Long-term treatment of bipolar depression in the elderly has not been well-studied.

To evaluate the long-term safety and tolerability of lurasidone in older adults (age ≥55 years) with bipolar I depression (BPD).

The older adult sample was analyzed from an extension study in which patients who completed one of three 6 week, double-blind, placebo-controlled trials received 6 months of open-label treatment with flexible doses of lurasidone 18.5-111 mg/d, either as monotherapy, or adjunctive to lithium or valproate.

The older adult sample consisted of 55 patients (17.4% of total) on lurasidone monotherapy and 86 patients (17.3%) on adjunctive lurasidone. At the end of 6 months of treatment with lurasidone, monotherapy and adjunctive therapy, respectively, minimal changes were observed in mean weight (-1.0 kg; -0.4 kg); and median total cholesterol (-2.0 mg/dL; +6.0 md/dL), triglycerides (+2.5 mg/dL; +6.0 mg/dL), and HbA1c (0.0%; -0.1%). The 3 most common adverse events were fatigue (18.4%), insomnia (18.4%), headache (15.8%) in the monotherapy group, and akathisia (31.7%), insomnia (22.0%), tremor (19.5%) in the adjunctive group. Discontinuation due to adverse events was low in both groups (monotherapy, 7.3%; adjunctive, 9.3%). Improvement in depression was maintained during 6 months of treatment, with a mean change in MADRS scores of -15.7 for the monotherapy group, and -17.8 for the adjunctive therapy group (from acute study baseline).

Results of these secondary analyses suggest that lurasidone, in doses of 18.5-111 mg/day, was a safe and well-tolerated long-term treatment for bipolar depression in older adults.

NCT00868959.

Sponsored by Sunovion Pharmaceuticals Inc.

Pharmacotherapy of bipolar disorder (BD) is crucial to alleviate symptoms of acute mania, depression, mixed states or prevent recidivism. Symptomatology over the course of the disease can manifest in different ways. Adherence of patients with BD is complex, and psychiatric comorbidities play an important role.

National and international guidelines on treatment modalities of BD have been developed in recent years. This paper recapitulates similarities and discrepancies of international and national treatment guidelines of BD, and it puts the meaningfulness of those guidelines in the clinical context.

Comprehensive literature review on treatment guidelines of BD and compilation of recently held symposia during EPA congresses.

Pharmacotherapy of BD is challenging, not only due to the potentially severe course of the disorder, but also due to extremely long duration of untreated BD of over 10 years and a complex and alternating clinical picture. Treatment guidelines mostly suggest first-, second-, third-and fourth-line recommendations for acute mania, bipolar depression, mixed states and maintenance treatment. Least surprisingly, there are obvious differences between guidelines, especially when weighing efficacy and tolerability of mono- and combination therapies. This appears especially relevant for first-line recommendations.

This review discusses important national and international treatment guidelines, and puts those recommendations in a clinical framework using state-of-the-art literature of bipolar disorder.

The acute treatment of bipolar depression in the elderly has not been well-studied.

To evaluate the acute efficacy and tolerability of lurasidone in older adults (age ≥55 years) with bipolar I depression (BPD).

The older adult sample was analyzed from two, randomized, double-blind, 6-week studies of BPD patients with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥20: a monotherapy trial (lurasidone 18.5-56 mg/d vs 74-111 mg/d vs placebo); and an adjunctive trial (with lithium or valproate; lurasidone 18.5-111 mg/d vs placebo).

The older adult sample consisted of 83 patients (17.1%) on monotherapy, and 53 patients (15.6%) on adjunctive therapy. At Week 6, mean change in MADRS was significantly greater for lurasidone 18.5-56 mg (-15.4; P<0.01; effect size=0.86) and 74-111 mg (-14.1; P<0.02; effect size=0.74) vs placebo (-7.1). Adjunctive therapy with lurasidone (vs placebo) was associated with numerically greater improvement at Week 6 in MADRS (-13.9 vs. -11.1; ns; effect size=0.26). Among older adults in the monotherapy study, discontinuation due to adverse events occurred in 7.7% of patients on lurasidone 18.5-56 mg, 6.7% on lurasidone 74-111 mg, and 3.7% on placebo; and in the adjunctive therapy study, discontinuation due to adverse events occurred in 3.8% of patients on lurasidone, and 7.4% on placebo.

Results of these analyses suggest that lurasidone, in doses of 18.5-111 mg, was an efficacious and well-tolerated acute treatment for bipolar depression in older adults. Significance vs placebo was achieved with lurasidone monotherapy, however, adjunctive therapy with lurasidone did not reach statistical significance.

NCT00868699, NCT00868452.

Sponsored by Sunovion Pharmaceuticals Inc.

Neuropsychiatric manifestations are common among patients with thyroid dysfunctions. Depression and cognitive impairments are the most frequent symptoms of hypothyroidism. Few cases of mania associated with primary hypothyroidism were observed in the literature.

We report a case illustrating the association between the two diseases. A literature review was conducted through searches of PubMed and Medline.

Miss R, 35 years old, who had no previous history of psychiatric disorders, was admitted in 2014 with symptoms associated to acute manic episode (diagnosed using DSMIV).

Signs of florid hypothyroidism were noted at the exam and confirmed by biological tests.

Family revealed multinodular goiter surgical operation (in 2013) with poor adherence to thyroxin replacement. Both antipsychotic drugs, mood stabilizers and thyroxin replacement were required for his remission .

This case leads us to ask the following question: is it a fortuit comorbidity or does the mania is due to hypothyroidism?

According to the results of literature, hypothyroidism with manic presentation is not common (10 reports of mania consistent with primary hypothyroidism). While occurrence of mania in hyperthyroidism involves the beta adrenergic system, mechanisms underlying the occurrence of mania in hypothyroidism remains unclear. However, recent studies begin to provide a better understanding of the links between thyroid dysfunctions and mood disorders.

Psychiatric manifestations of hypothyroidism are various and lead to a better screening of thyroid dysfunctions, especially in patients with mood disorders

We present the case of a 51-years-old Caucasian woman with Bipolar Disorder I (BDI), treated for a long time with typical antipsychotics and mood stabilizers. She referred to our outpatient service because she wished to revise her precriptions, which had caused several side-effects, including metabolic syndrome, gain of body weight, sedation, cognitive impairments, and extrapiramidal symptoms. Moreover, treatment was poorly effective, the patient's compliance was lacking and she experienced frequent relapses.

We started treating the patient with aripiprazole at a daily dose of 15 mg. Our aim is to describe the substantial clinical and metabolic improvements of a patient who poorly responded to previous prescriptions.

Psychometric measures for the assessment of mood and social functioning were administered at baseline and at the follow-up interviews. Body Mass Index was monitored and blood tests were performed to evaluate the lipid profile (LDL, HDL, total cholesterol, triglycerides), blood glucose, and glycated haemoglobin.

In the last two years the patient has regularly taken her therapies and attended to follow-up visits. Her social functioning and tolerance to stressful situations have improved, as well as her metabolic profile. Noteworthy, she had not needed further hospitalizations.

Our clinical observations support the efficacy of aripiprazole in the treatment of BDI. Switching to aripiprazole should be considered in cases similar to the one we have described, characterized by poor compliance, obesity or metabolic syndrome, sensitivity to manifest extrapiramidal syndrome (especially tardive dyskinesia) and other side effects such as sedation and cognitive impairments.

Patients with bipolar disorder are at a higher risk of metabolic complications and associated mortality than the general population.

To evaluate the extent to which treatment with lurasidone was associated with clinically relevant shifts in key weight and metabolic parameters in patients with bipolar I depression (BPD).

Data were from 3 short-term studies in patients with BPD who were randomized to 6 weeks of double-blind, placebo-controlled treatment with lurasidone (18.5-111 mg/d), either as monotherapy (one study, N=499), or adjunctive therapy with lithium or valproate (2 studies, N=694). Patients completing the 6-week trials continued in a 6 month open-label extension study (N=494). The proportion of patients with shifts in metabolic parameters were analyzed at the 6 week and 6 month end-points, and are reported descriptively. Shifts were defined as changes in weight (≥7% change), BMI category, triglycerides (increase ≥50 mg/dL), total cholesterol (increase ≥40 mg/dL), LDL (increase ≥30 mg/dL), and glucose (shift to ≥110 mg/dL).

At Week 6 in the monotherapy study, a similar proportion of patients treated with lurasidone vs placebo, respectively, had shifts in weight (2.0% vs 0.6%), triglycerides (15.7% vs 10.1%), total cholesterol (5.5% vs 3.4%), LDL (6.4% vs 3.4%), and glucose (11.3% vs 9.5%). Results were similar for lurasidone vs placebo in the adjunctive therapy study. At Month 6 of the extension study, a relatively low proportion of the patients on lurasidone met shift criteria.

These data add to the substantial and growing body of information regarding the metabolic safety of lurasidone.

NCT00868699, NCT01284517, NCT00868452, NCT00868959.

Sponsored by Sunovion Pharmaceuticals Inc.

Bipolar disorder is quite heterogeneous; first-episode polarity has been proposed as course predictor.

This study aimed to compare sociodemographic and clinical aspects, as well as illness course, in bipolar 1 disorder patients according to the polarity of the first episode.

We conducted a retrospective and comparative survey of all patients hospitalized in the department of psychiatry “A” in the Hedi Chaker University Hospital, in Sfax (Tunisia), during the period from January 2008 to December 2012, and in whom bipolar 1 disorder was diagnosed (DSM IV-TR).

Patients whose follow-up does not exceed one year were excluded. Subjects were sorted into two groups: group 'M” those with manic/hypomanic first episode and group 'D” those with depressive one.

Seventy-six patients were included (group 'M” = 58; group 'D” = 18).

The depressive first episode was significantly correlated with early-onset of bipolar disorder (p = 0.01), more frequent family history of bipolar disorder (p = 0.02), more suicide attempts (p = 0.00) and higher number of mood episodes (p = 0.02).

Group 'M” had more frequently psychotic features (p = 0.00) and more psychiatric hospitalization history (p = 0.04).

No statistical difference was found in gender and substance abuse between the two groups.

Our study confirmed literature data that bipolar patients with depressive onset seem to have a poorer prognosis.

Asenapine is an atypical antipsychotic indicated for the treatment of schizophrenia and of the manic or mixed episodes in bipolar I disorder [1]. The different therapeutics option like mood stabilizers and atypical antipsychotics are used to better treat the single episode but also to stabilize manic/depressive cyclicity [2]. The aim of this case report is to underline a possible augmentation of asenapine to clozapine.

'Mrs. T.P.', is a caucasian woman aged 45 suffering from bipolar disorder type I followed by mixed depressive phases with subsequent short free period. The patient was treated with different typical and atypical antipsychotics, combined with mood stabilizers, with a partial response. With lithium 900 mg/day, valproate 1500 mg/day and clozapine 250 mg/day showed a partial improvement and remission of the symptoms. To that point we introduced asenapine 20 mg/day with rapid clinical improvement without major side effects. After 1 year the patient is still showing a good affective stability, with an improvemnt of metabolic and without cognitive side effects.

Our case report underlines the possibility of asenapine augmentation of clozapine in bipolar I disorder therapy resistant manic patients [3]. Asenapine can increase the plasmatic levels of clozapine, exhibits a unique effect and his pharmacodynamic characteristics may mediate its symptom relief in positive, negative and mood symptoms. Further research is warranted to replicate our clinical observation.

Illustrated by a case the variables that influence the clinical course and therapeutic management of the case

Exhibition of a case and a brief review of the literature.

Women 35 years of age who presented to the emergency hospital with her partner and her mother, for insomnia, increased habitual activity and bizarre behavior. Cesarean delivery 28 days of a healthy baby girl makes 3,800 kg.

While in the hospital, they did not observe anything unusual about his behavior, but a fortnight since birth and being at home, began to notice her excited and irritable. He was strong and constant arguments with his mother and her partner, about caring for your baby, spoke tirelessly and began fighting with neighbors and friends,

The correct action and early and effective treatment in these cases, help to reduce the length of hospital stay and morbidity of bipolar affective disorders.

It is clinically important to recognize both bipolar disorder (BD) and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. However, in routine clinical practice, the differentiation remains difficult.

The aim of the study was to illustrate the difficulty in the practice, to distinguish BD and BPD in depressed patients through a case report.

Mr IK 27-year-old, without medicals history. He is a single man with an animated life, professional instability, substance abuse, sensibility in the refusal, a tendency to impulsiveness and a feeling of meaning devoid. He was hospitalized for three consecutive suicide attempts. We found an unstable patient on the psychomotor plan, with depressive humour and anhedonia. The final diagnosis was major depressive episode without signs of bipolarity. He was putted under fluoxetine. The evolution was marked by a turn maniac. Diagnosis of BD and BPD were discussed. Aspect of the BPD appears and confirmed by Rorschach test.

At present the links between BD and BPD remains a subject of controversy. This case suggests that BPD needs to be diagnosed with a narrower set of criteria that cover all of its domains.

The world-wide interest in bipolar disorder is illustrated by an exponential increase in annual publications on the disorder registered in Pubmed since 1990. This inspired an overview on the clinical development.

To assess bipolar disorder in a coherent timeframe to identify changing patterns in incidence and mortality.

To investigate secular trends in incidence of bipolar disorder in psychiatric care, examine the time lapse from first affective diagnosis to diagnosis of bipolar disorder and determine mortality and causes of death.

First-ever diagnoses of bipolar disorder (ICD-10 code F31) between 1995 and 2012 were identified in the nationwide Danish Psychiatric Central Research Register. Prior affective disorders were found as well. Causes of death were obtained from The Danish Register of Causes of Death.Age- and gender standardized incidence rates and standardized mortality ratio were calculated.

A total of 15,334 incident cases of bipolar disorder were identified. The incidence rate increased from 18.5/100,000 person-years (PY) in 1995 to 28.4/100,000 PY in 2012. The age group with the highest incidence decreased from 60-79 years to 20-39 years. The mean time from first affective diagnosis to diagnosis of bipolar disorder was 7.9 years (SD=9.1). The standardized mortality ratio was 1.7 (95%-CI=1.2-2.1). Causes of death were mainly natural, but 9% died from suicide.

The incidence of bipolar disorder increased significantly over a timeframe of 17 years mortality was higher compared to the general population. Treatment to lower mortality needs focus on both natural and unnatural causes.

The objective of this post-hoc analysis was to evaluate recovery-related outcomes in patients with bipolar depression treated with lurasidone.

Subjects meeting DSM-IV-TR criteria for bipolar I depression, with or without rapid cycling, were randomized to 6 weeks of once-daily, double-blind treatment with either lurasidone 20-60 mg (LUR20-60), lurasidone 80-120 mg (LUR80-120) or placebo (PBO), followed by a 6-month, open-label, continuation study of lurasidone.

At end of the 6-week acute phase, a significantly higher proportion of subjects met both symptomatic (MADRS total score ≤ 12) and functional (mean SDS total score ≤ 3 and all SDS domain scores ≤ 3 for mildly impairment) remission criteria in the lurasidone group (33%,N=273 pooling the LUR20-60 and LUR80-120 groups) compared to the placebo group (15%, N=143,p<0.05, NNT = 6). In the 6-month continuation study, the proportion of subjects achieving symptomatic and functional remission at both week 19 and week 32 (month 3 and month 6 of the continuation study, respectively) was 61% (85/140) in subjects who continued lurasidone treatment (LUR-LUR) and 45% (31/69) in subjects who switched from placebo to lurasidone (PBO-LUR). Multivariate logistic modeling revealed that statistically significant predictors of symptomatic and functional recovery included: lower baseline symptom severity, non-white race, and taking lurasidone (rather than placebo) during the acute phase.

Our findings support the potential for attainment of remission in patients with bipolar I depression treated with lurasidone, which might lead to clinical and functional recovery.

To compare the clinical and sociodemographic profiles of patients discharged from the specialized wards of 'Mood Disorders and OCD” and &Schizophrenia and Schizoaffective Disorders” with the diagnosis of Bipolar Disorder (BD), and of Schizophrenia and Schizoaffective Disorders (SSD)

To improve the quality of services provided, by implementing specialized programs adapted to the specific characteristics and needs of these patients.

Retrospective analysis of patients’ clinical charts, discharged from two specialized wards at Lisbon’s Psychiatric Hospitalar Centre, with a diagnosis of BD or SSD according to the ICD-10, during the first six months after the implementation of these services, in October 2013. The statistical analysis was performed with SPSS.

During the six month period 230 patients were discharged (BD, n=130; SSD, n= 100).

Compared to BD patients, SSD patients were predominantly male, younger, unemployed, with a lower educational level, and had an earlier onset of the disease. They also had a longer length of stay and were more commonly admitted on a compulsory regimen.

There were no statistically significant differences regarding disease duration between the two groups.

In BD patients we found a positive correlation between age and length of hospital stay.

Our sample shows statistically significant differences regarding demographic and social features between BD and SSD patients. Thus, our hospital’s recent specialization is being accompanied by specialized treatment strategies, which are already ongoing and should be the subject of evaluation in the near future.

Bipolar disorder (BP) and schizophrenia (SCZ) are severe, heritable psychiatric disorders. Genome-wide research suggests that the molecular basis of BP and SCZ overlap (Cross Disorder PGC Group, Lancet, 2013).

of our work was to investigate whether poligenic scores based on SCZ-associated SNPs in the PGC sample (www.med.unc.edu/pgc/) might predict the age of onset (AO) in BP-I. We hypothesized that the SCZ associated SNPs might predict the late AO of BP-I due to the common character of the SCZ-associated variants.

We selected 10,681 non-ambigous SNPs among the 102,637 SNPs present in the PGC SCZ-sample. Using these SNPs we derived poligenic scores in a Romanian sample of 243 BP-I patients with genome-wide data (604,064 SNPs) to predict the patient AO as dichotomous variable (early onset: AO≤24 years; late onset: AO>24 years). The genotyping of the Romanian patients was performed at the Institute of Human Genetics of Bonn. PLINK 1.07 (Purcell, 2009) was used for computing polygenic scores, means of which were compared by t-test between the early- and the late-AO patient groups.

2114 out of 10, 681 SCZ-SNPs were informative in our sample contributing to polygenic scores in BP-I patients. There was no significant difference in mean polygenic scores between the early- and the late-onset group of BP-I patients (t=1.14, P=0.25).

The polygenic scores based on 2114 SCZ-associated common variants did not predict the onset group in our BP-I patients under the AO-cutoff 24 years. Other AO-cutoffs and phenotypic traits (e.g. incongruent psychosis) might be tested.

(Hypo)mania is a known consequence of antidepressants in type I, type II and type III bipolar disorder. This conceptualization often induces the generalized belief that only the introduction of the antidepressant induces the mood switch.

Report the occurence of an understudied therapeutic event with unknown mechanism and associations. Promote clinical attention and further investigation.

Case report of a patient who developed a hypomanic switch upon venlafaxine discontinuation; bibliographic search using PubMed/MedLine database with the following keywords: bipolar; mania; hypomania; venlafaxine; antidepressant; discontinuation.

We report and discuss the case of a 48-year-old woman with previous history of a recurrent depression. The patient was successfully treated with Venlafaxine (300mg/day), Pregabalin (300mg/day) and Clonazepam (0.5mg/day) completing the acute and continuation phases of the treatment. She was then discharged with the indication to maintain treatment for her maintenance phase. After a couple of months the patient initiated slow Venlafaxine discontinuation after which she developed a clinical picture characterized by talkativeness, persistently elevated mood, increased goal-directed activity and unreasonable expenses lasting for an unspecified number of weeks and subsequent severe depressive episode without psychotic symptoms. The patient was again referred to our consultation and medicated with Venlafaxine (300mg/day) and Valproic acid (1000mg/day) remaining depressed and treatment resistant to this day.

Studies show that antidepressant-withdrawal (hypo)mania is a known but rarely reported leading to its unawareness an consequent unknown true incidence. Two hypothetical models may explain this clinical entity: Withdrawal-induced cholinergic overdrive; and Noradrenergic hyperactivity.

Asenapine is a second-generation antipsychotic approved in Europe for the treatment of moderate to severe manic episodes in adults affected by Bipolar Disorder I (BD I).

We aimed to assess the efficacy of asenapine in controlling manic, mixed and/or depressive symptoms in an inpatient psychiatric population.

A total of 119 voluntarily hospitalised patients with DSM-IV-TR BD I diagnosis received flexible asenapine doses ranging 5 to 20 mg/day. Patients were assessed with clinician-rated questionnaires, i.e., Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Global Assessment of Functioning (GAF). Assessment was carried-out at baseline (T0, prior to treatment), and three (T1), seven (T2), 15 (T3), and 30 days (T4) after starting treatment for all clinical scales and at T0 and T4 for the GAF.

Patients improved on all scales (p<.001) across time-points, as shown both by paired-sample comparisons and by applying a repeated-measures, generalized linear model (GLM). Substance abuse was associated with greater reductions in anxious-depressive scores. Side effects were few and not severe.

Asenapine showed effectiveness and safety in a hospitalised bipolar I population. Its effect was greater in the presence of substance abuse.