It is well known that hyperprolactinemia increases the risk of hypogonadism, osteoporosis and cardiovascular diseases. Atypical anti-psychotics are directly related with its development. Despite its importance, pharmacological hyperprolactinemia it is not considered and treated by psychiatrists as much as expected. Nowadays, long-acting aripiprazole is one of the main treatments that barely increase the prolactin (PRL) levels.

To determine the number of cases in which PRL levels are detected. To quantify the reduction of PRL levels with patients treated with long-acting aripiprazole.

Observational, descriptive study, from February 2015 to July 2016, of 52 patients treated with anti-psychotics, in two Sevillian community mental health centers.

In 56% of cases, PRL level was measured at least one time: in 77% of cases with prescription of long-acting aripiprazole, PRL levels are reduced.

First step to reduce the impact of hyperprolactinemia in patients is to determine the PRL levels in a systematic way being this practice a must to be considered. In the study carried out and described in this abstract, reduction of PRL levels in target populations using long-acting aripiprazole is observed.

The authors have not supplied their declaration of competing interest.

Clozapine is an atypical anti-psychotic used in the treatment of schizophrenia and other psychotic disorders. It is associated with several side effects, namely, hematologic disorders, the more common being agranulocytosis. Some cases of eosinophilia have been described. This work describes a case of transient eosinophilia caused by clozapine.

Description of a clinical case.

A 22-year-old female patient, with a treatment resistant psychotic disorder initiated clozapine in a slow titration to 300 mg. Ten days after initiating clozapine, the patient presented with eosinophilia (started with 6.6 × 108/L and peaked at 10.0 × 108/L). Two weeks later, the patient presented with a skin rash in the arms and legs. The case was discussed with internal medicine service and other causes of eosinophilia were excluded. Since the eosinophilia was mild, the rash was not severe and the patient did not present any other symptoms or signs, it was not considered necessary to stop clozapine. During the next three months, with close monitoring, the eosinophilia and the skin rash slowly resolved.

This is a case of a patient who presented mild eosinophilia and skin rash, associated to clozapine, with spontaneous resolution. We draw attention to the need of close monitorization and exclusion of other causes of eosiniphilia and rash. Furthermore, other hematologic disorders should be considered besides agranulocytosis, namely eosinophilia, when prescribing clozapine.

The authors have not supplied their declaration of competing interest.

Objective was to compare the prevalence of probable polycystic ovarian syndrome (PCOS) in females treated with atypical anti-psychotics with normal controls.

To compare the prevalence of PCOS in patients treated with atypical anti-psychotics and normal controls. To study the hormone profiles in these two groups.

Cases consisted of 102 reproductive age females with schizophrenia treated with atypical anti-psychotics for ≥6 months and had gained ≥10% body weight. Control group was 123 age and BMI matched females. Menstrual history, physical examination for hirsuitism, acne, androgenic alopecia, anthropometrics measures, Ultrasound abdomen and hormone analysis were done.

Mean age of cases = 33.17 years (SD 8.9) and controls = 33.08 years (SD 5.6). Mean BMI of cases = 25.92 (SD 5.2) and controls = 25.03 (SD 4.3). Polycystic ovarian morphology of ovaries on ultra sound scan was significantly more in cases 49 (48%) than controls 16 (13.%) (P < 0.001). Probable PCOS was significantly more in atypical anti-psychotic treated females (n = 22, 21.56%) than in normal controls (n = 10, 8.13%) (P = 0.04). Atypical anti-psychotic treated patients with PCOS had significantly lower mean LH levels 6.69 mIU/L than those without PCOS 10.30 (P = 0.35). There was no significant difference in testosterone, FSH, prolactin, TSH and free T4 levels.

Treatment with atypical anti-psychotics is associated with higher prevalence of PCOS. This has not been reported previously. The hormonal profile in these patients may be different with low testosterone and LH levels.

The authors have not supplied their declaration of competing interest.

The aim of this study was to investigate the unconventional side-effects of selective serotonin reuptake inhibitors (SSRIs) and tricyclics (TCAs) antidepressants during long-term treatment of depression, with a special focus on emotional blunting and, in particular, on the possible changes of some features of loving relationships.

Two hundred outpatients (130 women and 70 men, mean age ± SD: 43.4 ± 11.1 years) were enrolled. They were suffering from mild or moderate depression, according to DSM–5 criteria, treated with one antidepressant for at least six months and involved in a long-term loving relationship. A specifically designed test, the so-called “sex, attachment, love” (SALT) questionnaire was built to assess the possible changes of the loving relationship.

The results showed differences between the two genders, in particular women taking TCAs reported more sexual side effects than men, whereas men taking SSRIs complained a reduction of the feelings of love and attachment towards the partner.

Antidepressants seem to have a dimorphic effect on some elements of loving relationships, however these results need to be further explored.

The authors have not supplied their declaration of competing interest.

Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressants worldwide. In older adults, citalopram is generally well tolerated and safe in the therapeutic dose range of 20 to 40 mg/day. In literature, there are cases of SSRI-induced psychosis, but mainly with fluoxetine. There are only three reported cases of citalopram-induced delusions, however, these case-reports did not involve an older adult.

To provide a case of citalopram–induced psychosis in an older adult, followed by the review of available literature.

A case report is presented and discussed followed by a literature review.

A 64-year-old woman without somatic illnesses was referred by a general practitioner with depressive symptoms. One week after initiation of citalopram 10 mg/day she suddenly developed delusions, predominantly in the early morning. No other medical evidence was found that could explain her delusions. After discontinuation of citalopram her delusions quickly resolved.

This is the first case report of a SSRI-induced delusion in an older adult. Citalopram has been reported to be one of the safest SSRIs. Although most SSRI's have a mild side-effect profile, care should be taken when initiating SSRIs since unpredictable adverse effects may occur.

The authors have not supplied their declaration of competing interest.

Anti-psychotics constitute a class of psychotropic drugs used for the treatment and prophylaxis of several disorders, including schizophrenia, bipolar disorder and psychotic depression. Frequently, clinicians are asked by their patients to withdraw this medication. In some cases, that may be related to notable side effects. However, it may actually indicate an inadequate control of the psychiatric disorder with poor insight.

The goal of this work is to systematically review the scientific literature in order to understand if there are consistent data that support anti-psychotics withdraw in specific clinical situations.

The literature was reviewed by online searching using PubMed®. The authors selected scientific papers with the words “anti-psychotics” and “withdraw” in the title and/or abstract, published in English.

Anti-psychotics improve prognosis and enhance patients’ quality of life. There are few data in the literature regarding recommendations that support anti-psychotic withdraw in psychiatric patients. Very specific conditions must exist for withdrawing anti-psychotics, like neuroleptic malignant syndrome, cardiac side effects, and change of diagnosis or prolonged remission after a first and single psychotic event. When that decision is made, it should be done slowly and carefully and both the patient and his family should be involved.

There is no evidence in the literature that supports withdraw of anti-psychotics for the majority of psychiatric situations. When specific conditions are present that possibility must then be considered, however, with careful consideration and after discussion with the patient and parties involved in patient's care.

The authors have not supplied their declaration of competing interest.

The aim of this study was to investigate the relationship between metabolic factors and use of selective serotonin reuptake inhibitors (SSRIs) combined with olanzapine, quetiapine or risperidone.

Data from a cross-sectional study on 1301 patients with schizophrenia or bipolar disorder were analyzed. The main outcome variables were levels of total cholesterol, low – and high-density lipoprotein (LDL and HDL) cholesterol, triglycerides and glucose.

One defined daily dose (DDD) per day of an SSRI in addition to olanzapine was associated with an increase in total cholesterol of 0.16 (CI: 0.01 to 0.32) mmol/L (P = 0.042) and an increase in LDL–cholesterol of 0.17 (CI: 0.02 to 0.31) mmol/L (P = 0.022). An SSRI serum concentration in the middle of the reference interval in addition to quetiapine was associated with an increase in total cholesterol of 0.39 (CI: 0.10 to 0.68) mmol/L (P = 0.011) and an increase in LDL-cholesterol of 0.29 (0.02 to 0.56) mmol/L (P = 0.037). When combined with risperidone, no such effects were revealed. No clear-cut effects were seen for HDL-cholesterol, triglycerides and glucose.

The findings indicate only minor deteriorations of metabolic variables associated with treatment with an SSRI in addition to olanzapine and quetiapine, but not risperidone. These results provide new insight in the cardiovascular risk profile associated with concomitant drug treatment in patients with severe mental illness, and suggest that SSRIs can be combined with anti-psychotics without a clinically significant increase of adverse metabolic effects.

Co-author Dr. Ole Andreassen has received speakers’ honoraria from GSK, Lundbeck and Otsuka.

Psychosis in childhood and adolescence could be defined as having hallucinations, with the hallucinations occurring in the absence of insight. A broader definition includes symptoms such as delirious thoughts, disorganized speech, disorganized behavior, cognitive and mood symptoms and what is called negative symptoms. Several researches have been done focused in the treatment of first episode of psychosis showing clozapine as a keystone in the treatment of psychosis, especially in refractory first episodes.

Clozapine has unique efficacy in improving treatment-resistant patients with chronic schizophrenia but the moment of instauration remains unclear. There have always been doubts about the right moment to start clozapine, after two or more previous anti-psychotics or as first option.

We report a 18-year- old woman with family history of severe psychosis. Her mum reasserted patient's symptoms contributing to a longer period of non-treating psychosis (about 10 months). Auditory hallucinations, incongruent mood and incoherent language appeared for the first time at the age of 17. High doses of two consecutive anti-psychotics were tried without remission and finally clozapine was initiated with clinical improvement.

In clinical practice, a subgroup of psychotic patients experience, significant ongoing positive symptoms despite of using first line anti-psychotic medication.

Most recent research; suggest that clozapine may have an important role in the early treatment of first-episode patients, even becoming a first line option to consider.

The authors have not supplied their declaration of competing interest.

Several trials have shown the efficacy of long acting injectable (LAI) second-generation anti-psychotics compared with other anti-psychotics. LAI aripiprazole is a novel therapeutic tool in the management of patients with schizophrenia.

The present study aimed to evaluate the clinical outcomes of patients who initiated treatment with LAI aripiprazole, by comparing their clinical outcomes prior and after initiating treatment with LAI aripiprazole.

This observational, retrospective, mirror study assessed a series of socio-demographic and clinical variables during the 12 months prior to commencing LAI aripiprazole, while on another anti-psychotic medication, and the first 12 months of LAI aripiprazole. The sample included a series of consecutive patients receiving LAI aripiprazole at the Doctor Peset university hospital health area, in Valencia (Spain). The variables analyzed in the study included: emergency room visits, number and average length of hospitalizations, relapse, rate of abandonment of treatment and number of anti-psychotics needed as maintenance treatment.

The preliminary analysis showed a reduction in the rate of emergency room visits and the number of relapse and total hospitalizations while on LAI aripiprazole; however, there is no a reduction of the average length of hospitalizations. A reduction in the number of anti-psychotics as maintenance treatment was not appreciated, however, there was an improvement in treatment adherence.

The preliminary results showed that LAI aripiprazole is an useful option that could suppose a benefit concerning treatment adherence, a decreased in number of relapses and hospitalizations and use of health resources.

The authors have not supplied their declaration of competing interest.

Some diseases relapses involve functional impairment that sometimes takes years to recover. We present our experience using long-acting aripiprazole as maintenance therapy in patients diagnosed with psychotic episode, acute mania (bipolar disorder) or personality disorder, who were previously treated with another anti-psychotic.

Analyze what treatment were they taking before aripiprazole depot. Determine the number of hospital admissions and relapses before and after long-acting aripiprazole treatment.

Descriptive analysis based on a sample of 37 patients, aged 18–65 years, treated during one year with anti-psychotics at two community mental health units.

Reduction of hospitalization average: 0.59/year with non-long-acting-aripiprazol anti-psychotic, 0.18/year with long-acting aripiprazol (66.6%).

Long-acting aripiprazole appears to reduce the number of hospitalizations and relapses compared to other anti-psychotics. However, the sample size is small and more studies are needed.

The authors have not supplied their declaration of competing interest.

It's known that, patients with schizophrenia smoke more tobacco than general population, and that tobacco is a potent inducer of cythocrome P450 isoenzyme 1A2 (CYP 1A2). In addition, clozapine and quetiapine, drugs frequently used in the treatment of schizophrenia, are CYP1A2 substrates. So, tobacco smoking may reduce blood levels of clozapine and quetiapine.

To revisit the influence of changes in tobacco consumption in clozapine and quetiapine side effects.

Case report.

A 48-year-old male diagnosed of schizophrenia following DSM IV-TR criteria. He required five hospital admissions from 2008 to 2013 because of psychotic episodes. Since 2013, he was asymptomathic receiving clozapine, 600 mg/day, and quetiapine, 1200 mg/day. Recently, he came to the emergency service due to sudden extreme sedation, thinking impairment, sialorrhea, and walking disability. The patient denied treatment abuse and his family confirmed this statement. When asked about toxics he referred progressive tobacco reduction in the last 3 months (from 60 to 20 cigarettes/day). Bearing in mind the relationship between clozapine and quetiapine metabolism and tobacco, treatment was slowly reduced until the doses of clozapine 500 mg/day and quetiapine 400 mg/day. One week after admission, side effects disappeared, psychotic symptoms were not detected, and the patient was discharged.

Inquiring about changes in tobacco consumption may be useful when anti-psychotics side effects appear suddenly without an alternative explanation.

The authors have not supplied their declaration of competing interest.

It is not known whether sex and age are risk factors for neuroleptic malignant syndrome (NMS).

To examine sex and age distributions in NMS patients based on a systematic review of the literature.

Estimate the sex-specific relative risk of an NMS diagnosis.

EMBASE and PubMed databases were searched in November 2014 using broad, unrestricted criteria to identify any published observation of NMS. Any physically (online or hard copy) accessible and interpretable (using language translation software) report published from January 1, 1998 through November 1, 2014 was considered for inclusion. Secondary sources (e.g., reviews) were included when primary sources could not be accessed. All cases for which the patient's sex or the sample's sex distribution was provided were included, except for redundant reports and cases in which NMS was not the most likely clinical diagnosis. Sex ratio and age distributions were examined using standard graphical techniques and measures of association.

Twenty-eight independent NMS sex ratio estimates were included. Most sex ratio estimates (75%) indicated male preponderance, with a median of 1.47 (95% CI: 1.20–1.80). NMS incidence peaked at age 20–25 years and declined steadily thereafter; males consistently outnumbered females at all age intervals. Major study limitations are the heterogeneity of case ascertainment procedures and the potential for publication bias.

NMS patients are 50% more likely to be males, and NMS is most likely to occur in young adulthood. Men, and all young adults, appear to be at increased risk for NMS.

The authors have not supplied their declaration of competing interest.

Neuroleptic malignant syndrome (NMS) requires prompt recognition for effective management, but there are no established diagnostic criteria.

To validate the recently published international expert consensus (IEC) diagnostic criteria for NMS, which assign priority points based on the relative importance of each criterion for diagnosing NMS.

Determine optimal diagnostic cutoff for priority point score.

Data were extracted from 221 archived telephone contact reports of clinician-initiated calls to a national telephone consultation service from 1997–2009; each case was given a total priority point score based on the IEC criteria. DSM-IV-TR research criteria, in original form and modified to accept less than ‘severe’ rigidity, served as the primary diagnostic reference standard. Consultants’ diagnoses served as an additional reference standard. The optimal priority point cutoff score was determined using receiver operating characteristic (ROC) curve analysis.

Area under the ROC curve ranged from 0.715 (95% CI = 0.645–0.785, P < 0.001) for consultant diagnoses to 0.857 (95% CI = 0.808–0.907, P < 0.001) for modified DSM-IV-TR criteria. The latter was associated with 69.6% sensitivity and 90.7% specificity.

Agreement was best between IEC criteria with a cutoff score of 74 and modified DSM-IV-TR criteria (sensitivity 69.6%, specificity 90.7%); this cutoff score demonstrated the highest agreement in all comparisons. Consultant diagnoses showed much better agreement with modified, compared to original, DSM-IV-TR criteria, suggesting that the DSM-IV-TR criterion of “severe” rigidity may be more restrictive than what most knowledgeable clinicians use in practice.

The authors have not supplied their declaration of competing interest.

Several studies suggested that second-generation long-acting injectable anti-psychotics (SGA-LAIs) might be effective on preventing relapse and admission/readmission rates among patients affected by schizophrenic and bipolar disorders. Moreover, studies highlighted that SGA-LAIs may reduce costs and healthcare resource utilization (HRU) among community psychiatric settings.

The objective of the present study was to evaluate whether the increased use of SGA-LAIs among community psychiatric services in southern Tuscany was related to:

– reduced costs and HRU;

– reduced hospital admission/readmission.

Data consisted of both regional registry and data prospectively collected at admission and/or follow up assessments. Patients included were: patients affected by schizophrenia/schizoaffective or bipolar disorders, treated with SGA-LAIs.

The increased use of SGA-LAIs was related to a significant reduction of admission and/or readmission rates, as long as a significant reduction in costs and HRU among the community services included in the study.

The present findings suggest that SGA-LAIs might have a positive cost/effectiveness profile and could reduce hospitalizations, costs and HRU among a community sample. This could be related to a better tolerability of SGA-LAIs compared to FGA-LAIs, and less adverse effects. More studies on community samples should focus on the cost/effectiveness profile of SGA-LAIs.

The authors have not supplied their declaration of competing interest.

Tardive syndromes (TS) resulting from prolonged exposure to dopamine receptor blocking agents are frequent. Clozapine is considered to have a low risk of causing new onset TS and accounts therefore as an interesting option in patients with invalidating TS.

Our study aims to describe clozapine indications in patients experiencing TS.

Presentation of the clinical cases of five patients, who experienced different kinds of TS secondary to 1st and 2nd generation anti-psychotic treatment.

We present the cases of AB aged 41, MJ aged 40, HM aged 31 and AS aged 30, diagnosed with schizophrenia; and FB aged 24,diagnosed with schizoaffective disorder. Adverse side effects to conventional anti-psychotics such as limb and trunk tremors were described for AB, choreic limb movements, axial and segmental dystonia for MJ, AS, FB and oculogyration for FB. All patients were switched to atypical anti-psychotics without improvement of the TS. The switch to clozapine, associated with abotulinum injection for MJ, led to regression of the TS and improvement of clinical signs. In fact, according to several studies, clozapine seems to be an interesting option when invalidating TS occurs. The low prevalence of TS under clozapine can be explained by its low affinity for striatal-D2 receptors, its anti-serotonin and anti-cholinergic effects.

Clozapine should be considered in symptomatic patients who develop TS while receiving other anti-psychotics. Further research on mechanism of TS and clozapine effect on TS is needed.

The authors have not supplied their declaration of competing interest.

Atypical anti-psychotics are increasingly prescribed, given their tolerance. Among these anti-psychotic olanzapine, known for its adverse metabolic effects. By against an adverse event type rhabdomyolysis with olanzapine appears uncommon (<1%) and few clinical cases have been reported in the literature.

The aim of our study is to illustrate with a clinical case the occurrence of an isolated rhabdomyolysis with olanzapine.

Starting from the study of the case of a patient with rhabdomyolysis with olanzapine we studied the literature data. Clinical vignette: it is about a patient aged 25 followed for bipolar disorder type I. He responded to the association olanzapine and valproic acid then to valproic acid only. His last hospitalization for manic relapse dating to September 9, 2015 occurred in a context of treatment discontinuation. Upon admission the patient underwent an oral treatment based olanzapine and valproic acid. A dosage of creatine phosphokinase (CPK) done systematically, on September 11 showed high levels of (CPK) to 973 (U/L) without clinical signs of neuroleptic malignant syndrome. The electrocardiogram and biological tests results were normal. Other etiologies can lead to elevated (CPK) were eliminated. The persistent elevation of CPK motivated the arrest of olanzapine. The evolution was marked by a return to normal CPK rates after 15 days. The olanzapine was replaced by haloperidol and vaproic acid maintained. The pharmacovigilance investigation conclude to the accountability of olanzapine in this rhabdomyolysis.

Second generation, anti-psychotics are known for their better tolerance compared to conventional antipsychotics. However, they are not devoid of side effects.

The authors have not supplied their declaration of competing interest.

Clozapine, is widely prescribed for treatment of refractory schizophrenia, but its use may be limited by potentially serious adverse effects. The most feared complication remains agranulocytosis [absolute neutrophil count (ANC) < 500/mm3], which occurs in 1% of patients. Guidelines recommend immediate cessation until the granulocyte count normalizes, but little is known about the subsequent treatment and the possibility of restoring clozapine.

To know procedures that allow clozapine rechallenge after induced agranulocytosis in refractory schizophrenia.

We present a clinical case of agranulocytosis and evolution after simple reinstitution of clozapine.

A 38-year-old woman diagnosed refractory schizophrenia. After 10 years with clozapine (300 mg/day), we find neutropenia (ANC 1420/mm3) in a monthly control blood count with progression to agranulocytosis (ANC 460/mm3) in the following month. We suspend clozapine and started olanzapine (20 mg/day) with restoration of haematological values in a period of one month. The patient had psychotic decompensation at two months after the change with lack of response to different psychopharmacological strategies for five months. According to the hematology department we decided to re-introduce clozapine (200 mg/day) in combination with olanzapine with complete clinical remission. Between the 3rd and 9th week after rechallenge we observe a progressive decline in ANC, while remaining within the range of normal. From the 9th week and in the last 6 months neutrophil counts remained stable.

Although, more research is needed to establish the safety to rechallenge of clozapine after agranulocytosis, it must be an alternative to consider when other treatment strategies fail.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Agranulocytosis is a potentially life-threatening haematological side effect induced by typical and atypical neuroleptic. When agranulocytosis is associated with a specific anti-psychotic, the medication should be discontinued. This severe side effect is troublesome.

We report the case of a 60-year-old man, treated with amisulpride for schizophrenia, who developed an agranulocytosis. This patient had been treated with first and second generation anti-psychotic drugs during his life and had already been exposed to many neuroleptics without any signs of toxicity. However, after three days of the introduction of amisulpride he presented a rapid onset agranulocytosis (leukocytes 1.2 G/L and neutrophils 0.4 G/L). After discontinuation of amisulpride, blood count returned to normal. The favorable evolution after discontinuation of treatment: the normality of biological and cytological examinations is in favor of a causal relationship between this severe neutropenia al introduction of amisulpride.

This case report highlights the risk of amisulpride in inducing agranulocytosis, a risk underestimated in regard of the clozapine risk to induce agranulocytosis or neutropenia. For this reason, it seems reasonable to recommend performing a blood count before introduction and during the treatment by anti-psychotics.

The authors have not supplied their declaration of competing interest.

Drug-induced liver injury is a major problem of pharmacotherapy and is also frequent with anti-depressive psychopharmacotherapy.

However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepressants.

We performed a quantitative signal detection analysis using pharmacovigilance data from the Uppsala monitoring center from the WHO that records adverse drug reaction data from worldwide sources; we calculated reporting odds ratios (ROR) as measures for disproportionality within a case-/non-case approach for several frequently prescribed anti-depressants.

Both positive controls, amineptine (ROR 38.4 [95% CI: 33.8–43.6]) and nefazodone (ROR 3.2 [95% CI: 3.0–3.5]), were statistically associated with hepatotoxicity. Following amineptine, agomelatine (ROR 6.4 [95% CI: 5.7–7.2]) was associated with the second highest ROR, followed by tianeptine (ROR 4.4 [95% CI: 3.6–5.3]), mianserin (ROR 3.6 [95% CI: 3.3–3.4]) and nefazodone.

In line with previous studies our results support the hypothesis that agomelatine and several other anti-depressants may be associated with relevant hepatotoxicity. However, the used data and applied method do not allow a quantitative evaluation of hepatotoxicity or assessment of substance–specific differences regarding the extent of hepatotoxicity.

The authors have not supplied their declaration of competing interest.