Lithium is a drug which may cause thyroid dysfunction. The most widely known dysfunctions associated with long-term lithium treatment are goiter and hypothyroidism.

Lithium associated thyrotoxicosis is however uncommon.

This current review explores the common mechanisms of lithium induced hyperthyroidism.

A systematic review of database was made using PubMed. The search keywords used were lithium therapy, thyroid side effects, thyroid dysfunction mechanism, hyperthyroidism, thyrotoxicosis.

Lithium induced hyperthyroidism is uncommon, the incidence rate varying from 0.1% to 1.7%.

The mechanisms of lithium associated hyperthyroidism are uncertain.

Recent studies have proved that high proportion of investigated patients experienced transient thyrotoxicosis and painless thyroiditis.

Different mechanisms have been discussed, including autoimmune inflammation, direct cellular destruction, susceptible individuals with preexisting Grave’s disease, a rebound effect of lithium therapy interruption…

The pathogenesis of painless thyroiditis is unclear but different studies suggest a possible direct toxic effect of lithium on the thyroid gland.

Lithium stimulates thyroid autoimmunity: lithium treated patients presented more positive antithyroid peroxidase antibodies than not lithium treated patients. This could be explained by an increased activity of B-cell lymphocyte activity and reduced ratios of suppressor to cytotoxic T-cell lymphocyte.

Long term lithium treated patients should be monitored for the development of thyroid dysfunction. It’s recommended to perform thyroid function test, thyroid antibodies and thyroid ultrasonography with a closer follow-up for lithium-treated patients with thyroid antibodies, or family history of thyroid disease.

Self stigmatization is an important factor playing role in social life of patients, but also discourages therapy. Aim of our study was to found connection between self stigmation, adherence and discontinuation of drug treatment.

It is a cross-section study of ambulatory patients of Department of psychiatry, University hospital Olomouc, Czech Republic. Data were gathered from 332 probands from six basic diagnostic categories.

From defined variables these affected self-stigamtization: education level, marital status, age, age of onset of disorder, number of hospitalizations, number of attended psychiatrist, dose of antidepresantns, score of subjective and objective CGI and level of adherence. Level of adherence was influenced by marital status, age, age of onset of disorder, dose of anxiolytics, score of subjective and objective and ISMI score. There was no significant difference is ISMI score between patients from different diagnostic categories. Level of adherence significantly differs between patients with depression and schizophrenic patients.

Level of self-stigmatization proved to be an important factor in influencing both level of adherence and discontuniation of drugs. More attention should be payed to issue of self-stigmation.

The evaluation of safety represents the our interest, especially with references to older people that receive at the same time many drugs for psychiatric disorders and physical diseases. The polypharmacy between older people is a frequent phenomenon but little is know about adverse effects of antidepressants.

We have examined the prescriptions in 10 nursing homes to collect adverse effects, included cause mortality, during a follow up of 2 years.

The incidence of adverse events with Trazodone is very low, as so compared to other antidepressants. Also, older people, are a special population with high comorbidity. Still it is very difficult to reduce the recurrence to polypharmacy in these field but we must become integrated with general practitioners and other specialists.

Monitoring serum clozapine levels can be of great value in determining patient’s concordance with treatment and detecting abnormal levels associated with increased serious side effects.

To compare the current practice in ordering clozapine serum level assays with the local guidelines and to establish trends in requesting the test across the 3 hospitals.

We reviewed the electronic notes of 105 patients who had 181 results over a period of 6 months to gather demographics, indications for clozapine assays and management after results.

In 44% (n=80) of cases there was no clear documentation of the reason for requesting the test. 70% (n=71) of the documented indications were in line with the local guidelines. The most common reason for testing clozapine levels was monitoring compliance (n=25, 24.8%), followed by side effects suggesting high serum levels (n=19, 18.8%). the third was smoking cessation (n=16, 15.8%). 30% of the documented indications were classed as 'other', where the indication was not stated in the guidelines.

43% of cases had abnormal levels (< 0.35 mg/l or >1.0mg/l), 26% had borderline levels (0.61-0.99mg/l) and 31% had levels within the recommended range (0.35-0.60mg/l).

A high degree of inconsistency was observed in the management of clozapine levels especially levels between 0.61-0.99mg/l and levels above1.0mg/l.

Monitoring compliance, side effects and smoking cessation were the most common reasons for requesting serum clozapine level assays. The observed inconsistency in managing borderline and abnormal results demonstrates the need for expert consensus guidelines on managing clozapine serum levels.

In patients receiving long acting injectable (LAI) antipsychotics, the risk of medication side effects needs serious attention.

The study objective is to determine in which measure co-morbid psychiatric symptoms influence the presence of the metabolic syndrome (MS).

Patients receiving LAI antipsychotics have a history of medication non-adherence, with recurrences and partial remissions. The aim of the study is to assess the contribution of residual psychiatric symptoms in the development of the MS in these patients.

The study includes two samples of psychotic remitted subjects, one including patients on olanzapine LAI and the other one patients receiving risperidone LAI for at least six months. The presence of co-morbid symptoms was assessed with BPRS. The International Federation of Diabetes diagnostic criteria for the MS were used. The following information was analyzed: medication, gender, fasting glycemia, lipid profile, waist circumference, blood pressure, and psychiatric symptoms.

The study included 28 patients, 15 (53.6%) on olanzapine LAI, and 13 (46.4%) on risperidone LAI. 15 patients were women and 13 men. 11 (39.2%) patients were diagnosed with MS. The whole sample presented higher scores at the following BPRS items: anxiety, somatic concern, and motor retardation.

Symptoms such as anxiety, somatic concern, and motor retardation may contribute to the development of the MS. 39% of the subjects presented the criteria of the MS.

Bipolar patients are at higher risk for cardiovascular morbidity and mortality than their counterparts in the general population. In a recent in vitro study, Asenapine, a new antipsychotic for the treatment of mania/mixed mania, was found to keep physiological endothelial function by activation of eNOS-related NO release and to protect endothelial cells against peroxidation by interference with mitochondria, apoptosis and cell survival.

To examine the cardiac protective effects elicited by Asenapine against peroxidation and on the Ca2+ movements.

In HL-1 that had undergone oxidative stress by 20 min hydrogen peroxide the effects of 30 min pre-treatment with Asenapine on survival and proliferation will be examined. In Fura-2AM loaded HL-1 we will next analyze the effects of Asenapine on Ca2+ movements and the related involvement of cAMP/PKA and PLC pathways, CaMKII, L and T type Ca2+ channels and 5HT1A receptors. The role of ‘capacitative” Ca2+ entry, plasma-membrane Ca2+ pump inhibitor (PMCA) and Na+/Ca2+ exchanger will be analyzed. Changes of membrane potential caused by interference with K+ channels will be examined, as well.

We expect to find a proliferative and anti-peroxidative effect of Asenapine in HL-1 cells. Asenapine could also affect Ca2+ movements through cAMP/PKA and PLC-dependent signalling and the involvement of 5HT1A receptors. The effects of Asenapine could also be related to changes of plasma membrane by interference with K+ channels and the modulation of PMCA activity and Na+/Ca2+ exchanger.

We expect to further confirm the protective effect of Asenapine against peroxidative injuries. Implications will be discussed

Tapentadol is a centrally-acting synthetic analgesic which acts as a mu-opioid receptor agonist as well as a norepinephrine re-uptake inhibitor. It is use to treat cronic pain. Most prevalence adverse effects are gastrointestinal and nervous symptoms. Furthermore, it has objectified, with less frequency, psychiatric disturbances.

To analyse the relationship between a maniac episode and tapentadol.

Forty-nine-year-old female, with personal history of dyslipidemia and lumbar herniated discs in L4-L5, L5-S1, in treatment with tapentadol 200 mg/day for 20 days and no past psychiatric history. She was admitted to the Psychiatry Department due to a maniac episode, with desinhibition, pressure and loud speech, euphoria, megalomaniac delusion and sleep disturbance for the last 10 days. Young Mania Rating Scale (YMRS) was 36 points. Olanzapina 15 mg/day was introduced and tapentadol was removed. Symptoms remitted quickly and 6 days later, at discharge, YMRS was 4 points. One year later, the patient continued to be asymptomatic.

Opioids can produce psychiatric disorders like hallucination, sleep disorders, depressed mood, disorientation, agitation, nervousness, restlessness, euphoric mood. Secondary mania to tapentadol mechanism is unknown, but having opiate cases described, it is possible to attribute this episode to tapentadol.

– Secondary mania is associated with various medical conditions, including vitamin B12 deficiency, brain injury, HIV infection and drugs such as alcohol, caffeine, sympathomimetics, steroids, bupropion, isoniazid, clarithromycin and opioids.

– Further research is required to determine if the maniac episode was only isolated by the tapentadol or it is the beginning of a bipolar disorder.

Atypical antipsychotic induced weight gain and metabolic side effects are a key contributor to discontinuations and relapses among schizophrenia patients. Current treatment guidelines in Scotland recommend aripiprazole for adults with schizophrenia 'who are particularly concerned about weight gain, or who may be at the greatest risk of weight gain”. Lurasidone, recently approved in Europe for schizophrenia, is effective in treating acute symptoms and preventing long-term relapse, and demonstrates minimal effects on weight and metabolic parameters.

To conduct a cost-utility analysis of lurasidone versus aripiprazole in adults with schizophrenia.

A 10-year Scotland-specific Markov model, incorporating a 6-week acute phase and a maintenance phase across three health states (discontinuation, relapse, death) was constructed. Six-week probabilities of discontinuation and adverse events (weight gain, extrapyramidal side effects, long-term diabetes) were based on a published independent mixed treatment comparison; long-term risks of relapse and discontinuation were from an internal indirect comparison. Costs (discounted at 3.5%) included drug therapy, relapse, outpatient, primary and residential care. Literature based utility estimates were expressed as Quality Adjusted Life Years (QALYs).

Lurasidone yielded a cost saving of £3,863 and a small QALY improvement compared with aripiprazole. Deterministic sensitivity analysis demonstrated that results were sensitive to relapse rates. Probabilistic sensitivity analysis suggested that lurasidone had the highest expected net benefit at willingness-to-pay thresholds of £20-30,000 per quality-adjusted life-year.

This analysis suggests lurasidone could be a valuable and less costly treatment option than aripiprazole among adults with schizophrenia at risk of weight gain and metabolic adverse effects.

Asenapine is a second-generation antipsychotic approved in Europe for the treatment of manic or mixed episodes.

To describe the clinical features of Asenapine responders and non-responders.

A naturalistic, observational study is ongoing in patients treated with Asenapine. We have already recruited 37 manic patients with a lifetime diagnosis of Bipolar I (BDI) or Schizoaffective Disorder referring to our Psychiatric Ward. Patients are assessed with the Young Mania Rating Scale (YMRS) at baseline (T0), and after 1 (T1) and 4 weeks (T2) of treatment. According to YMRS scores, patients are classified as responders and non-responders.

The preliminary results highlight a significant improvement of the YMRS score from T0 to T2 in most patients. Asenapine seems particularly effective in patients with less severe manic symptoms, and responders are more likely to have lower baseline YMRS score. No correlation has currently emerged between responder status and diagnosis. Non-responders in our sample are females sharing some clinical features: early onset BDI diagnosis, several previous treatments (antipsychotics, mood stabilizers), initial cognitive impairment confirmed with the Mini Mental State Examination, Alzheimer Disease Assessment Scale and neuroimaging.

Elderly manic patients with neurological impairment and/or dementia may have poorer therapeutic outcomes and poorer response to pharmacological treatment, which may prove effective in reducing agitation but not mania ratings. Diagnosis (BDI or schizoaffective disorder) does not seem to have a significant impact on Asenapine efficacy. The further recruitment and assessment of patients is expected to support the results described above.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioural disorder with considerable costs. Lisdexamfetamine dimesylate (LDX) is approved in the UK for ADHD treatment in children and adolescents.

To perform an economic analysis of LDX for adults with ADHD from the UK National Health Service (NHS) perspective.

To estimate cost-effectiveness of LDX compared with methylphenidate (MPH) and atomoxetine (ATX).

A 1-year decision-analytic model was developed. Health events included response, non-response and unable to tolerate. Efficacy data were taken from a mixed-treatment comparison (MTC) analysis of all clinical trials. Response was defined as a score of 1 or 2 on the Clinical Global Impression–Improvement scale. Tolerability was assessed by discontinuation rates due to adverse events. Utility weights were identified via a systematic literature review. Healthcare resource use estimates were obtained via a survey of clinicians. Daily drug costs were based on mean doses reported in the trials used in the MTC. One-way and probabilistic sensitivity analyses were performed.

The comparison of LDX and MPH for 100 people resulted in an increased annual cost of £34 and quality-adjusted life-years (QALYs) of 0.5, with an incremental cost-effectiveness ratio of £64 per QALY. When compared with ATX for 100 people, LDX was a dominant strategy, with lower annual costs (–£26,700) and higher QALYs (1.0). There was a 62% probability of LDX being cost-effective versus MPH-ER at a threshold of £20,000 per QALY.

From the perspective of the UK NHS, LDX provides a cost-effective treatment option for adults with ADHD.

Non-drug-related healthcare resource use represents an under-investigated contribution to the total healthcare cost of adult patients with attention-deficit/hyperactivity disorder (ADHD).

To assess non-drug healthcare resource use in adult patients with ADHD undergoing pharmacotherapy.

Practising psychiatrists in Scotland, Sweden and Denmark were invited from a healthcare professional database to complete an online survey between January and August 2014. Resource use estimations were based on typical adult patients (≥18 years) diagnosed with ADHD and showing either adequate or inadequate responses to ADHD medication.

Participating psychiatrists in Scotland (n=20), Sweden (n=20) and Denmark (n=15) saw a mean (standard deviation [SD]) of 10.3 (8.2), 17.8 (12.7) and 16.9 (16.5) adult patients with ADHD per month, respectively. Methylphenidate was the most commonly utilised first-line medication (74% of psychiatrists). Tables 1 and 2 show mean prescribed daily drug doses and resource use estimates.

Findings suggest that patients with an inadequate response to pharmacotherapy consume more non-drug healthcare resources than those with an adequate response. Whilst limited in sample size, this study provides initial data on non-drug healthcare resource use in adult ADHD. Table 1.Daily drug dose (mg) by country. n/a, not asked.

Table 2.Estimated mean resource use (visits/consultations) per year per patient.

R Oberguggenberger1,2, N Ruiz 1, M Ortega1, C Roset1, Y Rendal1, J Salva1, Lago E1, P Herbera1

1. Hospital Son Espases, Palma de Mallorca, Spain

2. Hospital Psiquiátrico. Palma de Mallorca, Spain

Polypharmacy in patients with schizophrenia is frequent in the short term and long term treatment. Prevalence of up to 50% of polypharmacy has been shown in some clinical settings. There is scare evidence of the prevalence of polypharmacy in inpatient settings.

The goal of this retrospective study is to assess the prescription patterns of patients with schizophrenia in a Spanish inpatient setting.

Records of all admissions between 2010 until 2012 in the adult ward of a public heatlh service in Palma de Mallorca will be analysed in this study.

The results will show current prescription patterns of patients with schizophrenia in a Spanish inpatient setting.

FGAs are successful for treatment, they are associated with significant adverse effects, some of which are irreversible. SGAs were developed for overcoming difficulties of managing adverse effects and are less associated with the physiological side effects, but are associated with an increased risk of dyslipidaemia, significant weight gain, metabolic syndrome and diabetes.

Comparison of the efficacy and tolerability of FGAs and SGAs in schizophrenic patients in a period of 14 months, and accordingly, reference to the global functioning of patients.

The sample consists of 30 patients diagnosed with schizophrenia, males and females aged between 18 and 55 years. They were divided into two groups, patients taking depo injection of the FGAs (15) and another group that received a depot preparation of the SGAs (15). We have used BPRS scale, CGI-S, CGI-I, the PANSS scale, GAF .

Comparing the results of this scale in both groups were used descriptive statistics T-test, X2 test and correlation tests.

FGAs group had worsening of 60% as measured by BPRS scale, 53% had a CGI-I scale assessment “severe ill” while not worsening occurred during the same time period in patients who have used the SGAs and the CGI-I had “significant improvement” (p<0.001). Differences between groups were in global functioning (GAF), which showed that patients with FGAs have a score of 41-50 (60%), whereas patients with SGAs have a score of 70-81 (80%) (p<0.001)

Comparison of FGAs and SGAs could improve the therapy protocol related to the benefits and adverse effects.

Preclinical and first clinical studies suggested that the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen might be effective in the treatment of alcohol dependence. However, previous randomized controlled trials have reported inconsistent results, possibly related to the low to medium dosages of baclofen used in these studies.

To assess the efficacy and safety of individually titrated high-dose baclofen (30-270 mg/d) for the treatment of alcohol dependence.

Fifty-six alcohol-dependent patients were randomized to a double-blind treatment with individually titrated baclofen or placebo. Multiple primary outcome measures were total abstinence and cumulative abstinence duration during a 12-week high-dose phase.

Preliminary results of this clinical trial will be presented.

To carry out a cost-consequences analysis for 50mg-desvenlafaxine in the second-line outpatient treatment of major depressive disorder (MDD) from the payer (National Health System) perspective in Spain.

The model (Markov simulation) follows a cohort of MDD patients through 1 year after failure of first-line treatment with a SSRI and estimates outcome measures (% remission and depression-free days) accrued and costs incurred during outpatient treatment of MDD. Selected comparator is usual care (UC), which is assumed to be made of a mix of duloxetine and venlafaxine that make up the majority of the serotonin-norepinephrine reuptake inhibitor (SNRI) market in Spain. The model also considers drug treatment beyond the second-line of therapy (3rd and 4th-lines) in cases of patient discontinuation or lack of remission according with outcomes from STAR-D trial and other clinical trial published. The model generates outcomes and cost from the NHS in year 2014.

Due to fewer discontinuations, desvenlafaxine was associated with numerically more depression-free days and a higher percentage of patients in remission versus UC: 1.7 days and 0.5% more in remission. Also, healthcare costs were lower with desvenlafaxine than with UC: €1,114 vs. €1,224 (-110€).

In patients who have not responded to a first-line SSRI therapy, desvenlafaxine-50mg was clinically similar in effectiveness but a less costly option, approximately 9% lower, compared with a weighted average of duloxetine and venlafaxine for the second-line treatment of MDD patients from a payer (NHS) perspective in Spain.

To model the cost and consequences of desvenlafaxine and venlafaxine in the second-line outpatient treatment of major depressive disorder (MDD) from the payer (National Health System) perspective in Spain.

The model (a Markov simulation) follows a cohort of MDD patients through 1 year after failure of first-line treatment with a Selective-Serotonin-Reuptake-Inhibitor (SSRI) and estimates outcome measures (% in remission and depression-free days) accrued and costs incurred during outpatient treatment of MDD. Selected comparator is venlafaxine because its actual generic price. The model also considers drug treatment switching beyond the second-line of therapy (3rd line) or changing to another drugs in 4th-line in cases of patient discontinuation or lack of remission according with outcomes from STAR-D trial. Efficacy of drugs was extracted from clinical trial published. The model generates outcomes and cost from the NHS in year 2014.

Due to fewer discontinuations, desvenlafaxine was associated with numerically more depression-free days and a higher percentage of patients in remission versus venlafaxine: 1.7 days and 0.5% more in remission. Also, healthcare costs were a little bit lower with desvenlafaxine than with venlafaxine: €1,114 vs. €1,166 (-52€).

In patients who have not responded to a first-line SSRI therapy, desvenlafaxine-50mg was clinically similar in effectiveness but a less costly option (about 5% lower) compared with venlafaxine for the second-line treatment of MDD patients from a payer (NHS) perspective in Spain.

Saikosaponin B is one of the main ingredients of Bupleurum. Among the many effects of Bupleurum, saikosaponin B may be contributing molecules.human neuroblastoma cell line SH-SY5Y is a tumor cells of low degree of differentiation. Its cell morphology, physiology and biochemical functions similar to normal nerve cells, are widely used to study the mechanism of diseases and drug, of the nervous system.

To investigate the effect of Saikosaponin B on SH-SY5Y cells.

Cultured SH-SY5Y cells and drawed cell growth curve. Then based on the cell growth curve, using hydrogen peroxide of different doses(110?120?130?140?150?160?180?200?220μmol/L) to treated SH-SY5Y cells. At same time, volume fraction 0.05 serum contained Saikosaponin B was added. Cultured SH-SY5Y cells were observed by morphology and tested by the MTT assay.

Less than 140μmol/L hydrogen peroxide, SH-SY5Y cells does not be caused damage. Saikosaponin B of volume fraction 0.05 can relieve the damage of SH-SY5Y cells treated with 140μmol/L hydrogen peroxide, also can increase the survival of the SH-SY5Y cells.

Saikosaponin B can strongly protect the cultured SH-SY5Y cells from damage induced by hydrogen peroxide.

Dopamine D2 receptors (D2R) are the primary target of antipsychotic drugs and have been shown to regulate Akt/glycogen synthase kinase-3b (GSK-3b) signaling through scaffolding protein b-arrestin 2.

In the present study, we researched the effects of saikosaponin B1 on the b-arrestin 2-mediated Akt/GSK-3b pathway in human neuroblastoma cell lineSH-SY5Y cells.

To determine whether saikosaponin B1 affected neuronal morphology in human neuroblastoma cell line SH-SY5Y cells.

We investigated the effects of saikosaponin B1 on neurite outgrowth using immunostaining. We examined the effects of saikosaponin B1 on Akt and GSK-3b and its well-known downstream regulators, cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and Bcl-2 levels using Western blot analysis.

Saikosaponin B1 was found to enhance neurite outgrowth. Small interfering RNA (siRNA) for b-arrestin 2 knockdown blocked the increase in saikosaponin B1-induced neurite outgrowth. Furthermore, saikosaponin B1 increased the levels of Akt and GSK-3b phosphorylation. The elevation of Akt phosphorylation induced by saikosaponin B1 was reduced by b-arrestin 2 siRNA. Moreover, saikosaponin B1 effectively increased the levels of phospho-CREB, BDNF, and Bcl-2.

Together, these results suggest that regulation of the b-arrestin 2-dependent pathway via blockade of the D2R in SH-SY5Y cells is one mechanism underlying the neuroprotective effect of saikosaponin B1.