SSRI Group Research Articles

Evaluation of the effect of long-term use of antidepressants in the SSRI group on bone density with dental volumetric tomography.

AimThe present study aims to employ dental volumetric tomography to examine bone mineral density among men that used antidepressants in the SSRI group for a long time.MethodThe present study was conducted through the utilisation of data related to patients that presented to the Faculty of Dentistry of Dicle University and had a dental volumetric tomography (DVT) scan for any reason. The patients were divided into 2 groups based on the use of antidepressants: Group 1 included 68 patients as the control group, and Group 2 consisted of 68 patients that used antidepressants. Radiomorphometric measurements were performed on DVT data: DVT-Mandibular Index (DVT-MI), DVT-Cortical Index (DVT-CI), Hounsfıeld Unit (HU) CORTICAL, and HU SPONGIOSIS values were calculated.ResultsThe group of patients that used antidepressants exhibited a significant increase in DVT CI and a significant decrease in HU CORTICAL, HU SPONGIOSIS and DVT MI values. These findings were suggestive of osteoporosis.ConclusionLong-term use of antidepressants should be taken into consideration as a risk factor for osteoporosis in men.

SUN-356 The Effects of Selective Serotonin Reuptake Inhibitors on Urinary Free Cortisol in Patients with Carney Complex and Primary Pigmented Nodular Adrenocortical Disease

PPNAD is a rare cause of ACTH-independent Cushing syndrome mainly associated with Carney complex (CNC). It is diagnosed by histologic examination or a 6-day Liddle test (LT) showing a paradoxical increase of >50% in 24-h urinary free cortisol (UFC) on the 2nd day of high-dose dexamethasone administration (Day 6 [D6]). PPNAD tissue has neuroendocrine features and can overexpress the serotonin (5-HT) synthesizing enzyme tryptophan hydroxylase type 2 and the 5-HT receptors types 4, 6, and 7, with formation of an illicit stimulatory serotonergic loop whose pharmacological inhibition in vitro decreases cortisol production [1]. SSRIs inhibit the reuptake of 5-HT and are used as 1st-line antidepressants. This is a retrospective cohort study of patients with CNC and PPNAD that underwent a LT with the objective to evaluate the effect of SSRIs on UFCs in these patients. Of the 34 patients (4-65 y) with CNC and PPNAD that had a LT at our institution between 2004 and 2018, 4 patients took an SSRI during testing. No statistically significant differences were demonstrated between the SSRI (S) group and the non-SSRI (NS) group in baseline UFCs and urine 17-hydroxycorticosteroids (17OHS) and the percent increase in UFC and 17OHS on D6. Specifically, the median (IQR) baseline UFC in the S group was 36 (13-252) mcg/24h (nl 4-56) vs 35 (13-98) mcg/24h in the NS group (P=0.95). Baseline 17OHS were 11 (8-18) mg/mg creatinine (Cr) (nl ≤6) in the S group vs 8 (5-11) mg/mgCr in the NS group (P=0.27). The percent change in UFC was 208 (93-683)% in the S group and 185 (28-364)% in the NS group (P=0.89), while the percent change in 17OHS was 56 (40-87)% in the S group and 67 (16-92)% in the NS group (P=0.91). On D6, the S group appeared to have higher UFC [118 (63-635) mcg/24h vs 112 (58-201) mcg/24h; P=0.64] and 17OHS [16 (10-39) mg/mgCr vs 13 (7-17) mg/mgCr; P=0.25] than the NS group, but these were not statistically significant. Though these data do not confirm an effect of SSRIs on UFC and ultimately cortisol production in PPNAD, and the percent change in UFC during the LT was similar between both groups, the higher D6 UFC in the S group, when the baseline UFCs between the 2 groups were similar may suggest a degree of increased cortisol production in the S group. The data are limited by the small number of patients in the S group (n=4). In addition, 50% of patients in the S group vs 77% in the NS group underwent adrenalectomy, which is indicative of more severe disease in the NS group. More data are needed from this cohort to determine if SSRI use affects cortisol production in vivo, as this may have significant diagnostic and therapeutic implications for patients with CNC and PPNAD. Reference: 1. Bram, Z., et al., PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease. JCI Insight, 2016. 1(15): p. e87958.

Electroconvulsive therapy in drug-resistant paranoid schizophrenia on patient with transplanted kidney – Case study

The 22-year-old female patient had her first direct encounter with a psychiatrist in 2009 due to low mood, anxiety, anhedonia, lack of energy and olfactory hallucinations. Diagnosed with delusional depression syndrome, she was treated with SSRI group, and then combined with LLP group. In 2009, she was hospitalized in the Ward of kidney diseases and dialysis due to severe kidney failure, HA affecting the heart and the kidneys and facial nerve paralysis. In May 2012, she had a kidney transplanted from the deceased donor, which led to graft-versus-host disease. She received immunosuppressive therapy. In October 2012, she was diagnosed with paranoid syndrome. She was initially treated with levomepromazine 75 mg/d and amisulpride 800 mg/d (no results), then Olanzapine 20 mg/d and aripiprazole 15 mg/d (no results). After 10 week hospitalization she was discharged in a slightly improved mental state. Three weeks later, she was hospitalized again in a psychiatric institution where she received olanzapine 20 mg/d and haloperidol 6 mg/d (no results). Due to the severe mental condition, she was qualified for electroconvulsive therapy. In the end, the therapy met with the general positive reviews of consultants of different specialties. After 7 (of the 18) treatments the patient reached a significantly improved mental state with almost no sign of psychotic experiences and with a better day-to-day functioning. To the best of the authors’ knowledge, it is the first case of ECT on the patient who was the subject of a kidney transplant, and is one of the very few that have taken place in the entire world.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Treatment of maternal antenatal depression

IntroductionWorld statistical data show that a large number of mothers suffer from antenatal or postnatal depression and that it is linked with difficulties in personal and emotional development in child.AimTo present the importance of treatment of antenatal depression.Material and methodsWe present is a 32-year-old woman man, with completed high level of education, married, mother of one child, pregnant in first trimester, who suffered of depression several years ago. Diagnosis was made in line with the ICD 10 (F33), and the following diagnostic instruments were used: HAMA, HAMD, clinical interview.We present is a 32-year-old woman man, with completed high level of education, married, mother of one child, pregnant in first trimester, severe depression with depressive mood, weight lost, insomnia, agitation, suicidal thoughts.She was treated in the day hospital of our clinic with SSRI antidepressants, individual and group psychotherapy.ResultsDuring the day hospital stay patient was treated with pharmacologic agents (SSRI anti-depressants – tbl. Sertralline), which showed a great success, that is reduction in the depression, sleep improvement, normal gain weight and regular pregnancy and baby birth with APGAR score 9/9.DiscussionLiterature shows that antenatal depression is associated with poor mother self-care during pregnancy including poor visit of antenatal clinics, substance misuse, low birth weight, preterm delivery and significant intellectual and emotional deficits in children whose mothers were suffered of antenatal or postnatal depression.ConclusionTreatment of antenatal or postnatal depression is very important for mothers’ mental health and for the normal develops of child also.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: A systematic review and meta-analysis.

To obtain the risk estimates of autism spectrum disorder (ASD) in the offspring exposed to serotonin reuptake inhibitors (SSRI) in utero, we performed systematic review and meta-analysis of relevant studies. Five case-control and three cohort studies were eligible for the analysis. The SSRI group had significantly higher risk of ASD than the SSRI non-exposed group (pooled OR 1.45, 95% CI 1.15-1.82). In the subgroup analyses, however, the risk of ASD was similar between the SSRI group and other antidepressants group (pooled OR 1.14, 95% CI 0.67-1.96). Furthermore, when the analysis was confined to those born to the women with psychiatric disorders, the SSRI group did not show an increased ASD risk (pooled OR 0.96, 95% CI 0.57-1.63) compared to non-exposed groups. In conclusion, SSRI use in pregnancy is associated with an increased risk of ASD in the offspring, but maternal psychiatric condition is a major confounding factor.

Does SSRI Antidepressant Use Influence APGAR Scores? [29N

INTRODUCTION: SSRIs have been associated with low APGAR scores, independent of maternal depression, and with preterm birth. Our objective was to determine the association of SSRIs with low APGARs. METHODS: We performed a retrospective matched cohort study on patients who delivered at a tertiary care center from 2009–2014. Women who reported SSRI use on admission were matched to contemporary controls in a 2:1 fashion by completed weeks of gestation and mode of delivery. Fetal anomalies, stillbirths, and multiple gestations were excluded. Odds ratios and 95% confidence intervals were calculated. Fisher's exact test was used to determine significance in the number of APGAR scores <7. RESULTS: 112 SSRI users (2% of deliveries) and 224 controls were included. Women reported using the following: citalopram (n=23), escitalopram (n=4), paroxetine (n=2), fluoxetine (n=34), and sertraline (n=49). 25% delivered preterm. Infants exposed to SSRIs had an increased rate of low APGAR scores at 1 minute (OR 2.0, 95% CI 1.1–3.5, P=.02) and 5 minutes (OR 8.8, 95% CI 2.4–32.0, P=.0009). 1 minute APGAR scores <7 (24% vs 14%, P=.02) and 5 minutes (11% vs 1%, P=.0002) were significantly higher in the SSRI group. CONCLUSION: SSRIs are associated with an increased risk of APGAR scores <7 at 1 and 5 minutes, with an almost 9-fold increased risk of 5 minute APGAR <7. APGAR scores <7 have previously been associated with future cognitive impairment. Further investigation into the impact of SSRI exposure is essential.

The Effects of Antidepressants and Quetiapine on Heart Rate Variability.

Introduction: The autonomic effects of antidepressants and quetiapine on heart rate variability (HRV) are inconsistent based on past studies. The aim of this study was to explore their influence on the HRV of psychiatric patients without psychotic symptoms. Methods: A total of 94 patients with depression, anxiety, or somatic symptoms, were recruited into this study. Based on their medication, 4 groups were identified: the no antidepressant group (n=19), the SSRI group (using sertraline or escitalopram, n=53), the other antidepressants group (using venlafaxine or mirtazapine, n=9), and the augmentation group (AG, using an antidepressant+quetiapine, n=13). The HRV of the 4 groups were compared. The correlations between HRV and the medication(s) used were clarified. Results: Among the 4 groups, the AG had the lowest HRV with its total power (TP), very low frequency power (VLF) and low frequency power (LF) of HRV being significantly different from those of the other groups. Age and using quetiapine were found to be negatively correlated with TP, VLF and LF. With this study group, the autonomic effects of antidepressants were found not to be significant. Discussion: Among psychiatric patients without psychotic symptoms, quetiapine causes an overt decrease in HRV.

The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month

The purpose of this article was to systematically compare the developmental trajectory of neurobehavior over the first postnatal month for infants with prenatal exposure to pharmacologically untreated maternal depression, selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors (collectively: SSRIs), SSRIs with concomitant benzodiazepines (SSRI plus benzodiazepine), and no maternal depression or drug treatment (no exposure). Women (N=184) were assessed at two prenatal time points to determine psychiatric diagnoses, symptom severity, and prenatal medication usage. Infants were examined with a structured neurobehavioral assessment (Neonatal Intensive Care Unit Network Neurobehavioral Scale) at multiple time points across the first postnatal month. SSRI exposure was confirmed in a subset of participants with plasma SSRI levels. General linear-mixed models were used to examine group differences in neurobehavioral scores over time with adjustment for demographic variables and depression severity. Infants in the SSRI and SSRI plus benzodiazepine groups had lower motor scores and more CNS stress signs across the first postnatal month, as well as lower self-regulation and higher arousal at day 14. Infants in the depression group had low arousal throughout the newborn period. Infants in all three clinical groups had a widening gap in scores from the no-exposure group at day 30 in their response to visual and auditory stimuli while asleep and awake. Infants in the SSRI plus benzodiazepine group had the least favorable scores on the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Neonatal adaptation syndrome was not limited to the first 2 weeks postbirth. The profile of neurobehavioral development was different for SSRI exposure than depression alone. Concomitant benzodiazepine use may exacerbate adverse behavioral effects.

Pregnancy outcome following maternal exposure to mirtazapine: a multicenter, prospective study.

This multicenter, observational prospective cohort study addresses the risk associated with exposure to mirtazapine during pregnancy. Pregnancy outcomes after exposure to mirtazapine were compared with 2 matched control groups: (1) exposure to any selective serotonin reuptake inhibitor (SSRI, control subjects with a psychiatric condition) and (2) no exposure to medication known to be teratogenic or any antidepressant (general control subjects). Data were collected by members of the European Network of Teratology Information Services between 1995 and 2011. Observations from 357 exposed pregnancies were compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; odds ratio [OR], 1.1; 95% confidence interval [95% CI], 0.5-2.3; P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general control subjects (4.5% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08) reached statistical significance after exclusion of chromosomal or genetic anomalies (4.1% vs 1.3%; OR, 3.3; 95% CI, 1.04-10.3; P = 0.03), but this difference became again nonsignificant if cases of exposure not comprising the first trimester were excluded from the analysis (3.4% vs 1.9%; OR, 1.8; 95% CI, 0.6-5.0; P = 0.26). The crude miscarriage rate did not differ significantly between the mirtazapine, the SSRI, and the general control groups (12.1% vs 12.0% vs 9.3%; P = 0.44). However, a higher rate of elective pregnancy termination was observed in the mirtazapine group compared with SSRI and general control subjects (7.8% vs 3.4% vs 5.6%; P = 0.03). This study did not observe a statistically significant difference in the rate of major birth defects after first-trimester exposure between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A marginally higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general control subjects. Overall pregnancy outcome after mirtazapine exposure was similar to that of the SSRI-exposed control group.

Brain-derived neurotrophic factor Val66Met polymorphism association with antidepressant efficacy: a systematic review and meta-analysis.

Previous studies of the association of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with antidepressant efficacy are inconsistent. Thus, we conducted a systematic review and meta-analysis. We searched MEDLINE, PubMed, EMBASE, and Chinese Databases (Biomedical Literature Database, National Knowledge Infrastructure, Weipu, and WanFang) up to March 2013 for relevant studies (584 retrieved, 16 met inclusion criteria). We conducted six comparisons for both response and remission rates for three genotypes in Caucasians and Asians (4 weeks or ≥6 weeks; selective serotonin reuptake inhibitors [SSRIs], serotonin-noradrenaline reuptake inhibitors, or mixed antidepressants). Met carriers had a better response rate than Val/Val. In Asians, the Met carrier was positively associated with response rate (odds ratio; 95% confidence interval: 1.48; 1.02-2.14) in the SSRI group (1.81; 1.10-2.97) and with treatments ≥6 weeks. Met/Val showed a positive association with the response rate versus homozygotes (1.60; 1.20-2.13) and for ≥6 weeks (mixed antidepressant, 1.36; 1.04-1.77; SSRI, 1.55; 1.11-2.17). There was a weak effect of Met/Val versus Val/Val in response to SSRIs (mixed time, 2.07; 1.48-2.89; ≥6 weeks, 2.25; 1.53-3.32). For remission, Met/Val was better than the homozygotes (1.71; 1.09-2.68, Asians, SSRIs only). Our meta-analysis confirms the effects of the BDNF polymorphism on SSRI response in Asians. This effect may be dependent on ethnic origin because BDNF had a lesser influence on response in mixed race studies. Antidepressants were more effective in groups with a treatment duration ≥6 weeks. Thus, future investigators should carefully consider their outcome observation end point.

EPA-0087 - Cost - consequence analysis of major depressive disorder treatment - could heterocyclic antidepressants offer optimal value for money in a middle income setting?

There is paucity of published literature on antidepressants in a cost-consequence study design. Measuring clinical outcomes of pharmacotherapy. Costs and consequences determination in depressive episode acute medical care. Cost-consequence analysis;Setting-Serbian tertiary university clinic(2010-2012). Patient visits to attending psychiatrists:baseline, 3,8 weeks. HDRS-17 and Q-LES-Q-SF scale were applied in each of control visits. Resource use patterns and costs were evidenced for up to 14 weeks from study entry. Micro-costing approach allowed for most direct and indirect costs measurement. Costs were expressed in national currency-Central Serbian Dinar(1€≈115.85CSD;2012). Societal perspective and 14 weeks time horizon were adopted. Random selection of 65 depressive patients was based on clinical criteria and their assignment to either one of three different treatment protocols.5 patients were lost to follow up. There was no statistically significant difference in terms of therapeutic response by the HDRS scores before and after introducing treatment groups(χ2=4.339; ?=0.362). QALY value increased by 11.77(SSRI group);8.93(SNRI)and 12.54 (heterocyclics). Mean cost per QALY was 9,937.51 CSD for SSRI; 7,138.27 CSD in SNRI; and 6,164.96 CSD for heterocyclics. There were 28.69 depression with free days in SSRI, 21.78 days in SNRI, and 30.59 days in heterocyclic group. Cost-effectiveness assessment was was 346.38 CSD per day(SSRI); 327.74 CSD(SNRI), and 201.54 CSD(heterocyclics). Heterocyclic antidepressants provide highest'value for money' in terms of QALY in depressive episode treatment and its treatment is most cost effective. Cost-consequence evaluations have heavier impact to clinical decision making with regards to major depressive disorder treatment in the absence of clear clinical superiority of any major pharmacological protocol.

Comparison of Treatment Adherence between Selective Serotonin Reuptake Inhibitors and Moclobemide in Patients with Social Anxiety Disorder

ObjectiveWith respect to the pharmacotherapy of social anxiety disorder (SAD), it has been suggested that treatment duration is an important factor that can significantly predict responses. The present study aimed to compare the treatment adherence of SAD patients who were taking either SSRIs or reversible inhibitors of MAO-A (moclobemide) by measuring treatment duration and all-cause discontinuation rates of pharmacotherapy in a natural clinical setting.MethodsWe retrospectively analysed the data of 172 patients diagnosed with SAD. Depending on their medication, we divided the patients into two groups, SSRI (n=54) or moclobemide (n=118). The expected number of all-cause discontinuation every 2 weeks after starting treatment was calculated by life table survival methods. A multi-variable Cox proportional hazard regression was used to analyze the potential influence of explanatory variables.ResultsTreatment duration was significantly longer in the SSRI group [46.41±56.96, median=12.0 (weeks)] than in the moclobemide group [25.53±34.74, median=12.0 (weeks), Z=2.352, p=0.019]. Overall, all-cause discontinuation rates were significantly lower with SSRIs (81%) than moclobemide (96%, χ2=4.532, p=0.033).ConclusionThe SSRI group had a longer treatment duration and lower all-cause discontinuation rate than moclobemide. Further, only the type of medication had a significant effect on all-cause discontinuation rates and therefore, we could predict better treatment adherence with the SSRIs in the treatment of SAD.

Maternal use of selective serotonin reuptake inhibitors during pregnancy and neonatal bone density

BackgroundSelective serotonin reuptake inhibitors (SSRI) are commonly used to treat depression in pregnant women. Several adverse effects of prenatal SSRI exposure on the offspring have been described, including decreased growth. SSRI use by adults decreases bone mineral density, but this effect had not been examined in infants. AimTo examine growth parameters and bone mineral density of infants born to mothers using SSRIs during pregnancy. Study designAnthropometric variables and bone density were compared between 40 newborns exposed to SSRIs in utero, and 40 gestational-age matched control infants. Tibial bone speed of sound, a marker of bone density and strength, was measured using quantitative ultrasound. The difference in bone speed of sound between the two groups was compared using linear models, adjusting for relevant confounders. ResultsInfants in the SSRI-exposed group were shorter, with a marginal statistical significance (49.3±2.1 vs. 50.1±1.3cm, p=0.07), while mean birth weight did not differ substantially between study groups. Head circumference was significantly smaller in the SSRI group (33.8±1.2 vs 34.4±1.1cm, p=0.005), remaining so even after adjustment for several confounders. No considerable difference was found in the bone speed of sound between SSRI-exposed infants and controls (3011±116 vs. 3029±129m/s). ConclusionsWe found no evidence that prenatal SSRI exposure hindered neonatal bone quality, yet a marginally shorter length and a smaller head circumference raise the possibility of an effect on bone growth. We conclude that the effect of SSRIs on fetal bone density seems minimal or absent.

Group cognitive-behavioral therapy versus selective serotonin reuptake inhibitors for obsessive-compulsive disorder: A practical clinical trial

Clinical effectiveness of group cognitive-behavioral therapy (GCBT) versus fluoxetine in obsessive-compulsive disorder outpatients that could present additional psychiatric comorbidities was assessed. Patients (18–65 years; baseline Yale-Brown Obsessive-Compulsive-Scale [Y-BOCS] scores ≥ 16; potentially presenting additional psychiatric comorbidities) were sequentially allocated for treatment with GCBT ( n = 70) or fluoxetine ( n = 88). Mean Y-BOCS scores decreased by 23.13% in the GCBT and 21.54% in the SSRI groups ( p = 0.875). Patients presented a mean of 2.7 psychiatric comorbidities, and 81.4% showed at least one additional disorder. A reduction of at least 35% in baseline Y-BOCS scores and CGI ratings of 1 (much better) or 2 (better) was achieved by 33.3% of GCBT patients and 27.7% in the SSRI group ( p = 0.463). The Y-BOCS reduction was significantly lower in patients with one or more psychiatric comorbidities (21.15%, and 18.73%, respectively) than in those with pure OCD (34.62%; p = 0.034). Being male, having comorbidity of Major Depression, Social Phobia, or Dysthymia predicted a worse response to both treatments. Response rates to both treatments were similar and lower than reported in the literature, probably due to the broad inclusion criteria and the resulting sample more similar to the real world population.

P01-30 LAMOTRIGIN as psyhostabilisation by drug addicts with psychiatric comorbidity (personality disorder)

Poster shows attempt to reduce aggressive and impulsive behavior to drug addicts who have co morbidity, by using medication.At he Special Hospital on Addictions in Belgrade, Serbia, for the past two years LAMOTRIGIN was introduced as a medicament in prevention of impulsive behavior and aggressive behavior by patients who are diagnosed with F60. 2,F19. 2 Test group that didn't use this medication had 35 patients, same as experimental group, All patients, both groups were given Antaxon, opioid antagonist, anti-depressive from SSRI group of medication, also Alprozalam was given for the duration of 24 weeks. By using Barratt's scale for the evaluation of impulsivity and Stuart's scale for the evaluation of aggressiveness, noted results show that LAMOTRIGIN is medication of choice for this kind of dependency. For the efficient evaluation, questionnaires were completed about eventual interventions (pharmacological treatment, psychotherapy).After all, the question remains, was the addiction one that caused personal disorder or the other way around but the is less important, most important is neutrlised addiction and destructive behavior.

Use of SSRIs Not Associated with Increased Bleeding Events in Children: An Analysis of the Michigan Medicaid Database from 2000–2003

Background and Aim: Serotonin reuptake inhibitors (SSRIs) have been used in children for a variety of psychiatric illnesses including depression, anxiety and eating disorders. In adults, there have been several studies demonstrating an association between SSRIs and increased bleeding events, particularly gastrointestinal bleeds. It is thought that SSRIs affect platelet aggregation by inhibiting serotonin uptake by platelets, resulting in decreased intra-platelet serotonin concentration. To date there are no pediatric studies evaluating bleeding risk in children taking SSRIs. The objective of this study was to evaluate the incidence of bleeding events in children who are prescribed SSRIsMethods: We performed a review of the Michigan Medicaid database from 2000–2003 and identified all children ages 0–18 years prescribed six commonly used SSRIs: citalopram, escitalopram, fluvoxamine, fluoxetine, paroxetine and sertraline. Children prescribed Attention deficit hyperactivity disorder (ADHD) or antipsychotic medications were used as comparison groups. We obtained demographic data including age, gender and race for individuals with both SSRI prescriptions and bleeding events. Bleeding events were defined according to previously published definitions for major and minor bleeding using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 CM) diagnostic codes. Bleeding events must have occurred within 90 days of an SSRI prescription. For individuals with bleeding events, we evaluated all inpatient, outpatient and long term records during the 6 months before and after the event. We compared the incidence of bleeding events in the SSRI, ADHD, and antipsychotic medication groups by using Proc GENMOD in SAS 9.1.3. This accounted for the fact that there were patients on multiple medications. We found no statistical difference in the total number of bleeding events between the three medication categories.Results: Of 20,631 children prescribed SSRIs in the study population, six children experienced bleeding events (Table 1). The incidence of bleeding was 29 in 100,000 persons. Two events were associated with traumatic injuries and one was observed in a critically ill patient. There were 52,050 children on ADHD medication and 17,340 on atypical antipsychotics. The incidence of bleeding events in these groups was 13 in 100,000 and 40 in 100,000 respectively. Of note, two of six children in the SSRI group with bleeding events were also prescribed ADHD medication.TABLE 1PatientAge (years)GenderRaceBleeding EventAssociated Diagnosis111.3MaleBlackIntracerebral hemorrhage Subdural hemorrhageLymphoid leukemia Sepsis Aspergillosis Acute respiratory failure Acute renal failure Perforation of intestine Adjustment disorder212.3MaleWhiteHematoma-complication of procedureFemur fracture Closed reduction of fracture ADHD with hyperactivity Depressive disorder313.4FemaleWhiteSubarachnoid hemorrhage Extradural hemorrhageClosed fracture base of skull Convulsive disorder Developmental delay417.7FemaleWhiteSubdural hemorrhageADHD with hyperactivity Intracranial injury517.5FemaleWhiteHemorrhage complicating a procedureAcute pharyngitis and tonsillitis Tonsillectomy615.4FemaleWhiteSubdural hemorrhageCerebral palsy Spastic hemiplegiaDiscussion: We found that the incidence of bleeding events in children taking SSRIs is not increased as compared to those taking ADHD and antipsychotic medication. The majority of bleeding events that occurred in the 6 children prescribed SSRIs were either associated with trauma or a known complication of a surgical procedure. There were no gastrointestinal bleeding events in the SSRI group. Our study suggests that the use of SSRIs does not confer an increased risk of abnormal bleeding events in children.

SSRIs and Birth Defects

The authors respond: We thank Burt et al1 and Kelly et al2 for their interest in our study. Burt and colleagues1 argue that “positive” studies on the safety of antidepressants need special care in conduct and presentation due to potential high media attention. In line with that opinion, Kelly et al2 argue that SSRI use in pregnancy is a “controversial public health issue” and accordingly these studies should be presented with scrutiny. We disagree in that all studies, and not positive studies in particular, should be conducted with the highest possible quality. The awareness of possible media interest or controversy as benchmarks for how to conduct and present studies may, in the long run, threaten the credibility of research. We are aware that we did not find a pattern of specific defects as mentioned by Burt et al1 (the only exception was the rate of malformations of the digestive organs, which seem to be increased among the offspring of SSRI users.) However, the finding of increased risk of malformations in children born to mothers with drug prescriptions during 2nd and 3rd pregnancy month compared with women with prescriptions during 1st trimester and one month before the conception date provides support for a causal effect, because the 2nd and 3rd pregnancy months constitute the critical period for most birth defects. This may represent a generalized serotonin-mediated effect rather than a specific effect from different SSRIs that do not share chemical structure.3 The lack of separation between major and minor malformations was questioned by Burt et al.1 We want to underscore the fact that we excluded congenital dislocations of the hip and undescended testes. Furthermore, we identified the 3 most prevalent congenital malformations in the offspring of women with a SSRI prescription in early pregnancy and did not find that the increased risk could be caused by minor malformations. Another point of criticism from both groups was the uncertainty of compliance. Our analyses showed that many of the exposed women filled more than one prescription. Furthermore, drugs are paid for in part by the women and therefore there is likely to be a considerable degree of compliance in taking the pills that were purchased. Finally, noncompliance would likely bias the results by attenuating an effect.4 Burt et al1 and Kelly et al2 mentioned failure to control for maternal illness and other possible confounders as a limitation in our study. This is a well-established problem in nonrandomized observational studies of drug effects5—for example, the finding of an increased mortality among patients with cystic fibrosis treated with tobramycin for inhalation.6 To explore the influence of depression-related factors, we analyzed the risk of malformations among another group of women with depression—women exposed to non-SSRI antidepressants in early pregnancy. Finding no increased risk of malformations among these women suggests that the underlying disease is of less importance than the SSRI medications. Bonari et al7 reviewed the literature on perinatal risks after untreated depression during pregnancy. While there were suggestions of an increased risk of adverse pregnancy outcomes such as preterm delivery; no studies demonstrated increased risk of malformations. Kelly et al2 noted that the rate of smoking in our study was nearly twice as high among the SSRI group as compared with the non-SSRI group. Although the evidence for smoking as a general teratogen is weak, we agree that smoking may be indicative of an unhealthy lifestyle. Our best options for examining the influence of the underlying disease in our setting were 1) to control for smoking and 2) to examine the risk among non-SSRI antidepressant users. The results of these analyses did not allow us to exclude a causal association. Our findings should be discussed in a context of adverse effects of depression itself. However, we actually outlined the possibility of the underlying disease as a confounding factor, and already stressed in the conclusion, as well as in the abstract, that the observed association may not be causal. We believe that clinicians with the final responsibility for counseling individual patients have the full ability to combine their knowledge from research, clinical experience and understanding of the patient's situation into the best treatment. Thus in each counseling situation the absolute risk of malformations associated with and without drug use in pregnancy should be related to the benefits of drug use. Pia Wogelius Mette Nørgaard Mette Gislum Lars Pedersen Estrid Munk Department of Clinical Epidemiology Aarhus University Hospital Aarhus, Denmark [email protected] Preben Bo Mortensen National Centre for Register-based Research Aarhus University Aarhus, Denmark Loren Lipworth Department of Preventive Medicine Vanderbilt University Medical Center Nashville, TN Henrik Toft Sørensen Department of Clinical Epidemiology Aarhus University Hospital Aarhus, Denmark

Remission Rates Following Antidepressant Therapy With Bupropion or Selective Serotonin Reuptake Inhibitors

Although it is widely believed that the various classes of antidepressants are equally effective, clinically meaningful differences may be obscured in individual studies because of a lack of statistical power. The present report describes a meta-analysis of original data from a complete set of studies comparing the norepinephrine/dopamine reuptake inhibitor (NDRI) bupropion with selective serotonin reuptake inhibitors (SSRIs; sertraline, fluoxetine, or paroxetine). Individual patient data were pooled from a complete set of 7 randomized, double-blind studies comparing bupropion (N = 732) with SSRIs (fluoxetine, N = 339; sertraline, N = 343; paroxetine, N = 49) in outpatients with major depressive disorder (DSM-III-R or DSM-IV); 4 studies included placebo (N = 512). Response and remission rates were compared at week 8 or endpoint in both the intent-to-treat sample, using the last-observation-carried-forward (LOCF) method to account for attrition, and the observed cases. Tolerability data, including incidence of sexual side effects, were also compared. The LOCF response and remission rates for the bupropion (62% and 47%) and SSRI (63% and 47%) groups were similar; both active therapies were superior to placebo (51% and 36%; all comparisons, p < .001). The same pattern of results was demonstrated on the observed cases analyses. Although bupropion and SSRIs were generally well tolerated, SSRI therapy resulted in significantly higher rates of sexual side effects as compared to both bupropion and placebo. SSRIs were also associated with more somnolence and diarrhea, and bupropion was associated with more dry mouth. Bupropion and the SSRIs were equivalently effective and, overall, both treatments were well tolerated. The principal difference between these treatments was that sexual dysfunction commonly complicated SSRI therapy, whereas treatment with bupropion caused no more sexual dysfunction than placebo.

Culture, Religion Frame Care for Muslim Patients

Culture, Religion Frame Care for Muslim Patients

A retrospective study of SSRI treatment in adolescent anorexia nervosa: insufficient evidence for efficacy

Although selective-serotonin-reuptake-inhibitors (SSRI) have been of limited efficacy in the treatment of eating disorder psychopathology and comorbid symptoms of malnourished patients with anorexia nervosa (AN), there is recent data suggesting that SSRI may play a role in preventing relapse among weight-restored patients. Though some previous studies included patients in late adolescence, the vast majority of investigated subjects have been adults. The aim of our retrospective study was to assess the effects of SSRI treatment in partially weight-restored children and adolescents with AN. Thirty two females with AN (mean 14.5 ± 1.4 years) were investigated three times during inpatient treatment and at 3- and 6-month follow-up for BMI, eating disorder psychopathology, depressive symptomology, and obsessive-compulsive symptomology. Medication history during inpatient and outpatient treatment was reconstructed at the 6-month follow-up. Nineteen patients received SSRI treatment, while 13 subjects were non-medicated. In comparison to the non-SSRI group, the SSRI group had similar BMI and obsessive-compulsive scores, but higher levels of core eating disorder psychopathology and depressive symptoms at the start of medication. Rates of re-admissions were similar in both groups (SSRI group: 36%, non-SSRI group: 31%, Φ: p = 0.72). Repeated measures ANOVA revealed no significant group with time interactions for BMI-SDS ( p = 0.84), core eating disorder symptoms (ANIS, p = 0.79), depression (DIKJ, p = 0.75), and obsessive-compulsive (CY-BOCS, p = 0.40) scores indicating minimal or no effects of SSRI medication on the course of these variables. In conclusion, our results challenge the efficacy of SSRI medication in the treatment of eating disorder psychopathology as well as depressive and obsessive-compulsive comorbidity in adolescent AN. Clinicians should be chary in prescribing SSRI in adolescent AN unless randomized controlled trials have proofed the benefit of these drugs.