P.2.f. Mood disorders and treatment − Treatment (clinical) S399

P.2.f.006 Efficacy of omega-3 fatty acids in the

treatment of borderline personality disorder:

a study of association with valproic acid

P. Bozzatello1 °, S. Bellino1, F. Bogetto2 1Centre for PersonalityDisorders Psychiatric Clinic 1, Department of NeuroscienceUniversity of Turin, Turin, Italy; 2Psychiatric Clinic 1,Department of Neuroscience University of Turin, Turin, Italy

Purpose of the study: Omega-3 fatty acids have received increas-ing interest for their stabilizing effects on plasmatic membranesand cell signalling. In recent years, a growing number of clinicaltrials on omega-3 fatty acids, such as eicosapentaenoic acid (EPA)and docosahexaenoic acid (DHA) have got promising resultssupporting their use in several psychiatric disorders, in particularmood disorders and other syndromes characterized by impulsivity,hostility, and aggression.As disturbances in regulation of mood and impulse behaviors

are core features of borderline personality disorder, omega-3 fattyacids may represent a potential tool for the treatment of thisclinical population.Data concerning the use of these agents in BPD patients are

still sparse.Only two trials [1] and [2] have tested the effects of (EPA) and

(DHA) in patients with BPD.In order to further investigate the role of omega-3 fatty acids

in the therapy of BPD, the present study is aimed to assess theefficacy and tolerability of EPA and DHA in association with themood stabilizer valproic acid.

Methods: 43 outpatients who received a DSM-IV-TR diagnosisof BPD were recruited. Patients were randomly assigned to oneof two treatment arms for 12 weeks: (1) valproic acid (at adose corresponding to a plasma level of 50–100mg/ml); (2) EPA(1.2 g/day) and DHA (0.8 g/day) in combination with the samedose of valproic acid.Patients were evaluated at baseline and after 12 weeks with:

CGI − Severity Item, HAM-D, HAM-A, SOFAS, BPDSI for BPDrelated symptoms, BIS-11 for impulsivity, MOAS for aggres-siveness, SHI for self-injuries, and DOTES for adverse effects.Statistical analysis was performed on each rating scale with theunivariate General Linear Model with two factors: duration andtype of treatment.

Results: Statistical analysis was conducted on the 34 com-pleters. Changes of CGI-S, SOFAS, and HAM-A scores did notdiffer between treatments. The time factor and the interactionbetween time and treatment factors had both a significant effecton the HAM-D score and on the item affective instability of theBPDSI. The time and the treatment factors had both a significanteffect on the SHI score. Significant effects on the BIS-11 score,the BPDSI total score, and the items ‘impulsivity’ and ‘outburstsof anger’ were found for the time factor, the treatment factor andthe interaction between time and treatment factors.

Conclusions: Valproate monotherapy and combination of val-proate and omega-3 fatty acids can both be proposed as usefultherapeutic options for the treatment of BPD: they have a similarefficacy on global symptoms, anxiety, and socio-relational func-tioning.However, combined therapy with fatty acids and valproate is

more effective than valproate alone in reducing severity of severalBPD symptoms, such as impulsivity, outbursts of anger, andself-mutilating conducts. The difference between treatments ondepressive symptoms and mood instability is not significant at 12

weeks, but increases with the length of therapy. Adverse effectswere mild to moderate dyspepsia, nausea, and weight gain.

References

[1] Zanarini M.C., Frankenburg F.R., 2003. Omega-3 Fatty acid treatmentof women with borderline personality disorder: a double-blind, placebo-controlled pilot study. Am J Psychiatry 160, 167–169.

[2] Hallahan B., Hibbeln J.R., Davis J.M., 2007. Omega-3 fatty acidsupplementation in patients with recurrent self-harm. Single-centredouble-blind randomised controlled trial. Br J Psychiatry 190, 118–122.

P.2.f.007 Psychopharmacological treatment in

pregnancy and in breastfeeding: focus on

escitalopram

L. Orsolini1 °, F. Bozzi1, C. Bellantuono1 1Polytechnic Universityof Marche, Psychiatric Unit and DEGRA Center United Hospitaland Academic Department of Experimental and ClinicalMedicine,Ancona, Italy

Background and Purpose: Psychiatric disorders during preg-nancy are relevant both from a clinical standpoint and froman epidemiological perspective. For instance, Major Depressiveor Anxiety Disorders frequently occur in pregnancy, affectingbetween 9% to 14% of pregnant women [1]. In Italy, the lifetimeprevalence of these disorders in pregnancy has been estimatedby Borri et al. (2008) in a sample of 1066 women; according toDiagnostic and Statistical Manual for Mental Disorders (DSM)-IV-TR criteria (Axis I) the prevalence of anxiety disorders andmood disorders was respectively 35.5% and 28.3% [2].In the last decade, the use of SSRIs in pregnancy has consider-

ably increased. In fact, the rates of pregnant women treated withselective serotonin reuptake inhibitors (SSRI) has increased from5.7% (1999) to 13.4% (2003). Nowadays, escitalopram (ESC) isconsidered one of the most effective SSRI for the treatment ofmoderate-severe major depression [3].However, little is known on its safety and tolerability profile

in pregnancy and lactation, such as risk of major malformations(MM) and/or perinatal complications (PC) related to ESC expo-sure. Aim of the present study was to provide a review of theavailable literature on the safety profile of ESC during pregnancyand breastfeeding and to compare it with data on maternal andneonatal outcomes of 8 cases of pregnant women coming fromdatabase of the Clinic of Affective Disorders in Pregnancy andPostpartum of the United Hospital of Ancona (DEGRA Center −www.depressionegravidanza.it).

Methods: MEDLINE and PubMed databases were searched forEnglish language articles by using the following set of keywords:(escitalopram OR selective serotonin reuptake inhibitors) AND(pregnancy OR major malformations OR perinatal complications)AND (escitalopram OR selective serotonin reuptake inhibitors)AND (lactation OR breastfeeding). Further, being ESC firstlyavailable in the United States and European Countries by theend of 2003, only papers published from January 2003 wereconsidered. We also reported 8 cases of pregnant women treatedwith ESC during their pregnancy and breastfeeding at the DEGRAcenter. All women were assessed by means of the Structured Clin-ical Interview for DSM-IV Axis I Disorders, the Brief PsychiatricRating Scale and the Hamilton Rating Scale for depression.

Results: According to the literature, absolute and relative riskfor MM after maternal exposure to ESC during early pregnancy,

S400 P.2.f. Mood disorders and treatment − Treatment (clinical)

there is not a statistically significant increase than general pop-ulation. Very few data have been published on the occurrenceof PC and miscarriage after exposure to ESC but it is reportedan higher rate of newborns with low birth weight. No short-termadverse effects were reported in babies exposed to ESC duringbreastfeeding. Data coming from DEGRA Center seem to beconsistent with the literature. In fact, all pregnancy were full term.All newborns had normal APGAR score. There were no MM or

miscarriage after ESC exposure. We report only one case of a mildwithdrawal syndrome in a baby also exposed to benzodiazepinesand paroxetine. Only two babies were exposed during the lactationand they have not reported any health problems.

Conclusions: In conclusion, available data seem to support thenotion that ESC has a good safety profile during pregnancy andbreastfeeding. Nevertheless, given the paucity of the studies sofar published, no definitive conclusions should be drawn.

References

[1] Grant, B.F., Goldstein R.B., Chou S.P. et al, 2009. Sociodemographicand psychopathologic predictors of first incidence of DSM-IV sub-stance use, mood and anxiety disorders: results from the wave 2 nationalepidemiologic survey on alcohol and related conditions. Mol Psychiatry14 (11): 1051−66.

[2] Borri C, Mauri M, Oppo A et al, 2008. Axis I psychopathology andfunctional impairment at the third month of pregnancy: results from theperinatal depression-research and screening unit (PND-ReScU) study.J Clin Psychiatry 2008, 69(10): 1617−24.

[3] Cipriani A., Furukawa T.A., Salanti G. et al, 2009. Comparative efficacyand acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet, 373(9665): 746−58.

P.2.f.008 Duloxetine increased plasma levels of

3-methoxy-4-hydroxyphenylglycol in patients

with major depressive disorder

K. Atake1 °, R. Yoshimura1, H. Hori1, A. Katsuki1, J. Nakamura11University of Occupational and Environmental Health,Psychiatry, Kitakyushu, Japan

Purpose: Duloxetine affects neurotransmitters, the chemicals thatnerves within the brain make and release in order to communi-cate with one another. Many experts believe that an imbalanceamong neurotransmitters is the cause of depression as well asother psychiatric disorders. Duloxetine, a selective serotonin andnoradrenaline reuptake inhibitor, is an effective first-line treatmentfor patients with major depressive disorder (MDD). We previouslyreported that milnacipran, another SNRI increased plasma levelsof 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabo-lite of noradrenalin, in patients with MDD. Duloxetine potentlyinhibits both serotonin and noradrenalin transporters. Therefore,we hypothesized that duloxetine which belongs to SNRI alsoincreases plasma MHPG levels in patients with MDD. To confirmthe hypothesis, we investigated effects of duloxetine on plasmalevels of catecholamine metabolite in the present study. To thebest of our knowledge, this is the first study examining influenceof duloxetine on plasma MHPG levels.

Subjects and Methods: Sixty-four patients were recruited.Major depressive episode was diagnosed by using the StructuredClinical Interview for DSM-IV according to the DSM-IV-TRcriteria. The severity of depression was evaluated using the 17-item Hmilton Rating Scale for Depression (HAMD17). Exclusioncriteria were any history of neurological diseases or other physicaldiseases, and comorbidities with other disorders, bipolar disorder

or Axis II, personality disorders and mental retardation. All pa-tients were not administered antidepressants and benzodiazepinesat least one week before starting the study. Blood sampling andclinical evaluation were performed day 0, day 14, day 28. Forty-five of 64 patients were finished the study.We defined the patients whose HAMD17 decreased 50% or

more as responders.The plasma concentrations of HVA and MHPG were analyzed

by high-performance liquid chromatography with electrochemicaldetection (HPLC-ECD). The plasma levels of MHPG and ho-movanillic acid were analyzed by HPLC-ECD. About statistics, theBonferonni method was used for post-hoc analysis at comparisonbetween 3 groups using repeated measures ANOVA.Pearson’s correlation coefficients was used for comparison be-

tween 2 groups.Results: Forty-five of 64 patients have completed the medica-

tion for 8 weeks by duloxetine. Nineteen patients’ main reasonsfor dropout the treatment course are as follows. Since 8 patientsdid violation of protocol, 6 patients transferred to another hospitaland 5 patients got side effects, they were dropped out. Thirtyof 45 (66.7%) patients responded to duloxetine treatment until8 weeks. Treatment with duloxetine for 8 weeks significantlyincreased plasma MHPG levels (P = 0.0066) in responders, butdid not change plasma MHPG levels in nonresponders. Whereas,duloxetine did not change plasma HVA levels both in respondersand nonresponders (P = 0.9905). No significant correlation washowever observed between the changes in the total HAMD17scores and the changes in plasma levels of MHPG or HVA.

Conclusion: Treatment with duloxetine for 8 weeks increasedplasma MHPG levels in responders, but not nonresponders inpatients with MDD.

P.2.f.009 Treating pharmacoresistant depression in

psychogeriatry − should electroconvulsive

therapy or intravenous seropram be used?

J. Luzny1 ° 1Psychiatricka lecebna, Psychogeriatry, Kromerız,Czech Republic

Introduction: Major depression in elderly with partial or noresponse to peroral antidepressants is a serious clinical problem.In these case, combination of different types of antidepressant [1],combination of antidepressants with antipsychotics or mood sta-bilizers [2] or electroconvulsive therapy [3] can improve severemajor depression. In psychogeriatry, electroconvulsive therapymay lead to severe memory impairment and therefore shouldbe concidered carefully, as well as combination of different psy-chotropic drugs (risk of druh interactions).

Purpose: Effectiveness evaluation of intravenous seropramtherapy compared to unilateral electroconvulsive therapy in phar-macoresistant depression among seniors.

Ethical consideration: Informed consent obtained from allpatients. Ethical board consent.

Methods: Design: Patients hospitalized in Mental hospitalKromerız, in 2012, aged 65+, fulfilling diagnostic criteria formajor depression (ICD-10) and failing to prior antidepressanttherapy with two different antidepressants in monotherapy (phar-macoresistant major depression). Randomization of patients intotwo groups. Group 1: patients treated with intravenous seropram(N= 12, women = 8, men = 4, age 68.2±4.1).

Group 2: patients treated with electroconvulsive therapy (N= 8,women = 7, men = 1, age 67.3±3.9).