Serotonin reuptake inhibitors and breastfeeding: a systematic review.

OBJECTIVE: The postnatal period represents a critical phase for mothers because of physiological hormonal changes, the increase of emotional reactions and a greater susceptibility for the onset/recrudescence of psychiatric disorders. Despite the evidence of an increasing utilization of antidepressant drugs during breastfeeding, there is still few reliable information on the neonatal safety of the selective serotonin reuptake inhibitors (SSRIs) and selective noradrenergic reuptake inhibitors (SNRIs) [serotonin reuptake inhibitors (SRIs)] in nursing mothers. The aim of this study is to provide a systematic review on the neonatal safety profile of these drugs during breastfeeding, also assessing the limits of available tools. METHODS: MEDLINE and PubMed databases were searched without any language restrictions by using the following set of keywords: ((SSRIs OR selective serotonin inhibitor reuptake OR SNRIs OR selective serotonin noradrenaline inhibitor reuptake) AND (breastfeeding OR lactation OR breast milk)). A separate search was also performed for each SSRIs (paroxetine, fluvoxamine, fluoxetine, sertraline, citalopram and escitalopram) and SNRIs (venlafaxine and duloxetine). RESULTS: Sertraline and paroxetine show a better neonatal safety profile during breastfeeding as compared with other SRIs. Less data are available for fluvoxamine, escitalopram and duloxetine. Few studies followed up infants breastfeed for assessing the neurodevelopmental outcomes. CONCLUSIONS: Literature review clearly indicates paroxetine and sertraline as the drugs that should be preferred as first line choice in nursing women who need an antidepressant treatment.

The safety of serotonin-noradrenaline reuptake inhibitors (SNRIs) in pregnancy and breastfeeding: a comprehensive review.

OBJECTIVE: The present study provides a comprehensive review of the existing literature on the safety of serotonin-noradrenaline reuptake inhibitors (SNRIs) in pregnancy and lactation. METHODS: Studies published in English, reporting the use of SNRIs in pregnant and/or breastfeeding women, were identified by searching MEDLINE/Pubmed, PsycINFO, and EMBASE. RESULTS: Twenty-nine studies were included in the review. Altogether, the initial evidence coming from the reviewed studies suggests a lack of association between SNRIs and an increased risk of major congenital malformations. Conversely, exposure to SNRIs seems to be significantly associated with an increased risk of some perinatal complications. No neonatal adverse events emerged, so far, in the few studies concerning the safety of SNRIs during breastfeeding. CONCLUSIONS: Available data suggest that venlafaxine is relatively safe during pregnancy, in particular as far as major malformations are concerned, whereas considering the small number of studies published, no definitive conclusions can be drawn on its safety during breastfeeding. Because of the few studies so far published, the safety of duloxetine during pregnancy and breastfeeding remains to be well established.

[Antidepressants-SSRIs in pregnancy and risk of major malformations: treat or not to treat]. / Antidepressivi-SSRI in gravidanza e rischio di malformazioni maggiori: trattare o non trattare?

Considering teratogenic risk, recent data suggest that selective serotonin reuptake inhibitors (SSRIs) can be prescribed during pregnancy, even though some SSRIs are to be considered as a second choice. In any case, antidepressive treatment during pregnancy must be carefully tailored to the pregnant woman, considering absolute risk/benefit ratio of SSRIs, but also availability of other effective treatments, as well as woman's preferences.

Psychotropic drug treatment in anorexia nervosa. Search for differences in efficacy/tolerability between adolescent and mixed-age population.

BACKGROUND: During the last 10 years, the use of psychotropic medications in youth with psychiatric disorders, including eating disorders, has significantly increased, but their role in the treatment of adolescent anorexia nervosa is still controversial. OBJECTIVE: This paper aims to review the literature on the use of antidepressants and antipsychotics in adolescents with anorexia nervosa, comparing the efficacy and tolerability in this population with those reported in trials with patients not selected by age. METHOD: A systematic review of the available literature published so far. RESULTS: Only few studies met the selection criteria. No strong evidence of beneficial effects was found in using antidepressants and antipsychotics neither in adults nor in adolescents. Side effects were more frequently reported in studies including adolescent population. Among psychotropic drugs, the majority of studies focused on olanzapine, which seems to have, in some studies, only positive effects on body mass index, eating disorder symptoms and functional impairment in both age groups.

The safety of escitalopram during pregnancy and breastfeeding: a comprehensive review.

OBJECTIVE: Escitalopram (ESC) is considered one of the most effective selective serotonin reuptake inhibitors for the treatment of major depression. However, little is known on its potential risk of inducing major malformations (MMs) and perinatal complications (PCs). Hence, aim of the present study is to provide a comprehensive review of the available literature on the safety profile of ESC during pregnancy and breastfeeding. METHODS: MEDLINE and PubMed databases were searched for English language articles by using the following keywords: escitalopram, selective serotonin reuptake inhibitors, major malformations, perinatal complications, pregnancy, and breastfeeding. RESULTS: Although some cases of MMs have been reported after maternal exposure to ESC during early pregnancy, the rate of these adverse events is substantially in the range of those reported in unexposed women. On the contrary, exposure to ESC seems to be significantly associated with some PCs. No adverse effects have been reported in the few studies evaluating its safety during breastfeeding. CONCLUSIONS: The available data seem to support the notion that ESC might be considered safe during pregnancy, in particular as far as MMs is concerned. However, similar to other selective serotonin reuptake inhibitors, it could be associated with an increased risk of PCs. Given the paucity of the studies published so far, no definitive conclusions can be drawn on its safety profile during breastfeeding.

Determinants of ante-partum depression: a multicenter study.

INTRODUCTION: Ante-partum depression (APD) is usually defined as a non-psychotic depressive episode of mild to moderate severity, beginning in or extending into pregnancy. APD has received less attention than postpartum depression. This is a cross-sectional study carried out in the Obstetrics and Gynaecology (OG) departments of four different general hospitals in Italy. METHODS: Women attending consecutively the OG departments for their first ultrasound examination were asked to fill in the Edinburgh Postnatal Depression Scale (EPDS) in its Italian validated version. We used the total scores of the EPDS as a continuous variable for univariate and linear regression analyses; in accordance with the literature, the item analysis of EPDS was carried out by classifying the sample as women with "no depression" (scores 0-9), "possible depression" (scores 10-12), "probable depression" (scores 13+) and "probable APD" (scores 15+). RESULTS: The number of women recruited was 1,608. The EPDS assessment classified 10.9 % of the women as possibly depressed, 8.3 % as probably depressed and 4.7 % probably affected from an APD. EPDS score distribution was associated with nationality (higher scores for foreigners), cohabitation (higher scores for women living with friends or in a community), occupation (higher scores for housewives), past episodes of depression and use of herbal drugs. Non-depressed women had significantly lower values on all ten items as compared with depressed women, however, the pattern of item distribution on the EPDS scale remained similar across depression severity groups. In all four groups item 4 (anxious depression) attained the highest scores, while item 10 (suicidality) attained the lowest scores.

The Mini Questionnaire of Personal Organization (MQPO): preliminary validation of a new post-rationalist personality questionnaire.

BACKGROUND: The Mini Questionnaire of Personal Organization (MQPO) has been constructed in order to comply with the inward/outward Personal Meaning Organization's (PMO) theory. According to Nardi's Adaptive Post-Rationalist approach, predictable and invariable caregivers' behaviours allow inward focus and a physical sight of reciprocity; non-predictable and variable caregivers' behaviours allow outward focus and a semantic sight of reciprocity. METHODS: The 20 items of MQPO have been selected from 29 intermediate (n = 160) and 40 initial items (n = 204). Psychometric validation has been conducted (n = 296), including Internal Validity (Item-Total Correlation; Factor Analysis), Internal Coherence by Factor Analysis, two analyses in Discriminant Validity (n = 132 and n = 80) and Reliability by Test-Retest Analysis (n = 49). All subjects have been given their written informed consent before beginning the test. RESULTS: The validation of the MQPO shows that the ultimate version is consistent with its post-rationalist paradigm. Four different factors have been found, one for each PMO. Validity of the construct and the internal reliability index are satisfying (Alpha = 0.73). Moreover, the results obtained are constant (from r = 0.80 to r = 0.89). There is an adequate agreement between the MQPO scales and the clinical evaluations (72.5%), as well as an excellent agreement (80.0%) between the scores of the MQPO and those of the Personal Meaning Questionnaire. CONCLUSION: The MQPO is a tool able to study personality as a process by focusing on the relationships between personality and developmental process axes, which are the bases of the PMO's theory, according to the APR approach.

[Efficacy, tolerability and safety of paliperidone extended-release in the treatment of schizophrenia and schizoaffective disorder]. / Efficacia, tollerabilità e sicurezza di paliperidone a rilascio prolungato nella terapia della schizofrenia e del disturbo schizoaffettivo.

INTRODUCTION: The paper represents a systematic review on the efficacy, tolerability and safety of paliperidone, an antipsychotic drug recently approved in Italy for the treatment of schizophrenia and of schizoaffective disorder. METHODS: A comprehensive PubMed search using the term "paliperidone" was performed from January 1980 to February 2011. Papers reporting data on efficacy in the treatment of schizophrenia and of schizoaffective disorder were included, also if published as abstracts and all retrieved articles were manually searched for other references of interest. RESULTS: Paliperidone was found to be effective in short and long-term treatment of schizophrenia, as well as in the treatment of schizoaffective disorder. For both disorders, paliperidone showed to be effective in improving psychotic and affective symptoms. In the studies analyzed it was well tolerated and the most frequent reported adverse events were mild extrapyramidal symptoms and an increase in serum prolactin levels. CONCLUSIONS: Paliperidone has been shown to be an effective and safe medication for the treatment of schizophrenia and schizoaffective disorder. Further controlled clinical trials are needed to confirm this clinical profile in the long-term treatment, as well as for specific conditions such as schizophrenic patients with medical comorbidities.

[Is the cognitive-behavioural therapy an effective strategy also in the prevention of post partum depression? a critical review]. / La terapia cognitivo-comportamentale è una strategia efficace anche nella prevenzione della depressione post partum? Una revisione critica.

OBJECTIVE: The aim of this study was to evaluate the efficacy of cognitive-behavioural therapy (CBT) in the prevention of post partum depression (PPD) in pregnant women at risk. METHODS: PubMed, Medline, PsychInfo, Embase, and the Cochrane Library databases were searched from January 1991 to June 2011 to review studies on the efficacy of CBT in the prevention of PD. RESULTS: The literature analyzed recommends that depression in pregnancy requires an efficient management to provide mother's symptoms relief as well as to prevent PD. While several studies demonstrated the efficacy of CBT in the treatment of PD, only a few controlled studies focused on its efficacy in the prevention of PD in women identified at risk during pregnancy. The efficacy of CBT in preventing PD in pregnant women at risk is supported by only a few studies, presenting some methodological flaws. DISCUSSION: Better designed trials are needed to strongly support the efficacy of such psychotherapeutic preventive strategy in women at risk for PD.

Patient characteristics and process factors associated with antipsychotic polypharmacy in a nationwide sample of psychiatric inpatients in Italy.

PURPOSE: The present study investigated: (i) the rate of prescription of antipsychotic (AP) polypharmacy (APP) in a large, representative sample of psychiatric inpatients; and (ii) the relationship between APP prescription and the characteristics of patients and facilities. METHODS: The sample included 1022 psychiatric patients scheduled to be discharged from acute inpatient facilities with drug therapies including AP. Demographic and clinical data were obtained from the treating physician or retrieved from patients' records through a standardized Patient Form. Patients were administered the 24-item Brief Psychiatric Rating Scale. Three indicators were used to describe the process of care in the facilities: a Restrictiveness score, a Standardization score, and a Treatment score. A multilevel mixed-effect logistic regression was used to predict APP using patient and facility as the variables. RESULTS: APP was prescribed to 333 (32.5%) patients, the most common patterns being a first-generation and a second-generation AP (n = 178, 17.6%) or of two first-generation APs (n = 80, 7.8%). Patients with a diagnosis of schizophrenia and poorer insight into illness at admission were significantly more likely to receive APP. The availability of more complex therapeutic interventions in the facility was also associated with APP. CONCLUSIONS: In our nationwide sample of psychiatric inpatients, APP was frequently prescribed to treat the more severe patients. However, it was also associated with process of care characteristics such as delivery of more complex therapeutic interventions, and was therefore not used only to control patient behavior.

Bioinformatic analyses to select phenotype affecting polymorphisms in HTR2C gene.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) in serotonin related genes influence mental disorders, responses to pharmacological and psychotherapeutic treatments. In planning association studies, researchers that want to investigate new SNPs have to select some among a large number of candidates. Our aim is to guide researchers in the selection of the most likely phenotype affecting polymorphisms. Here, we studied serotonin receptor 2C (HTR2C) SNPs because, till now, only relatively few of about 2000 are investigated. METHODS: We used the most updated and assessed bioinformatic tools to predict which variations can give rise to biological effects among 2450 HTR2C SNPs. RESULTS: We suggest 48 SNPs that are worth considering in future association studies in the field of psychiatry, psychology and pharmacogenomics. Moreover, our analyses point out the biological level probably affected, such as transcription, splicing, miRNA regulation and protein structure, thus allowing to suggest future molecular investigations. CONCLUSIONS: Although few association studies are available in literature, their results are in agreement with our predictions, showing that our selection methods can help to guide future association studies.

Assessing mixed anxiety-depressive disorder. A national primary care survey.

Prevalence and risk factors associated with mixed anxiety-depressive disorder (MAD) have yet to be established. Using MINI 5.0.1 and HADS, a two-week survey involving 21,644 primary care patients was carried out. We found 1.8% of subjects with MAD and 20% of subjects with a co-morbid anxiety and depression (CAD) disorder. MAD patients without a past history of anxiety/affective episodes were defined as "pure MAD" (pMAD: 0.9% of the sample). While MAD patients showed a number of differences vs. the other groups of patients in the socio-demographic statistics, pMAD patients were not different, apart from a higher proportion of males vs. CAD patients. Nearly in all the comparisons, MAD and pMAD patients showed lower association with life events and with a familial predisposition than the other patients. On HADS assessment, MAD showed a higher risk of anxiety and depressive symptoms than anxiety diagnoses, a lower risk of depressive symptoms than depressive diagnoses and a lower risk of both anxiety and depressive symptoms than CAD. Since more than a half of MAD patients were classified as pMAD, the hypothesis that MAD should be viewed as a partial remission of a major depression is not entirely confirmed in our study.

An improved in silico selection of phenotype affecting polymorphisms in SLC6A4, HTR1A and HTR2A genes.

OBJECTIVE: Among the experimentally assessed DNA variations in serotonin related genes, some influence physiological expression of personality and mental disorders, others alter the responses to pharmacological and/or psychotherapeutic treatments. Because of the huge number of polymorphisms lying in genes and of the great length of time necessary to perform association studies, a selection of the variations being studied is a necessary and crucial step. METHODS: In this work we used the most updated and assessed bioinformatic tools to predict the phenotype affecting polymorphisms of the human HTR1A, HTR2A and SLC6A4 serotonin related genes. Moreover, we carried out a literature search to collect information about the recent association studies to compare it versus our prediction data. RESULTS: Gene polymorphism analysis indicated the variations that are worth considering in the association studies in the field of psychiatry, psychology and pharmacogenomics. The literature revision allowed to show both the few well and the most not enough investigated polymorphisms. CONCLUSIONS: Our data can be useful to select polymorphisms for new association studies, especially those not yet investigated that can be related to behaviour, mental disorders and individual treatment response.

[Neuropsychological modifications at high altitude: from Pamir to Karakorum]. / Modificazioni neuropsicologiche da alta quota: dal Pamir al Karakorum.

AIM: Neuropsychological modifications and acclimatization processes at over 8000 without auxiliary oxygen were investigated in two climbers, evaluating attentive abilities and matching their performances. METHOD: During rest in base-camp (4800 m), at other three Resorts - Resort I (5800 m), Resort II (6400 m), Resort III (7200 m) -, and four months after the return at low altitude, were administered: Temporal Orientation Test (TOT), Trail Making Test (TMT), Animal Naming (AN), Verbal Fluency Test (VFT), Arithmetical Judgment Test (AJT), and Drawing Test (DT). Results. At TOT and at AJT, both the climbers demonstrated scores at higher normal levels (Eq = 4) in all the Resorts in which they were performed. They showed an impairment at AN test, especially at Resort III, showing sensitivity of animal naming to hypoxia. At the DT, human figures were reduced in their dimensions and details, as consequence of the tendency to self closure and introversion that occurs at higher altitudes. DISCUSSION: Neuropsychological functions concerning verbal fluency showed sensitivity to hypoxia, especially at higher altitudes. TMT demonstrated that attentive ability can be preserved if acclimatization is good. Sensitivity to hypoxia and acclimatization processes showed a significant subjective variability. CONCLUSIONS: The results of this study show that exposure to high altitude produces some significant neuropsychological changes.

[Depression in pregnancy: focus on the safety of antidepressant drugs.] / Depressione in gravidanza: focus sulla sicurezza dei farmaci antidepressivi.

Antepartum depression, frequently in comorbidity with anxiety disorders, is a severe psychopathological condition frequently reported in pregnancy and in many cases associated with obstetric and neonatal complications and potential negative consequences on child neurodevelopment. However, the pharmacological treatment of depression, during pregnancy generates a lot of concerns about the risks of such treatment for the fetus development and the neonatal health. The aim of this review is to present a selection of the latest international literature including recent original studies, systematic reviews, meta-analyses and recommendations from the guidelines, both on the risks of an untreated depressive disorders and on the risk of antidepressant therapy during gestation with drugs belonging to the SSRI and SNRI (SRI) class. An updated information of the recent risk-benefit data of these drug treatments in women with affective disorders in pregnancy may actually enable better and more conscious management of these disorders, not only for those working in the mental health field but also for general practitioners and those of other medical specialties.

The management of bipolar mania: a national survey of baseline data from the EMBLEM study in Italy.

BACKGROUND: Although a number of studies have assessed the management of mania in routine clinical practice, no studies have so far evaluated the short- and long-term management and outcome of patients affected by bipolar mania in different European countries. The objective of the study is to present, in the context of a large multicenter survey (EMBLEM study), an overview of the baseline data on the acute management of a representative sample of manic bipolar patients treated in the Italian psychiatric hospital and community settings. EMBLEM is a 2-year observational longitudinal study that evaluates across 14 European countries the patterns of the drug prescribed in patients with bipolar mania, their socio-demographic and clinical features and the outcomes of the treatment. METHODS: The study consists of a 12-week acute phase and a < or = 24-month maintenance phase. Bipolar patients were included into the study as in- or out-patients, if they initiated or changed, according to the decision of their psychiatrist, oral antipsychotics, anticonvulsants and/or lithium for the treatment of an episode of mania. Data concerning socio-demographic characteristics, psychiatric and medical history, severity of mania, prescribed medications, functional status and quality of life were collected at baseline and during the follow-up period. RESULTS: In Italy, 563 patients were recruited in 56 sites: 376 were outpatients and 187 inpatients. The mean age was 45.8 years. The mean CGI-BP was 4.4 (+/- 0.9) for overall score and mania, 1.9 (+/- 1.2) for depression and 2.6 (+/- 1.6) for hallucinations/delusions. The YMRS showed that 14.4% had a total score < 12, 25.1% > or = 12 and < 20, and 60.5% > or = 20. At entry, 75 patients (13.7%) were treatment-naïve, 186 (34.1%) were receiving a monotherapy (of which haloperidol [24.2%], valproate [16.7%] and lithium [14.5%] were the most frequently prescribed) while 285 (52.2%) a combined therapy (of which 8.0% were represented by haloperidol/lithium combinations). After a switch to an oral medication, 137 patients (24.8%) were prescribed a monotherapy while the rest (415, 75.2%) received a combination of drugs. CONCLUSION: Data collected at baseline in the Italian cohort of the EMBLEM study represent a relevant source of information to start addressing the short and long-term therapeutic strategies for improving the clinical as well as the socio-economic outcomes of patients affected by bipolar mania. Although it's not an epidemiological investigation and has some limitations, the results show several interesting findings as a relatively late age of onset of bipolar disorder, a low rate of past suicide attempts, a low lifetime rate of alcohol abuse and drug addiction.

[Antidepressant drugs and breastfeeding]. / L'impiego dei farmaci antidepressivi nel puerperio.

The post-partum period, as well as pregnancy, is associated with an increased risk of anxiety and/or affective disorders. Postnatal depression, frequently in co-morbidity with anxiety symptoms, is recognised as the most frequent form of maternal morbidity after delivery, with a prevalence rate estimated between 5% to 15%. Among antidepressant drugs, the SSRIs are considered the drugs of choice in the treatment of post-partum affective disorders, particularly in the major depression. It is, thus, crucial from a clinical standpoint to establish, in the newborn whose mother needs to be treated with an SSRI, the safety profile of these drugs during breastfeeding. The benefits of breastfeeding, on the other hand, both for the nursing mother and the infant, are in fact very well documented. Unfortunately, all antidepressant drugs, including SSRIs, cross into breast milk and the milk-to-plasma ratio, a measure proposed to establish the amount of drug transferred to maternal milk, does not seem to be a reliable parameter to predict the safety of these drugs. From the available literature, however, it seems that among SSRIs, paroxetina and sertralina offer the best safety profile, as these drugs has never been associated with unsafe reports in suckling infants. Despite these reassuring but preliminary data, more studies are needed to better assess the safety of the antidepressant drugs in the infants exposed during breastfeeding. As general rule, it is important to recommend if the mother wishes to breastfeed her infant while taking an antidepressant, that the baby should be closely monitored in order to detect, as soon as possible, any unwanted drug-related side effect.

[Pharmacologic therapy of depression during pregnancy]. / L'impiego dei farmaci antidepressivi in gravidanza.

The pregnancy is considered to be relatively high risk period for depressive episodes in women, particularly for those with pre-existing affective disorders. Epidemiological studies indicate that between 10% to 16% of pregnant women fulfil the diagnostic criteria for major depression and on average 20% is affected by an anxiety disorder. Pharmacological treatment of depression during pregnancy, however, brings with it certainties and dilemmas. It has been reported that untreated depression is associated with impaired feto-placental function, premature delivery, miscarriage, low fetal growth and perinatal unwanted effects. On the other hand, the use of antidepressant drugs in pregnancy might be at risk of major malformations (teratogenesis), neonatal toxicity, especially withdrawal symptoms and neuropsychological-behavioural impairment. In addition, the abrupt discontinuation of antidepressants, because of fear for adverse fetal effects, exposes women to serious clinical problems, in particular the disease relapse. A number of reviews indicates that among antidepressant drugs, the older SSRIs (in particular fluoxetine, sertraline, citalopram) seem to be avoided of teratogenic risks; for these reasons such drugs are nowadays considered of choice for the treatment of depression during pregnancy. Less information is available for other drugs, including triciclycs, venlafaxine, mirtazapine, bupropion, escitalopram and duloxetine. Withdrawal symptoms have been reported for all antidepressants; these symptoms, however, were self-limiting in majority of cases and had a favourable outcome. Inconclusive findings emerge, so far, from the few longitudinal studies focusing on the long-term neurodevelopment outcome in children.