 and 2006 she was taking mirtazapine, paroxetine as well as olanzapine and since 2007 she has been taking sertraline and olanzapine.

There was an excessive wear of tooth surfaces and edges due to bruxism on seven-year-old bridge, which she noticed herself two years ago. She was awake during the diurnal bruxism and nocturnal bruxist activity was confirmed by her husband. Michigan splint was fabricated, thus alleviating the destructive impact of masticatory forces on the teeth and their supportive tissues.

Bruxism, associated with medications or mental disorders and very detrimental to teeth, the periodontium and oral health in psychiatric patients should be also treated as a general health problem and oral health problem. The prognosis for stopping bruxist activity is bad because a complete prosthodontic treatment was extremely limited due to the patient's psychiatric condition.